CHEMICAL SAFETY REPORT
Substance Name: cadmium sulphate
EC Number: 233-331-6
CAS Number: 10124-36-4
Registrant's Identity:
EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Table of Contents
Part A ...................................................................................................................................................................... 1
1. SUMMARY OF RISK MANAGEMENT MEASURES ................................................................................ 1
2. DECLARATION THAT RISK MANAGEMENT MEASURES ARE IMPLEMENTED ............................ 1
3. DECLARATION THAT RISK MANAGEMENT MEASURES ARE COMMUNICATED ........................ 1
Part B ...................................................................................................................................................................... 2
1. IDENTITY OF THE SUBSTANCE AND PHYSICAL AND CHEMICAL PROPERTIES ......................... 2
1.1. Name and other identifiers of the substance ............................................................................................ 2
1.2. Composition of the substance .................................................................................................................. 2
1.3. Physico-chemical properties .................................................................................................................... 3
2. MANUFACTURE AND USES ...................................................................................................................... 5
2.1. Manufacture ............................................................................................................................................. 5
2.2. Identified uses .......................................................................................................................................... 5
2.3. Uses advised against ................................................................................................................................ 8
3. CLASSIFICATION AND LABELLING ....................................................................................................... 8
3.1. Classification and labelling according to CLP / GHS .............................................................................. 8
3.2. Classification and labelling according to DSD / DPD ........................................................................... 11
3.2.1. Classification and labelling in Annex I of Directive 67/548/EEC .................................................. 11
3.2.2. Self classification(s) ........................................................................................................................ 13
3.2.3. Other classification(s) ..................................................................................................................... 13
4. ENVIRONMENTAL FATE PROPERTIES ................................................................................................ 13
4.1. Degradation ........................................................................................................................................... 15
4.1.1. Abiotic degradation ........................................................................................................................ 15
4.1.1.1. Hydrolysis ................................................................................................................................ 15
4.1.1.2. Phototransformation/photolysis ............................................................................................... 15
4.1.1.2.1. Phototransformation in air ................................................................................................ 15
4.1.1.2.2. Phototransformation in water ............................................................................................ 15
4.1.1.2.3. Phototransformation in soil ............................................................................................... 15
4.1.2. Biodegradation ................................................................................................................................ 15
4.1.2.1. Biodegradation in water ........................................................................................................... 15
4.1.2.1.1. Estimated data ................................................................................................................... 15
4.1.2.1.2. Screening tests .................................................................................................................. 15
4.1.2.1.3. Simulation tests (water and sediments) ............................................................................. 15
4.1.2.1.4. Summary and discussion of biodegradation in water and sediment .................................. 16
4.1.2.2. Biodegradation in soil .............................................................................................................. 16
4.1.3. Summary and discussion of degradation ........................................................................................ 16
4.2. Environmental distribution .................................................................................................................... 16
4.2.1. Adsorption/desorption .................................................................................................................... 17
4.2.2. Volatilisation................................................................................................................................... 18
4.2.3. Distribution modelling .................................................................................................................... 18
4.2.4. Summary and discussion of environmental distribution ................................................................. 18
4.3. Bioaccumulation .................................................................................................................................... 18
4.3.1. Aquatic bioaccumulation ................................................................................................................ 19
4.3.2. Terrestrial bioaccumulation ............................................................................................................ 27
4.3.3. Summary and discussion of bioaccumulation ................................................................................. 37
4.4. Secondary poisoning .............................................................................................................................. 39
4.5. Natural background ............................................................................................................................... 41
5. HUMAN HEALTH HAZARD ASSESSMENT .......................................................................................... 42
5.1. Toxicokinetics (absorption, metabolism, distribution and elimination) ................................................ 42
5.2. Acute toxicity ........................................................................................................................................ 44
5.2.1. Non-human information ................................................................................................................. 44
5.2.1.1. Acute toxicity: oral .................................................................................................................. 44
5.2.1.2. Acute toxicity: inhalation ......................................................................................................... 45
5.2.1.3. Acute toxicity: dermal ............................................................................................................. 47
5.2.1.4. Acute toxicity: other routes ...................................................................................................... 47
5.2.2. Human information ......................................................................................................................... 47
5.2.3. Summary and discussion of acute toxicity ...................................................................................... 48
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EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
5.3. Irritation ................................................................................................................................................. 49
5.3.1. Skin ................................................................................................................................................. 49
5.3.1.1. Non-human information........................................................................................................... 49
5.3.1.2. Human information .................................................................................................................. 49
5.3.2. Eye .................................................................................................................................................. 49
5.3.3. Respiratory tract .............................................................................................................................. 49
5.3.4. Summary and discussion of irritation ............................................................................................. 49
5.4. Corrosivity ............................................................................................................................................. 49
5.5. Sensitisation ........................................................................................................................................... 49
5.5.1. Skin ................................................................................................................................................. 49
5.5.1.1. Non-human information........................................................................................................... 50
5.5.1.2. Human information .................................................................................................................. 50
5.5.2. Respiratory system .......................................................................................................................... 50
5.5.3. Summary and discussion of sensitisation........................................................................................ 50
5.6. Repeated dose toxicity ........................................................................................................................... 51
5.6.1. Non-human information ................................................................................................................. 51
5.6.1.1. Repeated dose toxicity: oral, inhalation and other ................................................................... 51
5.6.1.2. Repeated dose toxicity: dermal ................................................................................................ 58
5.6.2. Human information ......................................................................................................................... 58
5.6.3. Summary and discussion of repeated dose toxicity ........................................................................ 62
5.7. Mutagenicity .......................................................................................................................................... 63
5.7.1. Non-human information ................................................................................................................. 63
5.7.1.1. In vitro data .............................................................................................................................. 63
5.7.1.2. In vivo data ............................................................................................................................... 66
5.7.2. Human information ......................................................................................................................... 66
5.7.3. Summary and discussion of mutagenicity ...................................................................................... 70
5.8. Carcinogenicity ...................................................................................................................................... 71
5.8.1. Non-human information ................................................................................................................. 71
5.8.1.1. Carcinogenicity: oral ................................................................................................................ 71
5.8.1.2. Carcinogenicity: inhalation ...................................................................................................... 72
5.8.1.3. Carcinogenicity: dermal ........................................................................................................... 76
5.8.1.4. Carcinogenicity: other routes ................................................................................................... 76
5.8.2. Human information ......................................................................................................................... 78
5.8.3. Summary and discussion of carcinogenicity ................................................................................... 90
5.9. Toxicity for reproduction ....................................................................................................................... 91
5.9.1. Effects on fertility ........................................................................................................................... 91
5.9.1.1. Non-human information........................................................................................................... 91
5.9.1.2. Human information .................................................................................................................. 97
5.9.2. Developmental toxicity ................................................................................................................. 100
5.9.2.1. Non-human information......................................................................................................... 101
5.9.2.2. Human information ................................................................................................................ 103
5.9.3. Summary and discussion of reproductive toxicity ........................................................................ 106
5.10. Other effects ...................................................................................................................................... 107
5.10.1. Non-human information ............................................................................................................. 107
5.10.1.1. Neurotoxicity ....................................................................................................................... 107
5.10.1.2. Immunotoxicity .................................................................................................................... 107
5.10.1.3. Specific investigations: other studies ................................................................................... 107
5.10.2. Human information ..................................................................................................................... 107
5.10.3. Summary and discussion of specific investigations .................................................................... 108
5.11. Derivation of DNEL(s) / DMEL(s) ................................................................................................... 109
5.11.1. Overview of typical dose descriptors for all endpoints ............................................................... 109
5.11.2. Correction of dose descriptors if needed (for example route-to-route extrapolation), application of
assessment factors and derivation of the endpoint specific DN(M)EL ................................................... 113
6. HUMAN HEALTH HAZARD ASSESSMENT OF PHYSICO-CHEMICAL PROPERTIES .................. 116
6.1. Explosivity ........................................................................................................................................... 116
6.2. Flammability ........................................................................................................................................ 116
6.3. Oxidising potential .............................................................................................................................. 116
7. ENVIRONMENTAL HAZARD ASSESSMENT ...................................................................................... 117
7.1. Aquatic compartment (including sediment) ......................................................................................... 118
7.1.1. Toxicity test results ....................................................................................................................... 118
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EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
7.1.1.1. Fish ........................................................................................................................................ 128
7.1.1.1.1. Short-term toxicity to fish ............................................................................................... 128
7.1.1.1.2. Long-term toxicity to fish ............................................................................................... 131
7.1.1.2. Aquatic invertebrates ............................................................................................................. 137
7.1.1.2.1. Short-term toxicity to aquatic invertebrates .................................................................... 137
7.1.1.2.2. Long-term toxicity to aquatic invertebrates .................................................................... 140
7.1.1.3. Algae and aquatic plants ........................................................................................................ 159
7.1.1.4. Sediment organisms ............................................................................................................... 164
7.1.1.5. Other aquatic organisms ........................................................................................................ 166
7.1.2. Calculation of Predicted No Effect Concentration (PNEC) .......................................................... 167
7.1.2.1. PNEC freshwater ................................................................................................................... 168
7.1.2.2. PNEC water Marine ............................................................................................................... 170
7.1.2.3. PNEC sediment ...................................................................................................................... 174
7.2. Terrestrial compartment ....................................................................................................................... 183
7.2.1. Toxicity test results ....................................................................................................................... 183
7.2.1.1. Toxicity to soil macro-organisms .......................................................................................... 187
7.2.1.2. Toxicity to terrestrial plants ................................................................................................... 192
7.2.1.3. Toxicity to soil micro-organisms ........................................................................................... 198
7.2.1.4. Toxicity to other terrestrial organisms ................................................................................... 200
7.2.2. Calculation of Predicted No Effect Concentration (PNEC soil) ................................................... 200
7.3. Atmospheric compartment................................................................................................................... 204
7.4. Microbiological activity in sewage treatment systems ........................................................................ 204
7.4.1. Toxicity to aquatic micro-organisms ............................................................................................ 205
7.4.2. PNEC for sewage treatment plant ................................................................................................. 205
7.5. Non compartment specific effects relevant for the food chain (secondary poisoning) ........................ 206
7.5.1. Toxicity to birds ............................................................................................................................ 206
7.5.2. Toxicity to mammals .................................................................................................................... 208
7.5.3. Calculation of PNECoral (secondary poisoning) .......................................................................... 208
7.6. Conclusion on the environmental hazard assessment and on classification and labelling ................... 208
8. PBT AND VPVB ASSESSMENT ............................................................................................................. 209
8.1. Assessment of PBT/vPvB Properties ................................................................................................... 209
8.1.1. Summary and overall conclusions on PBT or vPvB properties .................................................... 210
9. EXPOSURE ASSESSMENT ..................................................................................................................... 210
9.1. GES CdSO4 solution-0: Industrial isolation of the Intermediate Cadmium Sulphate solution (273-7213) from Cadmium and/or Cadmium compounds leaching, refining or extraction steps, by settling, filtering
and other hydrometallurgical processes ...................................................................................................... 210
9.1.1. Exposure scenario ......................................................................................................................... 210
9.1.2. Exposure estimation ...................................................................................................................... 217
9.2. GES CdSO4 solution-2: Industrial use of the Intermediate Cadmium Sulphate solution (273-721-3) in
the ultimate manufacturing of Cadmium or Cadmium compounds by several metallurgical processes. ... 217
9.2.1. Exposure scenario ......................................................................................................................... 217
9.2.2. Exposure estimation ...................................................................................................................... 224
10. RISK CHARACTERISATION ................................................................................................................ 224
10.1. (Title of exposure scenario 1) ............................................................................................................ 224
10.1.1. Human health .............................................................................................................................. 224
10.1.1.1. Workers................................................................................................................................ 224
10.1.1.2. Consumers ........................................................................................................................... 224
10.1.1.3. Indirect exposure of humans via the environment ............................................................... 224
10.1.2. Environment ............................................................................................................................... 224
10.1.2.1. Aquatic compartment (incl. sediment) ................................................................................. 224
10.1.2.2. Terrestrial compartment ....................................................................................................... 224
10.1.2.3. Atmospheric compartment ................................................................................................... 224
10.1.2.4. Microbiological activity in sewage treatment systems ........................................................ 224
10.2. (Title of exposure scenario 2) ............................................................................................................ 224
10.3. Overall exposure (combined for all relevant emission/release sources) ............................................ 224
10.3.1. Human health (combined for all exposure routes) ...................................................................... 225
10.3.2. Environment (combined for all emission sources)...................................................................... 225
REFERENCES ................................................................................................................................................... 226
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EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
List of Tables
Table 1. Substance identity ..................................................................................................................................... 2
Table 2. Constituents .............................................................................................................................................. 3
Table 3. Overview of physico-chemical properties ................................................................................................ 3
Table 4. Overview of quantities (in tonnes// year)) ................................................................................................ 5
Table 5. Uses by workers in industrial settings ...................................................................................................... 6
Table 6. Freshwater BCF (L kg-1) reported in the EU risk assessment (ECB 2008; ) Table 3.2.34a) .................. 19
Table 7. BAF values for whole body vertebrates (L kg-1). (from the EU RA: Table 3.2.34b) ............................ 20
Table 8. BAF values of some benthic organisms (from EU RA; table 3.2.40) ..................................................... 21
Table 9. Overview of studies on aquatic bioaccumulation ................................................................................... 21
Table 10. Bioaccumulation factors (BAF's) of soil dwelling organisms (from EU RA: table 3.2.37.). ............... 27
Table 11. Overview of studies on terrestrial bioaccumulation ............................................................................. 28
Table 12. Kidney concentration in mammals and predicted critical soil concentrations at which the renal
threshold for toxicity may be exceeded (after linear extrapolation of the critical soil levels (values taken from
the RA Cd, (ECB 2008)) ...................................................................................................................................... 40
Table 13. Ambient background concentrations in Europe according to FOREGS (2006) ................................... 41
Table 14. Water solubility of the eight cadmium compounds covered in this assessment ................................... 42
Table 15. Overview of selected experimental studies on acute toxicity after oral administration ........................ 44
Table 16. Overview of selected experimental studies on acute toxicity after inhalation exposure ....................... 46
Table 17. Overview of selected experimental studies on repeated dose toxicity after oral administration .......... 51
Table 18. Overview of selected experimental studies on repeated dose toxicity after inhalation exposure ......... 53
Table 19 . Overview of selected studies on repeated dose toxicity (other routes) ................................................ 55
Table 20. Thresholds for renal effects in recent/relevant studies in occupational settings (inhalation exposure)
(adapted from ‘Recommendation from the Scientific Expert Group on Occupational Exposure Limits for Cd and
its inorganic compounds’ SCOEL/SUM/136) ...................................................................................................... 59
Table 21. Overview of selected experimental in vitro genotoxicity studies ......................................................... 63
Table 22. Overview of selected exposure-related observations on genotoxicity in humans................................. 66
Table 23. Overview of selected experimental studies on carcinogenicity after oral administration ..................... 72
Table 24. Overview of selected experimental studies on carcinogenicity after inhalation exposure .................... 72
Table 25. Overview of selected experimental studies on carcinogenicity (other routes) ...................................... 77
Table 26. Overview of selected exposure-related observations on carcinogenicity in humans ............................ 79
Table 27. Overview of selected experimental studies on male fertility and reproductive organs (oral route) ...... 91
Table 28. Overview of selected experimental studies on female fertility and reproductive organs (oral route) ... 94
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EC number:
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cadmium sulphate
CAS number:
10124-36-4
Table 29. Overview of selected exposure-related observations on toxicity to reproduction / fertility in humans 97
Table 30. Overview of selected experimental studies on developmental toxicity .............................................. 101
Table 31. Overview of selected exposure-related observations developmental toxicity in humans ................... 103
Table 32. Available dose-descriptor(s) per endpoint for water-soluble cadmium compounds (cadmium nitrate,
chloride and sulphate) ......................................................................................................................................... 109
Table 33. Available dose-descriptor(s) per endpoint for slightly soluble cadmium compounds (i.e. cadmium
metal, oxide, hydroxide and carbonate) .............................................................................................................. 111
Table 34. Derivation of cadmium DNEL biomonitoring for workers ........................................................................ 113
Table 35. Derivation of cadmium DNEL general population based on animal data ..................................................... 115
Table 36. Derivation of cadmium DNEL general population based on general population monitoring data ............... 115
Table 37. Acute aquatic toxicity of cadmium by species as a function of pH and hardness. ............................. 119
Table 38. Lowest acute aquatic toxicity data observed for cadmium ................................................................. 119
Table 39. 'Case-by-case”- selected NOEC data of effects of Cd in freshwater and case-by-case calculation of
'geometric mean NOEC's. Bold, underlined data are selected for the HC5 calculation. (after table 3.2.9C of the
EU risk assessment). ........................................................................................................................................... 120
Table 40. Endpoints selected for use in SSD for the derivation of marine PNEC for Cd. .................................. 125
Table 41. Summary statistics for the SSD on chronic NOEC values for cadmium in saltwater (n=50). ............ 127
Table 42. Results of field experiments made on phytoplankton communities coming from various natural sea
waters.................................................................................................................................................................. 128
Table 43. Overview of short-term effects on fish ............................................................................................... 128
Table 44. Overview of long-term effects on fish ................................................................................................ 131
Table 45. Overview of short-term effects on aquatic invertebrates .................................................................... 137
Table 46. Overview of long-term effects on aquatic invertebrates ..................................................................... 140
Table 47. Overview of effects on algae and aquatic plants................................................................................. 159
Table 48. Overview of long-term effects on sediment organisms ...................................................................... 164
Table 49. Overview of short-term effects on other aquatic organisms ............................................................... 166
Table 50. PNEC water ........................................................................................................................................ 172
Table 51. PNEC sediment................................................................................................................................... 182
Table 52. Summary table of species geometric mean NOECs for the most sensitive endpoints of plants and
invertebrates used in the SSD. New species to the ones mentioned in the RA or species for which new
information was found are highlighted in bold. The newly added individual NOECs are underlined in the last
column. ............................................................................................................................................................... 185
Table 53. Overview of effects on soil macro-organisms .................................................................................... 187
Table 54. Overview of effects on terrestrial plants ............................................................................................. 192
Table 55. Overview of effects on soil micro-organisms ..................................................................................... 198
Table 56. Summary statistics for the SSD on chronic NOEC values for cadmium in soil ................................. 201
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EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Table 57. Phytotoxicity of Cd salts in field trials (from Cd RA, 2008) .............................................................. 203
Table 58. Chronic long term field NOEC values taken from table 54. ............................................................... 203
Table 59. PNEC soil ........................................................................................................................................... 204
Table 60. Overview of effects on micro-organisms ............................................................................................ 205
Table 61. PNEC sewage treatment plant ............................................................................................................ 205
Table 62. Overview of effects on birds ............................................................................................................... 206
Table 63. PNEC oral ........................................................................................................................................... 208
Table 64. GES CdSO4 solution-0 ....................................................................................................................... 210
Table 65. GES CdSO4 solution-2 ....................................................................................................................... 217
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EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
List of Figures
Figure 1. The BCF values (L kg-1) of fish or fish tissues as a function of the Cd concentration in water (µg L-1).
Data collated from experiments where solution Cd was artificially increased (Figure 3.2.10 of the EU risk
assessment, ECB 2008) ........................................................................................................................................ 20
Figure 2. The bioaccumulation factors (BAF kg kg-1) of earthworms as a function of the Cd concentration in
soil (mg kg-1)(taken from the EU RA, figure 3.2.11) .......................................................................................... 28
Figure 3. Cumulative frequency of the critical soil Cd concentration at which the critical kidney Cd
concentration (400µg/gDW) may be exceeded in the average population of different wildlife species (loglogistic curve fitting) ............................................................................................................................................ 41
Figure 4. Illustration of Eurometaux/ICdA medical supervision guidance (2006) (BI: biological indicators; C:
creatinine) ........................................................................................................................................................... 114
Figure 5. Species sensitivity distribution of selected chronic marine Cd endpoints (n=47) ............................... 127
Figure 6. The cumulative frequency distribution of the NOEC values of Cd toxicity tests of data quality group
and RI 1-3 used to calculate the HC5 (case-by-case geometric mean calculation; n = 44). Selected data and
logistic distribution curve fitted on the data (figure taken from the RA Cd/CdO, ECB 2008). .......................... 168
Figure 7. Species diversity in the marine environment (from ECETOC 2001). The stars highlight taxonomic
groups represented in the cadmium marine database.......................................................................................... 171
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EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Part A
1. SUMMARY OF RISK MANAGEMENT MEASURES
Under section 9, risk management measures and operational conditions are described in more detail.
2. DECLARATION THAT RISK MANAGEMENT
MEASURES ARE IMPLEMENTED
“I,
implemented.”
, declare hereby that risk management measures as described in this CSR are
3. DECLARATION THAT RISK MANAGEMENT
MEASURES ARE COMMUNICATED
“I,
, declare hereby that risk management measures as described in this CSR are
communicated to downstream users.”
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
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EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Part B
1. IDENTITY OF THE SUBSTANCE AND PHYSICAL
AND CHEMICAL PROPERTIES
1.1. Name and other identifiers of the substance
The substance cadmium sulphate is a mono constituent substance (origin: inorganic) having the following
characteristics and physical–chemical properties (see the IUCLID dataset for further details).
The following public name is used: cadmium sulphate.
Table 1. Substance identity
EC number:
233-331-6
EC name:
cadmium sulphate
CAS number (EC inventory): 10124-36-4
IUPAC name:
cadmium sulfate
Annex I index number:
048-009-00-9
Molecular formula:
CdSO4
Molecular weight range:
208.446
Structural formula:
1.2. Composition of the substance
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EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Name: cadmium sulphate
Degree of purity: >= 80.0 — < 100.0 % (w/w)
Table 2. Constituents
Constituent
Typical concentration
Concentration range
cadmium sulphate
96.3 % (w/w)
>= 80.0 — < 100.0 %
(w/w)
EC no.: 233-331-6
Remarks
1.3. Physico-chemical properties
Table 3. Overview of physico-chemical properties
Property
Results
Physical state at
20°C and 1013 hPa
The physical state of the substance is
Value used for CSA: liquid
homogenous liquid, its colour is green, it is
odourless (Outotec, 2010).
Value used for CSA / Discussion
Melting / freezing
point
Freezing point is below 0°C
Boiling point
Boiling point is ca. 100°C (IZA, pers.
comm.)
Relative density
The density of the substance is 1.257 g/cm³ Value used for CSA: 1.257 at 20°C
Vapour pressure
The vapour pressure of the substance is of
0.0268 and 0.0475 bar at 25 and 35°C,
respectively.
Viscosity
Viscosity was measured experimentally and Value used for CSA: Viscosity at 20°C:
resulted in a value of 2.41, 1.49 and 1.08
2.41 mPa · s (dynamic)
mPa S at 20, 40 and 60°C, respectively.
Value used for CSA: 2680 Pa at 25 °C
Data waiving
Information requirement: Surface tension
Reason: other justification
Justification: surface activity is variable and is not a desired property of the material (criteria Column 2 of
Annex VII of REACH regulation).
Information requirement: Water solubility
Reason: other justification
Justification: this parameter is not relevant for liquids
Information requirement: Partition coefficient n-octanol/water (log value)
Reason: other justification
Justification: Not applicable to metal compounds; The study does not need to be conducted if the substance
is inorganic (column 2 of Annex VII of the REACH regulation)
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EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Information requirement: Flash point
Reason: other justification
Justification: not applicable. The study does not need to be conducted if the substance is inorganic (Column
2 of Annex VII of REACH regulation)
Information requirement: Flammability
Reason: other justification
Justification: The substance has no flammability, explosiveness or auto-flammability properties.
Information requirement: Explosive properties
Reason: other justification
Justification: The substance has no flammability, explosiveness or auto-flammability properties.
Information requirement: Self-ignition temperature
Reason: other justification
Justification: The substance has no flammability, explosiveness or auto-flammability properties.
Information requirement: Oxidising properties
Reason: other justification
Justification: the substance has no oxidizing properties
Information requirement: Granulometry
Reason: other justification
Justification: particle size distribution is not relevant for liquids
Information requirement: Stability in organic solvents and identity of relevant degradation products
Reason: other justification
Justification: Stability in organic solvents and identity of relevant degradation products is not an applicable
endpoint for inorganic substances according to column 2 of Annex IX of the REACH Regulation.
Information requirement: Dissociation constant
Reason: other justification
Justification: The dissociation constant relating to the acidity constant, pKa, as required by the IUCLID
database and REACH Guidance document, is not relevant for the substance.
Discussion of physico-chemical properties
For generating an updated, consistent and well-referenced database on the physico-chemical properties of the
substance, a typical sample from the lead registrant was analysed for all parameters relevant for REACH at the
Outotec Oy laboratories, Pori, Finland.
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EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Outotec Research Oy has a certified Quality system ISO 9001:2000, Environmental system ISO14001 and
Occupational Health and Safety system ISO18001. Laboratory accreditation according to ISO/IEC 17025 covers
gas and emission measurements and metal analyses.
Inspecta Sertifiointi Oy evaluates the management systems and FINAS (Finnish Accreditation Service)
evaluates the accredited methods. These audits are carried out annually. A couple of internal audits are also done
every year, for instance laboratory functions are audited annually. Besides audits, Outotec Research Oy takes
part in interlaboratory comparisons concerning metal analytics and emission measurements.
In 2008, Outotec Research Oy took part in the Finnish Excellence Quality Awards and received the prestigious
award, "Recognised for Excellence". Outotec Research Oy achieved a score of over 500 points, which entitles
the winner to use the five-star Recognised for Excellence, R4E emblem.
By this approach, a consistent, high quality and complete dataset on physicochemical properties of the substance
has been established, using state-of-the-art anaylitical techniques. This updated information is encoded in the
IUCLID V format.
2. MANUFACTURE AND USES
Quantities
Table 4. Overview of quantities (in tonnes// year))
Year
Total tonnage
Own use Used for article
Used as intermediate
Used for
under strictly controlled research
conditions
purposes
2.1. Manufacture
Manufacturing process
- Primary Cd-material (Cd-metal cake and Cd-bearing recycled scrap) are fed into the mixing tank. The leaching
reaction with sulphuric acid solutions is kept at the proper temperature and proper pH (~4.2).
- Leach residue is filtered on pressfilters
- Oxidation of some of the present elements may be necessary (Te > TeO2), followed by another filtration step,
if necessary
- Further transfer of the Cadmium sulphate solution by pipes or in specially designed transfer units
2.2. Identified uses
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EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Table 5. Uses by workers in industrial settings
Confidential
IU number
Identified Use
(IU) name
Substance
supplied to
that use
Use descriptors
1
Cadmium
sulphate
production wet
as such
(substance
itself)
Process category (PROC):
PROC 2: Use in closed, continuous process with occasional controlled exposure
PROC 3: Use in closed batch process (synthesis or formulation)
PROC 8b: Transfer of substance or preparation (charging/discharging) from/to vessels/large
containers at dedicated facilities
PROC 9: Transfer of substance or preparation into small containers (dedicated filling line, including
weighing)
PROC 22: Potentially closed processing operations with minerals/metals at elevated temperature.
Industrial setting
PROC 26: Handling of solid inorganic substances at ambient temperature
Market sector by type of chemical product:
PC 20: Products such as ph-regulators, flocculants, precipitants, neutralisation agents
Environmental release category (ERC):
ERC 1: Manufacture of substances
Sector of end use (SU):
SU 8: Manufacture of bulk, large scale chemicals (including petroleum products)
SU 9: Manufacture of fine chemicals
Subsequent service life relevant for that use?: yes
2
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Use of
Cadmium
sulphate as
component for
production of
inorganic
Cadmium
compounds
as such
(substance
itself)
in a mixture
Process category (PROC):
PROC 2: Use in closed, continuous process with occasional controlled exposure
PROC 3: Use in closed batch process (synthesis or formulation)
PROC 8b: Transfer of substance or preparation (charging/discharging) from/to vessels/large
containers at dedicated facilities
PROC 9: Transfer of substance or preparation into small containers (dedicated filling line, including
weighing)
PROC 15: Use as laboratory reagent
PROC 21: Low energy manipulation of substances bound in materials and/or articles
CHEMICAL SAFETY REPORT
6
EC number:
233-331-6
Confidential
cadmium sulphate
IU number
Identified Use
(IU) name
Substance
supplied to
that use
CAS number:
10124-36-4
Use descriptors
PROC 22: Potentially closed processing operations with minerals/metals at elevated temperature.
Industrial setting
Market sector by type of chemical product:
PC 19: Intermediate
PC 20: Products such as ph-regulators, flocculants, precipitants, neutralisation agents
PC 21: Laboratory chemicals
Environmental release category (ERC):
ERC 6a: Industrial use resulting in manufacture of another substance (use of intermediates)
Sector of end use (SU):
SU 8: Manufacture of bulk, large scale chemicals (including petroleum products)
SU 9: Manufacture of fine chemicals
SU 10: Formulation [mixing] of preparations and/or re-packaging (excluding alloys)
Subsequent service life relevant for that use?: yes
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
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EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Most common technical function of substance (what it does):
Intermediates
2.3. Uses advised against
None
3. CLASSIFICATION AND LABELLING
3.1. Classification and labelling according to CLP / GHS
Name: cadmium sulphate
Implementation: EU
State/form of the substance: liquid
Related composition: cadmium sulphate
Classification
The substance is classified as follows:
 for physical-chemical properties:
Explosives:
Reason for no classification: conclusive but not sufficient for classification
Flammable gases:
Reason for no classification: conclusive but not sufficient for classification
Flammable aerosols: Reason for no classification: conclusive but not sufficient for classification
Oxidising gases:
Reason for no classification: conclusive but not sufficient for classification
Gases under
pressure:
Reason for no classification: conclusive but not sufficient for classification
Flammable liquids:
Reason for no classification: conclusive but not sufficient for classification
Flammable solids:
Reason for no classification: conclusive but not sufficient for classification
Self-reacting
substances and
mixtures:
Reason for no classification: conclusive but not sufficient for classification
Pyrophoric liquids:
Reason for no classification: conclusive but not sufficient for classification
Pyrophoric solids:
Reason for no classification: conclusive but not sufficient for classification
Self-heating
substances and
mixtures:
Reason for no classification: conclusive but not sufficient for classification
Substances and
mixtures which in
Reason for no classification: conclusive but not sufficient for classification
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CHEMICAL SAFETY REPORT
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EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
contact with water
emits flammable
gases:
Oxidising liquids:
Reason for no classification: conclusive but not sufficient for classification
Oxidising solids:
Reason for no classification: conclusive but not sufficient for classification
Organic peroxides:
Reason for no classification: conclusive but not sufficient for classification
Corrosive to metals: Reason for no classification: conclusive but not sufficient for classification
 for health hazards:
Acute toxicity - oral: Acute Tox. 3 (Hazard statement: H301: Toxic if swallowed.)
Acute toxicity dermal:
Reason for no classification: conclusive but not sufficient for classification
Acute toxicity inhalation:
Acute Tox. 2 (Hazard statement: H330: Fatal if inhaled.)
Skin
corrosion/irritation:
Reason for no classification: conclusive but not sufficient for classification
Serious damage/eye
irritation:
Reason for no classification: conclusive but not sufficient for classification
Respiration
sensitization:
Reason for no classification: conclusive but not sufficient for classification
Skin sensitation:
Reason for no classification: conclusive but not sufficient for classification
Aspiration hazard:
Reason for no classification: conclusive but not sufficient for classification
Reproductive
Toxicity:
Repr. 1B (Hazard statement: H360: May damage fertility or the unborn child <state
specific effect if known > <state route of exposure if it is conclusively proven that no
other routes of exposure cause the hazard>.)
Reproductive
Toxicity: Effects on
or via lactation:
Reason for no classification: conclusive but not sufficient for classification
Germ cell
mutagenicity:
Muta. 1B (Hazard statement: H340: May cause genetic defects <state route of exposure
if it is conclusively proven that no other routes of exposure cause the hazard>.)
Carcinogenicity:
Carc. 1B (Hazard statement: H350: May cause cancer <state route of exposure if it is
conclusively proven that no other routes of exposure cause the hazard>.)
Specific target organ Reason for no classification: conclusive but not sufficient for classification
toxicity - single:
Specific target organ STOT Rep. Exp. 1 (Hazard statement: H372: Causes damage to organs <or state all
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
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EC number:
233-331-6
toxicity - repeated:
cadmium sulphate
CAS number:
10124-36-4
organs affected, if known> through prolonged or repeated exposure <state route of
exposure if it is conclusively proven that no other routes of exposure cause the hazard>.)
Specific concentration limits:
Concentration (%)
Classification
>= 7.0
STOT Rep. Exp. 1
>= 0.1 — < 7.0
STOT Rep. Exp. 2
>= 0.01
Carc. 1B
 for environmental hazards:
Hazards to the
Aquatic Chronic 1 (Hazard statement: H410: Very toxic to aquatic life with long lasting
aquatic environment: effects.)
Hazardous to the
atmospheric
environment:
M-Factor:
Reason for no classification: data lacking
10
Labelling
Signal word: Danger
Hazard pictogram:
GHS06: skull and crossbones
GHS08: health hazard
GHS09: environment
Hazard statements:
H350: May cause cancer <state route of exposure if it is conclusively proven that no other routes of exposure
cause the hazard>.
H340: May cause genetic defects <state route of exposure if it is conclusively proven that no other routes of
exposure cause the hazard>.
H360: May damage fertility or the unborn child <state specific effect if known > <state route of exposure if it is
conclusively proven that no other routes of exposure cause the hazard>. (H360FD is exact statement (translation
of R60-61))
H330: Fatal if inhaled.
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EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
H301: Toxic if swallowed.
H372: Causes damage to organs <or state all organs affected, if known> through prolonged or repeated
exposure <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.
H410: Very toxic to aquatic life with long lasting effects.
Precautionary statements:
P270: Do not eat, drink or smoke when using this product.
P280: Wear protective gloves/protective clothing/eye protection/face protection.
P308+P313: IF exposed or concerned: Get medical advice/attention.
P273: Avoid release to the environment.
P391: Collect spillage.
P405: Store locked up.
P501: Dispose of contents/container to... (text according to local/national law)
----------------------------------------------------------------------------------------------------------------------------- ---------
3.2. Classification and labelling according to DSD / DPD
3.2.1. Classification and labelling in Annex I of Directive 67/548/EEC
Chemical name: cadmium sulphate
Related composition: cadmium sulphate
Classification
The substance is classified as follows:
 for health effects:
T+; R26 Very toxic; Very toxic by inhalation.
T; R25 Toxic; Toxic if swallowed.
T; R48/23/25 Toxic; Toxic: danger of serious damage to health by prolonged exposure through
inhalation, in contact with skin and if swallowed.
Carc. Cat. 2; R45 May cause cancer.
Muta. Cat. 2; R46 May cause heritable genetic damage.
Repr. Cat. 2; R60 May impair fertility.
Repr. Cat. 2; R61 May cause harm to the unborn child.
 for the environment:
N; R50/53 Dangerous for the environment; Very toxic to aquatic organisms, may cause long-term
adverse effects in the aquatic environment.
Labelling
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CHEMICAL SAFETY REPORT
11
EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Indication of danger:
T+ - very toxic
N - dangerous for the environment
R-phrases:
R45 - may cause cancer
R46 - may cause heritable genetic damage
R60 - may impair fertility
R61 - may cause harm to the unborn child
R25 - toxic if swallowed
R26 - very toxic by inhalation
R48/23/25 - toxic: danger of serious damage to health by prolonged exposure through inhalation and if
swallowed
R50/53 - very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment
S-phrases:
S36/37/39 - wear suitable protective clothing, gloves and eye/face protection
S53 - avoid exposure - obtain special instructions before use
S45 - in case of accident or if you feel unwell, seek medical advice immediately (show the lable where possible)
S60 - this material and its container must be disposed of as hazardous waste
S61 - avoid release to the environment. refer to special instructions/safety data sheets
Specific concentration limits:
Concentration (%)
Classification
>= 25.0
Carc. Cat. 2; R45 May cause cancer.
Muta. Cat. 2; R46 May cause heritable genetic damage.
Repr. Cat. 1; R60 May impair fertility.
T; R25 Toxic; Toxic if swallowed.
T+; R26 Very toxic; Very toxic by inhalation.
T; R48/23/25 Toxic; Toxic: danger of serious damage to health by prolonged
exposure through inhalation, in contact with skin and if swallowed.
N; R50/53 Dangerous for the environment; Very toxic to aquatic organisms,
may cause long-term adverse effects in the aquatic environment.
>= 10.0 — < 25.0
Carc. Cat. 2; R45 May cause cancer.
Muta. Cat. 2; R46 May cause heritable genetic damage.
Repr. Cat. 1; R60 May impair fertility.
Repr. Cat. 2; R60 May impair fertility.
T; R25 Toxic; Toxic if swallowed.
T+; R26 Very toxic; Very toxic by inhalation.
T; R48/23/25 Toxic; Toxic: danger of serious damage to health by prolonged
exposure through inhalation, in contact with skin and if swallowed.
N; R51/53 Dangerous for the environment; Toxic to aquatic organisms, may
cause long-term adverse effects in the aquatic environment.
>= 7.0 — < 10.0
Carc. Cat. 1; R45 May cause cancer.
Muta. Cat. 1; R46 May cause heritable genetic damage.
Repr. Cat. 1; R60 May impair fertility.
Repr. Cat. 2; R60 May impair fertility.
Xn; R22 Harmful; Harmful if swallowed.
T+; R26 Very toxic; Very toxic by inhalation.
T; R48/23/25 Toxic; Toxic: danger of serious damage to health by prolonged
exposure through inhalation, in contact with skin and if swallowed.
N; R51/53 Dangerous for the environment; Toxic to aquatic organisms, may
cause long-term adverse effects in the aquatic environment.
>= 2.5 — < 7.0
Carc. Cat. 2; R45 May cause cancer.
Muta. Cat. 2; R46 May cause heritable genetic damage.
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CHEMICAL SAFETY REPORT
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EC number:
233-331-6
Concentration (%)
cadmium sulphate
CAS number:
10124-36-4
Classification
Repr. Cat. 1; R60 May impair fertility.
Repr. Cat. 2; R60 May impair fertility.
Xn; R22 Harmful; Harmful if swallowed.
T; R23 Toxic; Toxic by inhalation.
Xn; R48/20/22 Harmful; Harmful: danger of serious damage to health by
prolonged exposure through inhalation and if swallowed.
N; R51/53 Dangerous for the environment; Toxic to aquatic organisms, may
cause long-term adverse effects in the aquatic environment.
>= 1.0 — < 2.5
Carc. Cat. 2; R45 May cause cancer.
Muta. Cat. 2; R46 May cause heritable genetic damage.
Repr. Cat. 1; R60 May impair fertility.
Repr. Cat. 2; R60 May impair fertility.
Xn; R22 Harmful; Harmful if swallowed.
T; R23 Toxic; Toxic by inhalation.
Xn; R48/20/22 Harmful; Harmful: danger of serious damage to health by
prolonged exposure through inhalation and if swallowed.
R52/53 Dangerous for the environment; Harmful to aquatic organisms, may
cause long-term adverse effects in the aquatic environment.
>= 0.5 — < 1.0
Carc. Cat. 2; R45 May cause cancer.
Muta. Cat. 2; R46 May cause heritable genetic damage.
Repr. Cat. 1; R60 May impair fertility.
Repr. Cat. 2; R60 May impair fertility.
Xn; R20/22 Harmful; Harmful by inhalation and if swallowed.
Xn; R48/20/22 Harmful; Harmful: danger of serious damage to health by
prolonged exposure through inhalation and if swallowed.
R52/53 Dangerous for the environment; Harmful to aquatic organisms, may
cause long-term adverse effects in the aquatic environment.
>= 0.25 — < 0.5
Carc. Cat. 2; R45 May cause cancer.
Muta. Cat. 2; R46 May cause heritable genetic damage.
Xn; R20/22 Harmful; Harmful by inhalation and if swallowed.
Xn; R48/20/22 Harmful; Harmful: danger of serious damage to health by
prolonged exposure through inhalation and if swallowed.
R52/53 Dangerous for the environment; Harmful to aquatic organisms, may
cause long-term adverse effects in the aquatic environment.
>= 0.1 — < 0.25
Carc. Cat. 2; R45 May cause cancer.
Muta. Cat. 2; R46 May cause heritable genetic damage.
Xn; R20/22 Harmful; Harmful by inhalation and if swallowed.
Xn; R48/20/22 Harmful; Harmful: danger of serious damage to health by
prolonged exposure through inhalation and if swallowed.
>= 0.01 — < 0.1
Carc. Cat. 2; R45 May cause cancer.
Notes:
Note E
3.2.2. Self classification(s)
3.2.3. Other classification(s)
4. ENVIRONMENTAL FATE PROPERTIES
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EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
General discussion of environmental fate and pathways:
The intermediates are as a principle not released in the environment. Still, if even minute, insignificant amounts
of the main substance (cadmium) is released, some of the information on environmental distribution of cadmium
is relevant and available. It is summarised in the IUCLID section 5.
General introduction to chapters 4, 5, 6 and 7.
Under Regulation 793/93/CEE, an extensive risk assessment on Cd metal and CdO has been recently prepared
by the Belgian authorities for the EU. The risk assessment report (RAR) on these cadmium substances has been
recently published (ECB 2008).
Since these RARs were the result of intensive discussions between all stakeholders, and were approved by
experts from all the member states; since they provide a recent review of the available evidence on cadmium
and cadmium compounds, they will be used as the main reference for this chemical safety report.
In this chemical safety report, the information, data and conclusions of the RAR will be summarised, focusing
on the principles applied, the assumptions made and the conclusions. Where available and relevant, new
information and data will be included and discussed.
General remarks on the chapter on environmental fate properties.
Cadmium is a natural element, which is present in all environmental compartments. It occurs in the metallic
state, or as cadmium compound, with one valency state (Cd++). All environmental concentration data are
expressed as “Cd”, while toxicity is caused by the Cd++ ion. For this reason, the sections on human toxicity and
ecotoxicity are applicable to all cadmium compounds, from which Cd ions are released into the environment.
Some compounds have however very low solubility and will therefore not release Cd ions, or to a lower extent;
this strongly decreases their potential for (eco-)toxicity. As a consequence, distinction can be made between Cd
compounds, as a function of their solubility (see chapters 5 and 7).
For checking the potential of metal substances to release ions in the environment, a specific test, the
transformation/dissolution (T/D) test is used. For metallic Cd and some of the Cd compounds, this test has been
performed. If applicable, the results of such T/D test are discussed in section 4.6. (data in IUCLID section 5.6.).
The issue of degradation (section 4.1.) is not applicable to inorganic compounds.
When Cd ions are present in the environment, they will further interact with the environmental matrix and biota.
As such, the concentration of Cd ions that is available to organisms, the bioavailable fraction, will depend on
processes like dissolution, absorption, precipitation, complexation, inclusion into (soil) matrix, etc. These
processes are defining the fate of Cd in the environment and, ultimately, its ecotoxic potential.
In the water, the bioavailability of Cd through interaction with components of the water and biota has been
discussed in the Cd RA (ECB 2008). This has resulted in an approach for quantifying Cd bioavailability into
risk assessment, using hardness as a driver for ecotoxicity. When the information on hardness is available, the
PNEC can be expressed on a water hardness basis (see chapter 7).
The ultimate fate of metals in water (in the water column) can be assessed via the “unit world model”, that can
quantify the “removal from the water column” of the Cd species. This phenomenon was not yet studied for Cd,
but can be considered for classification.
In sediment, Cd binds to the sulphide fraction to form insoluble CdS. As such, Cd is not bioavailable anymore to
organisms. The sulfide fraction in sediment, as quantified by the AVS, is a reactive pool that binds metals, e.g.
Cd and makes them unavailable for biota. The affinity for metal binding on the sulfide fraction in the sediment
has been well established for the metals Cu, Cd, Pb, Zn and Ni. In that order, these metals will be bound on the
sulfide present in the sediment and, as a consequence, will not be available anymore for uptake and possible
toxicity. If the molar difference between SEM and AVS (i.e., SEM-AVS) is less than zero, no toxicity is
expected, while a molar difference greater than zero suggests that toxic effects may occur. Although the
background and application of this method was described in detail in the Cd RAR (2008), the approach was not
applied in the EU risk assessment on cadmium. However, it was fully worked out in the subsequent discussions
on the Zn RA (ECB 2008), and applied for the risk characterisation. Because of the fact that Cd will bind to
2010-09-07 CSR-PI-5.2.1
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EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
sulfide preferentially over zinc, it can be anticipated that the AVS/SEM concept applies also to cadmium. It is
therefore considered possible to apply the concept on a local site-specific scale (Cd RAR, 2008) Due to the
insolubility of the CdS (6 x 10-7 mg/l) Cd will be sequestered in the (anaerobioc) sediments, and the remobilisation of Cd ions into the water column will be prevented.
In soil, short-term interaction of Cd ions upon spiking, and long term interactions (“ageing”) have been
discussed in the Cd RA (ECB 2008). The analysis was however based on the worst case of acid sandy soils,
without making further refinements related to soil type or ageing.
4.1. Degradation
4.1.1. Abiotic degradation
4.1.1.1. Hydrolysis
Data waiving
Reason: study scientifically unjustified
Justification: Waived: According to Annex IX of REACH Regulation, information on hydrolysis is not
required for inorganics
The following 4.1.-related endpoints are not relevant for inorganics:
4.1.1.2. Phototransformation/photolysis
4.1.1.2.1. Phototransformation in air
4.1.1.2.2. Phototransformation in water
4.1.1.2.3. Phototransformation in soil
4.1.2. Biodegradation
4.1.2.1. Biodegradation in water
4.1.2.1.1. Estimated data
4.1.2.1.2. Screening tests
Data waiving
Reason: other justification
Justification: Biodegradation is not applicable to metals/inorganic substances; study does not need to be
conducted if substance is inorganic (Annex VII of REACH regulation).
4.1.2.1.3. Simulation tests (water and sediments)
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EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Data waiving
Reason: other justification
Justification: Biodegradation is not applicable to metals/inorganic substances; study does not need to be
conducted if substance is inorganic (Annex VII of REACH regulation).
4.1.2.1.4. Summary and discussion of biodegradation in water and sediment
Discussion (screening testing)
Discussion (simulation testing)
4.1.2.2. Biodegradation in soil
Data waiving
Reason: other justification
Justification: Biodegradation is not applicable to metals/inorganic substances; study does not need to be
conducted if substance is inorganic (Annex VII of REACH regulation).
4.1.3. Summary and discussion of degradation
Abiotic degradation
Biotic degradation
Biodegradation is not applicable to metals/inorganic substances. Tests are not to be conducted if the substance is
inorganic (Column 2 of Annex VII of REACH regulation)
4.2. Environmental distribution
The environmental fate and release of Cd and Cd compounds has been discussed extensively in the RAR (ECB
2008).
Environmental distribution in water
Cd in freshwater or seawater can occur in both suspended and dissolved forms and is partitioned over a number
of chemical species. Depending on the concentration of suspended matter, about 25-40% of the Cd entering the
surface water is in dissolved form, the remaining part is bound to the suspended matter. For toxicity, only the
fraction not bound is important.
Dissolved forms of Cd in freshwater are e.g.: hydrated Cd ions, Cd ions complexed by inorganic or organic
ligands (humic and fulvic acids), Cd oxy ions and Cd adsorbed to solid matter.
The speciation of Cd in the aquatic compartment is of high complexity and depends highly on abiotic factors,
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EC number:
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cadmium sulphate
CAS number:
10124-36-4
such as pH, (dissolved) organic matter content, redox potential, etc. It is assumed that speciation is very relevant
for the migration of Cd through sediment, for the distribution of Cd among its truly dissolved and non-dissolved
forms, and for the uptake of Cd by some aquatic and sediment organisms. The relationship between the
physicochemical factor hardness and the bioavailability, and consequently, the toxicity of Cd has been
experimentally elucidated and has been quantified in the RA (see further).
Environmental distribution in soil; adsorption/desorption of Cd in soil
Speciation of Cd in soil
In soils, Cd interacts with various reactive soil surfaces. The most important in this respect are soil organic
matter, amorphous soil oxides (Al, Fe, Mn) and clay minerals. The major process by which metals are bound to
these surfaces is adsorption. Other processes including precipitation of carbonate type minerals can occur but
are, in non- and moderately polluted soils, unlikely to control the solubility of metals in soils. An exception to
this is the formation of sulphide minerals that are formed, in the presence of sulphate under reducing conditions.
Cd in soil is distributed between the following fractions :
1. Dissolved in pore water (which includes many species)
2. Exchangeable, bound to soil particles
3. Exchangeable, bound to organic ligands (of which a small part in the dissolved fraction and the major part
in the solid fraction)
4. Present in secondary clay minerals and metal oxides/hydroxides
5. Present in primary minerals
So, Cd is present in the soil in various forms, that have varying degree of extractability. The soil pH is an
important parameter that affects the speciation and the distribution of the Cd species over the soil and the
solution. Cd tends to be more sorbed and complexed at higher pH (pH > 7) than at lower pH. Below pH 7, the
amount of Cd in solution was reported to be inversely related to soil pH (Janssen et al., 1997). The pH of the soil
not only determines the degree of complexation and adsorption of Cd, but also the solubility of the various Cd
minerals. The solubility of Cd in soil decreases with increasing pH (ECB 2008).
After addition of a metal to a soil, often a slow decrease in the soil solution concentration, or the available
fraction as determined in an extraction solution (e.g. by CaCl 2) decreases as a result of (presumably) slow
diffusion processes of metals into the matrix of the reactive surfaces. It is this process, or sum of as of yet poorly
defined slow processes, that can be defined as ‘ageing’.
The bioavailability of Cd has however not been worked out further in the RA or in this analysis.
4.2.1. Adsorption/desorption
Data waiving
Reason: study scientifically unjustified
Justification: For metals, adsorption/desorption translates in the distribution of the metals between the
different fractions of the environmental compartment, e. g. the water (dissolved fraction, fraction bound to
suspended matter), soil (fraction bound or complexed to the soil particles, fraction in the soil pore water...).
This distribution between the different compartments is translated in the partition coefficients between these
different fractions. Information on partition coefficients is given under IUCLID section 5.6.
Discussion
For metals, the transport and distribution over the different environmental compartments e. g. the water
(dissolved fraction, fraction bound to suspended matter), soil (fraction bound or complexed to the soil particles,
fraction in the soil pore water...) is described and quantified by the metal partition coefficients between these
different fractions. The information on these partition coefficients is given under IUCLID section 5.6.
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EC number:
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cadmium sulphate
CAS number:
10124-36-4
Partition coefficients for cadmium in freshwater have been reviewed in the EU risk assessment report (ECB
2008). Based on this experimental evidence, a partition coefficient for the distribution between solid particulate
matter and water (Kpsusp) of 130 x 103l/kg has been defined for EU waters and was used throughout the RAR.
The Kp for the distribution between sediment and water (Kp sed) was estimated in the RAR from the ratio of the
average sediment (1.32mg/kgDW) to average water Cd concentrations (0.14µg/l). This "best fit" Kd yields
10000L/kgDW (ECB 2008).
These partition coefficients have been used since then in other legislative processes in the EU (e. g. the water
framework directive) and will also be used for REACH.
The marine Kd was derived based on data from several marine waters. The geomean value for cadmium in
seawater is 617 l/kg
The following information is taken into account for any environmental exposure assessment:
Kp for solid particulate matter and water (Kpsusp): 130000 l/kg (log value: 5.1)
Kp for water and sediment (Kpsed); 10000 l/kg (log value: 4)
Kd for marine waters is 617 l/kg (log value: 2.79)
4.2.2. Volatilisation
4.2.3. Distribution modelling
4.2.4. Summary and discussion of environmental distribution
For metals, the transport and distribution over the different environmental compartments e. g. the water
(dissolved fraction, fraction bound to suspended matter), soil (fraction bound or complexed to the soil particles,
fraction in the soil pore water...) is described and quantified by the metal partition coefficients between these
different fractions. The information on these partition coefficients is given under IUCLID section 5.6.
Partition coefficients for cadmium in freshwater have been reviewed in the EU risk assessment report (ECB
2008). Based on this experimental evidence, a partition coefficient for the distribution between solid particulate
matter and water (Kpsusp) of 130 x 103 l/kg has been defined for EU waters and was used throughout the RAR.
The Kp for the distribution between sediment and water (Kp sed) was estimated in the RAR from the ratio of the
average sediment (1.32mg/kgDW) to average water Cd concentrations (0.14µg/l). This "best fit" Kd yields
10000L/kgDW (ECB 2008).
These partition coefficients have been used since then in other legislative processes in the EU (e. g. the water
framework directive) and will also be used for REACH.
For the marine water, a partition coefficient water/suspended matter of 617 l/kg has been derived.
The summary of these Kp values is given under 4.2.1..
4.3. Bioaccumulation
Numerous data on bioconcentration and bioaccumulation were reviewed in the Cd RA, and in McGeer et al
(2003). Reviewed. For Cd (as for other metals), BCF and BAF values are not independent of exposure: the
higher BCF/BAF factors are observed generally at the lower Cd exposure levels. In other words, the BCF/BAF
will strongly decrease when exposure concentrations increase. This results in a general negative relationship
2010-09-07 CSR-PI-5.2.1
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EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
between BCF and exposure, and has implications forn the interpretation of BCF/BAF for hazard identification
and classification (McGeer et al 2003).
4.3.1. Aquatic bioaccumulation
Numerous data on BCFs for Cadmium and its compounds were reviewed in the EU risk assessment (ECB
2008). The analysis was based on BCF-values that are calculated on the basis of steady-state uptake and
depuration rate constants.
Data were considered adequate and relevant when based on measured concentrations in the water and the biota,
when the experiments span a long-term exposure, steady state was reached and the test conditions are relevant
for the real environment.
Most of the BC values were calculated from the concentration ratio between water and biota. BCF's for
cadmium are highest in algae and lowest in fish (see table below). In the RA, it was emphasised that a high BCF
in algae does not necessarily reflect high bioconcentration, because a significant part of the Cd is absorbed to the
outer side of the organisms, and not taken up. Another factor of error is the lack of gut clearance in
invertebrates. Organs (kidney, liver) contain most Cd.
Table 6. Freshwater BCF (L kg-1) reported in the EU risk assessment (ECB 2008; ) Table 3.2.34a)
algae wet weight
dry weight
invertebrates wet weight
dry weight
vertebrates wet weight
dry weight
vertebrates -total body
content- wet weight
dry weight
min
1636
2222
396
546
0.51
5
max
23143
310000
17560
33333
684
33333
median
7535
115116
994
5000
229
233
0.51
5
51
1385
15
80
Main influencing factors for Cd BCF identified in the RA were hardness and Cd concentration in the water.
Increasing water hardness reduces Cd uptake. BCF was also found to be inversely related to Cd concentration in
water.
McGeer et al (2003) recently reviewed extensive evidence on bioconcentration and bioaccumulation of
cadmium as a function of exposure concentration in a wide variety of taxonomic groups (algae, molluscs,
arthropods, annelids, salmonid fish, cyprinid fish, and other fish). The data clearly illustrated that there is a
significant degree of control by the organisms on their internal cadmium content.
In general and for all taxonomic groups, BCF data showed an inverse relationship to exposure concentrations. In
all cases, the relationship of BCF to exposure was significant and negative. The slopes of the BCF/BAF –
exposure relations were: algae: -0.72, insects: -0.32, arthropods: -0.61, molluscs: -0.50, salmonids: -0.87,
Centrarchids: -0.47, Killifish: -0.05, other fish: -0.72. Overall, species mean slope was -0.49 +/- 0.04 (McGeer
et al 2003). This confirms the observation of the RA:, increasing water Cd-concentrations results in decreasing
BCF. This is further illustrated by the BCF values of fish presented in figure below. The decreasing trend was
observed in all tissues.
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
19
EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Figure 1. The BCF values (L kg-1) of fish or fish tissues as a function of the Cd concentration in water
(µg L-1). Data collated from experiments where solution Cd was artificially increased (Figure 3.2.10 of
the EU risk assessment, ECB 2008)
For BAF, the data are more scarce. The risk assessment reported BAF from 4 up to 170000L/kgDW (for
Hyallela azteca). BAF are much lower in fish (see table below). Comparison of bioaccumulation factors and
bioconcentration factors of aquatic invertebrates reveals the latter to be significantly lower (EU RA).
Table 7. BAF values for whole body vertebrates (L kg-1). (from the EU RA: Table 3.2.34b)
min
max
median
vertebrates -total body–
4
2492
167
content- dry weight
vertebrates -total body
1
623
42
content- wet weight*
* calculated assuming a mean dry weight:wet weight ratio of 0.25 for whole fish
Munger and Hare (1997) found a BAF of 1345 L kg-1dw for the insect Chaoborus punctipennis in a laboratory
test. They also studied the relative importance of water and food as Cd sources to the insect. In artificial lake
water, a food chain was simulated, composed of the larvae of the insect, its crustacean prey (Ceriodaphnia
dubia), and the prey's algae food (Selenastrum capricornutum). Animals were exposed to a Cd concentration of
1.1 µg Cd2+ L-1. From this test it was possible to study the biomagnification. Selenastrum capricornutum
exposed to 1.1 µg Cd2+ L-1 had a Cd content of 1110 g g-1dw and was the food for Ceriodaphnia dubia.
Exposure of the latter to the same Cd2+ concentration in the water and to Cd-enriched algae resulted in a body
burden of 77 g g-1dw. Chaoborus punctipennis contained 16 g Cd g-1dw when fed by Cd-enriched
Ceriodaphnia in water containing 1.1 µg Cd L-1. The RA concluded that these results suggest no
biomagnification of Cd in the lower aquatic food chain Munger and Hare, 1997). This was also observed in an
experimental food chain study consisting of algae, zooplankton and fish, in which it was demonstrated that Cd
concentrations decreased with increasing throphic level (Ferard et al 1983)
The EU risk assessment also discussed some data on bioaccumulation in sediment. In the sediment, BAFs are
generally very low; most of the BAF’s of benthic organism are lower than 1 (either fresh weight based or dry
weight based (see table below). The BAF’s are smaller for vertebrates than for invertebrates.
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
20
EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Table 8. BAF values of some benthic organisms (from EU RA; table 3.2.40)
min
max
invertebrates, wet weight
0.38
0.44
(kgdw/kgww)
invertebrates, dry weight
0.01
1.15
(kgdw/kgdw)
vertebrates, wet weight
0.006
0.18
(kgdw/kgww)
median
0.43
0.28
0.07
The body burden Cd generally increases with increasing Cd concentration in the sediment but levels off at
higher Cd contents of the sediment. Low BAF values can therefore be found at high Cd concentrations in the
sediment (EU RA, ECB 2008)
The studies on aquatic bioaccumulation are summarised in the following table:
Table 9. Overview of studies on aquatic bioaccumulation
Method
Results
Remarks
Reference
Chaereborus punctipennis
BAF: 1345 (whole body d.w.)
(steady state)
2 (reliable with
restrictions)
Munger C and
Hare L (1997)
aqueous (freshwater)
key study
semi-static
read-across based on
grouping of
substances (category
approach)
Total uptake duration: 14 d
Details of method: measured
concentrations
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Laboratory study; BAF
calculation based on measured
concentrations in the water and
the exposed organisms
Lepomis macrochirus
aqueous (freshwater)
BAF: 240 (whole body d.w.)
(steady state)
2 (reliable with
restrictions)
Wiener JG and
Giesy JP Jr. (1979)
weight of evidence
field study
experimental result
Total uptake duration: 499 d
Test material
(IUPAC name):
cadmium
Details of method: measured
concentrations
Field study; BAF calculation
based on measured
concentrations in the water and
the exposed organisms
Asellus aquaticus
aqueous (freshwater)
field study
Total uptake duration: d
Details of method: measured
2010-09-07 CSR-PI-5.2.1
BAF: 65000 (whole body d.w.)
(steady state)
2 (reliable with
restrictions)
Lithner G, Holm K
and Borg H (1995)
weight of evidence
read-across based on
grouping of
substances (category
approach)
CHEMICAL SAFETY REPORT
21
EC number:
233-331-6
Method
cadmium sulphate
Results
concentrations
aqueous (freshwater)
BAF: 41000 (whole body d.w.)
(steady state)
Details of method: measured
concentrations
BAF: 27000 (whole body d.w.)
(steady state)
Details of method: measured
concentrations
Test material
(IUPAC name):
cadmium (See
endpoint summary
for justification of
read-across)
Laboratory study; BAF
calculation based on measured
concentrations in the water and
the exposed organisms
Total uptake duration: 116 d
Field study; BCF calculation
based on measured
concentrations in the water and
the exposed organisms
Elodea sp.
2010-09-07 CSR-PI-5.2.1
Lithner G, Holm K
and Borg H (1995)
read-across based on
grouping of
substances (category
approach)
Total uptake duration: d
field study
2 (reliable with
restrictions)
weight of evidence
field study
aqueous (freshwater)
Lithner G, Holm K
and Borg H (1995)
Test material
(IUPAC name):
cadmium (See
endpoint summary
for justification of
read-across)
Laboratory study; BAF
calculation based on measured
concentrations in the water and
the exposed organisms
periphyton
2 (reliable with
restrictions)
read-across based on
grouping of
substances (category
approach)
Total uptake duration: d
aqueous (freshwater)
Reference
weight of evidence
field study
Sialis lutaria
Remarks
Test material
(IUPAC name):
cadmium (See
endpoint summary
for justification of
read-across)
Laboratory study; BAF
calculation based on measured
concentrations in the water and
the exposed organisms
Libellulidae
CAS number:
10124-36-4
BCF: 130000 (steady state)
2 (reliable with
restrictions)
Stephenson M and
Turner MA (1993)
supporting study
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
BCF: > 4560 — < 11400 (whole 2 (reliable with
body w.w.) (steady state)
restrictions)
CHEMICAL SAFETY REPORT
Van hattum B, de
Voogt P, van den
22
EC number:
233-331-6
Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
Bosch L, van
BCF: > 6700 — < 22333 (whole supporting study
Straalen NM and
body w.w.) (steady state)
Joosse ENG
semi-static
read-across based on (1989)
BCF: > 7535 — < 23143 (whole grouping of
Total uptake duration: >= 14 d
body w.w.) (steady state)
substances (category
approach)
Details of method: BCF based on BCF: 1636 (whole body w.w.)
measured concnetrations
(steady state)
Test material
(IUPAC name):
Laboratory study; BCF
cadmium dichloride
calculation based on measured
(See endpoint
concentrations in the water and
summary for
the exposed organisms
justification of
read-across)
aqueous (freshwater)
Phytium sp.
aqueous (freshwater)
static
BCF: 44000 (whole body w.w.)
(steady state) (5d test)
2 (reliable with
restrictions)
BCF: 38000 (whole body w.w.)
(steady state) (7d test)
supporting study
Total uptake duration: > 5 — < 7
Details of method: based on
measured concentrations
aqueous (freshwater)
static
BCF: 89000 (whole body w.w.)
(steady state) (5d test)
2 (reliable with
restrictions)
BCF: 90000 (whole body w.w.)
(steady state) (7d test)
supporting study
Total uptake duration: > 5 — < 7
Details of method: based on
measured concentrations
aqueous (freshwater)
static
Total uptake duration: > 5 — < 7
Details of method: based on
measured concentrations
2010-09-07 CSR-PI-5.2.1
Duddridge JE and
Wainwright M
(1980)
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Laboratory study; BCF
calculation based on measured
concentrations in the water and
the exposed organisms
Scytalidium lignicola
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Laboratory study; BCF
calculation based on measured
concentrations in the water and
the exposed organisms
Dictyuchus sterile
Duddridge JE and
Wainwright M
(1980)
BCF: 50000 (whole body w.w.)
(steady state) (5d test)
2 (reliable with
restrictions)
BCF: 48000 (whole body w.w.)
(steady state) (7d test)
supporting study
Duddridge JE and
Wainwright M
(1980)
read-across based on
grouping of
substances (category
approach)
CHEMICAL SAFETY REPORT
23
EC number:
233-331-6
Method
cadmium sulphate
Results
Laboratory study; BCF
calculation based on measured
concentrations in the water and
the exposed organisms
Pteronarcys dorsata
aqueous (freshwater)
semi-static
Total uptake duration: 28 d
Details of method: measured
concentrations were used for
calculations of BCF
CAS number:
10124-36-4
Remarks
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
BCF: 1000 (whole body w.w.)
(steady state)
2 (reliable with
restrictions)
BCF: 2500 (whole body w.w.)
(steady state)
supporting study
BCF: 3614 (whole body w.w.)
(steady state)
BCF: 1818 (whole body w.w.)
(steady state)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
BCF: 546 (whole body w.w.)
(steady state)
Hydropsyche betteni
BCF: 2000 (whole body w.w.)
(steady state)
2 (reliable with
restrictions)
BCF: 33333 (whole body w.w.)
(steady state)
supporting study
semi-static
Total uptake duration: 28 d
Details of method: measured
concentrations were used for
calculations of BCF
BCF: 21084 (whole body w.w.)
(steady state)
BCF: 7455 (whole body w.w.)
(steady state)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
BCF: 798 (whole body w.w.)
(steady state)
Physa integra
BCF: 9000 (whole body w.w.)
(steady state)
2 (reliable with
restrictions)
BCF: 12333 (whole body w.w.)
(steady state)
supporting study
semi-static
Total uptake duration: 28 d
Details of method: measured
concentrations were used for
calculations of BCF
Laboratory study; BCF
calculation based on measured
concentrations in the water and
the exposed organisms
2010-09-07 CSR-PI-5.2.1
BCF: 5904 (whole body w.w.)
(steady state)
BCF: 5818 (whole body w.w.)
(steady state)
BCF: 672 (whole body w.w.)
(steady state)
Spehar RL,
Anderson RL and
Fiandt JT (1978a)
read-across based on
grouping of
substances (category
approach)
Laboratory study; BCF
calculation based on measured
concentrations in the water and
the exposed organisms
aqueous (freshwater)
Spehar RL,
Anderson RL and
Fiandt JT (1978a)
read-across based on
grouping of
substances (category
approach)
Laboratory study; BCF
calculation based on measured
concentrations in the water and
the exposed organisms
aqueous (freshwater)
Reference
Spehar RL,
Anderson RL and
Fiandt JT (1978a)
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
CHEMICAL SAFETY REPORT
24
EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Method
Results
Remarks
Asellus aquaticus
BCF: 17560 (whole body w.w.)
(steady state)
2 (reliable with
restrictions)
aqueous (freshwater)
flow-through
Total uptake duration: 30 d
Details of method: BCF based on
measured concentrations
aqueous (freshwater)
semi-static
Total uptake duration: > 0.3 d
Van Hattum B, de
Voogt P, van den
Bosch L, van
supporting study
Straalen NM and
Joosse ENG
read-across based on (1989)
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Laboratory study; BCF
calculation based on measured
concentrations in the water and
the exposed organisms
Gasterosteus aculeatus
Reference
BCF: 511 (whole body w.w.)
(steady state)
2 (reliable with
restrictions)
BCF: 173 (whole body w.w.)
(steady state)
supporting study
BCF: 216 (whole body w.w.)
(steady state)
Details of method: determined on
measured concentrations
BCF: 101 (whole body w.w.)
(steady state)
Laboratory study; BCF
calculation based on measured
BCF: 34 (whole body w.w.)
concentrations in the water and
(steady state)
the exposed organisms
BCF: 23 (whole body w.w.)
(steady state)
Pascoe D and
Mattey DL (1977)
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
BCF: 14 (whole body w.w.)
(steady state)
BCF: 15 (whole body w.w.)
(steady state)
BCF: 5 (whole body w.w.)
(steady state)
BCF: 3 (whole body w.w.)
(steady state)
Salmo salar
aqueous (freshwater)
flow-through
Total uptake duration: 92 d
BCF: 1385 (whole body d.w.)
(steady state)
2 (reliable with
restrictions)
BCF: 1277 (whole body d.w.)
(steady state)
supporting study
BCF: 1282 (whole body d.w.)
(steady state)
Details of method: determined on
measured concentrations
BCF: 213 (whole body d.w.)
(steady state)
Laboratory study; BCF
calculation based on measured
BCF: 213 (whole body d.w.)
concentrations in the water and
(steady state)
2010-09-07 CSR-PI-5.2.1
Rombough PJ and
Garside ET (1982)
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
CHEMICAL SAFETY REPORT
25
EC number:
233-331-6
Method
the exposed organisms
cadmium sulphate
CAS number:
10124-36-4
Results
Remarks
BCF: 95 (whole body d.w.)
(steady state)
summary for
justification of
read-across)
Reference
BCF: 60 (whole body d.w.)
(steady state)
BCF: 5 (whole body d.w.)
(steady state)
Salvelinus fontinalis
aqueous (freshwater)
flow-through
Total uptake duration: >= 266 d
BCF: 33333 (organ d.w.
(kidney)) (steady state) (1st
generation)
BCF: 1166 (organ d.w. (Gill))
(steady state) (1st generation)
BCF: 666 (organ d.w. (liver))
Details of method: determined on (steady state) (1st generation)
measured concentrations
BCF: 24000 (organ d.w.
Laboratory study; BCF
(kidney)) (steady state) (1st
calculation based on measured
generation)
concentrations in the water and
the organs of the exposed
BCF: 11000 (organ d.w. (gill))
organisms
(steady state) (1st generation)
BCF: 9000 (organ d.w. (liver))
(steady state) (1st generation)
2 (reliable with
restrictions)
supporting study
read-across based on
grouping of
substances (category
approach)
Benoit DA,
Leonard EN,
Christensen GM
and Fiandt JT
(1976a)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
BCF: 14118 (organ d.w.
(kidney)) (steady state) (1st
generation)
BCF: 2206 (organ d.w. (liver))
(steady state) (1st generation)
BCF: 2941 (organ d.w. (liver))
(steady state) (1st generation)
BCF: 1912 (organ d.w. (gonad))
(steady state) (1st generation)
Salvelinus fontinalis
aqueous (freshwater)
BCF: 882 (organ d.w. (spleen))
(steady state) (1st generation)
2 (reliable with
restrictions)
BCF: 29.4 (organ d.w. (muscle)) supporting study
(steady state) (1st generation)
read-across based on
Total uptake duration: >= 266 d BCF: 29.4 (organ d.w. (red blood grouping of
cells)) (steady state) (1st
substances (category
Details of method: determined on generation)
approach)
measured concentrations
BCF: 12647 (organ d.w.
Test material
Laboratory study; BCF
(kidney)) (steady state) (2nd
(IUPAC name):
calculation based on measured
generation)
cadmium dichloride
concentrations in the water and
(See endpoint
the organs of the exposed
BCF: 1765 (organ d.w. (gill))
summary for
organisms
(steady state) (2nd generation)
justification of
read-across)
BCF: 4412 (organ d.w. (liver))
(steady state) (2nd generation)
flow-through
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
Benoit DA,
Leonard EN,
Christensen GM
and Fiandt JT
(1976a)
26
EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Method
Results
Hyalella azteca
BAF: 170000 (whole body d.w.) 2 (reliable with
(steady state)
restrictions)
aqueous (freshwater)
Remarks
Reference
Stephenson M and
Turner MA (1993)
supporting study
field study
read-across based on
grouping of
substances (category
approach)
Total uptake duration: 116 d
Details of method: measured
concentrations
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Field study; BAF calculation
based on measured
concentrations in the water and
the exposed organisms
4.3.2. Terrestrial bioaccumulation
The EU risk assessment defined bioconcentration of Cd in the terrestrial compartment as the net result of the Cd
uptake, distribution and elimination in an organism due to exposure to Cd in soil only.
Results of cadmium bioaccumulation studies in soil were reviewed in the EU RA (see table below). The median
BAF observed on earthworms (85 results) was 15; the median BAF observed on arthropods (45 results) was 1.4
(EU RA, ECB 2008). All BAF values were calculated from the soil:biota concentration ratio’s. Most organisms
observed were earthworms.
Table 10. Bioaccumulation factors (BAF's) of soil dwelling organisms (from EU RA: table 3.2.37.).
min
max
median
5th
n
percentile
earthworms- wet weight basis
4
32
15
5
11
(kgdw/kgww)
earthworms- dry weight basis
1.6
151
15
5
85
(kgdw/k–dw)
arthropoda - dry weight basis
0.05
18.8
1.4
0.30
45
(kgdw/kgdw)
Overall, it was concluded that cadmium is concentrated from the soil into earthworms organisms (BAF values
all higher than 1). Most important factors affecting the bioaccumulation of Cd by earthworms are the Cd
concentration of the soil, soil type, pH, soil organic matter and CEC.
The influence of the Cd content of the soil on the bioaccumulation of Cd is illustrated in most of the studies.
Cadmium concentrations in earthworms increase with increasing Cd levels in a non-proportional way. As a
result, the BAF decreases with increasing soil Cd, (see figure below). In other words, the BAF observed on soil
containing higher Cd was lower than the BAF observed on control soils.
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
27
EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
1000
BAF, fresh weight basis
BAF, dry weight basis
BAF (mg kg-1)
100
10
1
0.01
0.1
1
10
100
1000
Cd concentration in soil (mg kgdw-1)
Figure 2. The bioaccumulation factors (BAF kg kg-1) of earthworms as a function of the Cd
concentration in soil (mg kg-1)(taken from the EU RA, figure 3.2.11)
The results of terrestrial bioaccumulation studies are summarised in the following table:
Table 11. Overview of studies on terrestrial bioaccumulation
Method
Results
Remarks
Reference
Lumbricus terrestris
BSAF: 14.64 (whole body d.w.)
(steady state) (control soil)
2 (reliable with
restrictions)
Wright MA and
Stringer A (1980)
Field study; BAF calculation
based on measured
BSAF: 5.58 (whole body d.w.)
key study
concentrations in the soil and the (steady state) (contaminated soil)
read-across based on
exposed organisms
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium (See
endpoint summary
for justification of
read-across)
Allobophora calluginosa
BSAF: 32.45 (whole body d.w.)
(steady state) (control soil)
2 (reliable with
restrictions)
Field study; BAF calculation
based on measured
BSAF: 6.43 (whole body d.w.)
key study
concentrations in the soil and the (steady state) (contaminated soil)
read-across based on
exposed organisms
grouping of
substances (category
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
Wright MA and
Stringer A (1980)
28
EC number:
233-331-6
Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
approach)
Test material
(IUPAC name):
cadmium (See
endpoint summary
for justification of
read-across)
Allolobophora chlorotica
BSAF: 14.91 (whole body d.w.)
(steady state) (control soil)
2 (reliable with
restrictions)
Field study; BAF calculation
based on measured
BSAF: 5.56 (whole body d.w.)
key study
concentrations in the soil and the (steady state) (contaminated soil)
read-across based on
exposed organisms
grouping of
substances (category
approach)
Wright MA and
Stringer A (1980)
Test material
(IUPAC name):
cadmium (See
endpoint summary
for justification of
read-across)
Allolobophora tuberculata
Field study; BAF calculation
based on measured
concentrations in the soil and the
exposed organisms
BSAF: 17.55 (whole body d.w.)
(steady state) (control soil)
2 (reliable with
restrictions)
Wright MA and
Stringer A (1980)
key study
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium (See
endpoint summary
for justification of
read-across)
Allolobophora longa
BSAF: 16.01 (whole body d.w.)
(steady state) (control soil)
2 (reliable with
restrictions)
Field study; BAF calculation
based on measured
BSAF: 3.99 (whole body d.w.)
key study
concentrations in the soil and the (steady state) (contaminated soil)
read-across based on
exposed organisms
grouping of
substances (category
approach)
Wright MA and
Stringer A (1980)
Test material
(IUPAC name):
cadmium (See
endpoint summary
for justification of
read-across)
Allolobophora rosea
2010-09-07 CSR-PI-5.2.1
BSAF: 16.27 (whole body d.w.)
(steady state) (control soil)
2 (reliable with
restrictions)
CHEMICAL SAFETY REPORT
Wright MA and
Stringer A (1980)
29
EC number:
233-331-6
Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
Field study; BAF calculation
BSAF: 6.06 (whole body d.w.)
key study
based on measured
(steady state) (contaminated soil)
read-across based on
concentrations in the soil and the
grouping of
exposed organisms
substances (category
approach)
Test material
(IUPAC name):
cadmium (See
endpoint summary
for justification of
read-across)
Lumbricus terrestris
BSAF: 40 (whole body d.w.)
(steady state) (control soil d))
Field study; BAF calculation
based on measured
BSAF: 62 (whole body d.w.)
concentrations in the soil and the (steady state) (control soil c))
exposed organisms
BSAF: 14 (whole body d.w.)
(steady state) (sludge amended
soil d))
BSAF: 54 (whole body d.w.)
(steady state) (sludge amended
soil c))
BSAF: 13 (whole body d.w.)
(steady state) (sludge amended
soil a))
Aporrectodea turgida
BSAF: 62 (whole body d.w.)
(steady state) (control soil c))
Field study; BAF calculation
based on measured
BSAF: 54 (whole body d.w.)
concentrations in the soil and the (steady state) (sludge amended
exposed organisms
soil c))
2 (reliable with
restrictions)
key study
Beyer WN,
Chaney RL and
Mulhern BM
(1982)
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium (See
endpoint summary
for justification of
read-across)
2 (reliable with
restrictions)
key study
Beyer WN,
Chaney RL and
Mulhern BM
(1982)
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium (See
endpoint summary
for justification of
read-across)
Aporrectodea Tuberculata
BSAF: 66 (whole body d.w.)
(steady state) (control soil a))
Field study; BAF calculation
based on measured
BSAF: 30 (whole body d.w.)
concentrations in the soil and the (steady state) (control soil b))
exposed organisms
2 (reliable with
restrictions)
key study
Beyer WN,
Chaney RL and
Mulhern BM
(1982)
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
30
EC number:
233-331-6
Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
cadmium (See
endpoint summary
for justification of
read-across)
Aporrectodea longa
BSAF: 20 (whole body d.w.)
(steady state) (sludge amended
soil b))
Field study; BAF calculation
based on measured
concentrations in the soil and the BSAF: 30 (whole body d.w.)
exposed organisms
(steady state) (control soil b))
2 (reliable with
restrictions)
key study
Beyer WN,
Chaney RL and
Mulhern BM
(1982)
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium (See
endpoint summary
for justification of
read-across)
pasture
field study with measurement of
Cd and other metals in soil
(contaminated and control) ,
plants and animals.
BCF: 0.8 (plant dry weight)
(steady state) (site 1)
2 (reliable with
restrictions)
BCF: 0.35 (plant dry weight)
(steady state) (site 2)
key study
BCF: 0.22 (plant dry weight)
(steady state) (site 3)
BCF: 5.3 (plant dry weight)
(steady state) (site 4)
Lumbricus rubellus
field study with measurement of
Cd and other metals in soil
(contaminated and control) ,
plants and animals.
read-across based on
grouping of
substances (category
approach)
BCF: 21 (plant dry weight)
(steady state) (site 5 (control))
Test material (CAS
name): cadmium
(See endpoint
summary for
justification of
read-across)
BSAF: 13 (whole body d.w.)
(steady state) (site 2)
2 (reliable with
restrictions)
BSAF: 12.4 (whole body d.w.)
(steady state) (site 3)
key study
BSAF: 190 (whole body d.w.)
(steady state) (site 5 (control))
Ma WC (1987)
Ma WC (1987)
read-across based on
grouping of
substances (category
approach)
Test material (CAS
name): cadmium
(See endpoint
summary for
justification of
read-across)
Talpa europea
field study with measurement of
Cd and other metals in soil
(contaminated and control) ,
plants and animals.
2010-09-07 CSR-PI-5.2.1
BSAF: 62 (organ d.w. (kidney))
(steady state) (site 1)
2 (reliable with
restrictions)
BSAF: 37 (organ d.w. (kidney))
(steady state) (site 2)
key study
Ma WC (1987)
read-across based on
CHEMICAL SAFETY REPORT
31
EC number:
233-331-6
Method
cadmium sulphate
CAS number:
10124-36-4
Results
Remarks
BSAF: 24 (organ d.w. (kidney))
(steady state) (site 3)
grouping of
substances (category
approach)
Reference
BSAF: 620 (organ d.w. (kidney)) Test material (CAS
(steady state) (site 4)
name): cadmium
(See endpoint
BSAF: 590 (organ d.w. (kidney)) summary for
(steady state) (site 5 (control))
justification of
read-across)
BSAF: 52 (organ d.w. (liver))
(steady state) (site 1)
BSAF: 38 (organ d.w. (liver))
(steady state) (site 2)
BSAF: 19 (organ d.w. (liver))
(steady state) (site 3)
BSAF: 483 (organ d.w. (liver))
(steady state) (site 4)
BSAF: 300 (organ d.w. (liver))
(steady state) (site 5 (control))
Microtus agrestis
BSAF: 0.4 (organ d.w. (kidney)) 2 (reliable with
Ma WC,
(steady state) (Budel soil, Febrestrictions)
Denneman W and
field study with measurement of March)
Faber J (1991)
Cd and lead in soil (contaminated
key study
and control) , plants and animals. BSAF: 0.18 (organ d.w. (kidney))
(steady state) (Budel soil, May- read-across based on
grouping of
June)
substances (category
BSAF: 0.5 (organ d.w. (kidney)) approach)
(steady state) (Budel soil, OctTest material (CAS
Nov)
name): cadmium
BSAF: 0.23 (organ d.w. (kidney)) (See endpoint
(steady state) (Arnhem soil, feb- summary for
March)
justification of
read-across)
BSAF: 0.08 (organ d.w. (kidney))
(steady state) (Arnhem soil, MayJune)
BSAF: 0.18 (organ d.w. (kidney))
(steady state) (Arnhem soil, OctNov)
BSAF: 0.06 (organ d.w. (liver))
(steady state) (Budel soil, FebMarch)
BSAF: 0.034 (organ d.w. (liver))
(steady state) (Budel soil, MayJune)
BSAF: 0.1 (organ d.w. (liver))
(steady state) (Budel soil OctNov)
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
32
EC number:
233-331-6
Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
2 (reliable with
restrictions)
Ma WC,
Denneman W and
Faber J (1991)
BSAF: 0.08 (organ d.w. (liver))
(steady state) (Arnhem soil, FebMarch)
BSAF: 0.1 (organ d.w. (liver))
(steady state) (Arnhem soil, MayJune)
BSAF: 0.11 (organ d.w. (liver))
(steady state) (Arnhem soil, OctNov)
Sorex araneus
BSAF: 36 (organ d.w. (kidney))
(steady state) (Budel soil, FebMarch)
field study with measurement of
Cd and lead in soil (contaminated
and control) , plants and animals. BSAF: 15 (organ d.w. (kidney))
(steady state) (Budel soil, MayJune)
BSAF: 23 (organ d.w. (kidney))
(steady state) (Budel soil, OctNov)
BSAF: 43 (organ d.w. (kidney))
(steady state) (Arnhem soil, febMarch)
BSAF: 12 (organ d.w. (kidney))
(steady state) (Arnhem soil, MayJune)
key study
read-across based on
grouping of
substances (category
approach)
Test material (CAS
name): cadmium
(See endpoint
summary for
justification of
read-across)
BSAF: 26 (organ d.w. (kidney))
(steady state) (Arnhem soil, OctNov)
BSAF: 49 (organ d.w. (liver))
(steady state) (Budel soil, FebMarch)
BSAF: 14 (organ d.w. (liver))
(steady state) (Budel soil, MayJune)
BSAF: 33 (organ d.w. (liver))
(steady state) (Budel soil OctNov)
BSAF: 38 (organ d.w. (liver))
(steady state) (Arnhem soil, FebMarch)
BSAF: 8 (organ d.w. (liver))
(steady state) (Arnhem soil, MayJune)
BSAF: 25 (organ d.w. (liver))
(steady state) (Arnhem soil, OctNov)
Castor fiber
2010-09-07 CSR-PI-5.2.1
BSAF: 4.7 (organ d.w. (kidney)) 2 (reliable with
CHEMICAL SAFETY REPORT
Nolet BA, Dijkstra
33
EC number:
233-331-6
Method
Field study on the
bioaccumulation of Cd in kidney
of local animals through
environmental exposure
cadmium sulphate
CAS number:
10124-36-4
Results
Remarks
Reference
(steady state)
restrictions)
VAA and
Heidecke D (1994)
supporting study
read-across based on
grouping of
substances (category
approach)
Test material (CAS
name): cadmium
(See endpoint
summary for
justification of
read-across)
Sorex araneus
Field study on the
bioaccumulation of Cd in kidney
of local animals through
environmental exposure
BSAF: 47 (organ d.w.) (steady
state)
2 (reliable with
restrictions)
Read HJ and
Martin MH (1993)
supporting study
read-across based on
grouping of
substances (category
approach)
Test material (CAS
name): cadmium
(See endpoint
summary for
justification of
read-across)
Sorex minutus
Field study on the
bioaccumulation of Cd in kidney
of local animals through
environmental exposure
BSAF: 13 (organ d.w.) (steady
state)
2 (reliable with
restrictions)
Read HJ and
Martin MH (1993)
supporting study
read-across based on
grouping of
substances (category
approach)
Test material (CAS
name): cadmium
(See endpoint
summary for
justification of
read-across)
Sorex araneus
Field study on the
bioaccumulation of Cd in kidney
of local animals through
environmental exposure
BSAF: 26 (organ d.w.) (steady
state)
2 (reliable with
restrictions)
supporting study
Hunter BA,
Johnson MS and
Thompson DJ
(1989)
read-across based on
grouping of
substances (category
approach)
Test material (CAS
name): cadmium
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
34
EC number:
233-331-6
Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
(See endpoint
summary for
justification of
read-across)
Microtus agrestis
Field study on the
bioaccumulation of Cd in kidney
of local animals through
environmental exposure
BSAF: 6 (organ d.w.) (steady
state)
2 (reliable with
restrictions)
supporting study
Hunter BA,
Johnson MS and
Thompson DJ
(1989)
read-across based on
grouping of
substances (category
approach)
Test material (CAS
name): cadmium
(See endpoint
summary for
justification of
read-across)
Apodemus sylvaticus
Field study on the
bioaccumulation of Cd in kidney
of local animals through
environmental exposure
BSAF: 3 (organ d.w.) (steady
state)
2 (reliable with
restrictions)
supporting study
Hunter BA,
Johnson MS and
Thompson DJ
(1989)
read-across based on
grouping of
substances (category
approach)
Test material (CAS
name): cadmium
(See endpoint
summary for
justification of
read-across)
Sorex araneus
Field study on the
bioaccumulation of Cd in kidney
of local animals through
environmental exposure
BSAF: 45 (organ d.w.) (steady
state)
2 (reliable with
restrictions)
supporting study
Hunter BA and
Johnson MS
(1982)
read-across based on
grouping of
substances (category
approach)
Test material (CAS
name): cadmium
(See endpoint
summary for
justification of
read-across)
Microtus agrestis
Field study on the
bioaccumulation of Cd in kidney
of local animals through
environmental exposure
2010-09-07 CSR-PI-5.2.1
BSAF: 3 (organ d.w.) (steady
state)
2 (reliable with
restrictions)
supporting study
Hunter BA and
Johnson MS
(1982)
read-across based on
CHEMICAL SAFETY REPORT
35
EC number:
233-331-6
Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
grouping of
substances (category
approach)
Test material (CAS
name): cadmium
(See endpoint
summary for
justification of
read-across)
Apodemus sylvaticus
Field study on the
bioaccumulation of Cd in kidney
of local animals through
environmental exposure
BSAF: 2 (organ d.w.) (steady
state)
2 (reliable with
restrictions)
supporting study
Hunter BA and
Johnson MS
(1982)
read-across based on
grouping of
substances (category
approach)
Test material (CAS
name): cadmium
(See endpoint
summary for
justification of
read-across)
Sorex araneus
Field study on the
bioaccumulation of Cd in kidney
of local animals through
environmental exposure
BSAF: 6 (organ d.w.) (steady
state)
2 (reliable with
restrictions)
supporting study
read-across based on
grouping of
substances (category
approach)
Hendriks AJ, Ma
W-C, Brouns JJ,
Deruiterdijkman
EM and Gast R
(1995)
Test material (CAS
name): cadmium
(See endpoint
summary for
justification of
read-across)
Sylvilagus floridanus
Field study on the
bioaccumulation of Cd in kidney
of local animals through
environmental exposure
BSAF: 28 (organ d.w. (kidney))
(steady state)
2 (reliable with
restrictions)
supporting study
Storm GL,
Fosmire GJ and
Bellis ED (1994)
read-across based on
grouping of
substances (category
approach)
Test material (CAS
name): cadmium
(See endpoint
summary for
justification of
read-across)
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
36
EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Method
Results
Remarks
Reference
Odocoileus virginianus
BSAF: 12 (organ d.w. (kidney))
(steady state)
2 (reliable with
restrictions)
Storm GL,
Fosmire GJ and
Bellis ED (1994)
Field study on the
bioaccumulation of Cd in kidney
of local animals through
environmental exposure
supporting study
read-across based on
grouping of
substances (category
approach)
Test material (CAS
name): cadmium
(See endpoint
summary for
justification of
read-across)
Sylvilagus floridanus
Field study on the
bioaccumulation of Cd in kidney
of local animals through
environmental exposure
BSAF: 53 (organ d.w. (kidney))
(steady state)
2 (reliable with
restrictions)
supporting study
read-across based on
grouping of
substances (category
approach)
Dressler RL,
Storm GL,
Tzilkowski WM
and Sopper WE
(1986)
Test material (CAS
name): cadmium
(See endpoint
summary for
justification of
read-across)
4.3.3. Summary and discussion of bioaccumulation
Aquatic bioaccumulation
BCF's for cadmium are highest in algae and lowest in fish; High BCF in algae does not necessarily reflect high
bioconcentration, because a significant part of the Cd is absorbed to the outer side of the organisms, and not
taken up. Another factor of error is the lack of gut clearance in invertebrates. Organs (kidney, liver) contain
most Cd.
Main influencing factors for Cd BCF are hardness and Cd concentration in the water. Increasing water hardness
reduces Cd uptake. BCF is also inversely related to Cd concentration in water.
McGeer et al (2003) recently extensively reviewed the evidence on bioconcentration and bioaccumulation of
cadmium as a function of exposure concentration in a number of taxonomic groups (algae, molluscs, arthropods,
annelids, salmonid fish, cyprinid fish, and other fish). The data clearly illustrated that there is a significant
degree of control on internal cadmium content. In general, BCF data showed an inverse relationship to exposure
concentrations. In all cases, the relationship of BCF to exposure was significant and negative. The slopes of the
BCF/BAF – exposure relations were: algae: -0.72, insects: -0.32, arthropods: -0.61, molluscs: -0.50, salmonids:
-0.87, Centrarchids: -0.47, Killifish: -0.05, other fish: -0.72. Overall, species mean slope was -0.49 +/- 0.04
(McGeer et al 2003. Environm. Toxicology & Chemistry, vol 22, nr 5, 1017 -1037).
The following information is taken into account for any hazard / risk / bioaccumulation assessment:
In general, BCF and BAF data show an inverse relationship to exposure concentrations.
BCF's for cadmium are highest in algae and lowest in fish. In algae, external adsorption of Cd is one of the
reasons for high BCF. Hardness and Cd concentration in the water are inversely related to BCF.
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
37
EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Median BCF (per dry weight) reported in the EU risk assessment (ECB 2008) are: 115116 (algae), 5000
(invertebrates), 233 (vertebrates)
The risk assessment mentions a median BAF for vertebrates of 167. Highest BAF is observed for the
invertebrate Hyalella (170000), at a very low Cd concentration.
Terrestrial bioaccumulation
The EU Risk assessment (ECB 2008) presents BAF values that were calculated from the soil: biota
concentration ratio’s. Most organisms are earthworms and the Cd levels were expressed on dry or wet weight
basis. All the data on earthworms were obtained from specimens with guts voided prior to analysis.
Cadmium is concentrated from the soil into earthworms organisms (BAF values are all higher than 1). Most
important factors affecting the bioaccumulation of Cd by earthworms are the Cd concentration of the soil, soil
type, pH, soil organic matter and CEC.
The influence of the Cd content of the soil on the bioaccumulation of Cd is illustrated in most of the studies.
Cadmium concentrations in earthworms increase with increasing Cd levels in a non-proportional way. As a
result, the BAF observed in Cd-contaminated or Cd-enriched soils is lower than the BAF observed in control
soils.
The following information is taken into account for any hazard / risk / bioaccumulation assessment:
Median BAF observed on earthworms is 15 (expressed on a dry weight basis). For arthropoda, the median BAF
is 1.4 (summary from the EU risk assessment, ECB 2008). The BAF observed in Cd-contaminated or Cdenriched soils is lower than the BAF observed in control soils. In a field study, the BAF observed under
contaminated conditions on Lumbricus rubellus was 12-123, under control conditions it was 190.
General conclusion
The available evidence makes it difficult to decide whether or not Cd is to be considered as a bioaccumulative
substance in the environment. The high BCF /BAF factors observed in the lower levels of the food chain (algae
notably) would suggest Cd is to be considered as bioaccumulative. However, there are some uncertainties with
the data: the high BCF/BAF factors observed in the algae are (at least partly) due to external absorption, not to
uptake; the higher levels in invertebrates maybe related to lack of gut clearance of the organisms studied. BCF
in fish are generally below the criterion for considering a substance bioaccumulative.
In terms of hazard identification/classification, several considerations speak against a conclusion of considering
Cd as bioaccumulative substance:
-the BCF/BAF values observed with Cd consistently decrease with increasing exposure, which clearly shows
some level of physiological regulation of uptake. One of the key theoretical conditions of the BCF model in
terms of its relevance for chronic toxicity and applicability to the hazard identification/classification of
chemicals is that the BCF/BAF should be independent of exposure. BCF/BAF values should in other words
remain fairly constant over a range of exposures, which is clearly not the case for Cd.
-Evidence related to biomagnification in the aquatic food chain consistently shows that Cd is not biomagnifying.
Based on an extensive review of evidence on a wide variability of taxonomic groups, McGeer et al (2003)
concluded that the BCF/BAF criteria, as conceived for organic substances, are inappropriate for the hazard
identification and classification of metals, including Cd. They highlighted the inconsistency between BCF/BAF
values and toxicological data, as BCF values are highest (suggesting hazard) at low exposure concentrations and
are lowest (indicating no hazard) at the highest exposure concentrations, were toxicity is likely.
So the case on Cd bioaccumulation for hazard identification/classification is inconclusive. In any case, the main
question to pose in this respect is on secondary poisoning. This aspect is discussed in the next section.
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
38
EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
4.4. Secondary poisoning
Secondary poisoning will be evaluated based on the interpretation of the available data with regard to the
potential to bio-accumulate in the food chain, presented in the EU RA (ECB 2008).
The EU RA assessed the toxicity of Cd through secondary poisoning based on laboratory studies where
organisms are exposed to variable Cd concentrations in their prey. The PNEC oral following fom such studies was
combined with the bioconcentration factors (BCF’s) or bioaccumulation factors (BAF’s) of the prey to assess
risks of secondary poisoning of the predator by Cd originating from soil, freshwater or sediment.
The risk of secondary poisoning in the RA was focussed on mammals and birds and not on lower organisms,
because no or little data were found to calculate the PNECoral for fish or aquatic invertebrates, benthic organisms
or lower terrestrial organisms. A short discussion was however, given about secondary poisoning in fish or
lower terrestrial organisms.
The importance of the bioconcentration factors soil-plant (the soil-plant transfer factors) for Cd exposure to the
general population is noted.
The following assessment is based on the EU RA.
In the freshwater compartment, BCFs can be high for primary producers, but they decrease significantly further
up the food chain. Bioconcentration and bio-accumulation are also inversely related to Cd-concentration or Cdexposure; in other words, BCF and BAF are lower when exposure to Cd is higher. Finally, there is evidence that
Cd is not biomagnifying in the (lower) aquatic food chain, where the observed BCFs (e.g. with the authotrophic
organisms) are highest.
The risk of secondary poisoning of fish eating birds by Cd is predicted to be smaller than the direct effects of Cd
in the aquatic environment. The RA demonstrated, using BCF’s of fish (mentioned in section 4.3) that the Cd
concentration in whole fish at the PNECwater of 0.19 µg Cd/l (section 7.) could be predicted to range between
0.0001 and 0.13 mg Cd/kg fresh weight using the whole range of BCF’s (0.5-684 l/kg fresh weight). It was
concluded that these Cd concentrations were below the PNECoral for birds or birds+mammals (ECB 2008).
In the terrestrial compartment, a PNEC for secondary poisoning was calculated from the lowest observed
PNECoral for mammals and birds, which was derived from feeding studies with Cd salt spiked diets. Nine
feeding studies were selected (sub-chronic and chronic studies), four studies with birds and 5 studies with
mammals. The PNECoral was calculated from the lowest NOEC using an assessment factor, (see section 7).
In the RA, the risk for secondary poisoning in a soil-worm-bird/mammal system was discussed in great detail.
Using the range of BCFs/BAFs, reported in section 4.3., exposure above the PNEC oral for birds in the soilworm-bird system were calculated starting from the PNEC soil of 2.3mg/kg soil. This model was however
questioned because a) a mean BAF would overestimate earthworm concentrations at more contaminated sites
because the BAF decreases with soil Cd and b) higher availability of Cd in metal salt spiked meals in the
laboratory tests than Cd in worms (EU RA, ECB 2008). This was confirmed by the observation that
concentrations of Cd in terrestrial birds (kidney and liver concentrations) did not indicate Cd-poisoning, even in
contaminated areas and in top-predators (EU RA, ECB 2008).
Several factors can explain this. In studies with shrew, it was demonstrated that Cd intake in the field is 4-times
less than under laboratory conditions. In general, it was observed that Cd is more available in laboratory spiked
meals than in the diet of field-exposed animals. These arguments were seen as suggesting that risk of secondary
poisoning by Cd may be overestimated when based on Cd salt feeding studies. Therefore, the risk assessment
developed an alternative approach for estimating risks from secondary poisoning, based on renal thresholds
(EU-RA, ECB 2008).
The alternative method used kidney Cd concentrations of wildlife as an indicator of Cd exposure and risk. The
kidney is regarded as the critical organ in chronic Cd toxicity. With continued exposure, there is a continued
increase in Cd concentration in the renal cortex until a critical value is reached and symptoms of renal
dysfunction are found (proximal tubular cell necrosis, proteinuria and glycosuria). This critical value is to be
regarded as a sublethal endpoint. The risk of secondary poisoning was assessed by calculating the exposure at
which this critical value was not exceeded for wildlife. The proposed approach could overcome the
uncertainties in the traditional approach which uses food chain modelling (i.e. soil-worm-mammal modelling)
because the proposed approach did not require assumptions about the diet (e.g. 100% earthworms) and about Cd
bioavailability during transfer soil-food-wildlife (i.e. the BAF value and assumption of equal exposure at equal
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diet Cd between spiked meals and environmental Cd).
The ecological relevance of kidney damage as the critical endpoint in the assessment of the Cd RA deviated
from traditional endpoints such as growth or reproduction which have obvious ecological relevance. Indeed, the
relationship between ecological fitness and kidney damage is unknown which is the major difficulty in
understanding effects of Cd in wildlife (Cooke and Johnson, 1996). The kidney has spare functional capacity
and proteinuria or calciuria might be tolerated without progression to renal failure. Several field observations
were discussed in the EU RA leading to the conclusion “that renal dysfunction could be used as an endpoint
with ecological relevance, realising that this endpoint leads to a more conservative approach than traditional
endpoints in most conditions” (EU RA , ECB 2008).
As critical concentration of Cd in the kidney, the lower limit of the critical range for mammals, as set by WHO
(IPCS 1992), was used, i.e. 400µg Cd/g DW kidney (range: 400-800 µg Cd/g DW; EU RA, ECB 2008).
The critical soil Cd concentration for secondary poisoning was defined as that concentration at which a critical
kidney Cd concentration of 400 g/g dw (whole kidney) could be predicted using a proportional extrapolation
from each paired soil/kidney Cd concentration set (often from only 1 point at lower concentration). It was noted
that the proportional extrapolation assumed full linearity, which was indicated not to be the case as Cd uptake
levels at higher concentrations would be lower. So the RA emphasised that using this proportional extrapolation
was an important element of conservatism in the approach used.
Table 12. Kidney concentration in mammals and predicted critical soil concentrations at which the renal
threshold for toxicity may be exceeded (after linear extrapolation of the critical soil levels (values taken
from the RA Cd, (ECB 2008))
species
Soil Cd
(µg/gDW)
beaver
Common shrew
24
3.3
0.8
3.1
2.9
0.3
1.8
~10
0.1
15.4
8.5
2.9
0.3
1.7
0.3
0.1
0.6
6-100
15.4
0.75
Cottontail rabbit
Field vole
mole
Pygmy shrew
White tailed deer
Woud mouse
Measured
kidney Cd
(µg/g DW)
113
154
15.6
139
126-200
14-51
11
284
5.3
88.8
23.3
1-3
0.1-0.3
112
186
59
7.9
70
41.7
1.46
Calculated critical soil Cd
(µg/g DW) to reach
400µg/g DW in kidney
85
8.6
15.6
8.9
5.8
2.4
65.5
14.1
7.5
69.4
145.9
368.7
400
6.1
0.6
0.7
30.4
30.4
147.7
205.5
reference
Nolet et al 1994
Read and Martin, 1993
Hunter et al 1989
Hunter & Johnson 1982
Ma et al 1991
Hendriks et al 1995
Storm et al 1994
Dressler eta l 1986
Hunter et al 1989
Hunter & Johnson 1982
Ma et al 1991
Ma 1987
Read & Martin 1993
Storm et al 1994
Hunter et al 1989
Hunter & Johnson 1982
In total, 20 critical concentrations could be calculated in the RA for 8 mammal species (see table above). The
frequency distribution of these 20 values allowed for a statistical extrapolation to an “HC5” value, conceptually
equal to the HC5 derived from ecotoxicity studies. This HC5, derived from all 20 data on critical concentrations,
was 0.9 µg Cd/g DW soil (log-logistic extrapolation, see figure below).
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Figure 3. Cumulative frequency of the critical soil Cd concentration at which the critical kidney Cd
concentration (400µg/gDW) may be exceeded in the average population of different wildlife species (loglogistic curve fitting)
This HC5 for protecting mammals is about twofold below the PNECsoil derived for protecting plants, soil fauna
and microflora (see chapter 7), effectively suggesting that biotransfer of Cd from soil to higher trophic levels is
the most critical pathway for Cd.
It is emphasised that this PNEC level has several elements of conservatism built-in, as indicated above (for
details see EU RA, section 3.2.6.5.1. (ECB 2008)).
According to the EU risk assessment, the PNEC soil based on protecting mammals is carried forward to the risk
characterisation in the present analysis. Since this PNEC is the most critical for soil, and more critical than
direct effects of Cd on higher plants, soil fauna or soil microbial processes, secondary poisoning and direct
effects are both integrated in the risk characterisations that use this most critical PNECof 0.9 µg Cd/g DW soil.
The PNECoral is 0.16 mg/kg food (see CSR chapter 7.5.3 "Calculation of PNECoral (secondary poisoning)".
4.5. Natural background
The natural background of cadmium in the different environmental compartments can vary with e.g. underlying
soil type, local geological conditions, etc.
FOREGS (2006) reported the following 10P, 50P and 90P values for Europe, based on a systematical analysis of
a 70X70km grid covering the whole of the EU. Sampling points were chosen to avoid local influences, so
concentrations are “ambient” background.
Table 13. Ambient background concentrations in Europe according to FOREGS (2006)
Compartment
10P
50P
90P
Freshwater (µg/l dissolved)
0.002
0.01
0.077
Topsoil (mg / kgDW)
0.03
0.14
0.83
Stream sediment (mg / kgDW)
0.09
0.29
1.39
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Floodplain sediment (mg /
kgDW)
cadmium sulphate
0.06
0.3
CAS number:
10124-36-4
1.46
5. HUMAN HEALTH HAZARD ASSESSMENT
General considerations
The present human health hazard assessment covers cadmium metal and 7 cadmium compounds, i.e. cadmium
oxide - CdO; cadmium hydroxide - Cd(OH)2; cadmium chloride - CdCl2; cadmium nitrate - Cd(NO3)2;
cadmium carbonate - CdCO3; cadmium sulphide - CdS and cadmium sulphate - CdSO4.
The cadmium compounds have been grouped into three categories on the basis of their water solubility, as
shown in Table 14.
Table 14. Water solubility of the eight cadmium compounds covered in this assessment
Cadmium compound
Cadmium nitrate
Cadmium sulphate
Cadmium chloride
Cadmium metal
Cadmium oxide
Cadmium hydroxide
Cadmium carbonate
Cadmium sulphide
1Values
Water solubility (mg/L)1
507.103
540.103
457.103
2.3
2.1
69.5
3.2
6.10-7
Ranking of solubility
Very soluble
Slightly soluble
Insoluble
are taken from section 4 of the IUCLID files on the respective substances. Data by Outotec Research Oy, Pori,
Finland.
There is a wealth of information available in the public domain regarding the effects of cadmium compounds on
human health. This data has been carefully reviewed and scrutinised in the framework of the discussions on the
EU Risk Assessment Report (RAR) developed according to EU Regulation 793/93/EEC, with a focus on
cadmium metal and cadmium oxide (JRC, 2007). Occupational exposure aspects have recently been assessed by
the Scientific Committee on Occupational Exposure Limits (SCOEL, 2009). The US Department of Health and
Human Services, Agency for Toxic Substances and Disease Registry also recently published a comprehensive
revised draft toxicological profile for cadmium (ATSDR, 2008).
The EU RAR, SCOEL recommendations and ATSDR profile are the main data source for this chapter. Given
the substantial amount of data, only selected studies have been included in the IUCLID5 files and the present
Chemical Safety Report (CSR).
Assumptions
For cadmium metal and the various cadmium compounds, systemic toxicity is attributed to the cadmium ion and
differences in toxicity are principally linked to bioavailability. Although several factors influence
bioavailability, the main physico-chemical property of importance is solubility in water or biological fluids.
Substances with higher solubility are expected to penetrate more easily into the organism and therefore
generally show higher toxicity.
A large amount of data is available on the effects of cadmium in humans and animals, but most of the studies
have been conducted using cadmium metal (powder or dust), chloride or oxide and information on other
cadmium compounds is limited. However, for the reasons presented above, read-across of toxicity data within
solubility groups can be conducted. In certain cases, it is also possible to read-across from one solubility group
to another.
As such, this section in the CSR makes an integrated case on the cadmium compounds mentioned above and is
relevant for all of them. For reasons of consistency, it was decided not to develop partial cases on separate
cadmium substances.
5.1. Toxicokinetics (absorption, metabolism, distribution and
elimination)
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Uptake of cadmium can occur in humans via the inhalation of polluted air, the ingestion of contaminated food or
drinking water and, to a minor extent, through exposure of the skin to dusts or liquids contaminated by the
element (JRC, 2008; SCOEL, 2009).
In occupational settings, mainly inhalation exposure occurs although the dermal route may also play a role when
metal, powder or dust is handled or during maintenance of machinery. Additional uptake is possible through
food and tobacco (for example in workers who eat or smoke at the workplace).
For the general population, uptake of cadmium occurs principally via the ingestion of food or, to a lesser extent,
of contaminated drinking water. In industrial sites polluted by cadmium, inhalation of air and/or ingestion of soil
or dusts may contribute to significant exposure. Tobacco is an important additional source of cadmium uptake in
smokers. Finally, the consumer could be exposed (skin, inhalation or oral) through the use of consumption
products.
Absorption
Gastrointestinal absorption of cadmium is usually less than 5% but varies with the form of cadmium present, the
composition of the diet, age and the individual iron status. High gastrointestinal absorption rates (up to 20%)
have been observed for example in women with lowered iron stores (serum ferritin <20 μg/L) (Sasser and
Jarboe, 1977; Weigel et al., 1984; JRC, 2007).
Cadmium is absorbed by the respiratory route at rates varying between 2 and 50% depending on the cadmium
compound involved (water soluble or insoluble), the size of the particles (dusts or fumes), the deposition pattern
in the respiratory tract and the ventilation rate. Values of 10 to 30% for dusts and 25-50% for fumes are cited in
the EU Summary Risk Assessment Report (RAR) (JRC, 2007) and various publications (Boisset et al., 1978;
Glaser et al., 1986; Oberdörster et al., 1979; Oberdörster and Cox, 1989; Oberdörster, 1992; Dill et al., 1994;
Hadley et al., 1980).
The results from studies in mouse, rat, rabbit and in vitro human skin models suggest that, although cadmium
may penetrate through skin, absorption of soluble and less soluble compounds is generally lower than 1%
(Kimura and Otaki, 1972; Lansdown and Sampson, 1996; Wester et al., 1992; JRC, 2008).
Distribution
Following absorption, the biodisposition of cadmium (Cd 2+) is assumed to be independent of the chemical form
to which exposure occured (JRC, 2007). Cadmium is a cumulative toxicant. It is transported from its absorption
site (lungs or gut) to the liver, where it induces the synthesis of metallothionein which sequestrates cadmium.
The cadmium-metallothionein complex is then slowly released from the liver and transported in the blood to the
kidneys, filtrated through the glomerulus and reabsorbed in the proximal tubule where it may dissociate
intracellularly (Chan and Cherian, 1993). There, free cadmium again induces the synthesis of metallothionein,
which protects against cellular toxicity until saturation.
In non-occupationally exposed individuals, cadmium concentrations in kidney is generally between 10 and 50
mg/kg wet weight, with smokers showing 2 to 5-fold higher values than non-smokers (Nilsson et al., 1995).
After long-term low level exposure, approximately half the cadmium body burden is stored in the liver and
kidneys, one third being in the kidney where the major part is located in the cortex (Kjellström et al., 1979). The
kidney:liver concentration ratio decreases with the intensity of exposure and is, for instance, lower in
occupationally exposed workers (7 to 8-fold ratio) (Ellis et al., 1981; Roels et al., 1981) than in the general
population (10 to 30-fold ratio) (Elinder et al., 1985). The distribution of cadmium in the kidney is important as
this organ is one of the critical targets after long-term exposure.
In blood, most cadmium is localised in erythrocytes (90%) and values measured in adult subjects with no
occupational exposure are generally lower than 1 μg/L in non-smokers. Blood cadmium (Cd-B) values are 2 to
5-fold higher in smokers than in non-smokers (Staessen et al., 1990; Järup et al., 1998; Ollson, 2002). In the
absence of occupational exposure, the mean urinary cadmium concentration (Cd-U) is generally below 1 to
2 μg/g creatinine in adults. While Cd-B is influenced by both recent exposure and cadmium body burden, Cd-U
is mainly related to the body burden (Lauwerys and Hoet, 2001). Smokers excrete more cadmium than nonsmokers and their Cd-U is on average 1.5-fold higher than for non-smokers.
The placenta provides a relative barrier, protecting the foetus against cadmium exposure. Cadmium can cross
the placenta but at a low rate (Trottier et al., 2002; Lauwerys et al., 1978; Lagerkvist et al., 1992).
Metabolism
Cadmium is not known to undergo any direct metabolic conversion such as oxidation, reduction or alkylation.
The cadmium (Cd2+) ion does bind to anionic groups (especially sulfhydryl groups) in proteins and other
molecules (Nordberg et al., 1985). Plasma cadmium circulates primarily bound to metallothionein and albumin
(Foulkes and Blanck, 1990; Roberts and Clark, 1988).
Excretion
Absorbed cadmium is excreted very slowly, with urinary and fecal pathways being approximately equal in
quantity (< 0.02% of the total body burden per day) (Kjellström et al., 1985). It accumulates over many years,
mainly in the renal cortex and to a smaller extent in the liver and lung. The biologic half-life of cadmium has
been estimated to be between 10 to 30 years in kidney and 4.7 to 9.7 years in liver (Ellis et al., 1985). The half-
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life in both organs is markedly reduced with the onset of renal toxicity when tubule loss of cadmium is
accelerated. The total cadmium body burden reaches about 30 mg by the age of 30.
Biomonitoring
Biomonitoring methods for either Cd-B or Cd-U are often used rather than airborne measurements because they
integrate all possible sources of occupational and environmental exposures (e.g. digestive exposure at the
workplace, tobacco smoking and diet). In addition, since cadmium is a cumulative toxicant, a measure of the
body burden (i.e. Cd-U) is the most appropriate exposure parameter for conducting risk assessments. In workers
with substantial cadmium exposure (i.e. Cd-U > 3 μg/g creatinine), 30 years exposure to 50 μg/m³ of cadmium
would lead to a Cd-U of 3 μg/g creatinine (SCOEL, 2009).
5.2. Acute toxicity
5.2.1. Non-human information
5.2.1.1. Acute toxicity: oral
Acute oral toxicity studies have been conducted in mouse and rat with cadmium chloride, oxide and metal
powder. The results of experimental studies are summarised in the following table. No data was found for other
cadmium compounds.
Table 15. Overview of selected experimental studies on acute toxicity after oral administration
Method
LD50 (mg Cd/kg bw)
Remarks
Reference
Cadmium chloride
Mouse
Oral: gavage
Observation 10 days
> 60.2 - < 89.9
2 (reliable with
restrictions)
key study
experimental result
Andersen O,
Nielsen JB and
Svendsen P (1988)
Rat
Oral: gavage
Observation for 8 d
29 - 147
2 (reliable with
restrictions)
key study
experimental result
Kostial K, Kello
D, Jugo S, Rabar I
and Maljkovic T
(1978)
Rat
Oral: gavage
Observation for 14 d
225
2 (reliable with
restrictions)
key study
experimental result
Kotsonis FN and
Klaassen CD
(1977)
Rat
Oral: gavage
Observation for 24 h
107 (24 h fasted rats)
327 (fed rats)
2 (reliable with
restrictions)
key study
experimental result
Shimizu M and
Morita S (1990)
Mouse
Oral: gavage
63
2 (reliable with
restrictions)
weight of evidence
experimental result
JRC, 2007
Rat
Oral: gavage
63-259
2 (reliable with
restrictions)
weight of evidence
experimental result
JRC, 2007
890
2 (reliable with
restrictions)
weight of evidence
experimental result
JRC, 2007
Cadmium oxide
Cadmium metal powder
Mouse
Oral: gavage
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Method
Rat
Oral: gavage
cadmium sulphate
LD50 (mg Cd/kg bw)
CAS number:
10124-36-4
Remarks
Reference
2,330
2 (reliable with
JRC, 2007
restrictions)
weight of evidence
experimental result
Reported acute oral LD50 values for the water-soluble cadmium chloride range from 29 to 327 mg Cd/kg
bodyweight (bw), with higher toxicity in fasted than in fed animals. The range of LD50 values for slightly
soluble cadmium oxide and cadmium metal powder is wider (63 to 2,330 mg/kg bw). This data suggest that
slightly soluble or insoluble cadmium compounds may be less acutely toxic. However, it should be noted that no
data on the original studies was available.
Where present, toxicity is generally characterized by lesions of the proximal sections of the intestinal tract
(Andersen et al., 1988).
5.2.1.2. Acute toxicity: inhalation
Acute inhalation toxicity studies have been conducted in multiple species using cadmium chloride, oxide and
carbonate. Results are presented in the following table. No data was found for cadmium metal or other cadmium
compounds.
To allow comparison across studies of different duration, LC50 values were converted to a 4 h value according
to the method of Health Canada (http://www.hc-sc.gc.ca/): LC50 at 4 hours= LC50 at Y hours x (Y hours)/4;
Y= actual number of hours of exposure duration, for a dust, mist or fume. The formula assumes a simple linear
relationship between time of exposure and concentration in the animal chamber for dust, mist and fume. It is
only valid for LC50 values obtained for exposure durations of 1 hour or longer.
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Table 16. Overview of selected experimental studies on acute toxicity after inhalation exposure
Method
LC50
(mg Cd/m3)
4 h LC50
(10-3 mg Cd/L)1
Remarks
Reference
> 4.5 (2h)
> 2.3
2 (reliable with
restrictions)
key study
experimental result
Grose EC,
Richards JH,
Jaskot RH,
Ménache MG,
Graham JA and
Dauterman WC
(1987)
> 9 (15 min)
-
2 (reliable with
restrictions)
key study
experimental result
Chaumard C,
Quero AM,
Bouley G, Girard
F, Boudene C and
German A (1983)
> 1 (3 h)
> 0.8
2 (reliable with
restrictions)
key study
experimental result
McKenna IM,
Waalkes M, Chen
LC and Gordon T
(1997)
> 8.4 (3 h)
> 6.3
2 (reliable with
restrictions)
key study
experimental result
Hart BA, Voss
GW and Willean
CL (1989)
> 8.63 (30 min)
-
2 (reliable with
restrictions)
key study
experimental result
Boisset M and
Boudene C (1981)
> 4.6 (3 h)
> 3.5
2 (reliable with
restrictions)
key study
experimental result
Buckley BJ and
Bassett DJ (1987)
> 10 (15 min)
-
3 (not reliable)
supporting study
experimental result
Bouley G,
Dubreuil A,
Despaux N and
Boudène C (1977)
Rat
Inhalation: aerosol
Observation for up to 1 y
60 (30 min)
-
3 (not reliable)
supporting study
experimental result
Hadley JG,
Conklin AW and
Sanders CL (1979)
Rat
Inhalation: fumes
Observation for 7 d
25 (30 min)
-
4 (not assignable)
supporting study
experimental result
Yoshikawa H and
Homma K (1974)
Rat
Inhalation: aerosol (fumes)
< 112 (2 h)
< 56
2 (reliable with
restrictions)
key study
experimental result
Rusch GM,
O'Grodnick J and
Rinehart WE
(1986)
Rat and rabbit
> 4.5 (2 h)
> 2.3
2 (reliable with
Grose EC,
Cadmium chloride
Rat and rabbit
Inhalation: aerosol
Observation for 72 h
Cadmium oxide
Mouse
Inhalation: fumes (nose
only)
Observation for 17 d
Rat and mouse
Inhalation: vapour (fumes)
(nose only)
Rat
Inhalation: aerosol (dust)
Observation for 7 d
Rat
Inhalation: aerosol (fumes)
(whole body)
Observation for 72 h
Rat
Inhalation: aerosol
Observation for 15 d
Rat and mouse
Inhalation: dust (nose only)
Observation for 24 h
1 The conversion to a 4 h value was only made for LC50 values obtained for exposure durations of 1 hour or more.
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Method
cadmium sulphate
LC50
(mg Cd/m3)
4 h LC50
(10-3 mg Cd/L)1
Inhalation: aerosol (dust)
Observation for 72 h
Rabbit
Inhalation: fumes
Remarks
Reference
restrictions)
key study
experimental result
Richards JH,
Jaskot RH,
Ménache MG,
Graham JA and
Dauterman WC
(1987)
> 22.4 (15 min)
-
2 (reliable with
restrictions)
key study
experimental result
Fukuhara M,
Bouley G, Godin
J, Girard F,
Boisset M and
Boudene C (1981)
-
28.4
4 (not assignable)
supporting study
experimental result
Friberg L (1950)
41 (mouse);
30 (rat);
204 (guinea-pig);
940 (monkey); 230
(dog) (15 min)
-
4 (not assignable)
supporting study
experimental result
Barrett HM, Irwin
DA and Semmons
E (1947)
<132 (2h)
<66
Rabbit
Inhalation: dust
Various species
Inhalation: fumes
CAS number:
10124-36-4
Cadmium carbonate
Rat
Inhalation: aerosol
Observation for 30 d
2 (reliable with
Rusch GM
restrictions)
O'Grodnick J and
key study
Rinehart WE
experimental result (1986)
The acute inhalation 4 h LC50 values for cadmium chloride, oxide and carbonate range from > 0.8 x 10-3 to
<66 x 10-3 mg Cd/L. No information is available for insoluble cadmium compounds.
Upon inhalation of high doses, cadmium causes severe pulmonary lesions. Several biochemical changes have
been show to parallel the morphological alterations (JRC, 2008).
5.2.1.3. Acute toxicity: dermal
No reliable studies were located regarding acute effects after dermal exposure to cadmium metal or cadmium
compounds.
In a study by Wahlberg (1965), 9/20 guinea pigs died several weeks after being exposed to cadmium chloride
applied dermally (0.14 mg/kg bw). However, it was difficult to attribute these deaths to cadmium exposure due
to the low dose compared to oral LD50 values and to the fact that no necropsy was done to determine whether
the exposed guinea pigs might have died from pneumonia (which killed some control animals) (ATSDR, 2008;
JRC, 2007).
5.2.1.4. Acute toxicity: other routes
As discussed in Section 5.1, there are no other relevant routes of exposure to cadmium metal and cadmium
compounds.
5.2.2. Human information
Reports of effects from oral and inhalatory exposure to cadmium in humans can be found in the literature.
Acute gastrointestinal symptoms have been recorded after ingestion of food or beverages contaminated with
high amounts of cadmium. Intoxication has also resulted in workers exposed to cadmium dust that ate their
meals with dirty hands, smoked or bit their fingernails at the workplace. In two recorded suicide attempts,
mortality occurred within 7 days and 33 hours of ingestion of 25 mg Cd/kg bw in the form of cadmium iodide
(Wisniewska-Knypl et al., 1971) and 1,840 mg Cd/kg bw in the form of cadmium chloride (Buckler et al.,
1986), respectively. The cause of death was massive fluid loss, oedema and widespread organ failure. As
summarised in Bernard and Lauwerys (1986)2, the no observed effect level (NOEL) of a single oral dose is
estimated to be equivalent to 3 mg Cd/person and the lethal dose is estimated to range from 350 to 8,900 mg
Cd/person.
2 These values are reported in several reviews without further evaluation. Primary studies are unavailable.
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Acute cadmium poisoning and in some cases death have been reported among workers shortly after inhalatory
exposure to fumes when cadmium metal or cadmium-containing materials were heated to high temperatures.
Cadmium metal fumes are reported to be instantly transformed into cadmium oxide when entering in contact
with air. Case reports after accidents and following short-term exposure of users extend over more than half a
century, as summarized in the European Risk Assessment Report (RAR) (JRC, 2007). During the acute
exposure phase, the general symptoms are relatively mild but, within a few days, severe pulmonary edema and
chemical pneumonitis develop, leading to death due to respiratory failure. The dose sufficient to cause
pulmonary edema is not exactly known. In one fatal case the average airborne concentration was estimated to be
8.6 mg/m³ during 5 hours, or approximately an 8-hour time-weighted average (TWA) of 5 mg/m³ (Beton et al.,
1966; Barrett et al., 1947). This estimate was based on lung Cd content at post-mortem examination, which may
have been greater than the dose necessary to cause death. The atmospheric concentration necessary to cause
pneumonitis may therefore be considerably less. It has been estimated that an 8 hour exposure to 1 mg Cd/m³ is
immediately dangerous for life (CRC, 1986).
5.2.3. Summary and discussion of acute toxicity
When administered orally, the water soluble cadmium chloride caused mortality at relatively low doses, with
LD50s in mouse and rat ranging from 29 to 327 mg Cd/kg bw. On this basis, cadmium chloride has been
classified as T; R25 (toxic if swallowed) in Annex I of Directive 67/548/EEC. Under GHS-CLP, the
corresponding classification would be ‘Acute toxicity (oral) category 3; H301’. Although no animal studies
are available, cadmium sulphate is also classified in Annex I as T; R25, which is justified given its comparable
solubility to cadmium chloride. Cadmium nitrate, also highly water soluble, is at present not classified for acute
oral toxicity but a similar classification should be considered.
Although original studies were not available, data for cadmium oxide and cadmium metal powder suggest that
the slightly soluble or insoluble forms of cadmium (like also cadmium hydroxide and cadmium carbonate) may
present lower oral acute toxicity. To date, they are not classified for this endpoint. The only exception is
cadmium sulphide which, despite being insoluble, carries an Xn; R22 (harmful if swallowed) in Annex I of
Directive 67/548/EEC (the corresponding GHS-CLP classification would be ‘Acute toxicity (oral) category 4;
H302). Given that there are no studies to support this classification, a revision of this classification may be
appropriate based on solubility properties.
In humans, the no observed effect level (NOEL) of a single oral dose is estimated to be equivalent to 3 mg
Cd/person (i.e. 0.05 mg/kg bw for a 60 kg person) and the lethal dose is estimated to range from 350 to 8,900
mg Cd/person (i.e. 5.8 to 148 mg/kg bw for a 60 kg person).
Cadmium chloride, oxide, carbonate and metal have a high acute toxicity by the inhalation route (0.8 x 10-3 <
4h LC50 < 66 x 10-3 mg Cd/L). Cadmium chloride, sulphate, oxide and metal have been classified as T+; R26
(Very toxic by inhalation) in Annex I of Directive 67/548/EEC (the corresponding GHS-CLP classification is
‘Acute toxicity (inhalation) category 2; H330). Based on comparable toxicity and/or solubility /
bioavailability, all other highly and slightly soluble cadmium forms, i.e. cadmium nitrate, hydroxide and
carbonate should carry a comparable classification. The insoluble cadmium compound cadmium sulphide is
however not expected to cause significant adverse effects via this route and is currently not classified for acute
inhalatory toxicity. For human health, observations indicate that an 8 hour inhalatory exposure to 5 mg
Cd/m3 is lethal and 1 mg Cd/m³ is immediately dangerous for life.
No information was located regarding effects in humans after dermal exposure to cadmium. However, acute
toxicity via the dermal route is not expected to be significant as uptake of soluble and less-soluble cadmium
compounds applied onto the skin of animals appears to be low (<1%) (see Section 5.1.1). Also in view of the
risk reduction measures which need to be taken as a result of the carcinogenicity of cadmium metal and some of
the cadmium compounds, acute dermal toxicity is not likely to pose an issue for human health. No
corresponding classification is therefore required.
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cadmium sulphate
CAS number:
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5.3. Irritation
5.3.1. Skin
5.3.1.1. Non-human information
No studies were located regarding the skin irritation potential of cadmium metal and cadmium compounds to
animals. However, given the carcinogenic properties of cadmium metal and some of the cadmium compounds,
risk reduction measures are in place at the workplace to prevent contact. Therefore, skin irritation is not
expected to be an issue for human health and further testing is not considered necessary for this endpoint, in
accordance with Annex XI (3) of the REACH directive.
5.3.1.2. Human information
Wahlberg (1977) reported that, among eczema patients routinely patch-tested with 2% cadmium chloride, 25 out
of 1,502 (1.7%) showed some reaction. Since no effects were seen at lower dilutions, toxicity was likely due to
direct irritation of the skin and was considered to be a LOAEL.
No information was located on cadmium metal or other cadmium compounds.
5.3.2. Eye
No studies were located regarding the eye irritation potential for humans or animals. However, given the
carcinogenic properties of cadmium metal and some of the cadmium compounds, risk reduction measures are in
place at the workplace to prevent contact. Therefore, eye irritation is not expected to be an issue for human
health and further testing is not considered necessary for this endpoint, in accordance with Annex XI (3) of the
REACH directive.
5.3.3. Respiratory tract
No studies were located regarding the respiratory tract irritation potential of cadmium metal or cadmium
compounds to humans or animals. According to the EU RAR (JRC, 2007), it may be appropriate to consider
cadmium oxide (fumes, dust) as an irritant to the respiratory tract after inhalatory exposure, based on results
from single and repeated inhalation exposure studies (see Sections 5.2 and 5.6). In animals, the lowest dose
reported to cause mild pulmonary damage (hypercellularity indicative of hyperplasia) after single exposure was
0.5 mg Cd/m3 (3 h) as cadmium oxide fumes. The lowest dose reported to cause lung changes after repeated
exposure to cadmium oxide fumes was 50 µg CdO/m3 in rats for 13 weeks and 10 µg CdO/m3 in hamster for 14
months (Dunnick, 1995; Aufderheide et al., 1989; JRC, 2007).
5.3.4. Summary and discussion of irritation
Limited information is available on the skin, eye and respiratory tract irritation potential of cadmium metal and
cadmium compounds. In a study on patients with eczema, cadmium chloride caused skin irritation in 1.7% of
the volunteers when applied at 2%. Based on single and repeated inhalation exposure studies, cadmium oxide
fumes may be considered irritating to the respiratory tract. However, given the carcinogenic properties of
cadmium metal and some of the cadmium compounds, risk reduction measures are in place at the workplace to
prevent contact. Therefore, neither skin, eye nor respiratory tract irritation are expected to be an issue for human
health and further testing is not considered necessary for these endpoints, in accordance with Annex XI (3) of
the REACH directive. This is in line with the conclusions of the EU RAR (JRC, 2007).
At present, none of the cadmium substances covered in the present assessment is classified for irritation
according to Directive 67/548/EEC.
5.4. Corrosivity
No studies were located regarding corrosivity for humans or animals. However, if at all, significant exposure is
expected to occur principally in occupational settings. Given the carcinogen properties of cadmium metal and
some of the cadmium compounds, risk reduction measures are in place to prevent contact. Therefore, corrosivity
is not expected to be an issue for human health and further testing is not considered necessary, in accordance
with Annex XI (3) of the REACH directive. This is in line with the conclusions of the EU RAR (JRC, 2007).
At present, none of the cadmium substances covered in the present assessment is classified for corrosivity in
Annex I of Directive 67/548/EEC.
5.5. Sensitisation
5.5.1. Skin
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cadmium sulphate
CAS number:
10124-36-4
5.5.1.1. Non-human information
The only skin sensitization study that could be found was a guinea-pig maximization test (GMPT) conducted
with water soluble cadmium chloride, which indicated no contact sensitisation following epicutaneous exposure
at concentrations up to 0.5% after intradermal or topical sensitisation (Wahlberg and Boman, 1979). However,
due to incomplete reporting and deviations from the current regulatory test protocols, the study was considered
unreliable.
No skin sensitization studies were located on cadmium metal or any of the other cadmium compounds.
5.5.1.2. Human information
Positive patch-test reactions to cadmium chloride and sulphate in human volunteers are summarised by
Wahlberg (1977). The results are not consistent and, according to the authors, the percentage of positive
reactions may have varied with the vehicle used for the cadmium solution (ethanol or water) or with possible
impurities contained in the test substance. No clear conclusion could therefore be drawn on the skin sensitization
potential of the substances (JRC, 2007).
With regard to cadmium metal and cadmium oxide, the accumulated experience in occupational practice over
decades does not indicate any sensitizing potential (JRC, 2007).
No further human information was located on cadmium metal or the other cadmium compounds.
5.5.2. Respiratory system
No studies were located on respiratory sensitisation in humans or animals. However, given the carcinogen
properties of cadmium metal and some of the cadmium compounds, risk reduction measures are in place at the
workplace to prevent contact. Therefore, respiratory sensitization is not expected to be an issue for human health
and further testing is not considered necessary, in accordance with Annex XI (3) of the REACH directive.
5.5.3. Summary and discussion of sensitisation
Only limited data were available on the skin or respiratory sensitization potential of cadmium metal and
cadmium compounds. Cadmium chloride did not show any skin sensitization effects at 0.5% in a GMPT test.
Cadmium chloride and sulphate were patch-tested in human volunteers but, across several studies, the evidence
remained inconclusive.
If at all, significant exposure is expected to occur principally in occupational settings. Given the carcinogen
properties of cadmium metal and some of the cadmium compounds, risk reduction measures are in place to
prevent contact. Therefore, neither skin nor respiratory tract sensitization are expected to be an issue for human
health and further testing is not considered necessary, in accordance with Annex XI (3) of the REACH directive.
This is in line with the conclusions of the EU RAR (JRC, 2007).
At present, none of the cadmium substances covered in the present assessment is classified for sensitization in
Annex I of Directive 67/548/EEC.
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cadmium sulphate
CAS number:
10124-36-4
5.6. Repeated dose toxicity
5.6.1. Non-human information
5.6.1.1. Repeated dose toxicity: oral, inhalation and other
Studies in various animal species using different cadmium substances (i.e. cadmium chloride and oxide)
demonstrate that repeated exposure via both the oral and inhalation routes can cause damage to kidney and
bone. Inhalatory exposure may additionally result in toxicity to the lung. The kidney (and possibly bone) is the
most sensitive target organ (JRC, 2008). The type of effects and the underlying mechanisms have been analysed
in more detail in testing conducted using other routes of administration (i.e. intravenous, intraperitoneal or
subcutaneous).
Selected studies are presented in the following tables. Results are then discussed by target organ rather than by
exposure route, as this is more relevant given the similarity of the effects observed.
Table 17. Overview of selected experimental studies on repeated dose toxicity after oral administration
Method
Results
Remarks
Reference
Mouse (CF-1) female
chronic (oral: feed)
0.25, 5 or 50 ppm Cd
Vehicle: none
Exposure: > 600 d (continuous)
A study was conducted to determine
the effect of Cd on body mass and
calcium levels in the postreproductive period. Confounding
effect of nutrient deficient diet,
multiparity and ovariectomy were
considered; the calcium-depleting
effect of each factor was evaluated
by determining calcium levels in
femur and lumbar vertebrae.
no NOAEL identified.
(limited role of Cd alone in
decreasing body mass during
the post-reproductive period
but combined Cd and dietary
nutrient deficiencies showed
this effect. 50 ppm Cd
depressed Ca levels in femur
and vertebrae. Skeletal
degeneration characteristic of
Itai-Itai syndrome not
reproduced, suggesting that
the full-blown disease
requires primary and
profound skeletal
demineralisation secondarily
supported and enhanced by
renal dysfunction)
1 (reliable without
restriction)
supporting study
experimental result
Whelton BD,
Peterson DP,
Moretti ES, Dare
H and
Bhattacharyya MH
(1997)
Rat (SPF-Wistar) male/female
chronic (oral: feed)
0, 1, 3, 10 and 30 ppm Cd
Vehicle: none
Exposure: 3 months
A study was conducted to determine
the repeated dose oral toxicity of
cadmium in rat. Clinical signs,
bodyweight, food consumption,
hematology were followed.
Histology was conducted at study
end.
NOAEL: 30 ppm ( i.e. ca. 3
mg Cd/kg bw/d)
(no effects on any parameters
followed but Cd accumulated
dose-dependently in the
kidneys and liver
2 (reliable with
restrictions)
key study
experimental result
Loeser E and
Lorke D (1977a)
Rat (Wistar) male
Chronic (oral: water)
Drinking water: 0, 1, 5 and 50 mg
Cd/L
Exposure: 12 months
NOAEL: 0.2 mg Cd/kg bw/d
(increased lumbar spine
deformities, decreased lumbar
spine mineralization, altered
bone turnover parameters)
2 (reliable with
restrictions)
key study
experimental result
Brzoska MM and
MoniuszkoJakoniuk J (2005a
and 2005b)
Dog (Beagle) male/female
chronic (oral: feed)
0, 1, 3, 10 and 30 ppm Cd
NOAEL: 30 ppm (i.e. ca. 0.75 2 (reliable with
mg Cd/kg bw/d)
restrictions)
(no effects on any parameters key study
Cadmium chloride
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Loeser E and
Lorke D (1977b)
51
EC number:
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Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
Vehicle: none
followed but Cd accumulated experimental result
Exposure: 3 months
dose-dependently above all in
A study was conducted to determine kidney and liver)
the repeated dose oral toxicity of
cadmium in dog. Clinical signs,
bodyweight, food consumption,
hematology were followed.
Histology was conducted at study
end.
Dog (Beagle) female
subchronic (diet (capsules), drinking
water)
Diet: increasing doses of 1, 5, 15 and
50 ppm. Drinking water: 15 ppm
Vehicle: none
Exposure: capsules in diet: 1 month,
drinking water: 6 months
A repeated exposure study was
conducted to determine the effects of
oral Cd on calcium release from
bone tissues. Skeletons of
ovariectomised dogs were
prelabelled with 45Ca and Cd was
administered through capsules and in
drinking water. The release of 45Ca
from bone was observed.
no NOAEL identified.
(Cd increased bone resorption
(skeletal 45Ca release) in
ovariectomized and shamoperated dogs without renal
dysfunction or calcitropic
hormone interaction. Cd
appears to be an exogenous
factor exacerbating bone
mineral loss in postmenopausal osteoporosis)
2 (reliable with
restrictions)
supporting study
experimental result
Sacco-Gibson N,
Chaudhry S, Brock
A et al. (1992)
Monkey (Macaca mulatta) male
chronic (oral: feed)
0.27 (controls), 3, 10, 30 and 100
ppm Cd
Vehicle: none
Exposure: 462 wks (9 y)
A study was conducted to determine
the repeated dose oral toxicity of
cadmium in monkey. General health
parameters were followed.
NOAEL: 3 ppm Cd (i.e. ca.
0.12 mg/kg bw/d)
(reduced bodyweight and
body length as of 10 ppm.
Early effects on renal function
at 100 ppm but no aggravated
renal dysfunction or renal
failure during the 9 years of
the study)
2 (reliable with
restrictions)
supporting study
experimental result
Masoaka T,
Akahori F, Arai S
et al. (1994)
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CAS number:
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Table 18. Overview of selected experimental studies on repeated dose toxicity after inhalation exposure
Method
Results
Remarks
Reference
Mouse (B6C3F1) male/female
subchronic (inhalation: aerosol)
(whole body)
0, 0.025, 0.05, 0.1, 0.25 or 1 mg
CdO/m3 (nominal conc.)
Vehicle: unchanged (no vehicle)
Exposure: 13 wk (6 h and 20 min/d;
5 d/wk)
equivalent or similar to OECD
Guideline 413 (Subchronic
Inhalation Toxicity: 90-day)
No NOAEL identified.
LOAEL: 0.025 mg CdO
(0.022 mg Cd)/m3/6h
(lung effects)
1 (reliable without
restriction)
key study
experimental result
Dunnick JK
(1995)
Rat (Fischer 344) male/female
subchronic (inhalation: aerosol)
(whole body)
0, 0.025, 0.05, 0.1, 0.25 or 1 mg
CdO/m3 (nominal conc.)
Vehicle: unchanged (no vehicle)
Exposure: 13 wk (6 h and 20 min/d;
5 d/wk)
equivalent or similar to OECD
Guideline 413 (Subchronic
Inhalation Toxicity: 90-day)
NOAEL: 0.025 mg
CdO/m³/6h (male/female)
(lung effects)
LOAEL: 0.05 mg CdO/m³/6h
(male/female) (lung effects)
1 (reliable without
restriction)
key study
experimental result
Dunnick JK
(1995)
Rat (Wistar) female
subchronic (inhalation: aerosol)
25, 50, 100 µg Cd/m3 (nominal
conc.)
Vehicle: unchanged (no vehicle)
Exposure: 90 d at 25 and 50 µg
Cd/m3; 63 d at 100 µg Cd/m3 (24
h/d)
A repeated dose inhalation exposure
study was conducted to determine
the effects of the test material on
lungs. Female rats were exposed to
CdO for 90 d at 25 and 50 μg
Cd/m3, and for 63 d at 100 µg
Cd/m3.
LOAEL: 0.025 mg
Cd/m3/24h (female) (cell
proliferations of the bronchi,
bronchioli and alveoli,
indicating hyperplasia of the
lungs; histiocytic cell
granulomas)
2 (reliable with
restrictions)
key study
experimental result
Prigge E (1978)
Rat (Lewis) male
subchronic (inhalation: aerosol)
(nose only)
1.6 +/- 0.03 mg cadmium/m3
Vehicle: unchanged (no vehicle)
Exposure: 1-6 wk (3 h/d; 5 d/wk)
A study was conducted to determine
the effects of the test material in the
lungs of male Lewis rats. Groups of
rats were exposed to an atmosphere
of 1.6 mg Cd/m3 for several weeks
(as CdO for 80 ± 5%, 3 h/d, 5 d/wk,
1 to 6 wk). Histopathological
examination was then performed on
the lungs.
no NOAEL identified.
LOAEL: 1.6 mg Cd/m³/3h
(male) (interstitial
pneumonitis)
3 (not reliable)
supporting study
experimental result
Hart BA (1986)
Rat (Wistar) male
no NOAEL identified.
3 (not reliable)
Glaser U, Klöppel
Cadmium oxide
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CAS number:
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Method
Results
subchronic (inhalation: aerosol)
0.1 mg Cd/m3 (nominal conc.)
Vehicle: unchanged (no vehicle)
Exposure: 30 d (22 h/d; 7 d/wk)
A study was conducted to determine
the effects of subchronic exposure in
rat lungs. Wistar rats were exposed
to an aerosol of CdO (0.1 mg/m3, 22
h/d, 7 d/wk for 30 d), and evaluation
of clinical signs, bodyweight,
heamotological and clinical
parameters were performed. Lung
lavage and histopathology of the
lungs were carried out at
termination.
LOAEL: 0.1 mg CdO/m³/22 h supporting study
(male) (increased total
bronchoalvelolar macrophage
numbers, leukocytes, and
macrophage cytotoxicity)
K and Hochrainer
D (1986)
Rat (Wistar) female
subchronic (inhalation: aerosol)
0.02, 0.16 and 1.0 mg Cd/m3
(nominal conc.)
Exposure: 6 months (15 wk for the
high-exposed group) (5 h/d; 5 d/wk)
A study was conducted to examine
the effecs of the test material on
arterial blood pressure, lipid content
in serum and some organs, cadmium
level in blood, aorta wall, lung and
liver in rats. The rats were repeatedly
exposed to CdO fume 5 h daily, 5
d/wk, for 6 months. Measurement of
blood pressure was carried out
before exposure and at the end of 6,
12, 15, 22 and 27 wk. Clinical
biochemical examinations and
determination of the cadmium
content in different organs such as
lungs, kidneys and aorta wall were
also carried out at termination.
NOAEL: 0.16 mg Cd/m³/ 5
3 (not reliable)
h(female) (absence of effects supporting study
on bodyweight, clinical signs experimental result
and blood pressure)
LOAEL: 1.0 mg Cd/m³/5 h
(female) (decrease of systolic
blood pressure + mortality)
Baranski B,
Opacka J and
Wronska-Nofer
TL et al. (1983)
Rat (Wistar) female
subchronic (inhalation: aerosol)
0.16-1.0 mg CdO/m3 (nominal
conc.)
Exposure: 3 and 6 months at 0.16
mg/m3; 3 and 4 months at 1.0
mg/m3 (5 h/d; 5 d/wk)
A study was conducted to evaluate
the effects of the test material on the
ultra structure of the cardiac muscle
in rats. The experimental rats were
exposed by inhalation to CdO fumes
(0.16 and 1.0 mg/m³ 5 h daily, 5
d/wk for 3 and 6, 3 and 4 months
respectively) was evaluated.
Microscopic and macroscopic
examination of the cardiac papillary
muscles (left ventricle) and arterioles
were performed at termination.
no NOAEL identified.
3 (not reliable)
(differences in ultrastructure supporting study
of intercalated discs in cardiac experimental result
papillary muscle compared to
controls)
Kolakowski J,
Baranski B and
Opalska B (1983)
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Remarks
CHEMICAL SAFETY REPORT
Reference
54
EC number:
233-331-6
Method
cadmium sulphate
Results
Rat (Sprague-Dawley)
LOAEL: 0.1 mg Cd/m³/6 h
subchronic (inhalation)
(lung fibrosis and first-stage
0, 0.1 and 1.0 mg/m3
emphysema at high doses)
Exposure: 12 wk (6 h/d; 5 d/wk)
A study was conducted to determine
the pulmonary effects of the test
material in rats. The experimental
rats were exposed to CdO fumes (0.1
or 1.0 mg Cd/m³) for up to three
months.
Hamster (Syrian (SxHU)) male
subchronic (inhalation: aerosol)
0.01, 0.09, 0.27 mg Cd/m3 (nominal
conc.)
Exposure: 16 months (8 h/d; 5 d/wk)
A study was conducted to determine
the chronic exposure effects of the
test material in hamster lungs. Syrian
Golden hamsters were exposed to
aerosols of CdO, followed by
microscopic examination of the
lungs.
NOAEL: 0.01 mg Cd/m3/8 h
(i.e. ca. 0.013 mg Cd/m3/6h)
(hyperplasia in
peribronchiolar region)
CAS number:
10124-36-4
Remarks
Reference
4 (not assignable)
supporting study
experimental result
Yoshikawa H,
Kawai K, Suzuki
Y and Nozaki K,
Ohsawa M (1975)
2 (reliable with
restrictions)
key study
experimental result
Aufderheide M,
Thiedemann KU,
Riebe M and
Kohler M (1989)
Table 19 . Overview of selected studies on repeated dose toxicity (other routes)
Method
Results
Remarks
Reference
Mouse (Metallothionein (MT)
knock-out mice (129/SvPCJ
background) and
129/Sv+P+C+MGFSLJ))
male/female
subchronic (subcutaneous)
wild-type mice: 0.05-0.8 mg Cd/kg
bw
MT-null mice: 0.0125-0.1 mg Cd/kg
bw
Vehicle: physiol. saline
Exposure: 10 wk (6 d/wk)
A study was conducted to determine
the repeated dose effect of the test
material on the bone tissue of wildtype and MT-knockout mice and the
protective effect of MT on bone.
Repeated sc injections of CdCl2 over
a wide range of doses for 10 weeks.
no NOAEL identified.
(male/female)
LOAEL: 0.0125 mg Cd/kg
bw (total dose) (male/female)
(LO(A)EL bone damage: in
MT-null mice: 0.0125 mg
Cd/kg bw)
LOAEL: 0.1 mg Cd/kg bw
(total dose) (male/female)
(LO(A)EL bone damage: in
wild-type mice: 0.1 mg Cd/kg
bw)
2 (reliable with
restrictions)
key study
experimental result
Habeebu SS, Liu J,
Liu Y and
Klaassen CD
(2000)
Rat (Sprague-Dawley) female
subchronic (intravenous)
1 and 2 mg CdCl2/kg bw/d
Vehicle: physiol. saline
Exposure: 13 wk (5 d/wk)
The repeated exposure effect of the
test material on bone was
determined. Young, ovariectomised,
female rats were administered CdCl2
intravenously (1.0 or 2.0 mg
CdCl2/kg bw, 5 d/wk during 13 wk).
General clinical observations,
no NOAEL identified.
(bone toxicity at high doses;
results do not allow
discrimination of whether
bone effects are due to direct
action of Cd or are a
consequence of kidney
damage).
2 (reliable with
restrictions)
key study
experimental result
Katsuta O,
Hiratsuka H,
Matsumoto J et al.
(1994)
Cadmium chloride
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EC number:
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Method
cadmium sulphate
CAS number:
10124-36-4
Results
Remarks
Reference
Rat (Sprague-Dawley) male/female
subchronic (intraperitoneal)
0.228 mg/rat
Vehicle: physiol. saline
Exposure: 16 months (3 times/wk)
A repeated dose exposure study was
conducted to determine the effects of
the test material to the bone and
kidney. Males and females (42
females underwent bilateral
ovariectomy at 11 wk of age) were
used. CdCl2 was administered i.v.
for 16 months. Bodyweights were
measured and urinalysis for females
was performed before sacrifice.
Macroscopic and microscopic
analysis were performed on bone,
kidney, liver and spleen.
no NOAEL identified.
(severe pathological and
functional renal toxicity. Bone
calcium content significantly
affected by Cd treatment)
2 (reliable with
restrictions)
key study
experimental result
Li J P, Akiba T
and Marumo F
(1997)
Rat (Sprague-Dawley) female
subchronic (intraperitoneal)
0.18 mg CdCl2/rat
Vehicle: water
Exposure: 28 wk (3 times/wk)
A study was conducted to determine
the repeated dose exposure effects of
the test material on bone metabolism
and kidneys of ovariectomised
rats.0.18 mg CdCl2 was
administered intraperitoneally 3
times/wk for 28 weeks in
ovariectomised Sprague-Dawley rats
(15 rats treated with cadmium and 10
controls). Urinalysis and
examination of the femur and
vertebrae were performed at
termination.
no NOAEL identified.
LOAEL: 0.18 mg CdCl2/rat
(female)
(severe renal toxicity,
decreased bone mineral
content in lumbar vertebral
body and femur, resulting in
reduced mechanical strength)
2 (reliable with
restrictions)
key study
experimental result
Uriu K, Morimoto
I, Kai K, Okazaki
Y, Okada Y et al.
(2000)
Rat and monkey (Sprague-Dawley
and Macaca fascicularis) female
subchronic (intravenous)
4 experiments: doses ranged from
0.05 to 3.0 mg Cd/kg bw
Vehicle: physiol. saline
Exposure: 14days up to 13-15
months (see table 1 IUCLID entry)
Four repeated dose studies were
conducted to explore the
pathological mechanism of ItaiItaidisease in rat and monkey. Toxic
effects of different doses of
cadmium were assessed in
ovariectomised and nonovariectomised rats and in monkeys
after repeated i.v. injection of CdCl2.
No NOAEL identified
(tubular nephropathy, anemia
and bone changes; not clear
whether bone changes were a
result of direct action of Cd or
a secondary effect linked to
kidney toxicity)
2 (reliable with
restrictions)
key study
experimental result
Umemura T
(2000)
bodyweights and relevant serum
levels were measured. Femurs and
humerus were examined upon
autopsy.
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Kidney
Numerous studies indicate that oral exposure to cadmium compounds causes kidney toxicity (Loeser and Lorke,
1979a and b; Masoaka, 1994; ATSDR, 2008; JRC, 2007). ATSDR (2008) also notes that other studies showed
no effect on renal function, which illustrates the existence of a critical cumulative dose. Oral cadmium exposure
in animals has been shown to increase or decrease relative kidney weight and cause histological (necrosis of the
proximal tubules, interstitial fibrosis) and functional (reduced glomerular filtration rate, proteinuria) changes.
There is no good agreement about the cadmium dose necessary to bring about these effects in animals. Critical
tissue concentrations reported in the literature vary between 50 and 300 µg Cd/g renal cortex. Most authors
agree however that a mean critical concentration of approximately 200 µg Cd/g renal cortex must be reached in
order to observe tubular proteinuria, which is the most sensitive indicator of cadmium-induced renal toxicity. At
these doses, the amount of free cadmium in the kidney (not bound to metallothionein) becomes sufficiently high
to cause tubular damage. The health significance of tubular proteinuria and its predictive value for the
development of end-stage renal failure is however not answered by experimental data (JRC, 2007).
Early animal studies confirmed that renal damage occurs also following inhalation exposure to cadmium
(ATSDR, 2008). Moderate proteinuria was seen in rabbit exposed to cadmium oxide dust at 8 mg Cd/m3 for 4
months. After 7 to 9 months, histopathological examination of the kidneys revealed interstitial infiltration of
leucocytes in the majority of the exposed animals (Friberg, 1950). Most subsequent experimental studies using
inhalation exposure have not found proteinuria (Glaser et al., 1986; Prigge, 1978) but these were limited by the
fact that the level of exposure and duration of follow-up that cause serious respiratory effects were not sufficient
to produce critical concentrations of cadmium in the kidney (ATSDR, 2008; JRC, 2007).
Bone
In vitro studies have demonstrated that cadmium compounds exert a direct effect on bone metabolism, affecting
both bone resorption and formation, and inducing calcium release (JRC, 2007). In animals, cadmium has been
shown to affect bone metabolism, manifested as osteopetrosis, osteosclerosis, osteomalacia and/or osteoporosis
after oral (Whelton et al., 1997; Brzoska and Moniuszko-Jakoniuk, 2005a and 2005b; Sacco-Gibson et al.,
1992), subcutaneous (Habeebu et al., 2000) or intraperitoneal (Li et al., 1997) exposure. In most experimental
studies, bone effects were accompanied or preceded by renal damage induced by cadmium treatment; these
studies therefore do not allow to determine whether cadmium bone toxicity occurs in parallel to or as a
consequence of nephrotoxicity (Katsuta et al., 1994; Umemura, 2000). Young age (growing bones), gestation,
lactation and ovariectomy (used as an animal model of menopause) appeared to exacerbate this toxicity. A clear
NOAEL/LOAEL for bone damage can therefore not be extrapolated from the studies (JRC, 2007).
Lung
Some lung effects have been observed after oral administration of cadmium compounds in rat for several weeks
(Petering et al., 1979) but no effects were seen in monkey exposed to higher doses for several years (Masoaka et
al., 1994). It has been suggested that the observed lung effects are related to liver or kidney damage and
subsequent changes in cellular metabolism (JRC, 2007).
Long-term inhalatory exposure to cadmium oxide in animals resulted in similar effects as seen in acute studies,
i.e. pneumonia and emphysema accompanied by histopathological alterations and changes in the cellular and
enzymatic composition of the bronchoalveolar fluid (Dunnick, 1995; Prigge, 1978; Hart, 1986; Glaser et al.,
1986; Yoshikawa et al., 1975; Aufderheide et al., 1989). Differences in metallothionein metabolism could be
noted as an explanation for differences (Habbeebu et al., 2000; JRC, 2007).
Some tolerance to cadmium appears to develop with duration so that lung lesions developed after a few weeks
of exposure do not progress, and may even regress after long exposure. Multiple mechanisms could explain this
tolerance, including the synthesis of lung metallothionein and proliferation of Type II cells (ATSDR, 2008).
Identified NOAELS are 0.025 mg CdO/m3 in F344/N rats exposed for 13 weeks (Dunnick, 1995) and 0.01 mg
Cd/m3 in hamster exposed for 16 months (Aufderheide et al., 1989).
Other
Contradictory findings have been reported in studies investigating effects on blood pressure after oral
administration of cadmium in animals. Inhalation exposure to cadmium oxide was not associated with an
increase in blood pressure (Baranski et al., 1983). In one study, exposure was reported to have induced
ultrastructural changes in the cardiac papillary muscle of rats at 0.16 mg Cd/m3 (Kolakowski et al., 1983).
Overall, evidence for cardiovascular toxicity resulting from oral and inhalatory exposure in animals is
suggestive of a slight effect.
Conflicting results have been reported about the haematological effects of cadmium after long-term exposure.
In the studies where such alterations (e.g. anemia) were seen, several mechanisms have been postulated,
including impaired iron absorption, direct cytotoxicity to bone marrow, inhibition of the heme system or
hypoproduction of erythropein (ATSDR, 2008; JRC, 2007).
Certain experimental studies using cadmium soluble compounds have reported morphological and metabolic
changes in the liver but this is not a universal finding. Inhalation studies show conflicting results; even when
signs of cadmium toxicity were seen, they were usually mild (ATSRD, 2008; JRC, 2007).
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Potential effects on the neurological or immunological systems are discussed in Section 5.10.
5.6.1.2. Repeated dose toxicity: dermal
No studies were located regarding chronic effects after dermal exposure to cadmium metal or cadmium
compounds. However, repeated dose toxicity via the dermal route is not expected to be significant as uptake of
soluble and less-soluble cadmium compounds applied onto the skin of animals appears to be low (<1%) (see
Section 5.1.1). Also in view of the risk reduction measures which need to be taken as a result of the
carcinogenicity of cadmium metal and some of the cadmium compounds, dermal toxicity is not likely to pose an
issue for human health.
5.6.2. Human information
Numerous studies have looked into the effects of cadmium exposure both in the general population and at the
workplace. In the general environment and in occupational settings, the main target organs are kidney and bone.
For workers, the lungs may also be affected. The following section presents some of the main human
information, by target organ, as summarized in SCOEL (2009).
Kidneys
In occupationally exposed subjects, the first manifestation of cadmium nephrotoxicity is usually tubular
dysfunction resulting in a reabsorption defect and, hence, an increased urinary excretion of low molecular
weight proteins such as the human complex protein (also called α1-microglobulin, ß2-microglobulin and/or
retinol-binding protein) but also calcium and amino-acids (Lauwerys et al., 1979; Elinder et al., 1985;
Jakubowski et al., 1987; Mason et al., 1988; Chia et al., 1989; Roels et al., 1993; Järup and Elinder, 1994).
Other biomarkers of tubular toxicity such as urinary alanine aminopeptidase, gamma-glutamyltranspeptidase
and the lysosomal enzyme N-acetyl-beta-Dglucosaminidase have also been used to demonstrate the tubular
effects associated with occupational exposure to cadmium (Mueller et al., 1989; Bernard et al., 1995).
Studies conducted in the 1980s on active workers in the cadmium industry have demonstrated that low
molecular weight (tubular) proteinuria is likely to occur in approximately 10% of workers when the cadmium
concentration in kidney cortex exceeds about 200 ppm (μg Cd/g wet weight of renal cortex) (Nordberg et al.,
2007; Bernard, 2008; Roels et al., 1981; Roels et al, 1983). These studies have also shown that, before renal
dysfunction develops, the amount of cadmium stored in the kidneys can be assessed non-invasively by
measuring the concentration of the metal in urine (Cd-U) (Norberg et al., 2007). On the basis of the relationship
between cadmium concentrations in urine and in kidney cortex in workers with no renal dysfunction, the Cd-U
value corresponding to the critical level of 200 ppm in kidney cortex was estimated at 10 μg Cd/g creatinine
(Norberg et al., 2007; Roels et al., 1981), a value that was in concordance with that derived from the
relationships between ß2-microglobulin urine concentration and Cd-U (Bernard et al, 1979; Roels et al., 1993).
Since then, a number of studies have further explored the dose-effect/response relationships for cadmiuminduced renal dysfunction in industrial workers, with threshold values ranging between 1.5 and 15 µg Cd/g
creatinine, as shown in Table 20.
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Table 20. Thresholds for renal effects in recent/relevant studies in occupational settings (inhalation
exposure) (adapted from ‘Recommendation from the Scientific Expert Group on Occupational Exposure
Limits for Cd and its inorganic compounds’ SCOEL/SUM/136)
Type of
industry
Electronic
workshop
Ni-Cd storage
battery factory
Cd-producing
plants
Alkaline battery
factory
Cd smelter
n
-
Glomerular
effects
HMW proteins,
serum ß2-M
and creatinine
Tubular
effects
ß2-M
102
ß2-M, RBP
53
ß2-M
Secondary Cd
users
Cd pigment
factory
Non-ferrous
smelter
26
ß2-M, RBP,
NAG
ß2-M, NAG
Zn-Cd smelter
108
Cd alloy factory
105
Zn-Cd smelter
37
Zn-Cd refinery
14
ß2-M
Battery factory
561
ß2-M
Cadmium
smelter
85
β2-M, NAG
29
58
Albumin,
transferrin,
serum ß2-M
GFR decline
ß2-M, RBP,
protein-1,
NAG
ß2-M
Albumin,
transferrin
ß2-M, RBP
and other
markers
Threshold
Reference
Cd-U : 10 µg/g
creatinine
(G and T)
Lauwerys et al. (1979)
Cd-U : 10-15 µg/g
creatinine
Cd-U : 13.3 µg/g
creatinine
Cd-U : 5.6 µg/L
Jakubowski et al. (1987)
Cd-U : < 10 µg/g
creatinine (NAG)
Cd-U : 10 µg/g
creatinine
Kawada et al. (1989)
Cd-U : 10 µg/g
creatinine
Cd-U : 10 µg/g
creatinine
Cd-U : 4 µg/g
creatinine (G)
Cd-U : 10 µg/g
creatinine (T)
Cd-U : 7 µg/g
creatinine
Cd-U : 1.5 µg/g
creatinine (> 60 y)
Cd-U : 5 µg/g
creatinine (< 60 y)
Cd-U : 5–10 μg/g
creatinine
Roels et al. (1991)
Shaikh et al. (1987)
Verschoor et al. (1987)
Bernard et al. (1990)
Toffoletto et al. (1992)
Roels et al. (1993)
van Sittert et al. (1993)
Järup and Elinder (1994)
Chen et al. (2006)
HMW: High Molecular Weight protein; ß2-M: ß2-microglobulin; RBP: Retinol Binding Protein; NAG: N-acetyl-betaDglucosaminidase; G: glomerular effects; T: tubular effects
Recently, a study by Chaumont et al. (2010) reassessed the somewhat contradictory findings reported for
industrial settings. The studied population was a cohort of 599 occupationally exposed workers from four Ni-Cd
manufacturing plants located in France, Sweden and the United States. The study focused on never smokers and
used as critical effect an increased urinary excretion of retinol-binding protein (RBP-U) or β2-microglobulin (β
2m-U). The Cd-U threshold for these two proteins to exceed the 95 th percentile value was constructed using as a
reference those workers with Cd-U < 1 µg Cd/g creatinine. For never smokers, the odds of abnormal RBP-U and
β2-m-U were increased only among workers with Cd-U > 10 µg Cd/g creatinine. Benchmark dose (BMD5) and
benchmark dose lower limit (BMDL5) for the two proteins were estimated at 12.6/6.6 and 12.5/5.5 µg Cd/g
creatinine. The reason for removing smokers is because it is now established that, beyond the direct effect of
cadmium originating from tobacco (which accumulates in the body along with cadmium coming from
occupational exposure and is consolidated in the Cd-U of individuals, irrespective of its source), smoking is
detrimental to the renal function, even in subjects without hypertension or abnormal glucose metabolism. This
effect, although distinct from those induced by cadmium, is likely to distort the dose-response relation between
low molecular weight proteins and cadmium in urine. Indeed, chronic smoking, even when moderate, is
associated with a marked increase of albuminuria, reflecting damage to the glomerular filter (which is most
likely due to the cardiovascular toxicity of tobacco smoke). As glomerular proteinuria is frequently associated
with a certain degree of tubular dysfunction, confounding is likely to arise from the co-excretion of cadmium
with both albumin (the main cadmium-binding protein in plasma) and low molecular weight proteins induced by
this tubular dysfunction.
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In other terms, because of these co-excretion mechanisms, the high albumin excretion associated with tobacco
smoking may be a so far unsuspected cause of secondary association between cadmium and low molecular
weight proteins in urine. This is confirmed by the fact that when including ever smokers in the statistics, BMD5
and BMDL5 decrease substantially and are estimated at 6.2/4.9 and 4.3/3.5 µg Cd/g creatinine respectively.
Additionally and interestingly, no BMD value could be derived in ever smokers when considered separately.
These findings thus mean that, when smokers are included in the analysis of the renal effects of cadmium, the
dose-response relationships are artificially shifted to the left since the renal effects of tobacco smoke are
unavoidably associated with a moderate increase of urinary cadmium. This study suggests that when sources of
bias (like tobacco smoke, age, sex and residual influence of diuresis) are avoided, the LOAEL or BMD for
urinary Cd are estimated around 12.0g/g creatinine and the corresponding NOAEL or BMDL can be reliably
estimated between 5.5 and 6.6 µg/g creatinine.
On the basis of studies conducted in Europe (Buchet et al., 1990; Hotz et al., 1999; Järup et al., 2000), the
United States (Noonan et al., 2002) and Asia (Jin et al., 2002), it appears that renal effects can be detected in the
general population for Cd-U below 5 μg Cd/g creatinine and even from 2 μg Cd/g creatinine or below. These
studies show associations between Cd-U and markers of tubular effect. The largest studies were conducted in
Belgium (Cadmibel study) in a population exclusively exposed via the environment (n=1700; geometric mean
Cd-U, 0.84 μg/24 h) (Buchet et al., 1990) and in Sweden (OSCAR study) in subjects with environmental and/or
occupational exposure (n=1021; Cd-U, 0.18-1.8 μg/g creatinine) (Järup et al., 2000). Both studies had a crosssectional design so that it cannot be excluded that some of the tubular effects observed in these cohorts are the
results of previous much higher exposures (particularly in occupationally exposed subjects included in the
OSCAR study) which may have contributed to shift the dose-effect/response relationship to the left. In the
Cadmibel study, it was found that, after adjustment for age, gender, smoking, use of medications and urinary
tract disease, tubular effects (mainly increased urinary calcium excretion) occurred in the general population at
Cd-U levels ≥ 2 μg/24 h (roughly equivalent to 2 μg/g creatinine according to SCOEL, 2009). Recently, de
Burbure et al. (2006) and Suwazono et al. (2006) have reported effects even at the environmentally relevant
concentration of 1 µg Cd/g creatinine in children and elderly populations.
The association between renal parameters and cadmium exposure has been further confirmed in a study in the
most exposed subgroup of the Cadmibel study (Pheecad study) (Hotz et al., 1999). In the OSCAR study,
excretion of protein HC (alpha-1-microglobulin) was found associated with Cd-U (0.18-1.8 μg/g creatinine) and
the prevalence of elevated values (> 95th percentile in a Swedish reference population) increased with Cd-U.
The exact health significance of tubular changes observed at Cd-U levels < 5 μg/ g creatinine is, however,
uncertain and subject to contrasting scientific opinions. Some authors believe that these changes represent the
earliest dysfunction of the renal tubular cells and should be considered as an adverse effect because the aim of
public health is to detect and prevent effects at their earliest stage in the most sensitive groups of the population
(Järup et al., 1998). Others believe that these changes most likely reflect benign, non-adverse responses (Hotz et
al., 1999; Bernard, 2004).
While mortality studies were not able to detect an excess of end-stage renal diseases in populations
environmentally exposed to cadmium compounds, an ecological study conducted in Sweden indicated that
cadmium exposure was a determinant of the incidence of renal replacement therapy in a population with
occupational/environmental exposure to cadmium (Hellström et al., 2001).
Cadmium may also potentiate diabetes-induced effects on kidney (Buchet et al., 1990, Akesson et al., 2005,
Chen et al., 2006, reviewed in Edwards and Prozialeck, 2009). A recent large cross-sectional study using US
NHANES data showed that urinary cadmium levels are significantly and dose-dependently associated with both
impaired fasting glucose and diabetes, suggesting that cadmium may be a cause of prediabetes and diabetes in
humans (Schwartz et al., 2003). Renal damage could cause cadmium to leak into urine, potentially leading to a
(noncausal) association between cadmium and diabetes. The investigators therefore restricted the analysis to
persons without evidence of renal damage, but this restriction did not appreciably affect their findings. There
were clear dose-response relationships between U-Cd and fasting glucose as well as diabetes. However, the
pathogenesis remains to be explored.
Finally, an additional effect on the kidney seen in workers with high cadmium exposures is an increased
frequency of kidney stone formation (Järup et al., 1997; JRC, 2007).
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Bone
In humans, the mechanism of bone toxicity is not fully elucidated and types of bone lesions associated with
cadmium exposure are not clearly identified. One likely mechanism is direct disturbance of bone metabolism
but another explanation is that cadmium-induced kidney damage and/or hypercalciuria might promote
osteoporosis and associated fractures. The most severe form of bone disease caused by cadmium intoxication is
Itai-Itai disease which led to kidney and bone lesions in aged Japanese women in the past (CRC 1986; Tsuchiya,
1992).
A follow-up of the population examined in the Cadmibel study (mean Cd-U, approx. 0.5 and 0.8 μg/g creatinine
in men and women, respectively) has shown that Cd-U was linked to an increased risk of fracture in women and,
possibly, an increased risk of height loss in men. The decline of bone mineral density in post-menopausal
women was significantly aggravated by cadmium exposure (Staessen et al., 1999). In the OSCAR study, bone
mineral density has been measured in the forearm of more than 1000 individuals with occupational (Cd-U, 0.064.7 μg/g creatinine) and/or environmental (Cd-U, 0.06-3.7 μg/g creatinine) exposure to cadmium. An
association between Cd-U and decreased bone mineral density was found in older men, and an increased risk of
osteoporosis was noted in men > 60 years with a similar tendency in women > 60 years. The threshold for these
effects was about 3 μg/g creatinine (Alfven et al., 2000). It has also been shown in the OSCAR cohort that
cadmium exposure was associated with increased risk of forearm fractures in people over 50 years of age
(Alfven et al., 2004). The association between cadmium exposure, tubular effects and osteoporosis has been
confirmed in a large cross-sectional study in a Chinese population with environmental exposure to cadmium
(mean Cd-U in the group with the highest exposure, 11.18 μg/g creatinine) (Jin et al., 2004). In a populationbased health survey conducted in southern Sweden among women with no known historical cadmium
contamination (Women's Health in the Lund Area (WHILA)), negative effects of low-level cadmium exposure
(median Cd-U = 0.67 μg/g creatinine) on bone, possibly exerted via increased bone resorption, seemed to be
intensified after menopause (Akesson et al., 2006). More recent Belgian data on 294 women from a Flemish
population with environmental cadmium exposure (PheeCad study) confirmed the negative effects of low-level
cadmium exposure (mean Cd-B = 7 - 10 nmol/L = 0.79 - 1.1 μg/L)) on bone mineral density. Even in the
absence of cadmium-induced renal tubular dysfunction, low-level environmental exposure to cadmium increases
calciuria with reactive changes in calciotropic hormones (Schutte et al., 2008). A very recent US study using
NHANES data reported an increased risk in 3207 women aged 50 years and older for osteoporosis in the hip at
Cd-U levels between 0.5 and 1.0 μg/g creatinine and 1.4 for Cd-U > 1.0 μg/g creatinine as compared to the
reference (< 0.5 μg/g creatinine) (Gallagher et al., 2008).
In workers exposed to cadmium compounds, clinical bone disease has been described but the number of cases is
limited. One cross-sectional study reported results compatible with a role of cadmium in the genesis of
osteoporosis in exposed workers who were also included in the OSCAR study mentioned above (Jarüp et al.
1998). The dose-effect/response relationship between cadmium body burden and bone effects has not been
defined.
Lung
Early reports indicated that anosmia was a common finding in workers often exposed to high airborne cadmium
levels (Friberg, 1950; Adams et al., 1961). A recent study in workers exposed to lower levels (mean Cd-B =
3.7 μg/L and Cd-U = 4.4 μg/g creatinine) confirmed that olfactory neurons are sensitive to cadmium, as
demonstrated by an elevation of the olfactory threshold in these workers (Mascagni et al., 2003). Similar
olfactory alterations have been reported among Polish workers from a nickel-cadmium production plant,
although with much higher exposure (mean Cd-B = 35 μg/L and Cd-U = 86 μg/g creatinine) (Rydzewski et al.,
1998).
Long-term inhalation exposure to cadmium and cadmium compounds may also affect lung function and is
associated with the development of emphysema. Surveys of workforces exposed to cadmium published in the
1950s already indicated that protracted occupational exposure to cadmium could cause emphysema (Friberg,
1950; Lane et al., 1954). Mortality studies in cadmium workers in the United Kingdom found that those who
had experienced high exposure had an increased mortality rate from “bronchitis” (Armstrong et al., 1983). In
copper-cadmium alloy producers, a marked excess of deaths from chronic non-malignant respiratory diseases
has also been found related to cadmium exposure (Sorahan et al., 1995). The respiratory impact of occupational
cadmium exposure has also been reported in more recent studies that were able to collect detailed lung function
measurements, good exposure assessment and to control for confounding such as other industrial exposures and
tobacco smoking. In a copper-cadmium alloy factory, it was found that the cadmium-exposed workforce had
evidence of airflow limitation (reduced FEV1 and Tiffeneau ratio), hyperinflated lungs (increased RV and TLC)
and reduced gas transfer (reduced DLCO and KCO), an overall pattern of functional abnormalities consistent
with emphysema. Regression analysis identified a significant relationship between the reduction in FEV1,
FEV1/FVC ratio, DLCO, and KCO, and both estimated cumulative cadmium exposure (years x μg/m³) and liver
cadmium content measured by neutron activation analysis (Davison et al., 1988). A moderate increase in
residual volume (+7% compared to controls matched for smoking habits) has also been reported in workers
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exposed to cadmium fumes in a factory producing silver-cadmium-copper alloys for brazing, already at
cumulative exposure levels below 500 years x μg Cd/m3 (mean Cd-U = 3.1 μg Cd/L) (Cortona et al., 1992).
Other studies have shown no cadmium-related impairment of respiratory function (Stanescu et al., 1977; Edling
et al., 1986) presumably because of differences in the intensity of exposure, the species of Cd involved, variable
diagnostic criteria or incomplete control for confounding factors, including tobacco smoking.
Other
While some studies reported an association between environmental exposure to cadmium and increased risks of
cardiovascular diseases (Everett and Frithsen, 2008; Schutte et al. 2008; Tellez-Plaza et al., 2008), other
studies did not detect such an increased risk (Staessen et al., 1991). Studies on the cardiovascular effects of
occupational exposure were not located.
No major effects of cadmium on the liver have been reported. Furthermore, cadmium-induced anemia is not
likely to be of concern for occupational or general population exposure (JRC, 2007).
Potential effects on the neurological or immunological systems are discussed in Section 5.10.
5.6.3. Summary and discussion of repeated dose toxicity
Results from studies in animals and observations in humans indicate that the sensitive targets of cadmium
toxicity are kidney and bone following oral exposure and kidney and lungs following inhalation exposure
(ATSDR, 2008).
Cadmium being a cumulative toxicant, the systemic manifestations associated with chronic exposure are related
to the body burden of the element (liver and kidney content), assessed with biomarkers such as urinary
concentration (Cd-U). In workers exposed to cadmium, a body burden corresponding to 200 ppm in kidney
cortex, ie ca. 10 μg Cd/g creatinine is considered to represent a critical level based on the occurrence of low
molecular weight proteinuria. SCOEL (2009) recommends an Occupational Exposure Level (OEL) equivalent
to 4 µg Cd/m3 (respirable fraction) as protective against long-term local effects (respiratory effects, including
lung cancer). This is based on human data that shows changes in residual volume of the lung for a cumulative
exposure to CdO fumes of 500 µg Cd/m3 x years, corresponding to 40 years exposure to 12.5 µg Cd/m3
(LOAEL) (Cortona et al., 1992). Applying an uncertainty factor of 3 (LOAEL to NOAEL) leads to a value of
4 µg/m3.
Based on the most recent studies, it seems that renal effects can be detected in the general European
population (mainly exposed by the oral route) for cadmium body burdens at or even below 2 μg Cd/g
creatinine. There is, however, a scientific debate about the health significance of these early changes. This
lower value in the general population compared to that identified in workers is thought to reflect, among other
parameters, an interaction of cadmium exposure with pre-existing, concurrent or subsequent renal diseases
(mainly renal complications of diabetes) that are less prevalent in healthy young individuals in occupational
settings. As workers exposed to cadmium may, however, suffer from such diseases during or most often after
their occupational career, and considering the long half-life of cadmium in humans and its accumulation with
age, it is considered prudent to recommend a Biological Limit Value (BLV) that would provide a sufficient
degree of protection in this respect (SCOEL, 2009).
Available NOAELs from repeated dose oral and inhalation studies range between 0.12 - 3 mg/kg bw/day and
0.013. 10-3 - 0.022 x 10-3 mg/L, respectively. This data supports a classification as T; R48/23/25 (Toxic: danger
of serious damage to health by prolonged exposure through inhalation and if swallowed), which has been
attributed to cadmium chloride, sulphate, oxide and metal in Annex I of Directive 67/548/EC (the corresponding
GHS-CLP classification would be STOT category 1; H372). By analogy, the other highly and slightly soluble
forms of cadmium (i.e. cadmium nitrate, hydroxide and carbonate) warrant comparable classifications.
Apart from cadmium sulphide, no other insoluble cadmium compounds (e.g. cadmium sulfoselenide, cadmium
zinc sulphide or cadmium telluride), not expected to penetrate easily into the organisms, are classified for
repeated dose toxicity. Cadmium sulphide is an exception. As there is no data to support its T; R48/23/25
classification, a revision of this classification may be appropriate based on solubility properties.
Repeated dose toxicity of cadmium via the dermal route is not expected given the relatively low skin
penetration of all forms of this metal. Also in view of the risk reduction measures which need to be taken as a
result of the carcinogenicity of cadmium metal and some of the cadmium compounds, chronic dermal toxicity is
not expected to be an issue for human health. No corresponding classification is therefore required.
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5.7. Mutagenicity
5.7.1. Non-human information
Numerous in vitro and in vivo studies have been conducted on cadmium compounds, mostly with cadmium
chloride. An extensive review is available in the EU Risk Assessment Report (RAR) (JRC, 2007). The
following section presents the main results, as discussed in CSTEE (2004), JRC (2007) and SCOEL (2009).
5.7.1.1. In vitro data
Various cadmium compounds (in particular water soluble forms) have been tested in vitro for direct DNA
damage, oxidative damage and inhibition of DNA repair in bacterial (e.g. S. typhymurium and E. coli), rodent
(e.g. mouse spleen, Chinese hamster V19 and V79, Chinese Hamster ovary, rat liver and rat myoblast) and
human (e.g. human lymphocyte, HSBP fibroblast and human diploids fibroblasts) cell lines. A detailed list of
experiments can be found in IARC (1993) and JRC (2007). Selected studies are summarised in the following
table:
Table 21. Overview of selected experimental in vitro genotoxicity studies
Method
Results
Remarks
Reference
Cadmium chloride
Bacterial gene mutation assay
S. typhimurium TA 1535, TA
1537, TA 98 and TA 100 (met.
act.: with and without)
0,05; 0,5; 5; 50; 500 µg/plate
The Ames Salmonella test was
used to test cadmium chloride for
reversion of his- auxotrophs of S.
typhimurium in the strains
TA1535, TA1537, TA98 and
TA100
2 (reliable with
restrictions)
key study
experimental result
Bruce WR and
Heddle JA (1979)
in vitro mammalian chromosome Positive (CA and SCE)
aberrations test and sister
chromatid exchange assay in
mammalian cells
mouse spleen cells
10, 15, 20 µg/ml
CA:
 incubation time: 48 hours
 number of cells observed:
100 metaphases per culture
 staining: Giemsa in
phosphate buffer (pH 6.8)
SCE:
 incubation time: 24 hours
 number of cells observed: 30
metaphases per culture
 staining: fluorescence dye
33258 Hoechst plus Giemsa
2 (reliable with
restrictions)
key study
experimental result
Fahmy MA and
Aly FA (2000)
Single cell gel/comet assay in
Positive (DNA damage and SCE)
mammalian cells for detection of Weak positive (gene mutation KDNA damage, sister chromatid
ras)
exchange assay in mammalian
cells and mammalian cell gene
mutation assay (gene mutation
(K-ras))
human lung fibroblast cell line
MRC-5
2 (reliable with
restrictions)
key study
experimental result
Mourón SA, Grillo
CA, Dulout FN,
Golijow CD
(2004)
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Negative (gene mutation)
met. act.: with and without;
cytotoxicity: no, but tested up to
limit concentrations
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Results
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Remarks
Reference
1, 2 and 4µM
SCE:
Number of cells observed: 50
metaphases per culture
Comet:
According to the method of
Singh et al., 1988
Point mutations in codon12 of the
K-ras protooncogene: PCR-SSCP
and RFLP enriched PCR methods
Cadmium oxide
bacterial gene mutation assay
S. typhimurium TA 1535, TA
1537, TA 98 and TA 100 (met.
act.: with and without)
Doses: 0, 3.3, 10.0, 33.0, 100.0,
333.0, 1000.0, 3333.0 µg/plate
3 plates per dose level
equivalent or similar to OECD
Guideline 471 (Bacterial
Reverse Mutation Assay)
equivalent or similar to EU
Method B.13/14 (Mutagenicity
- Reverse Mutation Test Using
Bacteria)
in vitro mammalian
chromosome aberrations test
and sister chromatid exchange
assay in mammalian cells
Chinese hamster Ovary (CHO)
Doses: CA: 0, 12.5, 25.0, 50.0,
100.0 µM
SCE: 0, 13.0, 25.0, 50.0, 100.0
µM
CA:
-incubation time: 20 hours
-number of cells observed: 100
metaphases per culture
-staining: 3% Giemsa
SCE:
-incubation time: 24 hours
-number of cells observed: 50
metaphases per culture
-staining: fluorescence dye
33258 Hoechst plus Giemsa
Cadmium sulphide
Negative (gene mutation)
met. act.: with and without;
cytotoxicity: no, but tested up
to limit concentrations
2 (reliable with
restrictions)
key study
experimental result
Mortelmans K,
Haworth S,
Lawlor T, Speck
W, Tainer B and
Zeiger E (1986)
CA: positive and SCE: negative
2 (reliable with
restrictions)
key study
experimental result
Wang TC and
Lee ML (2001)
in vitro mammalian chromosome Positive (CA)
aberration test
lymphocytesDoses: 6.2x10-2
µg/ml
CA:
-incubation time: 72 hours
-number of cells observed: 50
metaphases per culture
-staining: Giemsa
2 (reliable with
restrictions)
key study
experimental result
Shiraishi Y,
Kurahashi H and
Yoshida TW
(1972)
DNA damage and repair assay,
unscheduled DNA synthesis in
2 (reliable with
restrictions)
Robison SH,
Cantoni O, Costa
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Positive (DNA damage)
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Method
cadmium sulphate
Results
mammalian cells in vitro Chinese
hamster Ovary (CHO) Doses:
10µg/ml
-Analysis of DNA by alkaline
sucrose gradients
-DNA molecular weight
calculations
CAS number:
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Remarks
Reference
key study
experimental result
M. (1982)
2 (reliable with
restrictions)
key study
experimental result
Mourón SA, Grillo
CA, Dulout FN,
Golijow CD
(2004)
Cadmium sulphate
Single cell gel/comet assay in
Positive (DNA damage and SCE)
mammalian cells for detection of Weak positive (gene mutation KDNA damage, sister chromatid
ras)
exchange assay in mammalian
cells and mammalian cell gene
mutation assay (gene mutation
(K-ras))
human lung fibroblast cell line
MRC-5
0.033, 0.067 and 0.13µM
SCE:
Number of cells observed: 50
metaphases per culture
Comet:
according to the method of Singh
et al., 1988
Point mutations in codon12 of the
K-ras protooncogene: PCR-SSCP
and RFLP enriched PCR methods
Cadmium carbonate
in vitro mammalian chromosome CA: positive and SCE: negative 2 (reliable with
Wang TC and Lee
aberrations test and sister
restrictions)
ML (2001)
chromatid exchange assay in
key study
mammalian cells Chinese
experimental result
hamster Ovary (CHO) Doses:
CA: 0, 12.5, 25.0, 50.0, 100.0
µM
SCE: 0, 13.0, 25.0, 50.0, 100.0
µM
CA:
-incubation time: 20 hours
-number of cells observed: 100
metaphases per culture
-staining: 3% Giemsa
SCE:
-incubation time: 24 hours
-number of cells observed: 50
metaphases per culture
-staining: fluorescence dye 33258
Hoechst plus Giemsa
Overall, in vitro mutagenicity studies of cadmium give conflicting results. While some (especially in bacterial
systems) are negative, others (including those in mammalian cells) have yielded positive results for the
induction of DNA strand breaks, protein-DNA crosslinks, chromosome aberrations and other markers of
mutagenicity (Bruce and Heddle, 1979; Fahmy and Aly, 2000; Mouron et al., 2004; Mortelmans et al., 1986;
Wang and Lee, 2001; Shiraishi et al., 1972; Robison et al., 1982). According to several reviews, differences
between treatments as well as between the cells used may play a role in explaining the variability in findings
(IARC, 1992; ATSDR, 2008 and 1999; WHO, 1992).
With regard to mechanism of action, the data suggests that cadmium ions accumulated in cells may cause
genetic damage directly or indirectly by:
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
Interacting with chromatin to generate strand break, cross links or structural alterations in DNA,

Depleting antioxidant levels and thereby increasing intracellular hydrogen peroxide and other oxidants,
or
 Interacting at metal-binding sites of proteins involved in transcription, DNA replication or DNA repair.
According to JRC (2007), the various mechanisms of action described above are not mutually exclusive; their
relevance to in vivo situations may nevertheless be questioned since in vitro studies are conducted at
concentrations well above physiologically relevant levels.
5.7.1.2. In vivo data
Inhalation exposure for 13 weeks to cadmium oxide did not result in increased frequency of micronucleated
erythrocytes in peripheral blood of male or female B6C3F1 mice (McGregor et al., 1990; Dunnick, 1995).
However, this result should be interpreted with caution due to the absence of sufficient bioavailability to the
bone marrow and the fact that the most relevant target cells (lung) were not examined. Several experiments
using cadmium water-soluble compounds were identified and summarized by IARC (1993). Results were
judged conflicting (JRC, 2007). More recently, Fahmy and Aly (2000) found induction of micronuclei,
increased sister chromatid exchange in bone marrow and chromosomal aberration after a single intraperitoneal
treatment with cadmium chloride. Single strand breaks were observed after acute treatment of male albino rats
with cadmium chloride injected intraperitoneally. Cadmium also increased the amount of single strand breaks in
kidney (Saplakoglu et al., 1997).
Forni (1992) suggested that cadmium ions may act as co-mutagens rather than mutagens. Indeed, cadmium
appears to inhibit the repair of DNA damaged by other agents. For example, cadmium chloride given to mice at
300 ppm in water for 7 days enhanced the frequency of micronuclei resulting from dimethylnitrosamine, thereby
enhancing its mutagenicity (Watanabe, 1982; IARC, 1993).
Overall, although the results for the various cadmium substances are conflicting, it cannot be excluded that
cadmium exerts a mutagenic effect in vivo (JRC, 2007).
5.7.2. Human information
Mutagenicity studies of cadmium in humans have been reviewed by several organisations (CRC, 1986; IARC,
1992 and 1993; WHO, 1992 and ATSDR, 2008) and are summarised in JRC (2007). Both oral and inhalation
routes have been considered and endpoints include chromosomal aberration, sister chromatid exchange and
micronucleus. Selected data is presented in the table below, then discussed by type of population considered.
Table 22. Overview of selected exposure-related observations on genotoxicity in humans
Method
Results
Remarks
Reference
Study type: cross sectional study
Type of population: occupational
Subjects:
-Final population:
E: 14 (M) classified into 3 groups
 Group I: high level of Zn, low
levels of Cd and Pb (N=5)
 Group II: high levels of Zn, Cd,
Pb (N=5)
 Group III: high levels of Cd and
Pb, no Zn (N=4)
Age: 27-56 y.
C: 5; Age: 31-55 y.
- Selected from :
E: "workers in a Zn industry
classified into 3 groups according to
the type and duration of exposure”
C: N.I.
Non significantly increased
incidences of observed
aberrations in exposed groups
compared to control group
but significantly increased
prevalence of "more complex
aberrations"
2 (reliable with
restrictions)
key study
Deknudt G,
Léonard A and
Ivanov B (1973)
Study type: cross sectional study
Type of population: occupational
Subjects:
-Final population:
Non significantly increased
incidences of observed
aberrations in exposed groups
compared to control group
2 (reliable with
restrictions)
key study
Deknudt G and
Léonard A (1975)
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Results
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Remarks
Reference
E: 35 (M only?) classified into 2
but significantly increased
groups:
prevalence of "more complex
 "Cd-service": high levels of Pb aberrations"
and Cd, no Zn (N=23)
 "Rolling-mill": exposed mostly
to Zn, lower levels of Pb and Cd
(N=12)
Age (mean):
"Cd-service": 40.2 y.
"Rolling-mill": 34.8 y.
C: 12 (M only?)
Age (mean): 32.2 y.
-Selected from :
E: "workers in a Cd plant classified
into 2 groups according to the type &
duration of exposure”
C: "people from the administration
department of the same plant”
Study type: cross sectional study
Type of population: occupational
Subjects:
-Final population:
E: 24 (M only)
Age: 25-53 y.
C: 15 (11M/4F)
Age: 26-60 y.
-Selected from:
E: “Workers at a smelting plant”
C: “Unexposed, healthy controls
from the general population”
- Significantly increased
2 (reliable with
incidences of structural
restrictions)
chromosome aberrations in the key study
exposed group compared to the
control group
- No relationship detected
between the prevalence of
aberrations per person and Cd-B
or Pb-B or length of exposure
Bauchinger M,
Schmid E,
Einbrodt HJ and
Dresp J (1976)
Study type: cross sectional study
Type of population: occupational
Subjects:
-Final population:
E: 40 (M only)
Age: 23 – 58 y.
C: 40 (M only)
Age: 23 –63 y.
-Selected from:
E: “workers in a single factory
producing cadmium, zinc, copper and
silver alloys”
C: “ matched for age, sex and
smoking”
- The 22 workers with Cd-U
2 (reliable with
>10 µg/l had significantly
restrictions)
higher rates of abnormal
key study
metaphases (excluding gaps)
and chromosome type
aberrations than the controls and
the 18 other workers.
Forni A, Toffoletto
F, Ortisi E, and
Alessio L (1990)
- No increase in chromosometype aberrations was detectable
in the group of subjects with
mean Cd-U levels lower than 10
µg/l, the biological exposure
limit value at the time of the
study (Forni et al., 1990, Forni,
1992).
-long-term exposure associated
with significant increase in
frequency of chromosome-type
aberrations (2.37% in workers
with CEI>1000 vs. 0.8 in
workers with CEI<100, vs.0.5%
in controls .
Cadmium metal
Study type: cross sectional study
Type of population: general
Subjects:
- Significant difference in
chromosome aberration rates
between the exposed and the
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restriction)
and Zhu XQ
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(1999)
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Method
Results
Remarks
-Final population:
E: 56 (26M/ 30 F); Age: 36.8 ± 17.6
y.
C: 10 (4M/ 6 F); Age: 41.0 ± 10.6 y.
-Selected from:
E: "people environmentally exposed
to Cd and in Suichang county of
Zhejiang province"
C: “living in areas known to be
uncontaminated by Cd”
control group
- Micronucleus rates are
significantly elevated in all
exposed subgroups when
compared with controls, except
when Cd-U was <2.5 µg/l
- Prevalence of aneuploidy:
differences in numerical
aberrations were not significant
Study type: cross sectional study
Type of population: general
Subjects:
-Final population:
E: 7- 12 (F only) ; Age: 52-73 y
C: 6 (F) - 9 (6F/3M) ; Age: 58-78 y
-Selected from:
E:” Itai-Itai patients”
- Increased prevalence of
2 (reliable with
chromosomal aberrations in
restrictions)
Itai-Itai patients compared with key study
the results in control subjects
- Frequency of aneuploidy also
significantly higher than in the
controls
Reference
Shiraishi Y and
Yosida TH (1972)
Study type: cross sectional study
No differences in chromosome 2 (reliable with
Type of population: general
aberration frequencies between restrictions)
Subjects:
exposed and controls
key study
- Final population:
E: 4 (F only); Age: 55-71 y.
C: 4 (3F, 1M); Age: 65-94 y.
- Selected from:
E:” Itai-Itaipatients from Fuchu
(endemic cadmium-polluted area)”
C: “Living in an area known not to be
contaminated by cadmium”
-Lost subjects: 2
Bui TH, Lindsten J
and Nordberg GF
(1975)
Study type: cross sectional study
Type of population: general
Subjects:
-Final population:
E: 40 (21M/ 19 F); Age: 36.8 ± 17.6
y.
C: 11 (9M/ 2 F); Age: 41.9 ± 14.5 y.
-Selected from:
E: "lived in Cd-polluted area of
Suichang (China) (Cd-soil : 1.103
ppm)”
C: “lived in unpolluted region of the
same general area (Cd-soil: 0.20
ppm)”
-Lost subjects: 7
- Significantly higher increase
of chromosome aberrations in
cadmium-polluted groups
versus controls
- Significant correlations
between urinary cadmium
content and chromosome
aberration frequencies
- More aneuploidy and cells
with complex structural
chromosome aberrations in the
exposed groups
2 (reliable with
restrictions)
key study
Tang XM, Chen
XQ, Zhang JX and
Qin WQ (1990)
Study type: cross sectional study
Type of population: occupational
Subjects:
-Final population:
E: 5 (M only); Age: 44-57 y.
C: 3 (M only); Age: 52-54 y.
-Selected from:
E: “electrode department of an
alkaline battery factory”
C: "office workers of about the same
age, from the same factory”
- No increased frequency of
chromosome aberrations in the
exposed group versus control
group
2 (reliable with
restrictions)
key study
Bui TH, Lindsten J
and Nordberg GF
(1975)
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Method
Results
Remarks
Study type: cross sectional study
Type of population: occupational
Subjects:
-Final population:
E: 22 (7M+15F) Cd-exposed; 44(M)
Pb-exposed ; Age: 44-57 y.
C: 52 (35M+17F); Age: 52-54 y.
-Selected from:
E: battery plant located in the northwestern part of Poland where acid
and alkaline batteries were produced
and where occupational exposure to
respectively lead or cadmium by
inhalation was found.
C: the same battery plant but
recruited from departments with no
occupational exposure to lead and
cadmium, as well as health service
and office workers.
-Statistically significant
2 (reliable with
increases compared to the
restrictions)
control population in
key study
micronuclei rates and sister
chromatid exchanges as well as
evidence of an increased
incidence of leukocytes with
DNA fragmentation.
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Reference
Palus J, Rydzynski
K, Dziubaltowska
E, Wyszynska K,
Natarajan AT
(2003)
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Oral route (general population)
Overall, mutagenicity studies on the general population yield conflicting results (Fu et al, 1999; Shiraishi and
Yoshida, 1972; Bui et al., 1975; Tang et al., 1990). The main features common to the selected studies are:

Cross-sectional design (apart from Shiraishi (1972) in which part of the population was re-examined
several months later);

Small population sizes so that false negative findings may be due to chance and lack of statistical
power;

Many endpoints and inter-group comparisons used but independence of the endpoints not clearly
stated; chance findings may have occurred;

Lack of consistency regarding endpoints affected by cadmium;

Incomplete or missing data on cadmium blood or urine values or their quality control;

Not clear whether higher cadmium body burden is the cause of cytogenetic change or only a marker of
exposure to other variables (e.g. Itai-Itai disease, smoking, nutrition pattern, etc.).
Lack of attention in the selection procedures, use of small groups, different technical procedures and gaps in
information about exposure and confounding factors may contribute to explain most of the conflicting results
(JRC, 2007). Nevertheless, based on available data, it cannot be excluded that cadmium may exert mutagenic
effects in populations exposed via the oral route.
Inhalation route (workers)
Again, a consistent pattern of mutagenic effects associated with occupational exposure cannot be deduced from
the inhalation exposure studies (Deknudt et al., 1973; Deknudt and Léonard, 1975; Bauchinger et al., 1976; Bui
et al., 1975; Forni et al., 1990; Palus et al., 2003). The main features common to the selected studies are:

Cross-sectional design;

Many endpoints and inter-group comparisons used but independence of the endpoints not clearly
stated; chance findings may have occurred;

Lack of consistency regarding endpoints affected by cadmium;

Incomplete or missing data on cadmium blood or urine values or their quality control;
 Cadmium compound not always clearly defined.
Definition of population size, exposure characteristics and outcome, as well as incomplete analysis of
confounding factors may in part explain conflicting results. Overall, it cannot be excluded that cadmium may
exert mutagenic effects in populations exposed via inhalation.
5.7.3. Summary and discussion of mutagenicity
Data from in vitro and in vivo experimental systems are not consistent but suggests that cadmium, in certain
forms, has mutagenic properties. With regard to human exposure, data are also conflicting but again a mutagenic
potential both via oral and inhalation exposure routes cannot be excluded.
Different possible non-mutually exclusive direct and indirect mechanisms of mutagenicity have been identified
in vitro, although their relevance to in vivo situations is not clearly established. A recent review by Parry and
Parry (2009) (available in IUCLID 5 under ‘7.12 Additional toxicological information’) concluded that there is
considerable evidence to suggest that the primary mechanism of genotoxicity is the production of oxidative
lesions. In this case, there could be a threshold at low doses where the DNA repair enzymes remove the lesions,
thus reducing the potential for genetic changes in cells. The EU Risk Assessment Report (RAR) (JRC, 2007)
states that most of the mechanisms proposed to explain the mutagenicity of cadmium ions are dose-dependent
and support the possibility of a threshold for mutagenic effects (Madle et al., 2000; Kirsch-Volders et al., 2000).
Further research may be able to determine No Adverse Effect Levels (NOAEL) and generate dose-response
curves.
It should however be noted that cadmium has also been suggested to act as a co-mutagen rather than as a
mutagen, e.g. by decreasing fidelity in DNA synthesis or interfering with DNA repair mechanisms (Schwerdtle
et al., 2010). In this case, repair activity within a potential thresholded region of the dose-response-curve would
be limited (Parry and Parry, 2009).
If cadmium inhibits the repair of DNA damage induced by other agents, this could explain some of the
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differences in the results of cytogenetic studies in human populations. Indeed, chromosome aberrations might be
increased in the different populations/subjects with different additional occupational/environmental exposures as
a result of unrepaired damage (Forni, 1992).
Recently, SCOEL cited in his DRAFT NOTE on the 76th MEETING (March 2010) the study of Forni et al.
1990 for referring to the 10 µg/g creatinin in Cd/urine as a threshold for genotoxicity. SCOEL also published
that ‘having defined a threshold for genotoxicity, it was shown that renal and respiratory effects are more
sensitive than genotoxicity, in turn thought to be a pre-requisite for carcinogenicity’.
Based upon the available evidence at present it is concluded that cadmium has a threshold for genotoxicity. A
second important conclusion is that the renal respiratory effects are more sensitive than the genotoxic effects.
The risk management for cadmium consequently is based on the protection for renal and inhalatory effects.
Based on available data and read-across, cadmium chloride and sulphate are currently classified as Muta. Cat.
2; R46 (may cause heritable genetic damage) in Annex I of Directive 67/548/EC (the corresponding GHS-CLP
classification would be Mutagenic category 1B; H340). By analogy, the other highly soluble forms of
cadmium (i.e. cadmium nitrate) warrant comparable classifications.
At present, the slightly soluble cadmium metal and oxide are classified as Muta. Cat. 3; R68 (possible risk of
irreversible effects) in Annex I of Directive 67/548/EC (the corresponding GHS-CLP classification would be
Mutagenic category 2; H341). A similar classification for cadmium hydroxide and carbonate may therefore be
considered.
Apart from cadmium sulphide, none of the insoluble cadmium compounds (e.g. cadmium sulfoselenide,
cadmium zinc sulphide or cadmium telluride), not expected to penetrate easily into the organisms, are classified
for mutagenicity. Cadmium sulphide (Muta. Cat. 3; R68 or Mutagenic category 2; H341 under GHS-CLP) is
an exception for which a revision of the classification could be considered based on solubility properties.
5.8. Carcinogenicity
5.8.1. Non-human information
5.8.1.1. Carcinogenicity: oral
Numerous studies have been conducted in mice and rat to determine whether cadmium (mainly in the form of
water-soluble compounds such as cadmium sulphate, chloride and acetate) causes carcinogenicity in animals
when administered via gastric instillation, food or drinking water. These are summarised in JRC (2007).
Most early studies have not reported an increased overall cancer incidence or an increased incidence of specific
tumour types. However, the sensitivity was limited because the maximum doses used were clearly below the
maximum tolerated dose or exposure was too brief. Also, in some cases, histopathological examination was only
conducted on a restricted number of animals and tissues.
Waalkes and Rehm (1992) reported an oral study using cadmium chloride suggestive of carcinogenic activity
(see Table). Cadmium chloride, given to rats in the diet, was associated with large granular lymphocyte
leukemia and proliferative lesions of the prostate. Another neoplastic, albeit benign, effect was associated with
dietary cadmium: interstitial cell adenomas in the testes.
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Table 23. Overview of selected experimental studies on carcinogenicity after oral administration
Method
Results
Remarks
Reference
LOAEL (carcinogenicity): 3.5
mg/kg bw/d (male) (increased
rates of prostatic adenomas)
Neoplastic effects observed in
any test group: yes
2 (reliable with
restrictions)
key study
experimental result
Waalkes MP and
Rehm S (1992)
Cadmium chloride
Rat (Wistar) male
oral: feed
0, 25, 50, 100, 200 ppm (nominal
conc. (equivalent to 0, 1.75, 3.5, 7
and 14 mg Cd/ kg bw/d))
Exposure: 77 wk
A study was conducted to determine
the effect of chronic dietary zinc
deficiency on the carcinogenic
potential of dietary cadmium in rat.
Rats were exposed to cadmium (0,
25, 50, 100, 200 ppm), given as
cadmium chloride and mixed with
diets either adequate or marginally
deficient in zinc. Necropsy was
performed on all animals.
5.8.1.2. Carcinogenicity: inhalation
Carcinogenicity via the inhalation route has been studied in rat, mouse and hamster with various cadmium
compounds. The results of selected experimental studies are summarised in the following table.
Table 24. Overview of selected experimental studies on carcinogenicity after inhalation exposure
Method
Results
Remarks
Reference
Rat (Wistar) male/female
inhalation: aerosol
30 and 90 µg Cd/m3 (nominal conc.)
Vehicle: none
Exposure: max 18 months (22 h/d x
7 d/wk; 40 h/wk x 6 months)
A study was conducted to evaluate
the carcinogenic potential of the test
material in rats. Rats were exposed
to the aerosols of the test material at
30 and 90 µg Cd/m3 continuously
for a maximum period of 18 months
followed by a treatment-free
observation for 29 - 31 months.
Bodyweight, clinical signs,
hematological and clinical chemistry
examinations were performed
throughout the study. Cadmium
contents of lung, liver and kidneys
were determined along with the
histopathological examination of the
lungs.
LOAEL (carcinogenicity):
0.03 mg Cd/m³ (male/female)
(lung bronchioalveolar
adenomas, adenocarcinomas,
and squamous cell
carcinomas)
Neoplastic effects observed in
any test group: yes
2 (reliable with
restrictions)
key study
experimental result
Glaser U,
Hochrainer D,
Otto FJ and
Oldiges H (1990)
(update of
Oldiges,1989)
Rat (Wistar) male
LOAEL (carcinogenicity):
2 (reliable with
Takenaka S,
Cadmium chloride
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Method
Results
Remarks
Reference
inhalation: aerosol
12.5, 25 and 50 µg Cd/m3 (nominal
conc.)
Exposure: 18 months (continuously
(23 h/d, 7 d/wk))
A study was conducted to evaluate
the carcinogenic potential of the test
material in rats. Rats were
continuously exposed (23 h/d, 7
d/wk) to the test material aerosols at
12.5, 25 and 50 µg/m3 for 18 months
and then observed for 13 months.
Clinical signs and mortality were
observed in the treated groups
throughout the exposure period and
during the post-exposure observation
period. Histopathology of the lungs
was carried out to evaluate the
incidence of lung carcinomas.
0.0125 mg Cd/m³ (nominal) restrictions)
(male) (lung epidermoid
key study
carcinomas, adenocarcinomas experimental result
and mucoepidermoid
carcinomas)
Neoplastic effects observed in
any test group: yes
Oldiges H, König
H, Hochrainer D
and Oberdörster G
(1983)
Rat / mouse (Fisher 344 / Balb-c)
male
100 µg Cd/m3 (nominal conc.)
Groups of rats and mice were
exposed to the test material at 100
μg Cd/m³ in a subchronic inhalation
study (6 h/d, 5 d/wk for a total of 4
wk). Following exposure, evaluation
of pulmonary inflammatory changes,
determination of metallothionein
levels and cadmium content in lungs
in both the species were conducted.
NOAEL (rat)
(carcinogenicity): 0.1 mg/m³
(male)
LOAEL (mouse)
(carcinogenicity): 0.1 mg/m³
air (male) (increased
neutrophils, LDH and betaglucuronidase; pulmonary
inflammation)
3 (not reliable)
supporting study
experimental result
Oberdörster G,
Cherian MG and
Baggs RB (1994)
NMRI mice and Syrian golden
hamsters (male/female)
30 and 90 µg Cd/m3 (nominal conc.)
Vehicle: none
Exposure: Up to 14 months (19 h or
8 h/d, 5 d/wk)
A study was conducted to evaluate
the possible carcinogenic effects of
the test material in hamster and
mouse. Animals were exposed to the
test material aerosols at 30 and 90 µg
Cd/m3 for 19 h or 8 h/d, 5 d/wk for
up to 14 months. Following
exposure distribution of cadmium in
the lungs and histopathology of the
lungs were carried out.
no NOAEL identified for
mouse or hamster
(carcinogenicity)
(lung tumours)
3 (not reliable)
supporting study
experimental result
Heinrich U, Peters
L, Ernst He,
Rittinghausen S,
Dasenbrock C and
König H (1989)
Cadmium sulphate
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CAS number:
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Method
Results
Remarks
Reference
Rat (Wistar) male/female
inhalation: aerosol
90µg Cd/m3 (nominal conc.)
Vehicle: unchanged (no vehicle)
Exposure: max 18 months (22 h/d x
7 d/wk; 40 h/wk x 6 months)
A study was conducted to evaluate
the carcinogenic potential of the test
material in rats. Rats were exposed
to the aerosols of the test material at
90 µg Cd/m3 continuously for a
maximum period of 18 months
followed by a treatment-free
observation for 29 - 31 months.
Bodyweight, clinical signs,
hematological and clinical chemistry
examinations were performed
throughout the study. Cadmium
contents of lung, liver and kidneys
were determined along with the
histopathological examination of the
lungs.
LOAEL (carcinogenicity):
0.09 mg Cd/m³ (male/female)
(lung bronchioalveolar
adenomas, adenocarcinomas,
and squamous cell
carcinomas)
Neoplastic effects observed in
any test group: yes
2 (reliable with
restrictions)
key study
experimental result
Glaser U,
Hochrainer D,
Otto FJ and
Oldiges H (1990)
(update of
Oldiges,1989)
NMRI mice and Syrian golden
hamsters (male/female)
30 and 90 µg Cd/m3 (nominal conc.)
Vehicle: none
Exposure: Up to 14 months (19 h or
8 h/d, 5 d/wk)
A study was conducted to evaluate
the possible carcinogenic effects of
the test material in hamster and
mouse. Animals were exposed to the
test material aerosols at 30 and 90 µg
Cd/m3 for 19 h or 8 h/d, 5 d/wk for
up to 14 months. Following
exposure distribution of cadmium in
the lungs and histopathology of the
lungs were carried out.
no NOAEL identified for
mouse or hamster
(carcinogenicity)
(lung tumours)
3 (not reliable)
supporting study
experimental result
Heinrich U, Peters
L, Ernst He,
Rittinghausen S,
Dasenbrock C and
König H (1989)
LOAEL (CdO dust)
(carcinogenicity): 0.03 mg
Cd/m³ (male/female) (lung
bronchioalveolar adenomas,
adenocarcinomas, and
squamous cell carcinomas)
LOAEL (CdO fume)
(carcinogenicity): 0.03 mg
Cd/m³ (male) (lung
bronchioalveolar adenomas,
adenocarcinomas, and
squamous cell carcinomas)
Neoplastic effects observed in
any test group: yes
2 (reliable with
restrictions)
key study
experimental result
Glaser U,
Hochrainer D,
Otto FJ and
Oldiges H (1990)
(update of
Oldiges,1989)
Cadmium oxide
Rat (Wistar) male/female
inhalation: aerosol
CdO fumes: 10 and 30 µg Cd/m3;
CdO dust: 30 and 90 µg Cd/m³
(nominal conc.)
Vehicle: unchanged (no vehicle)
Exposure: max 18 months (22 h/d x
7 d/wk; 40 h/wk x 6 months)
A study was conducted to evaluate
the carcinogenic potential of the test
material aerosols in rats. Groups of
rats were exposed to the aerosols of
the test material at 10 and 30 (CdO
fume) and 30 and 90 (CdO dust) µg
Cd/m3 continuously for a maximum
18 months followed by a treatmentfree observation period of 29 - 31
months. Bodyweight, clinical signs,
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Results
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Remarks
Reference
hematological and clinical chemistry
examinations were performed
throughout the study. Cadmium
contents of lung, liver and kidneys
were determined along with the
histopathology of the lungs.
Rat (Wistar-SPF) male
inhalation: aerosol
60 µg/L air (nominal conc.)
Vehicle: none
Exposure: 30 min (single exposure)
Rats exposed to single dose of an
aerosol of cadmium oxide (60 µg/L
for 30 min) were observed for up to
1 year post-exposure.
Effect level (carcinogenicity): 4 (not assignable)
(male/female) (No dosesupporting study
response as a single dose with experimental result
a single exposure was used.
No relevance to
carcinogenicity)
Neoplastic effects observed in
any test group: yes
Hadley JG,
Conklin AW and
Sanders CL (1979)
Hamster and mouse (Syrian golden
hamsters (Hoe: SYHK (SPF Ars)
and NMRI Mice) male/female
CdO dust: 30, 90 and 270 µg Cd/m3;
CdO-fumes: 10, 30 and 90 µg Cd/m3
(nominal conc.)
Vehicle: none
Exposure: Up to 14 months (19 h or
8 h/d, 5 d/wk)
A study was conducted to evaluate
the possible carcinogenic effects of
the test material in hamster and
mouse. Animals were exposed to the
test material aerosols at 30, 90 and
270 (CdO dust) and 10, 30 and 90
(CdO fumes) µg Cd/m3for 19 h or
8 h/d, 5 d/wk for up to 14 months.
Distribution of Cd and
histopathology of the lungs analysed.
NOAEL (carcinogenicity): ca. 3 (not reliable)
0.01 mg/m³ (nominal)
supporting study
(mouse, female) (CdO fumes) experimental result
(lung tumours)
Heinrich U, Peters
L, Ernst He,
Rittinghausen S,
Dasenbrock C and
König H (1989)
No NOAEL identified for
CdO dust in mouse or for any
form of CdO in hamster
(carcinogenicity)
(lung tumours)
Cadmium sulphide
Rat (Wistar) male/female
inhalation: aerosol
90, 270, 810 and 2430 µg Cd/m3
(nominal conc.)
Vehicle: unchanged (no vehicle)
Exposure: max 18 months (22 h/d x
7 d/wk; 40 h/wk x 6 months)
A study was conducted to evaluate
the carcinogenic potential of the test
material in rats. Rats were exposed
to the aerosols of the test material at
90, 270, 810 and 2430 µg Cd/m3
continuously for a maximum period
of 18 months followed by a
treatment-free observation for 29 31 months. Bodyweight, clinical
signs, hematological and clinical
chemistry examinations were
performed throughout the study.
Cadmium contents of lung, liver and
kidneys were determined along with
the histopathological examination of
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LOAEL (carcinogenicity):
0.09 mg Cd/m³ (male/female)
(lung bronchioalveolar
adenomas, adenocarcinomas,
and squamous cell
carcinomas)
Neoplastic effects observed in
any test group: yes
2 (reliable with
restrictions)
key study
experimental result
CHEMICAL SAFETY REPORT
Glaser U,
Hochrainer D,
Otto FJ and
Oldiges H (1990)
(update of
Oldiges,1989)
75
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Results
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Remarks
Reference
the lungs.
Hamster and mouse (Syrian golden no NOAEL identified for
3 (not reliable)
Heinrich U, Peters
hamsters (Hoe: SYHK (SPF Ars)
mouse or hamster.
supporting study
L, Ernst H,
and NMRI Mice) male/female
experimental result Rittinghausen S,
90, 270 and 1000 µg Cd/m3
Dasenbrock C and
(nominal conc.)
König H (1989)
Vehicle: unchanged (no vehicle)
Exposure: Up to 14 months (19 h or
8 h/d, 5 d/wk)
A study was conducted to evaluate
the possible carcinogenic effects of
the test material in hamster and
mouse. Animals were exposed to the
test material aerosols at 90, 270 and
1000 µg Cd/m3 for 19 h or 8 h/d, 5
d/wk for up to 14 months.
Distribution of Cd and
histopathology of the lungs analysed.
An unequivocal relationship between cadmium exposure and lung cancer incidence was demonstrated in chronic
inhalation studies in Wistar rat exposed to CdCl2, CdO fumes and CdO dust. In certain studies, malignant lung
tumours were produced by cadmium oxide dust and fumes at low levels of exposure for short duration (JRC,
2007). The lowest dose to produce carcinogenic effects was 30 µg Cd/m3 as cadmium oxide dust and fumes
(Glaser et al., 1990). For cadmium chloride, the lowest dose to produce lung tumours in rats was 12.5 µg/m3
(Takenaka et al., 1983).
In mice, some groups exposed to cadmium oxide fumes or dust had increased incidences of lung tumours, but
the spontaneous rate of the tumours was high and variable. No increased incidence of lung tumours was seen in
hamsters exposed to cadmium oxide fumes and dust. This may have been linked to lung damage and subsequent
decreased survival at high doses. Some authors hypothesized that expression of metallothionein protein in the
lung after inhalation of cadmium differs between species, therefore providing varying degrees of cadmium
sequestration and protection from its carcinogenic effects (JRC, 2007).
5.8.1.3. Carcinogenicity: dermal
No studies were located regarding carcinogenicity after dermal exposure to cadmium metal or cadmium
compounds. However, toxicity via the dermal route is not expected to be significant as uptake of soluble and
less-soluble cadmium compounds applied onto the skin of animals appears to be low (<1%) (see Section 5.1.1).
Also in view of the risk reduction measures which need to be taken as a result of the carcinogenicity of
cadmium metal and some of the cadmium compounds via the inhalatory route, dermal carcinogenicity is not
likely to pose an issue for human health.
5.8.1.4. Carcinogenicity: other routes
A number of experiments were conducted looking into the carcinogenic potential of various cadmium
compounds when administered intrathoracically, intratracheally and subcutaneously (see following Table).
Although these routes of exposure are not relevant for the present risk assessment, the studies are presented as
supporting data.
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CAS number:
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Table 25. Overview of selected experimental studies on carcinogenicity (other routes)
Method
Results
Remarks
Reference
No NOAEL identified.
(severe inflammation 3 days
after injection; tumours in all
but 3 rats, principally
rhabdomyosarcomata)
3 (not reliable)
supporting study
experimental result
Heath JC and
Daniels MR
(1964)
Cadmium metal
Rat (hooded)
(intramuscular)
14 or 28 mg Cd/rat
Vehicle: fowl serum
Exposure: Single
Neoplastic effects observed in
any test group: yes
Rat (Fischer 344) male/female
no NOAEL identified.
3 (not reliable)
(intrathoracic injection)
supporting study
3 mg Cd/rat or 3 mg Cd + 6 mg
Neoplastic effects observed in experimental result
Zn/rat (nominal conc.)
any test group: yes
Vehicle: physiol. saline
Exposure: 5 administrations, 1 per
month
A study was conducted to evaluate
the carcinogenic potential of the test
material in rats through intrathoracic
administration. Rats were
administered test material at a dose
of 3 mg Cd or 3 mg Cd plus 6 mg Zn
through intrathoracic injection, a
total of 5 administrations once per
month. The animals were observed
for 10 months thereafter.
Furst A, Cassetta
DM and Sasmore
DP (1973)
Cadmium oxide
Rat (Fischer 344) male
no NOAEL identified.
3 (not reliable)
(intratracheal)
supporting study
25 µg CdO (nominal conc.)
Neoplastic effects observed in experimental result
Vehicle: physiol. saline
any test group: yes
Exposure: 30 days interval for all
three groups. Group 1 = single
exposure, Group 2 = two times
exposure and Group 3 = thrice)
A study was conducted to evaluate
the carcinogenic effect of single or
multiple intrathoracic
administrations of the test material in
rats. Animals were divided in 4
groups: a control group and three
groups with one, two or three
instillations of 25 µg CdO,
respectively, at an interval of 30 d.
Animals were observed for up to 880
days and all were examined
histologically.
Sanders CL and
Mahaffey JA
(1984)
Rat (Wistar) male/female
(subcutaneous)
25 µg CdO (nominal conc.)
Vehicle: physiol. saline
Exposure: single
This study was conducted to
Kazantzis G and
Hanbury WJ
(1966)
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no NOAEL identified.
3 (not reliable)
supporting study
Neoplastic effects observed in experimental result
any test group: yes
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CAS number:
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Results
Remarks
Reference
no NOAEL identified.
(peritoneal cavity tumours)
3 (not reliable)
supporting study
experimental result
Pott F, Ziem U,
Reiffer FJ, Huth F,
Ernst H and Mohr
U (1987)
examine the carcinogenic potential
of the test material in rats, when
administered via the subcutaneous
route. Rats were administered a
single subcutaneous dose of the test
material and thereafter observed for
a period of one year.
Rat (Fischer 344) male
(intraperitoneal)
25 µg CdO in saline
Cadmium sulphide
Rat (Wistar) male/female
no NOAEL identified.
3 (not reliable)
Kazantzis G and
(subcutaneous)
supporting study
Hanbury WJ
25 µg CdS in 0.25 ml saline
Neoplastic effects observed in experimental result (1966)
(nominal conc. (subcutaneous
any test group: yes
injection)); 50 µg CdS in 0.50 ml
saline (nominal conc. (intramuscular
injection))
Vehicle: physiol. saline
Exposure: single
This study was conducted to
examine the carcinogenic potential
of the test material in rats, when
administered through the
subcutaneous and intramuscular
routes. Rats were administered a
single subcutaneous/intramuscular
dose of the test material and
thereafter observed for a period of
one year.
Cadmium metal powder produced local sarcomas in rats following intramuscular administration, including some
fibrosarcomas which metastasised (Heath and Daniels, 1964). An inthratoracic injection of cadmium metal
associated with zinc metal induced pleural cavity tumours (Furst et al., 1973). An intraperitoneal injection of
cadmium oxide induced peritoneal cavity tumours (Pott et al., 1987). Single or multiple subcutaneous injections
of cadmium oxide or sulphide were observed to cause local sarcomas in rat (Kazantzis and Hanbury, 1966).
5.8.2. Human information
Food-borne cadmium is the major source of exposure for most of the non-smoking general population.
Occupational exposure to cadmium is mainly by inhalation but includes additional intakes through food and
tobacco. A review of cadmium carcinogenicity to humans has been conducted in the EU Risk Assessment
Report (RAR) (JRC, 2007). Selected exposure-related observations in humans are summarised by cadmium
compound in the following table, then commented according to the type of population considered.
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CAS number:
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Table 26. Overview of selected exposure-related observations on carcinogenicity in humans
Method
Results
Remarks
Reference
Study type: cohort study
(prospective)
Type of population: occupational
HYPOTHESIS TESTED (if cohort or
case control study): Cancer mortality
among cadmium-nickel exposed
workers
STUDY PERIOD: 1951-1980
STUDY POPULATION
- E: 528 (M only)
- S: “at least one year of cadmium
exposure”
Exposure to Cd, Ni
Prostate cancer (o/e): 4/3.09
SMR (95% CI) prostate: 130
Lung cancer (o/e): 6/5.03
SMR (95% CI) lung: 119
→non-significant increase in
deaths due to prostate and lung
cancer
1 (reliable
without
restriction)
key study
Andersson K,
Elinder C,
Hogstedt C,
Kjellström T and
Spang G (1984)
Study type: cohort study
(prospective)
Type of population: occupational
HYPOTHESIS TESTED (if cohort or
case control study): Cancer mortality
among cadmium production workers
STUDY PERIOD: 1940-1973
STUDY POPULATION:
- E: 292 ( white M only)
- S: “who had achieved 2 years of
employment between 01.01.1940 and
31.12.1969”
- Lost cases: 20
Exposure to Cd fumes & dust
Prostate cancer (o/e): 4/1.15
2 (reliable with
SMR (95% CI) prostate: 348 (94- restrictions)
891)
key study
Lung cancer (o/e) : 12/5.11
SMR (95% CI) lung: 235 (121410)*
*p<0.05
→ Significantly increased risk
for lung cancer
Lemen R, Lee JS,
Wagoner JK and
Blejer HP (1976)
Study type: cohort study
(prospective)
Type of population: occupational
HYPOTHESIS TESTED (if cohort or
case control study): Association
between the risk of dying from lung
cancer and occupational cadmium
exposure
STUDY PERIOD: 1947-2000
STUDY POPULATION
E: 926 (M)
S: “workers first employed in the
period 1947-1975 and having min of
12 months of employment at the
factory”
Lost cases: 26 emigrated, 4 untraced
Exposure to Cd(OH)2, nickel
hydroxide, cobalt, graphite, iron
oxide, potassium hydroxide
-overall:
prostate cancer (o/e) : 9/7.5
SMR (95% CI) prostate: 116 (53221)
Lung cancer (o/e) : 45/40.7
SMR (95% CI) lung: 111(81-148)
→ Non significantly increases in
lung/ prostate cancer deaths
1 (reliable
without
restriction)
key study
Sorahan T and
Esmen NA (2004)
Study type: cohort study
(prospective)
Type of population: occupational
HYPOTHESIS TESTED (if cohort or
case control study): Association
-Overall:
Prostate cancer (o/e): 8/6.6
SMR (95% CI) prostate: 121 (52239)
Lung cancer (o/e) : 89/70.2
1 (reliable
without
restriction)
key study
Sorahan T and
Waterhouse JA
(1983)
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Cadmium metal
Cadmium hydroxide
79
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Results
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Remarks
Reference
-Overall:
Lung cancer (o/e) : 110/84.5
SMR (95% CI) lung: 130 (107157)
→ Increase in lung cancer
deaths among workers with the
highest exposure first employed
between 1926 and 1946
1 (reliable
without
restriction)
key study
Sorahan T (1987)
Study type: cohort study
(retrospective)
Type of population: occupational
HYPOTHESIS TESTED (if cohort or
case control study): Association
between the risk of cancer and
occupational cadmium exposure
STUDY POPULATION
E: 6995 (M only)
S: "exposed for more than 1 year
between 1942 and 1970"
Lost cases: 90
Exposure to CdO dust & fumes, CdS,
dust from Cd stabilisers, silver,
copper + beryllium, nickel,
mineral oils, arsenic, lead
-Overall:
Prostate cancer (o/e): 23/23.3
SMR (95% CI) prostate: 99 (63148)
Lung cancer (o/e) : 199/185.6
SMR (95% CI) lung: 107 (92122)
-ever high (N=3%):
Prostate cancer (o/e): 0/0.4
SMR (95% CI) prostate: 0 (0962)
Lung cancer (o/e) : 5/4.4
SMR (95% CI) lung: 113 (37263)
-ever medium (N=17%):
Prostate cancer (o/e): 0/2.5
SMR (95% CI) prostate: 0 (0147)
Lung cancer (o/e) : 27/24.2
SMR (95% CI) lung: 112 (74163)
-always low (N=80%):
Prostate cancer (o/e): 23/20.4
SMR (95% CI) prostate: 113(72170)
Lung cancer (o/e) : 167/157.0
SMR (95% CI) lung: 106 (90123)
→ No statistically significant
1 (reliable
without
restriction)
key study
Armstrong BG and
Kazantzis G.
(1983)
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CHEMICAL SAFETY REPORT
between the risk of dying from
SMR (95% CI) lung: 127
cancer and occupational cadmium
→ Significant increase in
exposure
cancer of the respiratory tract
STUDY POPULATION
E: 3025 (2559 men)
S: “had a minimum period of
employment of one month between
1923 and 1975”
Exposure to CdO, Cd(OH)2 dust,
nickel hydroxide, oxyacetylene fumes
Study type: cohort study
(prospective)
Type of population: occupational
HYPOTHESIS TESTED (if cohort or
case control study): Association
between the risk of dying from lung
cancer and occupational cadmium
exposure
STUDY PERIOD: 1946-1984
STUDY POPULATION
E: 3025 (2559 men)
S: “minimum period of employment
of 1 month who started employment
between 1923 and 1975”
Lost cases: 78
Exposure to CdO, Cd(OH)2 dust,
nickel hydroxide
Cadmium oxide
80
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Method
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Results
CAS number:
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Remarks
Reference
1 (reliable
without
restriction)
key study
Elinder CG,
Kjellström T,
Hogstedt C,
Andersson K and
Spang G (1985)
excess of lung/prostate cancer
Study type: cohort study
(prospective)
Type of population: occupational
HYPOTHESIS TESTED (if cohort or
case control study): Association
between the risk of cancer and
occupational cadmium exposure
STUDY POPULATION
E: 522 (M only)
S: “exposed to cadmium for at least
one year”
Lost cases: 3 (+ 17 emigrated)
Exposure to CdO dust, nickel
hydroxide, asbestos
-all workers:
Prostate cancer (o/e): 4/3.7
SMR (95% CI) prostate: 108 (29277)
Lung cancer (o/e): 8/6.01
SMR (95% CI) lung: 133 (57262)
- ≥ 5 years of exposure, 20 years
latency
Prostate cancer (o/e): 4/N.I.
SMR (95% CI) prostate: 148/N.I.
Lung cancer (o/e): 7/4.0
SMR (95% CI) lung: 175(70-361)
- ≥ 5 years of exposure, 10 years
latency
Prostate cancer (o/e): 4/N.I.
SMR (95% CI) prostate: 125/N.I.
Lung cancer (o/e): 8/N.I.
SMR (95% CI) lung: 163/N.I.
→ Lung, prostate cancer: SMR
was increased but did not reach
statistical significance, even in
the high exposure group (20
years latency, at last 5 years of
exposure)
Study type: cohort study
(prospective)
Type of population: occupational
HYPOTHESIS TESTED (if cohort or
case control study): Association
between the risk of cancer and
occupational cadmium exposure
STUDY POPULATION
E: 347 (M only)
D: “who had been employed for at
least 12 months between 1922 and
1978”
Lost cases: E: 13 (+ 4 emigrated)
Exposure to CdO fumes, copper
Prostate cancer (o/e): 1/1.58
2 (reliable with
SMR (95% CI) prostate: 63 (1restrictions)
352)
key study
Lung cancer (o/e) : 10/12.35
SMR (95% CI) lung: 81 (N.I.)
-> Mortality slightly increased
from respiratory disease in
workers exposed to cadmium;
statistically significant positive
association with prostate cancer
Holden H (1980a)
Study type: cohort study
(prospective)
Type of population: occupational
HYPOTHESIS TESTED (if cohort or
case control study): Association
between the risk of cancer and
occupational cadmium exposure
STUDY POPULATION
E: 347 (M only)
S: ”who had been employed for at
least 12 months between 1922 and
1978” + 624 vicinity workers (M
only)
Lost cases: 25 (+ 27 emigrated)
Exposure to CdO fumes, copper
vicinity workers: arsenical copper,
silver, nickel
cadmium workers:
Prostate cancer (o/e): 1/1.58
SMR (95% CI) prostate: 63 (1352)
Lung cancer (o/e) : 10/13.14
SMR (95% CI) lung: 76 (N.I.)
Vicinity workers:
Prostate cancer (o/e): 8/3.0
SMR (95% CI) prostate: 267
(115-526)
Lung cancer (o/e) : 36/26.08
SMR (95% CI) lung: 138 (97191)
-> Mortality slightly increased
from respiratory disease in
workers exposed to cadmium;
statistically significant positive
Holden H (1980b)
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
2 (reliable with
restrictions)
key study
81
EC number:
233-331-6
Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
association with prostate cancer
Study type: cohort study
(prospective)
Type of population: occupational
HYPOTHESIS TESTED (if cohort or
case control study): Association
between the risk of cancer and
occupational cadmium exposure
STUDY POPULATION
E: 869 (M and F)
S: "employed at least one year
between 1940 and 1980"
Lost cases: 31
Exposure to CdO dust, nickel
hydroxide
total (male only):
Prostate cancer (o/e): 11/9
SMR (95% CI) prostate: 122
(61.1-219)
Lung cancer (o/e): 16/9.1
SMR (95% CI) lung: 176 (101287)
→ Significant increase in lung
cancer mortality, however no
relationship between
cumulative cadmium exposure
and lung cancer deaths
1 (reliable
without
restriction)
key study
Järup L, Bellander
T, Hogstedt C and
Spang G (1998)
Study type: cohort study
(prospective)
Type of population: occupational
HYPOTHESIS TESTED (if cohort or
case control study): Association
between the risk of cancer and
occupational cadmium exposure
STUDY POPULATION
E: 6910 (M only)
S: "exposed for more than 1 year
between 1942 and 1970"
Exposure to CdO dust and fumes,
CdS, dust from Cd stabilisers, silver,
copper + beryllium, nickel, mineral
oils, arsenic, lead
-Overall:
Prostate cancer (o/e): 37/49.5
SMR (95% CI) prostate: 75 (53103)
Lung cancer (o/e) : 339/304.1
SMR (95% CI) lung: 112 (100124)
-ever high (N=3%):
Prostate cancer (o/e): 1/1.0
SMR (95% CI) prostate: 97 (1540)
Lung cancer (o/e) : 14/8.6
SMR (95% CI) lung: 162 (89273)
-ever medium (N=17%):
Prostate cancer (o/e): 0/6.2
SMR (95% CI) prostate: 0 (0-59)
Lung cancer (o/e) : 55/45.6
SMR (95% CI) lung: 121 (91157)
-always low (N=80%):
Prostate cancer (o/e): 36/42.3
SMR (95% CI) prostate: 85 (60118)
Lung cancer (o/e) : 270/249.9
SMR (95% CI) lung: 108 (96122)
→ Absence of an increased risk
from prostate cancer
→ Significant excess mortality
for lung cancer
1 (reliable
without
restriction)
key study
Kazantzis G,
Blanks R and
Sullivan K (1992);
Kazantzis G and
Blanks R (1992)
Study type: cohort study
(retrospective)
Type of population: occupational
HYPOTHESIS TESTED (if cohort or
case control study): Association
between the risk of cancer and
occupational cadmium exposure
STUDY POPULATION
E: 6958 (M only)
S: "exposed for more than 1 year
-Overall:
Prostate cancer (o/e): 30/33.2
SMR (95% CI) prostate: 90 (61129)
Lung cancer (o/e) : 277/240.9
SMR (95% CI) lung: 115 (101129)
-ever high (N=3%):
Prostate cancer (o/e): 0/0.6
SMR (95% CI) prostate: 0 (0-
1 (reliable
without
restriction)
key study
Kazantzis G, Lam
TH and Sullivan
KR (1988)
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
82
EC number:
233-331-6
cadmium sulphate
Method
Results
between 1942 and 1970"
Lost cases: 67 + 184 emigrated
Exposure to CdO dust & fumes, CdS,
dust from Cd stabilisers, silver,
copper + beryllium, nickel, mineral
oils, arsenic, lead
615)
Lung cancer (o/e) : 12/6.2
SMR (95% CI) lung: 194 (100339)
-ever medium (N=17%):
Prostate cancer (o/e): 0/4.0
SMR (95% CI) prostate: 0 (0-92)
Lung cancer (o/e) : 41/34.0
SMR (95% CI) lung: 121 (84158)
-always low (N=80%):
Prostate cancer (o/e): 30/28.6
SMR (95% CI) prostate: 105 (71150)
Lung cancer (o/e) : 224/200.7
SMR (95% CI) lung: 112 (97126)
→ No excess risk from prostate
cancer
→ Significant increase in lung
cancer deaths in the cohort as a
whole and also in the high
exposure group
Study type: cohort study
(prospective)
Type of population: occupational
Subjects: E: 248 (M only)
S: “at least one year of exposure”
Lost cases: N.I.
Exposure to CdO dust
CAS number:
10124-36-4
Remarks
Reference
-Overall:
Prostate cancer (o/e): 4/0.58
SMR (95% CI) prostate: 690
(186-1766) (SIR)
Lung cancer (o/e) : 5/4.4
SMR (95% CI) lung: 114 (0.37265) (SIR)
→ Indication of elevation of
prostate cancer: 4 fatalities
2 (reliable with
restrictions)
key study
Kipling MD and
Waterhouse JAH
(1967)
Study type: cohort study
(prospective)
Type of population: occupational
HYPOTHESIS TESTED (if cohort or
case control study): Association
between the risk of cancer and
occupational cadmium exposure
STUDY POPULATION
E: 94
S: “all workers with a 5 years or
longer exposure to cadmium since
the factory started (1930’s)”
Exposure to CdO fumes
Prostate cancer (o/e): 4/2.69
SMR (95% CI) prostate: 149 (40381)
→ Mortality from prostate
cancer was above the expected
from national rates
1 (reliable
without
restriction)
key study
Kjellström T,
Friberg L and
Rahnster B (1979)
Study type: cohort study
(prospective)
Type of population: occupational
HYPOTHESIS TESTED (if cohort or
case control study): Association
between the risk of dying from
cancer and occupational cadmium
exposure
STUDY POPULATION
E: 74
S: “at least ten years of exposure”
Exposure to CdO dust
-Overall:
Prostate cancer (o/e): 3/N.I.
SMR (95% CI) prostate: N.I.
Lung cancer (o/e) : 1/N.I.
SMR (95% CI) lung: N.I.
→ Indication of elevation of
prostate cancer: 3 fatalities
2 (reliable with
restrictions)
key study
Potts CL (1965)
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
83
EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Method
Results
Remarks
Reference
Study type: cohort study
(retrospective)
Type of population: occupational
Subjects:
E: 571 (M only)
S: ”employed for at least 6 months as
plant production workers between
1940 and 1969 and first employed
after 1.1.1926”
Exposure to CdO fumes & dust,
CdSO4, CdS, arsenic
Lung cancer (o/e) :
< 400 mg Cd.d/m³: 6/N.I.
400 – 999 mg Cd.d/m³: 6/N.I.
1,000- 1,999 mg Cd.d/m³: 4/N.I.
≥ 2,000 mg Cd.d/m³: 5/N.I.
SMR (95% CI) lung:
< 400 mg Cd.d/m³: 100
400 – 999 mg Cd.d/m³: 225 (72702)
1,000- 1,999 mg Cd.d/m³: 341
(66-872)
≥ 2,000 mg Cd.d/m³: 413 (1211403)*
trend: 156 (1.06-2.28)*
*p<0.05
→ Significant positive trend
between cumulative exposure to
cadmium and risks of mortality
from lung cancer only in the
presence of concomitant
exposure to As
1 (reliable
without
restriction)
key study
Sorahan T and
Lancashire R
(1997)
Study type: cohort study
(prospective)
Type of population: occupational
HYPOTHESIS TESTED (if cohort or
case control study): Association
between the risk of dying from
cancer and occupational cadmium
exposure
STUDY POPULATION
E: 3025 (2559 men)
S: “had a minimum period of
employment of one month between
1923 and 1975”
Exposure to CdO, Cd(OH)2 dust,
nickel hydroxide, oxyacetylene fumes
- Overall:
Prostate cancer (o/e): 8/6.6
SMR (95% CI) prostate: 121 (52239)
Lung cancer (o/e) : 89/70.2
SMR (95% CI) lung: 127
→ Significant increase in
cancer of the respiratory tract
1 (reliable
without
restriction)
key study
Sorahan T and
Waterhouse JA
(1983)
Study type: cohort study
(prospective)
Type of population: occupational
HYPOTHESIS TESTED (if cohort or
case control study): Association
between the risk of cancer and
occupational cadmium exposure
STUDY POPULATION
E: 347 (M only)
S: “who had been employed for at
least 12 months between 1922 and
1978” + 624 vicinity workers (M
only)
Lost cases: 26 (+ 27 emigrated)
Exposure to CdO fumes, copper
vicinity workers: arsenical copper,
phosphor bronze, other copper alloys
cadmium workers:
Prostate cancer (o/e): 2/2.83
SMR (95% CI) prostate: 71 (9255)
Lung cancer (o/e) : 18/17.8
SMR (95% CI) lung: 101 (60159)
Vicinity workers:
Prostate cancer (o/e): N.I.
SMR (95% CI) prostate: N.I.
Lung cancer (o/e) : 55/34.3
SMR (95% CI) lung: 160 (N.I.)
Iron and brass foundry workers:
Prostate cancer (o/e): N.I.
SMR (95% CI) prostate: N.I.
Lung cancer (o/e) : 19/17.8
SMR (95% CI) lung: 107(N.I.)
→ No significant increases in
lung cancer deaths
1 (reliable
without
restriction)
key study
Sorahan T, Lister
A, Gilthorpe MS
and Harrington JM
(1995)
Study type: cohort study
(prospective)
-Overall:
Lung cancer (o/e) : 110/84.5
1 (reliable
without
Sorahan T (1987)
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
84
EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Method
Results
Remarks
Reference
Type of population: occupational
HYPOTHESIS TESTED (if cohort or
case control study): Association
between the risk of dying from lung
cancer and occupational cadmium
exposure
STUDY PERIOD: 1946-1984
STUDY POPULATION
E: 3025 (2559 men)
S: ”minimum period of employment
of 1 month who started employment
between 1923 and 1975”
Lost cases: 78
Exposure to CdO, Cd(OH)2 dust,
nickel hydroxide
SMR (95% CI) lung: 130 (107restriction)
157)
key study
→ Increase in lung cancer
deaths among workers with the
highest exposure first employed
between 1926 and 1946
Study type: cohort study
(prospective)
Type of population: occupational
HYPOTHESIS TESTED (if cohort or
case control study): Association
between the risk of cancer and
occupational cadmium exposure
STUDY POPULATION
E: 606 (white M only)
S: “all hourly employees and
foremen who had worked for at least
6 months in a production area of the
facility between 01.01.1940 and
31.12.1969…and first employed at
the facility on or after 1.1.1926”
Lost cases: 12
Exposure to CdO fumes & dust,
CdSO4, CdS, arsenic
Lung cancer (o/e) :
Overall: 24/16.07
≤584 mg Cd.d/m³: 2/5.73
585-2,920 mg Cd.d/m³: 7/4.28
1,461-2,920: 6/2.75
≥ 2,921 mg Cd.d/m³: 9/3.30
SMR (95% CI) lung:
Overall: 149 (95-222)
≤584 mg Cd.d/m³: 34
585-2,920 mg Cd.d/m³: 163
1,461-2,920: 217
≥ 2,921 mg Cd.d/m³: 272 (123513)*
p<0.05
→Significant dose response
relationship for lung cancer
2 (reliable with
restrictions)
key study
Stayner L, Smith
R, Thun M,
Schnorr T and
Lemen R (1992)
Study type: cohort study
(prospective)
Type of population: occupational
Subjects: E: 602 (white M only)
S: ”who had worked more than 6
months between 01.01.1940 and
31.12.1969”
Lost cases: 12
Exposure to CdO fumes & dust,
CdSO4, CdS, arsenic
Prostate cancer (o/e):
Overall: 3/2.2
SMR (95% CI) prostate:
Overall: 136
Lung cancer (o/e) :
Overall: 20/12.15
Hired before 1926: 4/0.56
Hired on or after 01.1926:
≤584 mg Cd.d/m³: 2/N.I.
585-2,920 mg Cd.d/m³: 7/N.I.
≥ 2,921 mg Cd.d/m³: 7/N.I.
SMR (95% CI) lung:
Overall: 165 (101-254)*
Hired before 1926:
Hired on or after 01.1926:
≤584 mg Cd.d/m³: 53
585-2,920 mg Cd.d/m³: 152
≥ 2,921 mg Cd.d/m³: 280 (113577)*
*p<0.05
→ Dose response relationship
between lung mortality and
cumulative exposure to
cadmium
2 (reliable with
restrictions)
key study
Thun MJ, Schnorr
TM, Blair SA,
Halperin W and
Lemen RA (1985)
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
85
EC number:
233-331-6
Method
cadmium sulphate
CAS number:
10124-36-4
Results
Remarks
Reference
Study type: cohort study
(retrospective)
Type of population: occupational
HYPOTHESIS TESTED (if cohort or
case control study): Association
between the risk of cancer and
occupational cadmium exposure
STUDY POPULATION
E: 571 (M only)
S: ”employed for at least 6 months
between 1940 and 1969 and first
employed after 1.1.1926”
Exposure to CdO fumes & dust,
CdSO4, CdS, arsenic
Lung cancer (o/e) :
< 400 mg Cd.d/m³: 6/N.I.
400 – 999 mg Cd.d/m³: 6/N.I.
1,000- 1,999 mg Cd.d/m³: 4/N.I.
≥ 2,000 mg Cd.d/m³: 5/N.I.
SMR (95% CI) lung:
< 400 mg Cd.d/m³: 100
400 – 999 mg Cd.d/m³: 225 (72702)
1,000- 1,999 mg Cd.d/m³: 341
(66-872)
≥ 2,000 mg Cd.d/m³: 413 (1211403)*
trend: 156 (1.06-2.28)*
*p<0.05
→ Significant positive trend
between cumulative exposure to
cadmium and risks of mortality
from lung cancer only in the
presence of concomitant
exposure to As
1 (reliable
without
restriction)
key study
Sorahan T and
Lancashire R
(1997)
Study type: cohort study
(prospective)
Type of population: occupational
HYPOTHESIS TESTED (if cohort or
case control study): Association
between the risk of cancer and
occupational cadmium exposure
STUDY POPULATION
E: 606 (white M only)
S: “all hourly employees and
foremen who had worked for at least
6 months in a production area of the
facility between 01.01.1940 and
31.12.1969…and first employed at
the facility on or after 1.1.1926”
Lost cases: 12
Exposure to CdO fumes & dust,
CdSO4, CdS, arsenic
Lung cancer (o/e) :
Overall: 24/16.07
≤584 mg Cd.d/m³: 2/5.73
585-2,920 mg Cd.d/m³: 7/4.28
1,461-2,920: 6/2.75
≥ 2,921 mg Cd.d/m³: 9/3.30
SMR (95% CI) lung:
Overall: 149 (95-222)
≤584 mg Cd.d/m³: 34
585-2,920 mg Cd.d/m³: 163
1,461-2,920: 217
≥ 2,921 mg Cd.d/m³: 272 (123513)*
p<0.05
→Significant dose response
relationship for lung cancer
2 (reliable with
restrictions)
key study
Stayner L, Smith
R, Thun M,
Schnorr T and
Lemen R (1992)
Study type: cohort study
(prospective)
Type of population: occupational
Subjects: E: 602 (white M only)
S: ”who had worked more than 6
months between 01.01.1940 and
31.12.1969”
Lost cases: 12
Exposure to CdO fumes & dust,
CdSO4, CdS, arsenic
Prostate cancer (o/e):
Overall: 3/2.2
SMR (95% CI) prostate:
Overall: 136
Lung cancer (o/e) :
Overall: 20/12.15
Hired before 1926: 4/0.56
Hired on or after 01.1926:
≤584 mg Cd.d/m³: 2/N.I.
585-2,920 mg Cd.d/m³: 7/N.I.
≥ 2,921 mg Cd.d/m³: 7/N.I.
SMR (95% CI) lung:
Overall: 165 (101-254)*
Hired before 1926:
Hired on or after 01.1926:
≤584 mg Cd.d/m³: 53
585-2,920 mg Cd.d/m³: 152
2 (reliable with
restrictions)
key study
Thun MJ, Schnorr
TM, Blair SA,
Halperin W and
Lemen RA (1985)
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
Cadmium sulphate
86
EC number:
233-331-6
Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
≥ 2,921 mg Cd.d/m³: 280 (113577)*
*p<0.05
→ Dose response relationship
between lung mortality and
cumulative exposure to
cadmium
Cadmium sulphide
Study type: cohort study
(prospective)
Type of population: occupational
HYPOTHESIS TESTED (if cohort or
case control study): Association
between the risk of cancer and
occupational cadmium exposure
STUDY POPULATION
E: 6995 (M only)
S: "exposed for more than 1 year
between 1942 and 1970"
Lost cases: 90
Exposure to CdO dust & fumes, CdS,
dust from Cd stabilisers, silver,
copper + beryllium, nickel,
mineral oils, arsenic, lead
-Overall:
Prostate cancer (o/e): 23/23.3
SMR (95% CI) prostate: 99 (63148)
Lung cancer (o/e) : 199/185.6
SMR (95% CI) lung: 107 (92122)
-ever high (N=3%):
Prostate cancer (o/e): 0/0.4
SMR (95% CI) prostate: 0 (0962)
Lung cancer (o/e) : 5/4.4
SMR (95% CI) lung: 113 (37263)
-ever medium (N=17%):
Prostate cancer (o/e): 0/2.5
SMR (95% CI) prostate: 0 (0147)
Lung cancer (o/e) : 27/24.2
SMR (95% CI) lung: 112 (74163)
-always low (N=80%):
Prostate cancer (o/e): 23/20.4
SMR (95% CI) prostate: 113(72170)
Lung cancer (o/e) : 167/157.0
SMR (95% CI) lung: 106 (90123)
→ No statistically significant
excess of lung/prostate cancer
1 (reliable
without
restriction)
key study
Armstrong BG and
Kazantzis G
(1983)
Study type: cohort study
(prospective)
Type of population: occupational
HYPOTHESIS TESTED (if cohort or
case control study): Association
between the risk of cancer and
occupational cadmium exposure
STUDY POPULATION
E: 6910 (M only)
S: "exposed for more than 1 year
between 1942 and 1970"
Exposure to CdO dust and fumes,
CdS, dust from Cd stabilisers, silver,
copper + beryllium, nickel, mineral
oils, arsenic, lead
-Overall:
Prostate cancer (o/e): 37/49.5
SMR (95% CI) prostate: 75 (53103)
Lung cancer (o/e) : 339/304.1
SMR (95% CI) lung: 112 (100124)
-ever high (N=3%):
Prostate cancer (o/e): 1/1.0
SMR (95% CI) prostate: 97 (1540)
Lung cancer (o/e) : 14/8.6
SMR (95% CI) lung: 162 (89273)
-ever medium (N=17%):
Prostate cancer (o/e): 0/6.2
SMR (95% CI) prostate: 0 (0-59)
Lung cancer (o/e) : 55/45.6
SMR (95% CI) lung: 121 (91-
1 (reliable
without
restriction)
key study
Kazantzis G,
Blanks R and
Sullivan K (1992);
Kazantzis G and
Blanks R (1992)
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
87
EC number:
233-331-6
Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
157)
-always low (N=80%):
Prostate cancer (o/e): 36/42.3
SMR (95% CI) prostate: 85 (60118)
Lung cancer (o/e) : 270/249.9
SMR (95% CI) lung: 108 (96122)
→ Absence of an increased risk
from prostate cancer
→ Significant excess mortality
for lung cancer
Study type: cohort study
(prospective)
Type of population: occupational
HYPOTHESIS TESTED (if cohort or
case control study): Association
between the risk of cancer and
occupational cadmium exposure
STUDY POPULATION
E: 6958 (M only)
S: "exposed for more than 1 year
between 1942 and 1970"
Lost cases: 67 + 184 emigrated
Exposure to CdO dust & fumes, CdS,
dust from Cd stabilisers, silver,
copper + beryllium, nickel, mineral
oils, arsenic, lead
-Overall:
Prostate cancer (o/e): 30/33.2
SMR (95% CI) prostate: 90 (61129)
Lung cancer (o/e) : 277/240.9
SMR (95% CI) lung: 115 (101129)
-ever high (N=3%):
Prostate cancer (o/e): 0/0.6
SMR (95% CI) prostate: 0 (0615)
Lung cancer (o/e) : 12/6.2
SMR (95% CI) lung: 194 (100339)
-ever medium (N=17%):
Prostate cancer (o/e): 0/4.0
SMR (95% CI) prostate: 0 (0-92)
Lung cancer (o/e) : 41/34.0
SMR (95% CI) lung: 121 (84158)
-always low (N=80%):
Prostate cancer (o/e): 30/28.6
SMR (95% CI) prostate: 105 (71150)
Lung cancer (o/e) : 224/200.7
SMR (95% CI) lung: 112 (97126)
→ No excess risk from prostate
cancer
→ Significant increase in lung
cancer deaths in the cohort as a
whole and also in the high
exposure group
1 (reliable
without
restriction)
key study
Kazantzis G, Lam
TH and Sullivan
KR (1988)
Study type: cohort study
(prospective)
Type of population: occupational
HYPOTHESIS TESTED (if cohort or
case control study): Association
between the risk of cancer and
occupational cadmium exposure
STUDY POPULATION
E: 571 (M only)
S: ”employed for at least 6 months
between 1940 and 1969 and first
employed after 1.1.1926”
Exposure to CdO fumes & dust,
Lung cancer (o/e) :
< 400 mg Cd.d/m³: 6/N.I.
400 – 999 mg Cd.d/m³: 6/N.I.
1,000- 1,999 mg Cd.d/m³: 4/N.I.
≥ 2,000 mg Cd.d/m³: 5/N.I.
SMR (95% CI) lung:
< 400 mg Cd.d/m³: 100
400 – 999 mg Cd.d/m³: 225 (72702)
1,000- 1,999 mg Cd.d/m³: 341
(66-872)
≥ 2,000 mg Cd.d/m³: 413 (1211403)*
1 (reliable
without
restriction)
key study
Sorahan T and
Lancashire R
(1997)
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
88
EC number:
233-331-6
cadmium sulphate
Method
Results
CdSO4, CdS, arsenic
trend: 156( 1.06-2.28)*
*p<0.05
→ Significant positive trend
between cumulative exposure to
cadmium and risks of mortality
from lung cancer only in the
presence of concomitant
exposure to As
Study type: cohort study
(prospective)
Type of population: occupational
HYPOTHESIS TESTED (if cohort or
case control study): Association
between the risk of cancer and
occupational cadmium exposure
STUDY PERIOD: 1940-1984
STUDY POPULATIONE: 606
(white M only)
S: “all hourly employees and
foremen who had worked for at least
6 months in a production area of the
facility between 01.01.1940 and
31.12.1969…and first employed at
the facility on or after 1.1.1926”
Lost cases: 12
Exposure to CdO fumes & dust,
CdSO4, CdS, arsenic
Study type: cohort study
(prospective)
Type of population: occupational
HYPOTHESIS TESTED (if cohort or
case control study): Association
between the risk of cancer and
occupational cadmium exposure
STUDY PERIOD: 1940-1978
STUDY POPULATION
E: 602 (white M only)
S: ”who had worked more than 6
months between 01.01.1940 and
31.12.1969”
Lost cases: 12
Exposure to CdO fumes & dust,
CdSO4, CdS, arsenic
CAS number:
10124-36-4
Remarks
Reference
Lung cancer (o/e) :
Overall: 24/16.07
≤584 mg Cd.d/m³: 2/5.73
585-2,920 mg Cd.d/m³: 7/4.28
1,461-2,920: 6/2.75
≥ 2,921 mg Cd.d/m³: 9/3.30
SMR (95% CI) lung:
Overall: 149 (95-222)
≤584 mg Cd.d/m³: 34
585-2,920 mg Cd.d/m³: 163
1,461-2,920: 217
≥ 2,921 mg Cd.d/m³: 272 (123513)*
p<0.05
→Significant dose response
relationship for lung cancer
2 (reliable with
restrictions)
key study
Stayner L, Smith
R, Thun M,
Schnorr T and
Lemen R (1992)
Prostate cancer (o/e):
Overall: 3/2.2
SMR (95% CI) prostate:
Overall: 136
Lung cancer (o/e) :
Overall: 20/12.15
Hired before 1926: 4/0.56
Hired on or after 01.1926:
≤584 mg Cd.d/m³: 2/N.I.
585-2,920 mg Cd.d/m³: 7/N.I.
≥ 2,921 mg Cd.d/m³: 7/N.I.
SMR (95% CI) lung:
Overall: 165 (101-254)*
Hired before 1926:
Hired on or after 01.1926:
≤584 mg Cd.d/m³: 53
585-2,920 mg Cd.d/m³: 152
≥ 2,921 mg Cd.d/m³: 280 (113577)*
*p<0.05
→ Dose response relationship
between lung mortality and
cumulative exposure to
cadmium
2 (reliable with
restrictions)
key study
Thun MJ, Schnorr
TM, Blair SA,
Halperin W and
Lemen RA (1985)
General population (oral route)
Information on the oral carcinogenic potential of cadmium may be derived from: 1) mortality studies in
populations considered to be exposed to high concentrations of cadmium, and 2) the comparison of cadmium
values measured in the tissue of healthy subjects with those obtained in tumour tissue of cancer patients (JRC,
2007).
Available epidemiological studies do not report reliable estimates of individual dose and therefore have limited
sensitivity to detect a possible carcinogenic effect. Classification of exposure and selection of appropriate
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control groups are two methodological problems encountered after analysis of these studies.
Elevated cadmium levels were found in malignant prostate tissue of cancer patients compared to healthy
subjects. Other authors have reported elevated levels of cadmium in other neoplastic tissues but differences with
healthy subjects failed to reach statistical significance or were attributed to other factors, e.g. smoking.
A prospective study conducted in a region of Belgium with historical industrial pollution by heavy metals found
an excess of lung cancer cases. The risk of lung cancer was positively associated with Cd-U measured during
the Cadmibel study (1985-89), suggesting a possible impact of inhalation exposure to Cd, but the role of other
associated pollutants cannot be excluded (Nawrot et al., 2006).
A statistically significant association between dietary cadmium intake (calculated from a food frequency
questionnaire) and the risk of endometrial cancer has been reported in a cohort of post-menopausal women in
Sweden followed during 16.0 years (484,274 person-years) (Akesson et al., 2008).
Overall, there is currently no conclusive evidence that cadmium acts as a carcinogen following oral exposure
(JRC, 2007).
Workers (inhalation route)
The concern that cadmium might cause cancer in humans was raised in the 1960s, before any experimental
evidence of carcinogenicity in laboratory animals was available. The first suspicion started with four men who
had worked in a factory of cadmium-nickel battery in UK who were reported to have died from prostate cancer
although, compared to national rates, less than one case would have been expected (Potts, 1965). Subsequently,
three additional studies conducted in small cohorts of workers employed in the production of batteries (Kipling
et al., 1967), alloys (Kjellström et al., 1979) and cadmium metal (Lemen et al., 1976) reported an association
between Cd exposure and an increased mortality from prostate cancer. However, later studies (Sorahan et al.,
1983; Thun et al., 1985; Kazantzis et al., 1988) failed to confirm this hypothesis.
In humans, a statistically significant increase in mortality from lung cancer has initially been reported in studies
involving cadmium recovery (Lemen et al., 1976; Thun et al., 1985), nickel cadmium battery (Sorahan, 1987)
and cadmium processing workers (Ades et al., 1988; Kazantzis et al., 1992). Based on these studies, IARC
(1993) concluded that there was sufficient evidence to classify cadmium and its compounds as human
carcinogens (category 1). However, the epidemiological data that have been used to support this classification
have been criticised because of the lack of control for confounding exposures (mainly arsenic) and smoking
habits. Studies conducted after this IARC evaluation, have tried to address these difficulties. In particular, the
dose-response relationship between Cd exposure and lung cancer mortality rates, previously reported by Thun et
al. (1985) and Stayner et al. (1992), has not been confirmed with a refined exposure assessment methodology. A
significant positive trend between cumulative exposure to cadmium and mortality from lung cancer was found
after adjustment for age, year of hiring and ethnicity but only in the presence of concomitant exposure to arsenic
(Sorahan et al., 1997). In two recent cohorts of workers from a nickel-cadmium battery plant (where arsenic is
not a confounder), a globally increased mortality from lung cancer was observed but the dose-response
relationships were not consistent with a causal role of cadmium (Järup et al., 1998; Sorahan et al., 2004). In the
latter cohort, 926 male workers from a nickel-cadmium battery factory were followed up for a very long period
of time (1947- 2000). Significantly increased mortality was obtained for pharynx cancer, diseases of respiratory
system and diseases of genitourinary system. For lung cancer, the mortality was modestly increased and without
any definite pattern or trend by time variables and cumulative exposure to cadmium. Interestingly, indications
exist in this cohort of increased risks from other known adverse effects associated with exposure to cadmium
compounds, specifically, a significantly increased mortality (although without dose-response trend) from nonmalignant respiratory diseases, and an increase of diseases of the genitourinary system possibly reflecting late
effects of kidney toxicity. If this were true, it could be assumed that measures protecting against
renal/respiratory effects should also be protective against lung cancer risk.
In a cohort of copper-cadmium alloy workers for whom individual cumulative exposure indexes were estimated,
a non significant, negative trend between cumulative cadmium exposure and risks of lung cancer was reported.
The dose-response trend was, however, significant for non-malignant diseases of the respiratory system
(Sorahan et al., 1995). The most recent studies therefore do not support the hypothesis that Cd compounds act as
lung carcinogens in humans (Verougstraete et al., 2003).
Some epidemiological studies suggest an association between occupational exposure to Cd and the occurrence
of renal cancer (reviewed by Il’yasova and Schwartz, 2005).
5.8.3. Summary and discussion of carcinogenicity
Data from experimental studies clearly indicates that cadmium is an animal carcinogen. Only one study reported
an increase in cancer after oral exposure to soluble cadmium compounds. However, strong evidence exists that
inhalation of cadmium oxide dust and fumes or cadmium chloride causes lung cancer in rat. Mice exposed to
equivalent levels of cadmium oxide had only marginally significant elevations in lung cancer and no evidence
for lung carcinogenicity was found in hamster, so that it has been suggested that interspecies and also interstrain differences may play a role in the sensitivity to cadmium-induced carcinogenesis. Intrathoracic,
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intratracheal and subcutaneous exposure to cadmium compounds have also been shown to produce carcinogenic
responses in rat.
Overall, there is currently no conclusive evidence from human studies that cadmium acts as a carcinogen
following oral exposure. In worker populations exposed via inhalation, a statistically significant increase in
mortality from lung cancer was initially reported but this has not been supported in later studies. More recent
analyses suggest that measures protecting against renal/respiratory effects should also be protective of lung
cancer.
Conclusive data is not available for all forms of cadmium but the weight of evidence collected from
mutagenicity tests, long-term animal studies and epidemiological studies leads to conclude that cadmium oxide
should be considered at least as a suspected human carcinogen (lung cancer). Cadmium metal is a carcinogen
when injected in experimental animals. No studies exist for the metal in humans or animals, which does not
allow to sufficiently document its carcinogenic potential.
Following long discussions, cadmium oxide was classified by the CMR Working Group as Carc. Cat. 2; R45
(may cause cancer), i.e. carcinogenic potential irrespective of the exposure route3 and appears as such in
Annex I of Directive 67/548/EC (the corresponding GHS-CLP classification would be Carcinogenic category
1B; H350). Cadmium sulphate, cadmium chloride and cadmium metal have been granted the same
classification, based on weight of evidence and read-across. By analogy, a comparable classification could be
considered for the other highly and slightly soluble cadmium compounds (e.g. cadmium nitrate, hydroxide and
carbonate).
Apart from cadmium sulphide, none of the insoluble cadmium compounds (e.g. cadmium sulfoselenide,
cadmium zinc sulphide or cadmium telluride), not expected to penetrate easily into the organisms, are classified
for carcinogenicity. Cadmium sulphide is an exception. As there is no strong evidence to specifically support its
Carc. Cat. 2; R45 classification, a revision of the classification may be appropriate based on solubility
properties.
5.9. Toxicity for reproduction
5.9.1. Effects on fertility
5.9.1.1. Non-human information
Numerous studies have been conducted to assess the effects of cadmium on fertility, most of them with soluble
compounds such as cadmium chloride. A complete review is available in the EU Risk Assessment Report
(RAR) (JRC, 2007). The following section presents main findings by route of administration and type of
compound. Effects on male and female reproductive organs/fertility and multigeneration experiments are
considered separately.
Oral route
Effects on male organs and male fertility
The acute and chronic toxicity of cadmium via the oral route on the testis have been investigated in several
experiments. The results of selected studies, as summarised in the European Risk Assessment Report (RAR)
(JRC, 2007) are summarised in the following table:
Table 27. Overview of selected experimental studies on male fertility and reproductive organs (oral
route)4
Method
Results (reproductive NOAEL/LOAEL)
Remarks
Reference
Cadmium chloride
3 Although there is evidence that cadmium may cause lung cancer after inhalation exposure, there is no indication for a
carcinogenic potential in the general population after oral exposure. A classification as Carc. Cat. 2: R49, i.e. may cause
cancer by inhalation, could have been envisaged.
4 For many of these studies, only abstracts were available therefore IUCLID datasets were not produced.
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Method
cadmium sulphate
Results (reproductive NOAEL/LOAEL)
Mouse
Exposure: gavage
0-270-530-790 µmol Cd/kg
(as CdCl2)
Exposure: single
CAS number:
10124-36-4
Remarks
NOAEL: 270 µmol/kg (30.4 mg Cd/kg bw)
LOAEL: 59.6 mg Cd/kg bw
(relative testicular deposition of cadmium,
nearly constant at doses not inducing testicular
damage but decreased at doses inducing
necrosis of tubules and interstitial tissue (60-90
mg Cd/kg bw). Decrease attributed to
cadmium-induced vascular damage and
reduced circulation. At this dose, tissular
damage also observed in the gastro-intestinal
tract and in the liver)
Rat
NOAEL: 25 mg CdCl2 (15 mg Cd/kg bw)
Only abstract
Oral: drinking water
(no effects on bodyweight, weight of testis,
available
0-6.25-12.5-25 mg CdCl2/
prostate and seminal vesicles. No change in
kg bw
testis histopathology. No effect on clinical
Exposure: single dose
parameters or serum hormone levels)
Rat
NOAEL: 50 mg CdCl2/ kg bw (30.6 mg Cd/kg
Oral: gavage
bw)
0-25-50-100-150 mg CdCl2/ LOAEL: 61.2 Cd/kg bw
kg bw
(focal testicular necrosis and reduced
Exposure: single dose
spermatogenesis at 100 and 150 mg/kg bw.
Concentrations of cadmium in testicles ca. 0.35
μg/g for the two highest dose groups 2 days
after dosing and decreased 20-35% after 14
days)
Rat (male)
NOAEL: 50 mg CdCl2/ kg bw (30.6 mg Cd/kg
Oral: gavage
bw)
0-50-100-200 mg CdCl2/ kg LOAEL: 61.2 Cd/kg bw
bw
(at 100 and 200 mg CdCl2/kg bw, severe
Exposure: single dose
lesions of the whole testicular parenchyma with
25 males treated once with
massive calcification of the necrotic tubuli and
200 mg CdCl2/kg bw and 35 pronounced fibrosis of the interstitium)
males with 100 mg
CdCl2/kg. Observation for 6
months
Rat
NOAEL: 51 mg CdCl2/ kg bw (31.3 mg Cd/kg
Oral: gavage
bw/d)
0-25-51-107-225 mg
LOAEL: 65.6 mg Cd/kg bw/d
CdCl2/kg
(testicular atrophy and loss of spermatogenic
Exposure: 10 days
element at 107 mg CdCl2/kg bw as well as
dose-dependent increase in mortality, kidney
and hepatic changes)
Rat
NOAEL: 323 mg CdCl2/L (24.7 mg Cd/kg
Oral: drinking water
bw/d*)
13-323 mg CdCl2/L (W)
(dose-dependent effects on bodyweight and
Exposure: 10 days
organ weights but no effect on testes)
Rat (Wistar) male
NOAEL: 5 mg CdCl2/ kg (3.6 mg Cd/kg bw)
Oral: gavage
(no effects on testes of mature animals)
0-5 mg CdCl2 /kg bw
Exposure: 10 weekly doses
Animals necropsied after 12
and 18 months, or kept up to
30 months
Rat
NOAEL : 5 mg Cd/kg bw/d
Only abstract
Oral: drinking water
(no effects on testis histopathology, clinical
available;
0-0.001-0.01-0.1 mg
parameters or hormone levels)
details of docing
CdCl2/L
not available
Exposure: 30-90 days
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Reference
Andersen et
al.(1988)
Dixon et al.
(1976)
cited in
ATSDR
(2008)
Kotsonis,
Klaassen
(1977)
Bomhard et
al. (1987)
Borzelleca et
al. (1989)
Borzelleca et
al. (1989)
Bomhard et
al. (1987)
Dixon et al.
(1976)
cited in
ATSDR
(2008)
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Method
Results (reproductive NOAEL/LOAEL)
Rat
Oral: drinking water
0-17.2-34.4-68.8 mg Cd/L
(as CdCl2)
Exposure: 70-80 days
Rat
Oral: drinking water
Dosing with CdCl2, details
not available
Exposure: 10 weeks
NOAEL: 34.4 mg Cd/L (4.64 mg Cd/kg bw/d)
(no effects on reproductive parameters)
Rat
Oral: drinking water
Dosing details not available
Exposure: 14 weeks
Rat
Oral: drinking water
Dosing details not available
Exposure: 6 months
Rat
Oral: drinking water
0-10-30-100 mg Cd/L (as
CdCl2)
Exposure: 24 weeks
Rat
Oral: drinking water
10 mg CdCl2/L
Exposure: 52 weeks (13
months)
At the end of the treatment,
animals were kept for
mating for an additional
period of 30 days
CAS number:
10124-36-4
Remarks
Reference
-
Zenick et al.
(1982)
LOAEL: 8.58 mg Cd/kg bw/d
(atrophy of seminiferous tubule epithelium)
Only abstract
available;
details of dosing
not available
Cha et al.
(1987) cited
in ATSDR
(1998)
NOAEL: 5 mg CdCl2/kg bw/d (2.9 mg Cd/kg
bw/d)
LOAEL: 5.8 mg Cd/kg bw/d
(cadmium-related increase in testis weight,
reduced by simultaneous administration of
vitamins A and D3)
LOAEL: 3 mg Cd/kg bw/d
(significant reductions in sperm number and
motility and significant desquamation of
spermatogenic epithelium; gonadotoxic effect
manifested on the same level as general toxic
effect 3 mg/kg bw)
NOAEL: 100 mg Cd/L (12.5 mg Cd/kg bw/d*)
(no altered testicular function; testicular tissue
within normal limits although concentration of
cadmium in the testes after 12 weeks was
greater (± 0.9 μg Cd/g) than that which caused
testicular injury in previous acute study)
NOAEL: 10 mg CdCl2/L
LOAEL: ca. 0.8 mg Cd/kg bw/d*
(necrosis of spermatogonia, spermatocyte and
spermatid in some tubuli seminiferi after 10
months. Some tubuli showed atrophy, oedema
and vascular hyperaemia in the interstitium.
After 13 months, also slight atrophy of the
testis and hyperaemia in the tunica vaginalis
and serosal vessels of the interstitium. Some
tubuli had no spermatozoa. Kidney alterations
also observed. Some rats reported to have “lost
their reproduction capacities”; however, test
report incomplete and no indication of whether
these rats were those in which histopathological
anomalies were observed)
Only abstract
available;
details of dosing
not available
Pleasants et
al. (1992 and
1993) cited
in ATSDR
(1998)
3 (not reliable)
supporting
study
experimental
result
Saygi S,
Deniz, G,
Kutsal O and
Vural, N
(1991)
LOAEL: 12.6 mg Cd/kg bw/d
(significantly increased relative testis weight,
decreased sperm count and motility, decreased
seminiferous tubular diameter and seminiferous
tubular damage)
Only abstract
available;
details of dosing
not available
Saxena et al.
(1989) cited
in ATSDR
(1998)
Only abstract
Krasovskii et
available;
al. (1976)
details of dosing
not available
-
Kotsonis,
Klaassen
(1978)
Cadmium acetate
Rat
Oral: drinking water
50 ppm (as Cd acetate)
Exposure: 120 days
* Estimated consumption of water: 25 ml/day; Estimated weight of the rat: 200 g (Derelanko, 2000)
The above studies suggest an effect of cadmium on fertility, including testicular aprophy, necrosis and decreased
fertility. Additionally, Sutou et al. (1980) noted that a dose of 10 mg Cd/kg bw/d (as CdCl2) for 9 weeks did not
affect fertility of male rats in a dominant-lethal test. All analysed fertility indices did not reveal a difference with
control rats when males were mated with untreated females. When treated males were mated with females
having undergone the same cadmium exposure, adverse effects were observed at 10 mg/kg bw/d on number of
copulation and pregnancies as well as number of implants and live fetuses (NOAEL: 1 mg Cd/kg bw/d). This
study appears to be the most critical with regard to effects on fertility.
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Effects on female fertility and reproductive organs
Table 28. Overview of selected experimental studies on female fertility and reproductive organs (oral
route)
Method
Results
Remarks
Reference
Mouse (CF-1) female
oral: feed
Multigeneration study
0, 0.25, 5.0 and 50 ppm Cd (as
CdCl2) (nominal conc.)
Exposure: continuously during 6
generations
For each cadmium concentration,
diets were either sufficient in all
dietary constituents or deficient in
certain minerals, vitamins and fat.
Dose of 5 ppm cadmium combined
with a deficient diet designed to
simulate conditions of Itai-Itai
disease
NOAEL (P): 5 ppm Cd
(female)
LOAEL (P): 50 ppm Cd +
deficient diet (female)
(decreased fertility and litter
size)
(No decrease in fertility for
mice on sufficient diet.
Combined exposure to
cadmium and nutritional
deficiencies had synergistic
effect on fertility and litter
size, statistically significant at
50 ppm. Low calcium content
of deficient diet possibly
allowed cadmium to interfere
with calcium pathways
important to maintain fertility.
Increases with time in the
extent of dietary deficiencies
and in cadmium burdens of
maternal organs had no
measurable effect on
reproduction)
2 (reliable with
restrictions)
key study
experimental result
Whelton B (1988)
Mouse (Charles River CD)
male/female
three-generation study
oral: drinking water
0 and 10 mg/L = 0 and 2.5 mg/kg
bw/day (nominal conc.)
Exposure: Exposure period: up to 6
months (continuously)
Method: other, no information
LOAEL (F1): 2.5 mg/kg bw/d 3 (not reliable)
(male/female) (low mating
supporting study
index)
experimental result
Schroeder HA and
Mitchener M
(1971)
Rat (Wistar) female
fertility
oral: gavage
0.04, 0.4, 4 and 40 mg Cd/kg bw/d
(nominal conc.)
Vehicle: water
Exposure: 14 wk (5 d/wk)
A study was conducted to evaluate
the effects of the test material on the
estrus cycle of female rats. Animals
received0, 0.04, 0.4, 4 and 40 mg
Cd/kg bw/d through oral gavage for
14 wk. Vaginal smears were taken
daily for 14 days before the onset of
cadmium exposure and then at 6 wk
intervals during exposure.
NOAEL (P): 4 mg Cd/kg
bw/d (female)
LOAEL (P): 40 mg Cd/kg
bw/d (female) (length of
oestrous cycle twice as in
control rats)
(cadmium did not affect the
sexual cycle unless other
overt signs of Cd toxicity
were induced)
Baranski B and
Sitarek K (1987)
Rat (Sprague-Dawley) male/female
NOAEL (P): ca. 1 mg Cd/kg 2 (reliable with
Cadmium chloride
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experimental result
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Method
Results
Remarks
Single generation
fertility/developmental test
combined with a dominant lethal
assay
oral: gavage
0, 0.1, 1.0 and 10.0 mg Cd/kg bw/d
Exposure: Exposure period: 6 wk
prior to mating + 3 wk mating period
Premating exposure period (males
and females): 6 wk
Method: males and females within
each treatment group (+ control)
were mated 6 d/wk for 3 wk
changing partners every week if
needed. Cadmium was administered
during the mating period. Pregnant
females were administered cadmium
during gestation and killed on GD20
for developmental test (fetal
examination). Non-pregnant females
were killed after 13 wk.
Additionally: After 9 wk, males
were mated with 2 virgin females per
male per week for 6 wk. Pregnant
females were killed on
GD13 for dominant lethal tests
(examination of the numbers of
corpora lutea, live fetuses, early
deaths (no remnants of fetuses), and
late deaths (remnants of fetuses)).
One week after the cessation of
dominant lethal tests, which
represents a recovery period of 50 d,
male rats were killed and examined.
restrictions)
bw/d (female)
NOAEL (reproductive) (P): key study
experimental result
1 mg Cd/kg bw/d (female)
LOAEL (reproductive) (P):
10 mg Cd/kg bw/d (female)
(>50% fewer copulating and
pregnant females)
NOAEL (F1): ca. 1 mg
Cd/kg bw/d (male/female)
LOAEL (F1): 10 mg Cd/kg
bw/day (male/female)
(delayed ossification,
decreased bodyweight)
Reference
Yamamoto K,
Sendota H and
Sugiyama M
(1980)
Cadmium oxide
Rat (Wistar) female
LOAEL (P): 1 mg Cd/m³ air 2 (reliable with
Baranski B and
fertility
(female) (increased duration restrictions)
Sitarek K (1987)
inhalation: dust
of oestrous cycle
key study
0 and 0.02, 0.16, 1 mg Cd/m3
(CdO inhalation)
experimental result
(nominal conc.)
(cadmium did not affect the
Exposure: 20 wk (5 h/d, 5 d/wk)
sexual cycle unless other
A study was conducted to evaluate overt signs of Cd toxicity
the effects of the test material on the were induced)
estrus cycle of female rats. Animals
were exposed to the test material at
doses of 0 and 0.02, 0.16, 1 mg
Cd/m3 for 20 wk. Vaginal smears
were taken daily through 14
consecutive days before the onset of
cadmium exposure and then at 6 wk
intervals during exposure.
Additionally to the experiments summarised above, Kreis et al. (1993) conducted a historic follow-up study that
addressed the possibility of diminished fertility, decreased twinning rate and other developmental effects
(increased foetal death) in cattle. The results suggest that long-term exposure to low levels of cadmium in soil,
grass and food is associated with impaired reproduction in cows. However, confounding exposures to other
chemicals might have been possible and this is not precisely documented in the study.
Overall, evidence from experimental studies indicates that higher doses of cadmium compounds are needed to
elicit a reproductive toxic response in females compared to the males (ATSDR, 2008). Effects included
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decreased percentage of fertilised females and percentage of pregnancies, and increased duration of the oestrus
cycle.
Multigeneration studies
Both female and male mice were treated over two generations with 2.5 mg CdCl2/kg bw/d via the drinking
water. Five pairs of mice were given cadmium from weaning and allowed to breed freely up to 6 months of age.
In the F1 litters, average litter size at birth was normal. Three of five pairs failed to breed in the second
generation (Schroeder and Mitchener, 1971; cited in Barlow and Sullivan, 1982).
The effects of a low-level exposure to cadmium (0, 0.1, 1.0 and 5.0 ppm) on reproduction and growth were
evaluated in rats by Laskey et al. (1980). Exposure started with conception of the first generation and continued
throughout the experiment (130 days). According to the water consumption data, the F1 rats received
approximately 1.3 mg Cd/kg bw/d as young animals. This decreased to 0.5 mg Cd/kg bw/d as they reached
adulthood. No gross testicular pathology or depression in fertility was observed. Epididymal sperm count at 130
days was reduced approximately 20% in the 5.0 ppm cadmium group but not at 50 days. No increase in serum
FSH accompanied this reduced sperm count. Liver weight was decreased in the 5.0 ppm group.
Three consecutive generations of Wistar rats were treated by gavage with 3.5, 7.0 or 14.0 mg/kg bw Cd/d (as
cadmium chloride) over the period of pregnancy, lactation and 8 weeks after weaning in a study carried out by
Nagymajtenyi et al. (1997). Aim of the study was to investigate possible behavioural and functional
neurotoxicological changes caused by cadmium. However, the effects on the reproductive function were not
assessed.
Inhalation route
Effects on male fertility and reproductive organs
Male rats were exposed for 13 weeks to 0, 0.025, 0.05, 0.1, 0.25 and 1 mg CdO/m³ (as CdO aerosol) to assess
effects on reproductive function at the end of the study (Dunnick, 1995). The number of spermatids per testis
was reduced at 1 mg CdO/m3 but no histopathological changes in the reproductive system were seen, suggesting
that the changes may have been related to other effects of cadmium, such as hormonal modifications. The
LOAEL for the study was 1 mg CdO/m3 (ca. 0.09 mg Cd/m3) and the NOAEL was 0.25 mg CdO/m3 (ca.
0.23 mg Cd/m3).
In male mice exposed to same concentrations of CdO, no reproductive toxicity was observed at any dose
(NOAEL: 1 mg CdO/m3) (Dunnick, 1995).
Effects on female fertility and reproductive organs
Female rats were exposed by inhalation to CdO for 20 weeks (5 h/d, 5 d/wk) at concentrations of 0.02, 0.16 and
1 mg Cd/m3 (Baranski and Sitarek, 1987). In the high dose group, a pronounced increase in the main duration of
the oestrous cycle was observed 7-8 weeks after exposure. Bodyweight gain of the females was significantly
decreased and lethality was significantly higher in this group compared to the other experimental groups and
increased with duration of exposure. At lower exposure levels, no changes in the main duration of the oestrous
cycle were found when compared with that of controls, although at the end of exposure it was significantly
longer than before the onset of treatment. During the last 2 weeks of exposure, the percentage of females (93%)
with prolonged cycle (> 6 days) in the group exposed to 0.16 mg Cd/m³ group was significantly higher than in
the control group but mean duration of the cycle was not reported to be significantly different from that in the
non-exposed group (LOAEL: 1 mg Cd/m3). Bodyweight gain of females exposed to 0.02 and 0.16 mg Cd/m3
remained unchanged. Authors concluded that alterations of the oestrous cycle evoked by repeated exposure to
Cd appeared only in female rats exhibiting other signs of intoxication (reduced bodyweight gain, increased
lethality).
In a further study, a significant increase in the length of the oestrous cycle was observed in female rats exposed
to 1.0 mg CdO/m3 (LOAEL) (Dunnick, 1995). However, there were no histopathologic lesions indicative of
toxicity of the reproductive system, suggesting that reproductive effects at the highest exposure level in rats may
be related to other effects of cadmium such as hormonal changes.
In female B6C3F1 mice exposed for 13 weeks to CdO (0, 0.025, 0.05, 0.1, 0.25 and 1 mg CdO/m3) (Dunnick
1995), no indication for reproductive toxicity was reported at any dose (NOAEL: 1 mg CdO/m3).
Toxicity to reproduction: other studies
Effects on male and female reproductive organs have been observed after subcutaneous, intratesticular or
intraperitoneal administration.
Martin and colleagues found that cadmium administered by single intraperitoneal injection mimics oestrogen
activity in breast cancer cells and that cadmium binds to and activates oestrogen receptor-α (Martin et al., 2003;
Stoica et al., 2000). Recently, they reported vaginal epithelial cornification and increased uterine weight after a
single dose of cadmium (5μg/kg bw) in ovariectomised rats and these effects did not occur in the presence of
anti-oestrogenic drugs (Johnson et al., 2003).
While these studies may help to understand how cadmium may cause adverse effects on reproduction, their
relevance for humans has not yet been explored; however, these routes are not considered to be relevant for a
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human risk assessment (JRC, 2007).
Summary
Effects of cadmium treatment on male and female reproductive organs have been observed after oral
administration of cadmium compounds in rats and mice. In several studies, effects were detected at dose levels
which caused also general toxicity. In male rats and mice, acute exposure to cadmium compounds at doses
higher than 50 mg/kg bw was shown to cause testicular atrophy and necrosis and concomitant decreased
fertility. In females, effects on length of oestrous cycle after administration of cadmium compounds by gavage
were observed at a dose of 40 mg/kg bw/d. Fertility was however reported to be affected at doses of 10 mg/kg
bw/d. Overall, the lowest concentration (LOAEL) of cadmium reported to affect fertility in male and female
rats upon oral administration was 10 mg Cd/kg bw/d (Sutou et al., 1980).
In male rats exposed by inhalation to 1 mg CdO/m3 for 13 weeks (Dunnick, 1995), the number of spermatids
per testis, as evaluated at necropsy, was reduced compared to controls. No histopathological changes of the
reproductive system were observed (reproductive LOAEL: 1 mg CdO/m3 ca. 0.9 mg Cd/m3). This effect on the
number of spermatids was not observed in mice (Dunnick, 1995). Exposure to cadmium oxide at a
concentration of 1 mg/m3 (for more than 10 weeks) has been associated with an increase in oestrous cycle
length in rats in two studies. It has been suggested that the effects on the oestrous cycle occur only when other
signs of cadmium intoxication are present and might be related to other cadmium-induced effects such as
hormonal changes; however, current data do not allow to definitely draw this conclusion. The reproductive
LOAEL for inhalation is therefore considered to be 1 mg CdO/m3 (ca. 0.9 mg Cd/m3), derived from the 13week rat study. The corresponding NOAEL is 0.25 mg CdO/m³ (ca. 0.23 mg Cd/m³).
5.9.1.2. Human information
A review of the fertility effects of cadmium to human has been conducted in the EU Risk Assessment Report
(RAR) (JRC, 2007). Selected exposure studies are summarised by cadmium compound in the following table,
then commented according to the type of population considered (general population or workers, with smokers
considered apart).
Table 29. Overview of selected exposure-related observations on toxicity to reproduction / fertility in
humans
Method
Results
Remarks
Reference
Cadmium metal
Study type: case control study
(prospective)
Type of population: occupational
Subjects: HYPOTHESIS TESTED
(if cohort or case-control study):
Effect of exposure to cadmium on
the reproductive function.
METHOD OF DATA
COLLECTION
- Type: By questionnaire,
information was gathered on age,
residence, educational level,
occupational and health history,
actual and previous occupations,
smoking, coffee and alcohol
consumption. The fertility section
of the questionnaire contained the
questions proposed by Levine et al.
for the monitoring of the fertility of
workers (Levine et al., 1980 cited
by Gennart et al., 1992).
STUDY POPULATION
- Final population:
E: 83 (M only), Age: 23.4-72.2 y
C: 138 (M only), Age: 19.9-71.9 y
- Selected from:
E: “workers from two primary
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No significant reduction in
1 (reliable without
fertility was detected in the
restriction)
exposed group compared with the key study
unexposed population.
CHEMICAL SAFETY REPORT
Gennart JP,
Buchet JP, Roels
H, Ghyselen P,
Ceulemans E and
Lauwerys R
(1992)
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cadmium sulphate
Results
CAS number:
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Remarks
Reference
cadmium smelters, exposed
uninterruptedly to cadmium for at
least 1 y before the study and at the
time of the study: Cd-U>2µg/g
creatinine, Pb-B <30 µg/100mL”
C: “workers from factories located
in the same area, never
occupationally exposed to heavy
metals, at the time of the survey:
Cd-U<2µg/g creatinine, Pb-B
<20µg/100mL”
For E and C, no pathologic
conditions which might interfere
with reproductive function, Belgian
nationality and married at least
once”
- Lost subjects: 29 in E, 127 in C
Endpoint addressed: toxicity to
reproduction / fertility
Study type: case control study
(prospective)
Type of population: general
Subjects: HYPOTHESIS TESTED
(if cohort or case control study):
Relationship between cadmium
concentrations with parameters of
conventional semen analysis and
fertility assessment & the effect of
cigarette smoking on cadmium
concentrations in seminal plasma
STUDY POPULATION
- Final population:
Cases: 44 (group II) + 118 (group
III), Age: 35-36 y
Controls: 12 (group I), Age: no
information
- Selected from:
Cases: Group II: patients (of the
infertility clinic) with unexplained
infertility whose semen analysis
revealed normozoospermia; Group
III: “consecutive patients attended
the infertility clinic due to
barenness
- Selection procedure: known
- Lost subjects: no information
Endpoint addressed: toxicity to
reproduction / fertility
- Mean cadmium concentrations 1 (reliable without
in seminal plasma did not differ restriction)
significantly for groups I (fertility key study
proven men), II
(normozoospermic patients), III
(unselected patients)
- There was no significant
correlation between seminal
cadmium concentrations and
conventional semen parameters or
between cadmium concentrations
and the fertility status of the
patients.
- In normozoospermic patients,
seminal plasma cadmium
concentrations were significantly
higher in the group of smokers,
compared with the group of nonsmokers (0.55 ± 0.81 versus 0.42
± 0.67 µg/L)
Keck C,
Bramkamp G,
Behre HM, Müller
C, Jockenhövel F
and Nieschlag E
(1995)
Study type: cohort study
(prospective)
Type of population: general
Subjects: HYPOTHESIS TESTED
(if cohort or case-control study):
Association between element
concentrations and semen
characteristics and sperm motion
parameters.
STUDY PERIOD: no information
- Extremely high within-subject 2 (reliable with
variations were observed for the restrictions)
concentrations of cadmium and
key study
Pb in semen
- No correlation was found
between cadmium concentration
in semen and sperm density
- Positive correlation between
cadmium concentration in semen
and sperm motility (r = 0.53,
Noack-Fuller G,
De Beer C and
Seibert H (1993)
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Method
Results
Remarks
Reference
STUDY POPULATION
- Final population: E: 22 (M); C: 0
- Age: 21 – 50 y
- Selected from: E: occupationally
unexposed volunteers; C: 0
- Selection procedure: no
information
- Lost subjects: no information
Endpoint addressed: toxicity to
reproduction / fertility
p<0.05), linear (r = 0.757,
p<0.001) and curvilinear velocity
(r = 0.643 p<0.002)
Study type: case control study
(prospective)
Type of population: general
Subjects: HYPOTHESIS TESTED
(if cohort or case-control study):
Relationships between the
concentrations of cadmium, Pb, Se
and Zn in blood and seminal
plasma, and sperm quality.
METHOD OF DATA
COLLECTION
- Type: subjects were interviewed
using a questionnaire to obtain
information on occupational
exposure, general health, living
habits, including cigarette smoking
and alcohol drinking and medical
history
STUDY POPULATION
- Final population:
cases: 221 (M), Age: 24-54 y
controls: 38 (M), Age: no
information
- Selected from:
cases: subjects who were
undergoing initial screening for
infertility in the Andrology Clinic
at the Singapore General Hospital
from January 1990 to June 1992
controls: cohort of fertility proven
males (wives had recently
conceived) analysed during same
study period
- Selection procedure: known for
“E”, exclusion of individuals with
significant past medical history,
and/or signs of defective
androgenisation or abnormal
testicular examinations, and
occupational exposure to metals
- Lost cases: no information
Endpoint addressed: toxicity to
reproduction / fertility
- The volume of semen was
1 (reliable without Xu B, Chia SE,
inversely proportional to the
restriction)
Tsakok M and
cadmium concentration in
key study
Ong CN (1993)
seminal plasma (r = -0.29;
p<0.05).
- Cadmium levels in blood had a
significant inverse relationship
with sperm density (r = -0.23,
p<0.05) in oligospermic (sperm
density below 20 million/mL) but
not in normospermic men. There
was a significant reduction in
sperm density in men with blood
cadmium of >1.5µg/L (7.8 ± 7.1
million/mL versus 17.8 ± 4.5
million for men with Cd-B<1 µg
/L).
- No differences were observed in
sperm quality (density, motility,
morphology, volume and
viability) in the cohort when
compared to 38 fertility proven
men.
Cadmium oxide
Study type: case control study
(prospective)
Type of population: occupational
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- no change in testicular
endocrine function (as measured
by serum levels of testosterone,
CHEMICAL SAFETY REPORT
1 (reliable without Mason HJ (1990)
restriction)
key study
99
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Method
cadmium sulphate
Results
CAS number:
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Remarks
Reference
Subjects: HYPOTHESIS TESTED luteinising hormone, and follicle(if cohort or case control study):
stimulating hormone) was
Effects of occupational cadmium
observed in men exposed to
exposure on testicular endocrine
cadmium at levels causing dosefunction
related changes in glomerular and
STUDY POPULATION
tubular function in the same
- Final population:
population.
E: 77 (M), Age: 54 ± 13 y (mean ±
SD)
C: 101 (M), Age: 56 ± 12 y (mean
± SD)
- Selected from:
E: “all male current and ex-workers
who had produced copper-cadmium
alloy for one or more years since
the factory opened in 1926”
C: “from the current or past
workforce of the same company,
hourly paid workers without
occupational exposure to cadmium”
- Selection procedure: known
- Lost subjects: 26
Endpoint addressed: toxicity to
reproduction / fertility
General population (oral route)
In studies conducted by one group of authors, a significant inverse correlation was noted between semen volume
and the concentration of cadmium in seminal plasma (Xu et al., 1993). In their conclusion, they suggested that
cadmium may have a possible adverse effect on the prostate gland, as a significant amount of seminal plasma is
derived from this gland.
However, no clear prostate-specific cadmium accumulation could be demonstrated by Oldereid et al. (1993).
They determined the tissular concentration of cadmium in various reproductive organs removed at necropsy
from men who had died suddenly. The epididymis, and to a lesser extent the simal vesicles, appeared to be more
efficient than both the prostate gland and the testis in their capacity to accumulate cadmium. The age-related rise
in tissue cadmium in the testes and other organs was more apparent after the fourth decade. Amount of cadmium
in the tissues was not influenced by the rural or urban backgrounds or occupations of the subjects.
Xu et al. (1993) reported also a significant reduction in sperm density in men with blood cadmium of > 1.5 µg/L
but no differences were observed in sperm quality in the whole group compared to controls. One group of
authors reported a positive correlation between cadmium concentrations in semen and some parameters of
sperm motility (Noack-Füller et al., 1993). However, to draw some conclusions and assess the clinical relevance
of the modifications in seminal parameters, further studies would be required. Keck et al. (1995) did not find a
correlation between cadmium levels in seminal plasma and semen parameters and fertility in 12 men with
proven fertility and 44 normozoospermic patients as well as 118 unselected patients of an infertility clinic in
Germany.
Overall, the epidemiological evidence of clinically-relevant reproductive effects of cadmium in humans exposed
by the oral route is weak.
Workers (inhalation route)
In male workers exposed to cadmium by inhalation, studies dealing with endocrine and gonadal function found
no effects that may be attributed to cadmium (Mason et al., 1990; Gennart et al., 1992). Fertility was not
significantly different in exposed workers compared to unexposed subjects (Gennart et al., 1992).
Overall, available evidence is insufficient to determine an association between occupational inhalation exposure
to cadmium and effects on fertility or sex organs.
Smokers
In humans, cigarette smoke is an important source of cadmium and various studies have shown that there is no
apparent barrier to prevent cadmium from entering the male reproductive system from the circulation.
Nevertheless, the epidemiological evidence of an association between cadmium exposure through tobacco
smoking and reduction of reproductive function is weak (JRC, 2007).
5.9.2. Developmental toxicity
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5.9.2.1. Non-human information
Several studies have been conducted to assess the effects of cadmium (mainly cadmium chloride and oxide) on
developmental toxicity. A detailed review is available in the EU Risk Assessment Report (RAR) (JRC, 2007).
Selected studies are summarised below and main results are then discussed by route of exposure.
Table 30. Overview of selected experimental studies on developmental toxicity
Method
Results
Remarks
Reference
Rat (Wistar)
oral: gavage
0.04, 0.4, 4 mg Cd/kg bw/d
(nominal conc.)
Exposure: 5 weeks before mating,
during mating and gestation periods:
11 weeks (5 d/wk)
Vehicle: water
A study was conducted to evaluate
the effects of the test material on the
fertility of parental rats and fetal
development / locomotor activity of
offsprings. After 5 wk treatment,
females were mated with untreated
4-month-old males for a maximum
of 3 wk. Administration of Cd was
continued throughout mating and
gestation. Each group was further
divided into 2. Females from the first
subgroup, on Day 21 of gestation,
were sacrificed and subjected to
autopsy. The assessment of fetotoxic
and structural teratogenic effects and
the determination of Cd
concentration in the fetuses were
performed. Female rats from the
other subgroup were allowed to
deliver and feed their progeny. The
number of living and dead pups and
the bodyweight of offspring were
noted. Viability, lactation and
mortality were determined. At 2
months, spontaneous locomotor
activity and locomotor coordination
of movements were assessed
LOAEL (developmental
toxicity): 0.04 mg Cd/kg
bw/d
NOAEL (maternal toxicity):
4 mg/kg bw/d
2 (reliable with
restrictions)
key study
experimental result
Baranski B,
Stetkiewicz I,
Sitarek K and
Szymczak W
(1983)
Rat (Wistar)
oral: gavage
2, 12 and 40 mg Cd/kg bw/d
(nominal conc.)
Vehicle: water
Exposure: GD 7 - 16
A study was conducted to evaluate
the developmental and teratogenic
effects of the test material on rats.
The test material was administered
no NOAEL for maternal or
4 (not assignable)
developmental toxicity
Supporting study
identified (data insufficient
experimental result
for assessment)
(Congenital defects and raised
cadmium levels in tissues at
40 mg Cd/kg bw/d.
Retardation of intra-uterine
development in the other
groups. Cadmium
Cadmium chloride
Baranski B
(1985)5
5 It should be noted that the EU Risk Assessment Report (RAR (JRC, 2007) questions the robustness of the observations in
Baranski 1984 and 1985 in view of: 1) high and unexplained mortality in certain groups, 2) apparent inconsistencies in the
dose-effect relationship in a singme test (e.g. locomotor activity at 0.02 and 0.16 mg/m3), and 3) apparent inconsistencies
in the response between tests (e.g. locomotor activity and rearing).
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Method
Results
in doses of 2, 12 and 40 mg Cd/kg
bw/d by gavage to pregnant rats on
GD 7 - 16. At study end, the fetuses
were examined.
concentration increase not
found in the tissues of the
young so that postnatal
development changes may be
associated with a higher Cd
consumption with the milk of
exposed females or with a
lowered content of iron, zinc
and copper)
Rat (Sprague-Dawley)
oral: drinking water
0, 5, 50 and 100 ppm (nominal
conc.)
Exposure: GD 6 - 20
To examine the effect of cadmium
exposure on maternal and foetal zinc
metabolism, rats were exposed to
cadmium chloride in drinking water
on GD 6 - 20.
CAS number:
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Remarks
Reference
NOAEL (maternal and
developmental toxicity):
5 ppm (= 0.63 mg Cd/kg
bw/d)
LOAEL (maternal and
developmental toxicity):
50 ppm (= 4.7 mg Cd/kg
bw/d)
2 (reliable with
restrictions)
key study
experimental result
Sorell TL and
Graziano JH
(1990)
Mouse (Swiss)
inhalation (whole body)
0, 0.05, 0.5 or 2 mg CdO/m3
(nominal conc.)
Exposure: GD 4 - 17 (6h and 16
min/d; 7 d/wk)
OECD Guideline 414 (Prenatal
Developmental Toxicity Study)
equivalent or similar to EC TM B31
Dir. 87/302/EEC 30/05/88
NOAEL (maternal and
developmental toxicity): 0.05
mg CdO/m³ air
LOAEL (maternal and
developmental toxicity): 0.5
mg CdO/m³ air
1 (reliable without
restriction)
key study
experimental result
Dunnick JK
(1995)
Rat (Sprague-Dawley)
inhalation (whole body)
0, 0.05, 0.5 or 2 mg CdO/m3
(nominal conc.)
Exposure: GD 4 - 19 (6h and 16
min/d; 7 d/wk)
OECD Guideline 414 (Prenatal
Developmental Toxicity Study)
equivalent or similar to EC TM B31
Dir. 87/302/EEC 30/05/88
NOAEL (maternal and
developmental toxicity):
0.5 mg CdO/m³ air
LOAEL (maternal and
developmental toxicity):
2 mg CdO/m³ air
1 (reliable without
restriction)
key study
experimental result
Dunnick JK
(1995)
Rat (Wistar)
inhalation
0.02 and 0.16 mg Cd/m3 air
(nominal conc.)
Exposure: 5 months before mating,
then for a maximum period of 3 wk
of mating and from GD 1 - 20
(5 d/wk; 5 h/d)
A study was conducted to evaluate
the effects of the test material on the
behavioural development of the
NOAEL (developmental
toxicity): 0.02 mg Cd/m³ air
LOAEL (developmental
toxicity): 0.16 mg Cd/m³ air
(reduced viability)
LOAEL (pup behavioural
alterations): 0.02 mg Cd/m3
4 (not assignable)
Supporting study
experimental result
Baranski B
(1984)6
Cadmium oxide
6 It should be noted that the EU Risk Assessment Report (RAR) (JRC, 2007) questions the robustness of the observations in
Baranski 1984 and 1985 in view of: 1) high and unexplained mortality in certain groups, 2) apparent inconsistencies in the
dose-effect relationship in a single test (e.g. locomotor activity at 0.02 and 0.16 mg/m3), and 3) apparent inconsistencies in
the response between tests (e.g. locomotor activity and rearing).
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Method
Results
CAS number:
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Remarks
Reference
progeny in Wistar rats. Groups of
female rats were exposed to the test
material at 0.02 and 0.16 mg Cd/m3
air for 5 months before mating, then
for a maximum period of 3 wk of
mating and from GD 1 - 20.
Rat (Wistar)
NOAEL (developmental
4 (not assignable)
Baranski B (1985)6
inhalation: aerosol
toxicity): 0.02 mg Cd/m³ air Supporting study
0.02, 0.16 and 1 mg Cd/m3 air
LOAEL (developmental
experimental result
(nominal conc.)
toxicity): 0.16 mg Cd/m³ air
Exposure: 5 months before mating
(increased number of foetuses
for the two low concentrations and 4 with retarded development)
months for the high concentration,
then during mating and from GD 1 20 (5 d/wk; 5 h/d)
A study was conducted to evaluate
the effect of the test material on the
development of the progeny in
Wistar rats. Female rats were
exposed to cadmium oxide at 0.02
mg Cd/m3 or 0.16 mg Cd/m3 for 5
h/d and 5 d/wk for a period of 5
months or 1 mg Cd/m3 for 4 months.
The exposure was then continued
during mating and from GD 1 - 20
Oral route
Cadmium compounds have been reported to induce reduced bodyweight and malformations (primarily of the
skeleton) in offspring of animals exposed via gavage or diet at doses that produced maternal toxicity. In some
studies, information on maternal toxicity is lacking, but cross-reading with studies that provide this information
indicates that the reported developmental effects occur at doses levels expected to cause maternal toxicity
(overall > 5 ppm or ca. 0.6 mg CdCl2/kg bw/d) ( Sorell and Graziano, 1990; Baranski, 1985; JRC, 2007).
Neurobehavioral effects or changes in electrophysiological parameters were reported to occur at doses that did
not induce maternal toxicity. The lowest dose reported to generate behavioural changes in pups was 0.04 mg
Cd/kg bw/day (LOAEL) (Baranski et al., 1983). The significance of these changes and underlying mechanisms
for the observed effects on behavioural endpoints are not completely elucidated yet; some authors suggested that
the toxic effects might be mediated by placental toxicity or by interference with the normal foetal metabolism of
zinc and/or copper. Several other mechanisms of action (e.g. neurotransporters or ions channels) were suggested
to explain the neurobehavioral changes in the pups of exposed dams. There is a need for further studies to better
describe the effects of cadmium on the developing brain.
Inhalation route
Decreased foetal weight and a significant increase in retarded ossification frequency were reported in offsprings
of rats and mice exposed to CdO by inhalation at levels that produced maternal toxicity (0.5 and 2 mg CdO/m3
in mouse and rat, respectively) (Dunnick, 1995).
Neurobehavioural changes were reported in young rats from dams exposed to CdO (0.02 mg Cd/m3) in a single
experiment (Baranski, 1984) but observations should be confirmed in an independent study (JRC, 2007).
Taken together, these results indicate a potential for developmental toxicity.
5.9.2.2. Human information
A review of the developmental neurotoxicity effects of cadmium to human has been conducted in the EU Risk
Assessment Report (RAR) (JRC, 2007). Selected exposure studies are summarised by cadmium compound in
the following table, then commented according to the type of population considered (general population or
workers, with smokers considered apart).
Table 31. Overview of selected exposure-related observations developmental toxicity in humans
Method
Results
Remarks
Reference
Cadmium metal
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Method
Results
Study type: cohort study
(prospective)
Type of population: general
HYPOTHESIS TESTED:
Effects of maternal occupational
cadmium exposure on child
development.
STUDY POPULATION
- Final population:
E: 26 children; Age: 6 y.
C: 0
- Selected from:
E: new-born babies, samples of
hair were taken in 1977 in the
Hagenau Maternity”
- Lost subjects: no information
- With the exception of verbal or
3 (not reliable)
memory scores, other scores of the
supporting study
used McCarthy scales correlated
significantly with cadmium hair
levels in mothers
- With regard to cadmium hair levels
in children (at birth), there was a
significant negative correlation with
the perceptual and motor scores
- Decreased mean general cognitive
index in children whose degree of
exposure levels (cadmium hair) falls
above the third quartile
Bonithon-Kopp C,
Huel G, Moreau T
and Wendling R
(1986)
Study type: cohort study
(prospective)
Type of population: general
HYPOTHESIS TESTED: The
effect of low levels of cadmium
on the human placenta and the
consequences on birthweight
STUDY POPULATION
- Final population:
E: 102
C: 0
- Selected from:
E: "attending an obstetrical care
unit"
- A relationship was reported
3 (not reliable)
between a decrease in birth weight
supporting study
(mean ± SD) and an increase of
cadmium (for the first and last
quartiles) in newborn hair, depending
on the presence or absence of
placental calcifications
- Other placental parameters not
significantly related to placental
cadmium concentrations
Fréry N,
Nessmann C,
Girard F et al.
(1993)
Study type: cohort study
(prospective)
Type of population: general
HYPOTHESIS TESTED:
Effects of maternal occupational
cadmium exposure on child
development.
STUDY POPULATION
- Final population:
E: 108 F, Age: 25.4 y. (mean);
105 newborns
C: 0
- Selected from:
E: “110 births that occurred
during the spring of 1978 in
Hagenau Maternity”
- A correlation was observed between 3 (not reliable)
cadmium-hair of mother and infant
supporting study
- Higher levels of cadmium were
found in infant's hair of hypertensive
mothers compared to the infants of
normotensive mothers. Authors
attributed this to a preferential
accumulation in the infants of
hypertensive mothers
Huel G, Boudene
C and Ibrahim MA
(1981)
Study type: case control study
(prospective)
Type of population: general
HYPOTHESIS TESTED:
Influence of lead and cadmium
on human reproductive outcome
- Lower number of women with three 3 (not reliable)
or more pregnancies and deliveries at supporting study
full term in the exposed group
compared to the control group
- Correlation between cadmium
levels and number of preterm labours
Laudanski T,
Sipowicz M,
Modzelewski P,
Bolinski J and
Szamatowicz J
(1991)
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Reference
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Method
cadmium sulphate
Results
CAS number:
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Remarks
Reference
STUDY POPULATION
(r=0.17, p<0.05)
- Final population:
E: 136 (F), Age: 20 - >80 y
C: 264 (F), Age: 20 - 79 y
-Selected from: “405 of the total
of 814 women aged 17-75 y.
and living in the rural area of
Suwalki”
E: “136 came from villages
where the soil…has
approximately twice the normal
content of lead and
cadmium…”
C: “nearby villages with no
increased soil content”
Study type: case control study - No association was detected
3 (not reliable)
(prospective)
between placental cadmium and birth supporting study
Type of population: general
weight or gestational age at delivery
HYPOTHESIS TESTED (if
cohort or case control study):
The accumulation of tobaccoderived cadmium in the
placenta is responsible for the
adverse effect of cigarette
smoking on infant birthweight
-Final population:
E: 136 (F); Age: 20 - >80 y.
C: 264 (F); Age: 20 – 79 Y.
-Selected from: “405 of the total
of 814 women aged 17-75 y.
and living in the rural area of
Suwalki”
E: “136 came from villages
where the soil…has
approximately twice the normal
content of lead and
cadmium…”
C: “nearby villages with no
increased soil content”
-Selection procedure: partially
known (positive response to a
written invitation)
-Lost subjects: no information
-Final population:
E: 106 (F only); Age (mean ±
SD, years): 26.8 ± 5.0
C: 55 (F only); Age (mean ±
SD): 27.0 ± 4.8
- Selected from: E and C:”1502
women from areas in and
around the Yugoslavian cities of
T.Mitrovica and Pristina,
attending a single-out patient
clinic, who were in
approximately 12 to 20 weeks
of gestation, during the period
from May 1985 through
December 1986”
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Graziano JH,
Kline JK et al.
(1992)
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Results
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Remarks
Reference
- Selection procedure: known
-Lost subjects: 1341
Endpoint addressed: dev
toxicity / teratogenicity
Study type: case control study - Cadmium-hair values for both
2 (reliable with
Huel G, Everson
(prospective)
mothers and newborns were twice as restrictions)
RB and Menger I
Type of population:
high as the values for the matched
key study
(1984)
occupational
controls, suggesting that women
HYPOTHESIS TESTED:
whose occupations involved heavy
Effects of maternal occupational metals passed substantially more
cadmium exposure on child
cadmium to their offspring than
development.
controls.
STUDY POPULATION
- A non-significant decrease in birth
- Final population:
weight of exposed newborns was
E: 26 (F), Age: no information observed (250 g less when compared
C: 26 (F), Age: no information to controls)
- Selected from:
- No other adverse effects (by the
E: “women whose occupations clinical parameters measured)
involved heavy metals, seeking documented in newborns
obstetrical care at the Hagenau
Maternal Hospital”
C: “unexposed women who
delivered at the (same) hospital”
- Lost cases: 53/105
General population (oral route)
Several studies addressing developmental effects in humans exposed to cadmium via the oral route were located
(Bonithon-Kopp et al., 1986; Fréry et al., 1993; Huel et al., 1981; Laudanski et al., 1991; Loiacono et al., 1992).
However, study populations were mostly exposed to different pollutants and no study specifically addressed the
effects of an environmental exposure to cadmium. Moreover, several of these studies are of limited value for
hazard assessment due to significant drawbacks, i.e. in the definition of the study endpoints, selection of
population and assessment of exposure.
Decreased birth weight (or small-for-date) was reported in the studies of Huel et al., 1981 and Fréry et al., 1993,
related to concentration of cadmium in infant’s hair, which is however not a robust estimate of exposure. No
other major morphologic alterations of the placenta were evidenced in the studies that could explain an adverse
effect on the foetus (possibly due to the relatively low levels of cadmium compared to other studies and
experimental systems).
Overall, the epidemiological evidence for a developmental effect (on birth weight, malformations,
neurobehavioral performances) of cadmium compounds in the general population mainly exposed by the oral
route appears weak.
Workers (inhalation route)
One study was located regarding developmental effects in humans after inhalation exposure to cadmium (Huel
et al., 1984). A non-significant decrease in birth weight was found in offspring of women with some
occupational exposure to cadmium in France; however, no adverse effects were documented in these newborns.
The authors used hair samples to estimate exposure and this method is limited without controls to distinguish
between exogenous and endogenous sources.
Smokers
It is well-known that babies of mothers who are cigarette smokers are smaller at birth than those of non-smokers
and that smoking increases the uptake of cadmium. Some authors have suggested that in pregnant smokers, a
cadmium-zinc interaction takes place in the maternal-foetal-placental unit and results in zinc deficiency in the
foetus. A trapping of the zinc in the placenta would result in less zinc in the foetus’s red blood cells and
theoretically less zinc to grow (JRC, 2007).
The weight of evidence to attribute these developmental effects to cadmium from tobacco smoke is insufficient.
5.9.3. Summary and discussion of reproductive toxicity
Effects on fertility and sex organs have been noted in experimental studies at high doses of cadmium which
generally caused other manifestations of toxicity (e.g. changes in body or organ weights and/or lethality). The
lowest NOAELs correspond to 1 mg Cd/kg bw/d via the oral route and ca. 0.23 mg Cd/ m³ after inhalatory
exposure. Only a few publications on the effects on human fertility were found. Overall, epidemiological
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evidence does not speak for an association between exposure to cadmium and relevant effects on fertility or sex
organs.
In studies with mouse and rat, effects on development were observed after oral and inhalatory exposure to
cadmium compounds. Neurobehavioural changes were reported in the absence of maternal toxicity but the
robustness of these observations was not sufficient to derive an appropriate NOAEL. It is suggested that further
studies are needed to better document the possible effects of cadmium on the developing brain (JRC, 2007). No
clear evidence indicates that cadmium has adverse effects on the development of offprings from women exposed
indirectly via the environment or occupationally. Effects on birth weight, motor and perceptual abilities of
offsprings have been reported by some authors. However, these studies suffer from drawbacks either in the
definition of the study postulation, the definition of the effects, or in the assessment of exposure. Moreover, it is
not clear whether the effects on psychomotor development were related to cadmium or to a simultaneous
exposure to other substances such as lead. This aspect is not considered to have received enough attention in
humans and follow-up with a well designed epidemiology study has been proposed (JRC, 2007).
Water-soluble cadmium chloride and sulphate are currently classified as Repr. Cat. 2; R60-61 (May impair
fertility, may cause damage to unborn child) in Annex I of Directive 67/548 (the corresponding GHS-CLP
classification would be Reproduction category 1B; H360). By analogy, a similar classification for cadmium
nitrate could be considered.
Slightly soluble cadmium metal and oxide have been granted the classification Repr. Cat. 3; R62-63 (Possible
risk of impaired fertility, possible harm to unborn child) in Annex I of Directive 67/548 (the corresponding
GHS-CLP classification would be Reproduction category 2; H361). Other cadmium compounds in this
solubility class (e.g. cadmium hydroxide and carbonate) may warrant this classification as well.
Apart from cadmium sulphide, none of the insoluble cadmium compounds (e.g. cadmium sulfoselenide,
cadmium zinc sulphide or cadmium telluride), not expected to penetrate easily into the organisms, are classified
for reproductive toxicity. Cadmium sulphide is an exception. As there is no data to support its Repr. Cat. 3;
R62-63 classification, a revision of the classification may be appropriate based on solubility properties.
5.10. Other effects
5.10.1. Non-human information
5.10.1.1. Neurotoxicity
In rats, cadmium carbonate has been reported to produce tremors from exposure to 132 mg Cd/m3 for 2 h, and
cadmium fumes produced reduced activity at 112 mg Cd/m3 for 2 h (Rusch et al., 1986). Studies on continuous
exposure to cadmium for 30 d have shown no neurological effects at 0.105 mg Cd/m3 for cadmium chloride,
0.098 mg Cd/m3 for cadmium dusts or 1.034 mg Cd/m3 for cadmium sulphide (Glaser et al., 1986). Cadmium
chloride had no neurological effects at 0.33 mg Cd/m3 for 5 d/wk, 6 h/d for a total of 62 daily exposures, but did
significantly increase relative brain weight at 1.034 mg Cd/m3 (Kutzman et al., 1986). No other studies were
located regarding neurological effects in adult animals after inhalation exposure to cadmium.
5.10.1.2. Immunotoxicity
An effect of cadmium on the immune function has been reported in mice exposed to 0.190 mg Cd/m 3 (as
cadmium chloride, 2 h) which showed suppression of the primary humoral immune response (Graham et al.,
1978). The NOAEL for immunological effects from this study was 0.11 mg Cd/m 3 (ATSDR, 2008).
Krzystyniak et al. (1987) observed a reduction in spleen lymphocyte viability and humoral response at 0.88 mg
Cd/m3 in mice exposed to cadmium chloride for 60 minutes.
Prigge (1978) also observed increased relative spleen weights in pregnant females at 0.394 mg Cd/m3 for an
exposure of 24 h/d for 21 d during gestation. Oldiges and Glaser (1986) noted enlarged thoracic lymph nodes in
dead animals in a chronic-exposure study with cadmium sulphate at 0.092 mg Cd/m3 for 22 h/d, 7 d/wk for
413–455 d and in an intermediate study with cadmium oxide dust at 0.090 mg Cd/m3 for 22 h/d, 7 d/wk for
218 d.
However, other studies have found no effect on natural killer cell activity or viral induction of interferon in mice
(Daniels et al., 1987). Evidence concerning the effect of inhalation exposure to cadmium on resistance to
infection is conflicting, because the same exposure decreases resistance to bacterial infection while increasing
resistance to viral infection (Bouley et al., 1982).
5.10.1.3. Specific investigations: other studies
There are no other relevant specific investigations.
5.10.2. Human information
Neurotoxicity
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A few studies have reported an association between environmental cadmium exposure and neuropsychological
functioning. These studies used hair cadmium as an index of exposure. Endpoints that were affected included
verbal IQ in rural Maryland children (Thatcher et al., 1982), acting-out and distractibility in rural Wyoming
children (Marlowe et al., 1985) and disruptive behavior in Navy recruits (Struempler et al., 1985). The
usefulness of the data from these studies is limited because of the potential confounding effects of lead
exposure, lack of control for other possible confounders (including home environment, caregiving and parental
IQ levels) and an inadequate quantification of cadmium exposure.
Neurotoxicity is not generally associated with inhalation exposure to cadmium, although a few studies have
specifically looked for neurological effects. Hart et al. (1989) reported that in a group of 31 men occupationally
exposed to cadmium in a refrigerator coil manufacturing plant (average exposure = 14.5 years) there was a
modest correlation between cadmium exposure and decreased performance on neuropsychological tests for
attention, psychomotor speed and memory. The limited number of men studied makes it difficult to evaluate the
significance of this effect.
Rose et al. (1992) studied the presence and severity of olfactory impairment in 55 workers chronically exposed
to cadmium fumes generated during a brazing operation. A significant olfactory impairment was observed in the
workers compared to the reference group. The workers with both higher urinary cadmium levels and tubular
proteinuria had the most significant olfactory dysfunction, with a selective defect in odor threshold. The results
suggest that chronic occupational cadmium exposure sufficient to cause renal damage is also associated with
impairment in olfactory function. Some limitations of the study are that historical exposure to other confounders
cannot be ruled out, the classification for nephrotoxicity is based on a single 24 h urine β2-microglobulin level
and the smoking history of the reference group was unknown.
No other human neurological studies from inhaled cadmium were found.
Immunotoxicity
There is limited evidence for immunological effects following inhalation exposure to cadmium. The blood of
workers exposed to cadmium for 1–14 years had a slight but statistically significant decrease in the generation
of reactive oxygen species by leukocytes compared to unexposed controls (Guillard and Lauwerys, 1989). The
toxicological significance of this effect is unclear.
Karakaya et al. (1994) measured blood and urine concentrations of cadmium and serum IgG, IgM and IgA in a
group of 37 males employed in zinc-cadmium smelters and a small cadmium-electroplating plant. Blood
cadmium concentrations were significantly higher in exposed workers compared to controls in both urine and
blood. No differences between the exposed and control serum concentrations of IgG, IgM and IgA populations
were observed. No changes in blood counts of white blood cells (lymphocyte, neutrophil and eosinophil) were
found between exposed and control populations, except for significantly increased monocyte counts.
No other studies were located regarding immunological effects in humans following inhalation exposure to
cadmium.
5.10.3. Summary and discussion of specific investigations
Evidence from experimental systems indicates a potential neurotoxic hazard for cadmium in adult rats. In
humans, heavy occupational exposure to cadmium dust has been associated with olfactory impairment and
studies performed on a limited number of occupationally-exposed subjects are suggestive of an effect of
cadmium on the peripheral and central nervous system but these findings should be confirmed by independent
investigators before firm conclusions can be drawn. In the young age, there is some evidence that cadmium
exposure may affect the developing brain. This aspect warrants further attention (JRC, 2007).
There are some indications of immunotoxicity in animal studies and limited evidence for immunological effects
following inhalation exposure to cadmium in humans. The toxicological significance of these effects is unclear.
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5.11. Derivation of DNEL(s) / DMEL(s)
5.11.1. Overview of typical dose descriptors for all endpoints
The following section summarises available dose descriptors for cadmium metal and cadmium compounds by
solubility classes. Separate tables are presented for the water-soluble cadmium nitrate, chloride and sulphate
and the slightly soluble cadmium hydroxide, oxide, metal and carbonate. Practically no data is available for the
insoluble cadmium sulphide, therefore no dose descriptor summary is given. Based on its low bioavailability,
this subtance is expected to present lower toxicity than the more soluble forms of cadmium.
Table 32. Available dose-descriptor(s) per endpoint for water-soluble cadmium compounds (cadmium
nitrate, chloride and sulphate)
Endpoint
Acute toxicity
Quantitative dose descriptor
(appropriate unit) or qualitative
assessment7, 8
Local
Systemic
Sensitization
Acute LD50 studies
(mouse and rat);
qualify for
classification as T;
R25 / Acute toxicity
(oral) Category 2 or 3
-
NA
LD50 =
29 - 327
mg Cd/kg bw
Mortality; lesions
of the proximal
section of the
intestinal tract
dermal
NA
NA
inhalation
NA
0.8 < 4h LC50 ≤
66 x 10-3 mg Cd/L
Not expected to
be an issue for
human health
Mortality;
pulmonary lesions
skin
eye
respiratory tract
skin
-
NA
-
NA
oral
NA
dermal
NA
NOAEL = 0.12 - 3
mg/kg Cd bw/day
-
inhalation
NA
respiratory tract
Repeated dose
toxicity (subacute / subchronic /
chronic)
Remarks
on study
oral
Inhalation of 1 mg
Cd/m3 immediately
dangerous to life;
8h inhalation of
5 mg Cd/m3 lethal
Irritation /
corrosivity
Associated
relevant effect
NOAEL =
0.013 - 0.022 x 10-3
mg Cd/L
Toxicity;
mortality
Not expected to
be an issue for
human health
Not expected to
be an issue for
human health
Effects in kidney
and bone
Not expected to
be an issue for
human health
Effects in lung,
kidney and bone
Acute LC50 studies
(various species);
qualify for
classification as T+;
R26 / Acute toxicity
(inhalation) Category
1
Observations in
humans
-
-
Repeated-dose
toxicity studies in rat,
hamster and monkey;
qualify for
classification as T,
R48/23/25 / STOT
Category 1
7 Pooled results from studies conducted on one or several forms of cadmium
8 A large proportion of the inhalation data comes from studies with cadmium oxide. Cadmium oxide is considered to be
‘slightly’ and not ‘highly’ soluble but data was used to read-across to the highly soluble forms for classification and labelling
purposes.
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Endpoint
Mutagenicity
Carcinogenicity
Reproductive
toxicity
(fertility
impairment)
Reproductive
toxicity
(developmental
tox.)
Quantitative dose descriptor
(appropriate unit) or qualitative
assessment9
Local
Systemic
in vitro
-
-
in vivo
-
-
oral
-
-
dermal
-
-
inhalation
-
-
oral
NA
NOAEL =
1 mg Cd/kg bw/d
dermal
NA
-
inhalation
NA
-
oral
NA
-
dermal
NA
-
inhalation
NA
-
CAS number:
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Associated
relevant effect
Conflicting
results: negative
in bacterial
systems, positive
in some
mammalian cell
systems
Conflicting
results; negative
in certain studies,
positive in others
Evidence for
potential
carcinogenicity in
animals (rat) and
general
population
Not expected to
be an issue for
human health
Evidence of
carcinogenicity
(lung) in rat and
workers
Effects on male
and female
reproductive
parameters
Not expected to
be an issue for
human health
No inhalation
studies available
Evidence of
potential
developmental
effects in rat;
considered to
require follow-up
Not expected to
be an issue for
human health
Evidence of
potential
developmental
effects in rat;
considered to
require follow-up
Remarks
on study
In vitro and in vivo
mutagenicity cannot
be excluded; possible
threshold for
mutagenic effects;
considered to qualify
for classification as
Muta. Cat. 2: R46 /
Mutagenic Category
1B
Animal
carcinogenicity and
human epidemiology
studies; considered to
qualify for
classification as
suspected human
carcinogens (lung
cancer); attributed
classification as Carc.
Cat. 2; R45
(irrespective of
route) / Carcinogenic
Category 1B
Oral: one generation
fertility/developmental
test in rat;
developmental
toxicity studies in rat;
considered to qualify
for classification as
Repr. Cat 2: R60-61 /
Reproduction
Category 1B
9 Pooled results from studies conducted on one or several forms of cadmium.
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Table 33. Available dose-descriptor(s) per endpoint for slightly soluble cadmium compounds (i.e.
cadmium metal, oxide, hydroxide and carbonate)
Endpoint
Acute toxicity
Quantitative dose descriptor
(appropriate unit) or
qualitative assessment10
Local
Systemic
oral
NA
dermal
NA
inhalation
NA
LD50 = 63 2,330
mg Cd/kg bw
NA
0.8 < 4h LC50 ≤
66 x 10-3 mg
Cd/L
Inhalation of 1
mg Cd/m3
immediately
dangerous to life;
8h inhalation of
5 mg Cd/m3
lethal
Irritation /
corrosivity
Sensitization
skin
eye
respiratory tract
skin
respiratory tract
Repeated dose
toxicity (subacute / subchronic /
chronic)
Mutagenicity
oral
-
NA
-
NA
NA
NOAEL = 0.12 3 mg/kg Cd
bw/day11
-
dermal
NA
inhalation
NA
in vitro
-
NOAEL =
0.013 - 0.022 x
10-3 mg Cd/L
-
in vivo
-
-
Associated
relevant effect
Mortality
Not expected to be
an issue for human
health
Mortality;
pulmonary lesions
Toxicity; mortality
Not expected to be
an issue for human
health
Not expected to be
an issue for human
health
Effects in kidney
and bone
Remarks
on study
Acute LD50 study
(rat); no classification
Acute LC50 studies
(various species);
qualify for
classification as T+;
R26 / Acute toxicity
(inhalation)
Category 1
Observations in
humans
-
-
Not expected to be
an issue for human
health
Effects in lung,
kidney and bone
Repeated-dose
toxicity studies in rat,
hamster and monkey;
qualify for
classification as T,
R48/23/25 / STOT
Category 1
Conflicting results:
negative in
bacterial systems,
positive in some
mammalian cell
systems
Conflicting results;
negative in certain
studies, positive in
others
In vitro and in vivo
mutagenicity cannot
be excluded; possible
threshold for
mutagenic effects;
considered to qualify
for classification as
Muta. Cat. 3: R68 /
Mutagenic Category
2
10 Results from studies conducted on one or several forms of cadmium.
11 Read across from studies with cadmium chloride.
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Endpoint
Carcinogenicity
Reproductive
toxicity
(fertility
impairment)
Reproductive
toxicity
(developmental
tox.)
CAS number:
10124-36-4
Quantitative dose descriptor
(appropriate unit) or
qualitative assessment10
Local
Systemic
oral
-
-
dermal
-
-
inhalation
-
-
oral
NA
-
dermal
NA
-
inhalation
NA
oral
NA
NOAEL =
0.25 mg CdO/m3
,
ca. 0.23 mg
Cd/m3
-
dermal
NA
-
inhalation
NA
-
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Associated
relevant effect
Remarks
on study
Evidence for
potential
carcinogenicity in
animals (rat) and
general population
Not expected to be
an issue for human
health
Evidence of
carcinogenicity
(lung) in rat and
workers
Animal
carcinogenicity and
human epidemiology
studies; considered to
qualify for
classification as
supected human
carcinogens (lung
cancer); attributed
classification as Carc.
Cat. 2; R45
(irrespective of
route) / Carcinogenic
Category 1B
No oral toxicity
studies available
Not expected to be
an issue for human
health
Effects on number
of spermatids in
male rats
Evidence of
potential
developmental
effects in rat;
considered to
require follow-up
Not expected to be
an issue for human
health
Evidence of
potential
developmental
effects in rat;
considered to
require follow-up
CHEMICAL SAFETY REPORT
Inhalation: 13 week
inhalation study in
rat/ developmental
toxicity studies in rat;
considered to qualify
for classification as
Repr. Cat 2: R62-63 /
Reproduction
Category 2
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5.11.2. Correction of dose descriptors if needed (for example route-to-route
extrapolation), application of assessment factors and derivation of the endpoint specific
DN(M)EL
As presented in Section 5.1, uptake of cadmium can occur in humans via the inhalation of polluted air, the
ingestion of contaminated food or drinking water and, to a minor extent, through exposure of the skin to dusts or
liquids contaminated by the element. The critical routes of exposure are considered to be inhalation in
occupational settings and ingestion for the general population. Tobacco is an important additional source of
cadmium uptake in smokers.
On this basis, DNELS were derived for both workers and general populations. Long-term exposure was
considered, in accordance with Section R.8.1.2.5 of the ‘REACH guidance on information requirements and
chemical safety assessment, Chapter R.8’.
In general, the water soluble cadmium compounds show more toxicity due to their higher bioavailability. Where
possible, dose descriptors for these forms are therefore used for calculating DNELS. Much of the inhalation data
is however derived from CdO, so that data for that compound forms the basis for the inhalatory DNEL
extrapolations.
Workers
In worker populations exposed via inhalation, a statistically significant increase in mortality from lung cancer
was reported in early studies, but this has not been supported in later work. More recent analyses suggest that, in
occupational settings, measures protecting against renal/respiratory effects should also be protective of lung
cancer (see Section 5.8.2). SCOEL (2009) recommends an Occupational Exposure Level (OEL) equivalent to
4 µg Cd/m3 (respirable fraction) as protective against long-term local effects (respiratory effects, including lung
cancer). This is based on human data that shows changes in residual volume of the lung for a cumulative
exposure to CdO fumes of 500 µg Cd/m3 x years, corresponding to 40 years exposure to 12.5 µg Cd/m3
(LOAEL) (Cortona et al., 1992). Applying an uncertainty factor of 3 (LOAEL to NOAEL) leads to a value of
4 µg/m3.
Using this OEL value as a starting point and applying the default assessment factors proposed in Table R.8-6 of
the ‘REACH guidance on information requirements and chemical safety assessment, Chapter R.8’ yields the
following results:
Table 34. Derivation of cadmium DNEL biomonitoring for workers
Starting point
Value
4 µg Cd/m3
Assessment factor
Comment
OEL calculated based on critical levels producing
lung effects in worker populations
Interspecies difference
Intraspecies variation
Exposure duration
Dose-response
Quality of whole database
1
1
1
1
1
DNEL workers, biomonitoring
4 µg Cd/m3
All assessments factors are equivalent to 1 as actual biomonitoring data was used to derive the OEL, which
already integrates inter-individual variation. The proposed DNEL workers, biomonitoring is therefore equivalent to
4 µg Cd/m3.
Protection of workers based on this proposed DNEL is recommended to be done according to the
Eurometaux/ICdA medical supervision guidance (2006), complementary to all risk reductions measures
already in place. This management scheme has been derived from Swedish regulations and the medical part is
very similar to the official Guidelines for Occupational Medical examinations of the German Social Accident
Insurance. Nowadays it is applied throughout the cadmium-related industry in Europe.
The scheme integrates exposure through all possible routes by assessing the Cd-body burden and early
biological indicators (BI’s) of sub-clinical effect. It ensures that the risk to Cd-exposed workers is controlled.
The medical supervision system is based on measurement of:

Markers for integrated exposure: Cd-urine (Cd-U; indicator of life-long exposure) and Cd-blood (CdB; indicator of present-day or recent exposure)

Early biological indicators of renal dysfunction
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It is designed to be applied in a progressive way, as follows (see also Figure below):

Cd-U ≤ 2 µg Cd/g creatinine, a conservative threshold based on general population studies, as
described in Section 5.6.2 (green zone): general medical follow-up (complementary indicator: Cd-B <
5 µg Cd/L)

2 < Cd-U ≤ 5 µg Cd /g creatinine, a threshold based on studies at the workplace, as described in
Section 5.6.2 (orange zone): biological indicators (BI’s) of early renal dysfunction are being measured
on a regular basis (e.g. beta-2 microglobuline (B2-M) or retinol-binding protein (RBP); complementary
analysis: Cd-B).

If the BI’s remain stable and below the reference value (300 µg/g creatinine, the generally applied
standard for evaluating renal tubular function), the worker is kept at the workplace, and the reason for
the increased exposure is determined (e.g. due to current or previous exposure, due to personal hygiene
behavior), followed by additional hygiene measures, if appropriate.

If the BI’s are exceeding the reference values or showing a consistent pattern of increase, which may
lead to approaching the reference values, the worker is removed from cadmium exposure.

Cd-U > 5 µg Cd/g creatinine (red zone): worker is removed from exposure.
Figure 4. Illustration of Eurometaux/ICdA medical supervision guidance (2006)
(BI: biological indicators; C: creatinine)
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General population
Given the wealth of available animal and human data, the calculation of DNELs for general population can be
done using different approaches. In the following section, DNELs are derived based on the results of 1) longterm animal testing and 2) monitoring data. The resulting values are then compared and discussed.
DNEL general population derived from animal data
As there is currently no conclusive evidence from human studies that cadmium acts as a carcinogen following
oral exposure, DNELs for the general population can be calculated based on data from repeated-dose toxicity
studies in animals. The lowest oral NOAEL presented in Section 5.11.1 corresponds to 0.12 mg Cd/kg bw/day
from a 9 year study in monkey (Masoaka et al., 1994). Using this value as a starting point and applying the
default assessment factors proposed in Table R.8-6 of the ‘REACH guidance on information requirements and
chemical safety assessment, Chapter R.8’ yields the following results:
Table 35. Derivation of cadmium DNEL general population based on animal data
Starting point
Value
0.12 mg/kg bw/day
Assessment factor
2
DNEL general population
2.5
10
1
1
1
0.0024 mg Cd/kg bw/day
Comment
NOAEL from a 9 year repeated dose oral toxicity
study in monkey
Interspecies difference, allometric scaling monkey
- human
Interspecies difference - remaining differences
Intraspecies variation, general population
Exposure duration (9 years; chronic)
Dose-response
Quality of whole database
The resulting DNEL general population is therefore equivalent to 0.0024 mg (2.4 µg) Cd/kg bw/day.
DNEL general population derived from general population monitoring
As discussed in Section 5.6.2, data from several large general population studies indicate that early renal effects
(urinary excretion of low molecular weight proteins, occuring before the onset of overt clinical manifestations of
kidney disease) can be detected in the general population for Cd-U around 2 μg Cd/g creatinine. In the Belgian
Cadmibel study (Buchet et al., 1990), a urinary excretion of 2 µg/24 h (i.e. roughly 2 µg/g creatinine according
to SCOEL, 2009) is estimated to correspond to a mean renal cortex concentration of 50 ppm (wet weight),
which in non-smokers would be reached after 50 years of oral ingestion of approximately 1 µg Cd/kg bw/day.
This value of 1 µg Cd/kg bw/day can be used as the starting point for estimation of the DNEL general population. As
above, applying the default assessment factors proposed in Table R.8-6 of the ‘REACH guidance on information
requirements and chemical safety assessment, Chapter R.8’ yields the following results:
Table 36. Derivation of cadmium DNEL general population based on general population monitoring data
Starting point
Assessment factor
DNEL general population
Value
1 µg Cd/kg bw/day
(i.e. 2 µg Cd/g creatinine)
1
1
1
1
1
1
1 µg Cd/kg bw/day
(i.e. 2 µg Cd/g creatinine)
Comment
Estimated lifetime oral ingestion from general
population studies
Interspecies difference
Interspecies difference - remaining differences
Intraspecies variation
Exposure duration
Dose-response
Quality of whole database
All assessments factors are equivalent to 1 as actual biomonitoring data was used to derive the starting point,
which already integrates inter-individual variation and accounts for lifetime exposure.The resulting
DNEL general population is therefore equivalent to 1 µg Cd/kg bw/day (i.e. ca. 2 µg Cd/g creatinine).
Discussion
The DNELgeneral population derived using either animal or human monitoring data are in good accordance (i.e. 2.4
and 1 µg Cd/kg bw/day, respectively), with the second approach yielding a slightly lower value. As a
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comparison, the WHO calculate that, in order that levels of cadmium do not exceed 50 µg/g in renal cortex,
assuming an absorption rate of 5% and a daily excretion of 0.005% of body burden, total intake should not
exceed about 1 µg/kg bw/day continuously for 50 years (WHO, 1987).
6. HUMAN HEALTH HAZARD ASSESSMENT OF
PHYSICO-CHEMICAL PROPERTIES
6.1. Explosivity
Data waiving: see CSR section 1.3 Physico-chemical properties.
Classification according to GHS
Name: cadmium sulphate
Related composition: cadmium sulphate
State/form of the substance: liquid
Reason for no classification: conclusive but not sufficient for classification
Classification according to DSD / DPD
6.2. Flammability
Data waiving: see CSR section 1.3 Physico-chemical properties.
Data waiving: see CSR section 1.3 Physico-chemical properties.
Classification according to GHS
Name: cadmium sulphate
Related composition: cadmium sulphate
State/form of the substance: liquid
Reason for no classification (Flammable gases): conclusive but not sufficient for classification
Reason for no classification (Flammable aerosols): conclusive but not sufficient for classification
Reason for no classification (Flammable liquids): conclusive but not sufficient for classification
Reason for no classification (Flammable solids): conclusive but not sufficient for classification
6.3. Oxidising potential
Data waiving: see CSR section 1.3 Physico-chemical properties.
Classification according to GHS
Name: cadmium sulphate
Related composition: cadmium sulphate
State/form of the substance: liquid
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Reason for no classification (Oxidising gases): conclusive but not sufficient for classification
Reason for no classification (Oxidising liquids): conclusive but not sufficient for classification
Reason for no classification (Oxidising solids): conclusive but not sufficient for classification
7. ENVIRONMENTAL HAZARD ASSESSMENT
General considerations
Cadmium and cadmium compounds form a “data rich” substance group: a vast volume of information is
available on the effect of cadmium on the different ecotoxicity endpoints in the open scientific literature. This
vast volume of ecotoxicological information was carefully scrutinised by the Rapporteur (Belgium) in the
framework of the discussions on the EU risk assessment report (RAR) made under EU Regulation 793/93/EEC.
In that process, the Rapporteur’s analysis of the available ecotoxicity data was extensively discussed by the
experts from member states and other stakeholders during the meetings of the “Technical committee on new and
existing substances” (TCNES), where the data sets to be used for setting ecotoxicity reference values for
classification and for PNEC derivation were officially approved.
For this reason, we will use the data used in the RAR as the main data source for the environmental hazard
assessment. We will not come back to the decisions on data quality and relevancy that were approved by
TCNES, but use the data as they were qualified and used in the RA process. Consequently, we will use for the
current analysis the data that were considered useful in the RAR as such. Likewise, we will not use the data that
were found not useful in the RA process for the current analysis. Given the vast amount of data, we have only
reported the useful data in the IUCLID V file; the data not considered useful in the RA process have been
summarised in the RAR (ECB 2008).
For some endpoints, the extensive datasets from the RAR will be updated with significant and reliable
information that became available after the closure of the RA databases. These data are also reported under
IUCLID V and used for the present hazard assessments.
There are two exceptions to this general approach:
1) Setting of the PNEC for marine waters. In the RAR, no analysis was made for Cd toxicity to aquatic
marine organisms. Therefore a detailed literature search was made for marine ecotoxicity data on
cadmium, the information was scrutinised for quality and relevancy, and a PNEC for Cd in marine
waters was subsequently derived.
2) Setting of a PNEC for Cd in marine sediments, which was not done in the RAR either. For this
endpoint also, a detailed literature search was made for ecotoxicity data on the effect of cadmium in
marine sediments. The information was scrutinised for quality and relevancy, and a PNEC for Cd in
marine sediments was subsequently derived.
In the RAR, the datasets on freshwater ecotoxicity have resulted in derivation of a hardness-related
PNEC, that has been used afterwards for setting the water quality standard for Cd in EU waters
(according to directive 2008/105/EC). Considering on one hand that the PNEC was defined in the risk
assessment based on an extensive database covering a broad spectrum of taxonomic groups and, on the
other hand, that the EQS have been confirmed in EU legislation, we have not further updated the
aquatic database from the risk assessment.
In accordance to the scientific approach followed in the EU RA process, two assumptions are the key to the
cadmium environmental hazard assessment:
1) The basic assumption made in this hazard assessment and throughout this CSR is that the ecotoxicity of
cadmium and cadmium compounds is due to the Cd ++ ion. Consequently, all aquatic and terrestrial
toxicity data in this report are expressed as “cadmium”, not as the different cadmium compounds that
were used for the testing, because ionic cadmium is considered to be the causative factor for toxicity.
Hence, all ecotoxicity data obtained on different (soluble) cadmium compounds are mutually relevant
for each other. For that reason, the considered ecotoxicity data related to cadmium and the different
cadmium compounds are combined before calculating the PNECs. The only way cadmium compounds
can differ in this respect is in their capacity to release cadmium ions into (environmental) solution. That
capacity is checked eventually in the transformation/dissolution tests and may result in different
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classifications. But in principle, this section 7 of the CSR is the same for all soluble cadmium
substances.
2) Cadmium is a natural component of the earth’s crust and present in natural background concentration
in all environmental compartments. The natural cadmium background is rather low. To avoid
acclimation to elevated Cd levels prior to testing, only test results obtained under Cd-background in
test and/or nutrient solution were used e.g. for aquatic toxicity tests, only tests performed at Cd
Background <1µg Cd/l were used according to the RAR. The Cd-background was not further
considered in the derivation of the PNECs, except in the case of the sediments. Hence, most of the
PNECs are “total” PNECs, integrating the full concentration of cadmium, of both natural and
anthropogenic origin combined. Exception are the sediment PNECs, which are “added” PNECs, i.e. the
background concentration in sediment needs to be considered in the assessment.
7.1. Aquatic compartment (including sediment)
7.1.1. Toxicity test results
1. Aquatic toxicity: freshwater, short-term
Acute data- establishing the dataset
Numerous data are available on acute toxicity of cadmium to aquatic organisms. The quality and relevancy of
the unique data is of great importance because, in contrast to the PNEC derivation (where all the chronic data
are used in a species sensitivity distribution), one single value defines the ecotoxicity reference value for
classification. Therefore, for setting the reference value for acute aquatic toxicity (and classification), only data
from standardised test protocols and standardized test organisms were considered in the analysis.
The RAR made an in-depth analysis of the reliability of the acute toxicity data and assigned a “reliability index”
(RI) to each data point. For setting the reference value for acute aquatic ecotoxicity, only the results qualified as
RI 1 (standard tests) were used, complemented for the fish and invertebrates with RI 2 qualified data (not
standard test but from a similar protocol and with a complete background information on test conditions).
In the RAR, acute ecotoxicity reference values were specifically set for Cd (metal) and CdO. These values were
based on high quality (Q1=RI 1) test results. Since these data are expressed on basis of a measured cadmium
(ion) concentration, they were pooled with the data obtained on other Cd-compounds, also mentioned in the
RAR.
This strict selection of the highest quality data is possible because the high number of acute data that are
available. It ensures that the tests were performed under well defined and/or standard conditions, and provide a
sound basis for classification.
The acute aquatic ecotoxicity data base for cadmium was reviewed further according to the following principles:
 the data assigned RI 1 and RI 2 in the acute aquatic toxicity database of the RAR (ECB 2008, tables 3.2.2.,
3.2.4., and 3.2.6.) were used as such. Prescriptions from standard protocols were strictly followed, e. g.
duration for acute test: fish 96 hrs, daphnids 48 hrs, algae 72 hrs.
 Data that were assigned RI 3 (not reliable) and RI 4 (not assignable) in the RAR were not used for setting the
reference value for acute aquatic toxicity.
Hardness is the main determining factor for Cd toxicity to aquatic organisms (RAR 2008). Cd-toxicity is more
important under conditions of low hardness. Therefore, in the review of the acute data, special attention was
paid to considering and selecting data obtained under low hardness conditions. Only tests performed at Cd
background <1µg Cd/l were used, according to the RAR.
If 4 or more data points were available on a same species, and the data were obtained under similar conditions,
the geomean was calculated and used for the analysis.
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Acute data - results
The short-term acute aquatic toxicity data on cadmium for all species (1 algae species, 2 invertebrate species,
and 7 fish species) are summarised in the CSR.
The short-term acute aquatic toxicity data on cadmium for all species (algae, invertebrates, and fish) are
summarised per species and group in table below.
The full set of EC50 values are presented under sections 7.1.1.1.1.(fish), 7.1.1.2.1. (invertebrates) and 7.1.1.3.
(algae and plants). In the table below, the data are summarised together with the pH and hardness of the test
media. A significant number of data are available at both low and neutral/high pH.
Table 37. Acute aquatic toxicity of cadmium by species as a function of pH and hardness.
species
RI
pH
Hardness
(mg
CaCO3/l)
E(L, I)C50
value (µg
Cd/l)
reference
Algae (cfr RAR CdO,
table 3.2.6.)
Selenastrum capricornutum
Selenastrum capricornutum
Selenastrum capricornutum
1
1
1
7.7-10.4
7-10
7-9
49
49
23
23
18
70
Selenastrum capricornutum
1
7-8
23
120
LISEC 1998a
LISEC 1998b
Janssen Pharmaceutica
1993a
Janssen Pharmaceutica
1993b
Daphnids
Daphnia magna
1
7.76
247
110
2
2
8.0
8.05
11
226
1900
750
2
2
2
6.95
8-8.5
6.6-7.8
130
160-180
26-32
Daphnia pulex
Fish
Pimephales promelas
Salmo Salar
2
8.8.5
80-100
58
38
36 (static)
49
(continuous)
42
2
2
7.1-7.8
6.5-7.3
44
19-28
1500
34
Jordanella floridae
Lepomis macrochirus
L. macrochirus (juv)
Carassius auratus
Ictalurus punctatus
2
2
2
2
2
7.1-7.8
7.4-7.7
7.1-7.8
7.1-7.8
7.1-7.8
44
18
44
44
44
2500
2300
6470
748
4480
Janssen Pharmaceutica
1993c
Kühn et al. 1989
Janssen Pharmaceutica
1993d
Attar and Maly 1982
Lewis and Horning 1991
Schuytema et al, 1984
Lewis and Horning 1991
Phipps and Holcombe 1985
Rombough and Garside
1982
Spehar 1976
Bishop and McIntosh 1981
Phipps and Holcombe 1985
Phipps and Holcombe 1985
Phipps and Holcombe 1985
The lowest species values (µg Cd/l) are summarised in table below
Table 38. Lowest acute aquatic toxicity data observed for cadmium
species
algae
Selenastrum
capricornutum
Daphnids
Hardness <100mg
CaCO3/l
Hardness >100mg
CaCO3/l
18
/
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Daphnia magna
Daphnia pulex
fish
Salmo Salar
cadmium sulphate
36
42
38
/
34
/
CAS number:
10124-36-4
Discussion/conclusion: reference value for short term aquatic ecotoxicity
The data span for all groups a variety of hardnesses, from very low to high. Low hardness data are available for
all 3 taxonomic groups. Most data are obtained at neutral to higher pH (7-8.5).
The EC50 values show strong variability, but the lowest values observed at low hardness are of the same order
of magnitude for all 3 taxonomic groups.
In conclusion, the data set covers the 3 taxonomic groups (algae, daphnids and fish) and allows to set the
reference value for acute aquatic toxicity for Cd (dissolved, ionic form). The lowest value is obtained on the
algae Selenastrum capricornutum under low hardness conditions: 18 µg Cd/l. This value was also used as
reference value for acute aquatic toxicity in the RAR on CdO (ECB 2008), for both low and neutral/high pH,
and for low and high hardness.
2. Aquatic chronic toxicity: freshwater
Chronic data - establishing the dataset
As for the acute toxicity, numerous data are available on the chronic toxicity of cadmium to aquatic organisms.
The quality and relevancy of the data has been reviewed in detail by the Belgian rapporteur for the EU risk
assessment (RA; ECB 2008).
Data categorised as RI 3 are less reliable: they may lack key information to assess the quality and relevancy of
the test result, e. g. information on test conditions like pH may lack, there may be no information on measured
Cd concentrations or no indication that nominal Cd levels were close to measured levels, there may be no
information that Cd concentrations during testing were maintained, there may be no statistics on the dose
response relationship, no information on the origin of the test organisms or the tested concentration range. In
spite of those shortcomings, the RI 3 data are also considered for inclusion in the species sensitivity distribution,
because it was done as such in the EU risk assessment. The RA combined all 3 groups of data because the
species sensitivity distribution covers the sensitivity of all the species included and the RI 3 data also contribute
to the weight of evidence on the sensitivity of aquatic organisms to Cd. To avoid effects of acclimation, only
tests performed at Cd background <1µg Cd/l were used, according to the RAR.
Chronic data results
The dataset on chronic aquatic toxicity is presented in detail under sections 7.1.1.1.2. (long-term fish), 7.1.1.2.1.
(invertebrates), and 7.1.1.3. (algae and plants).
The chronic aquatic toxicity data (NOECs) that are used for PNEC derivation in the EU RA, are summarised in
table below. Chronic NOECs categorised RI 1 and RI 2 are combined with data categorised RI 3. According to
the EU RA, no species geomean was made for some species, because tests were done in different medium or
different endpoint was mentioned. Such “case-by-case” approach as it was called in the RA deviates from the
one generally used in statistical extrapolation; still, it was used in the EU risk assessment and therefore taken
over in the present analysis.
Table 39. 'Case-by-case”- selected NOEC data of effects of Cd in freshwater and case-by-case calculation
of 'geometric mean NOEC's. Bold, underlined data are selected for the HC 5 calculation. (after table
3.2.9C of the EU risk assessment).
organism
medium
H
Salmo gairdneri
aerated well water; T 10; O2 7.5; pH
8-8.6
375-390 mortality
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NOEC references
(µg L-1)
Lowe-Jinde and Niimi,
12
1984
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organism
medium
Salmo gairdneri
no geometric mean
calculation: different test
medium
Oncorhynchus kisutch
synthetic water (ISO 1977) ; T 25; pH 100
8.3
Salvelinus fontinalis
Salvelinus fontinalis
geometric mean
calculation: same test
medium, same endpoint
(biomass)
Salvelinus fontinalis
Salvelinus fontinalis
geometric mean
calculation: similar test
medium, same endpoint
(survival)
Salmo salar
Catostomus commersoni
Esox lucius
Salvelinus namaycush
Salmo trutta (late eyed
eggs)
Jordanella floridae
Brachydanio rerio
Oryzias latipes
no geometric mean
calculation: different test
medium
Xenopus laevis
Pimephaless promelas
geometric mean
calculation: same test
medium, same endpoint
(reproduction)
Daphnia magna
Daphnia magna
no geometric mean
calculation: different
endpoints
Daphnia magna
different medium
H
endpoint
median survival time
sand filtered Lake Superior Water;
45
continuous flow; DO 10.3; Al 41; Ac
3; pH 7.6
sand filtered Lake Superior Water;
45
continuous flow; DO 10.3; Al 41; Ac
3; pH 7.6
sterilised Lake Superior water; pH 7- 42-47
8; Al 38-46; Ac 1-10; DO 4-12; T 915
biomass
reconstituted soft water: T 14-16°C;
DO 9.3-11.4 mg/L; Cd(BG) <0.2
µg/L; pH 6.3-7.6; H 20
river water: T 14-16°C; DO 8.7-12.2
mg/L; Cd(BG) <4 µg/L; pH 6.6-7.4;
H 16-28
20
survival
16-28
survival
biomass
total weight of young
/female of the 2nd
generation
CAS number:
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NOEC references
(µg L-1)
Dave et al., 1981
4
(no
geomean)
Eaton et al., 1978
1.3
1.1
Eaton et al., 1978
0.9
Benoit et al, 1976
geomean
= 1.0
8
Jop et al., 1995
62
Jop et al., 1995
geomean
= 22
municipal water charcoal filtered and 19-28
UV sterilised; BC 0.13 µg Cd/L; pH
6.5-7.3; T 5-10; DO 11.1-12.5; Al 1417
sand filtered Lake Superior Water;
45
continuous flow; DO 10.3; Al 41; Ac
3; pH 7.6
total biomass
0.47
Rombough and
Garside, 1982
standing crop (biomass)
biomass
4.2
4.2
4.4
1.1
Eaton et al., 1978
untreated Lake Superior water; T 25; 44
DO 8.3; Al 42; Ac 2.4; pH 7.1-7.8
synthetic water (changed ISO) ; T 24; 100
DO >80%; pH 7.2
tap water; continuous flow; T 20
200
100
reproduction
4.1
Spehar, 1976
reproduction
1
Bresch ., 1982
mortality and
abn. behaviour
6
3
Canton and Slooff,
1982
inhibition of larvae
development
201-204 reproduction (pond fish)
reproduction (laboratory
fry)
9
Canton and Slooff,
1982
Pickering and Gast,
1972
tap water; continuous flow; T 20
pond water diluted with carbon
filtered demineralised tap water; DO
6.5-6.6; pH 7.6-7.7; Al 145-161; Ac
8-12; T 16-27
50 µm filtered and sterilised Lake
IJssel water; pH 8.1; T 20; H 224
NPR synthetic water; pH 8.4; T 20
170
224
200
intrinsic rate of natural
increase
mortality
13
14
geomean
= 13.5
Van Leeuwen et al.,
3.2
1985
Van Leeuwen et al.,
1
1985
synthetic water; T 25; pH 8; DO 69% 11
reproduction
Daphnia magna
Synthetic water; Al 65; T 25
90
reproduction
D. magna:
geometric mean
calculation: similar
medium, same endpoint)
well water: T 202°C; DO 4.9-7.9;
Cd(BG) 0.08; pH 7.9
103
reproduction
well water: T 202°C; DO 4.9-7.9;
Cd(BG) 0.08; pH 8.2
unchlorinated, carbon filtered well
water, aerated to saturation; Al 230;
pH 8; DO >5; T 23; Cd < 0.01 µg
Cd/L
aerated well water; DO >70%; pH 8;
T 22; Al 250
209
reproduction
0.21
Chapman et al., 1980t
240
reproductive impairment
2.5
Elnabarawy et al., 1986
300
reproduction
0.8
Knowles and McKee,
1987
Daphnia magna
Daphnia magna
no geometric mean
calculation: different
medium
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2
Kühn et al., 1989
Winner, 1988
0.16
Chapman et al., 1980
geomean
= 0.6
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organism
medium
H
endpoint
Daphnia magna
culture medium; pH8.4; T 20
150
Daphnia magna
no geometric mean
calculation: different
medium
Daphnia pulex
20 µm cloth filtered Lake Superior
water; pH 7.7; Al 42.3; DO 9; T 18
45.3
biomass
production/female
weight/animal
Daphnia pulex
Aplexa hypnorum:
immature
Physa integra
Whatman N° 1 filtered Lake
65
Champlain water; pH 7.7; Al 42.4; Cd
-1
< 1µg L
unchlorinated, carbon filtered well
240
water, aerated to saturation; Al 230;
pH 8; DO >5; T 23; Cd < 0.01 µg
Cd/L
Lake Superior water; DO 7.5; T 24
NOEC references
(µg L-1)
Bodar et al., 1988a
2.5
1
Biesinger and
Christensen, 1972
1
Bertram and Hart, 1979
reproductive impairment
7.5
Elnabarawy et al., 1986
growth
4.41
Holcombe et al., 1984
8.3
Spehar et al., 1978
longevity
untreated Lake Superior water; pH
7.1-7.7; T 15; DO 10-11; Al 40-44;
Ac 1.9-3
Daphnia galeata mendotae 10 µm filtered Lake Michigan water;
T 18.5
Ceriodaphnia reticulata
unfiltered river water; static; Ac 24.2; Al 41-65; pH 7.2-7.8
Ceriodaphnia reticulata
unchlorinated, carbon filtered well
no geometric mean
water, aerated to saturation; Al 230;
calculation: different
pH 8; DO >5; T 23; Cd < 0.01 µg/L
medium
Ceriodaphnia dubia
Synthetic water; Al 65; T 25
no geometric mean
calculation: different
medium, different endpoint
Ceriodaphnia dubia
reconstituted soft water: T 14-16°C;
DO 9.3-11.4 mg/L; Cd(BG) <0.2
µg/L; pH 6.3-7.6; H 20
Ceriodaphnia dubia
river water: T 14-16°C; DO 8.7-12.2
geometric mean
mg/L; Cd(BG) <4 µg/L; pH 6.6-7.4;
calculation: similar
H 16-28
medium, same endpoint
(reproduction)
Hyalella azteca
well water: T 23; pH 7.8
44-48
mortality
120
number of individuals
55-79
reproduction
3.4
240
reproductive impairment
0.25
Spehar and Carlson,
1984
Elnabarawy et al., 1986
90
mortality
1.5
Winner, 1988
20
reproduction
10
Jop et al., 1995
16-28
reproduction
280
Survival
0.51
Chironomus tentans
280
weight
5.8
Selenastrum capricornutum modified ISO 6341 medium; 0.2 µm
filtered; T 20.3-25.6; pH 7.7-10.4
Coelastrum proboscideum AM;T 31;pH 5.3;
49
cell number
2.4
Ingersoll and Kemble,
2000
Ingersoll and Kemble,
2000
LISEC, 1998a
32
biomass
6.3
Müller and Payer 1979
Asterionella formosa
121
growth rate
0.85
42
steady state cell number
7.5
Conway and Williams
1979
Lawrence et al. 1989
biomass (OD)
31
well water: T 23; pH 7.8
AM; pH 8
Chlamydomonas reinhardii AM; pH 6.7; T 20
Scenedesmus quadricauda AM; pH 7
Lemna paucicostata
no geometric mean
calculation: different
medium
AM; T 25
pH>6
pH 5.1
pH 5.1
2
Marshall, 1978
11
Jop et al., 1995
geomean
= 10.5
number of fronds
120
120
700
5
10
10
Bringmann and Kühn,
1980
Nasu and Kugimoto,
1981
T = temperature (°C); H = hardness (as mg CaCO3/L); DO = dissolved oxygen (mg O2/L); Al = alkalinity (mg
CaCO3/L); Ac = acidity (mg CaCO3/L); AM, artificial medium.
For classification purposes, the following lowest NOECs (µgCd/l) per taxonomic group can be identified (when
values are not grouped for the SSD, they are also not grouped for the chronic ecotoxicity reference value):
fish
Salmo salar
0.47
invertebrates
algae
Daphnia magna
Asterionella formosa
0.21
0.85
So, the lowest chronic NOEC for use as reference value in classification is 0.21 µg Cd/l (Daphnia magna)
Results' extensive table "Case-by-case"- selected NOEC data of effects of Cd in freshwater and case-by-case
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calculation of 'geometric mean NOEC's can be found in the CMR (after table 3.2.9C of the EU risk assessment).
3. Aquatic chronic toxicity: marine waters
Chronic data - establishing the dataset
The Cd Risk Assessment has not carried out an effect assessment on the aquatic marine environment, while
REACH requires protection of this environmental compartment, i. e. the derivation of a saltwater PNEC for Cd.
The saltwater PNEC derived in this section covers truly marine conditions. It is derived based on chronic
toxicity data from the literature. The available chronic cadmium toxicity data were derived from original papers,
published in peer-reviewed international journals. Literature and environmental databases, including AQUIRE
(US EPA), MARITOX, ECETOC, and BIOSIS, as well as review articles covering cadmium in marine waters
were searched and reviewed for sources of relevant and reliable chronic toxicity data on cadmium. Only original
literature was used.
Data reliability and relevance
Selection of ecotoxicity data for quality was done according to a systematic approach as presented by Klimisch
et al. 1997. Standardized tests, as prescribed by organizations such as ASTM, OECD and US EPA, are used as a
reference when test methodology, performance and data treatment/reporting are considered. A detailed
description of methods and conditions employed in the study should be provided. The thorough description of
key requirements guarantees the high reliability (Q1) of the reported ecotoxicity data. Non-standardized test
data, may also have a high reliability, but required a more thorough check on their compliance with reliability
criteria before being used for deriving a PNEC. As for data relevancy, tests should be performed in media that
reflect natural environmental conditions (e.g. salinity and other abiotic conditions). A set of criteria for checking
reliability and relevancy has been defined in this work and is presented here below. Those criteria were used to
discriminate between data accepted with restrictions (Q2) and unreliable data (Q3).
Test medium
Both natural sea water and artificial sea water were accepted as test medium. In case EDTA is present in the test
medium, the study is considered not reliable. Chelators other than EDTA (e.g. NTA, citrate,…) can be added. In
this case, the data were considered reliable. Only the results of tests with soluble cadmium salts were used. Data
where information on the salt used was not available were regarded as reliable with restrictions (Q2). In the
reported data, cadmium has been used as the test material with several salts being used. As with other risk
assessments on metals, it is generally recognized that under laboratory conditions almost all the cadmium is
present in the dissolved fraction, therefore these results can be regarded as being dissolved cadmium
concentrations. Tests with metal mixtures were not considered for this evaluation.
Salinity
The TGD does not define the salinity range of sea water. The Water Framework Directive allows for using the
saltwater EQS at salinities ≥ 5‰, which sets the limit between freshwater and brackish waters. Therefore, tests
performed at salinity levels down to a value of 5 g/kg were accepted for this marine dataset.
Measured versus nominal concentrations
The results of marine aquatic toxicity studies are expressed either as measured concentration, or usually as
nominal concentration. The measured concentrations include the background concentration. However, most of
the publications do not report Cd background concentrations as they are usually very minor compared to the no
effect or lowest effect levels. A total risk approach was then considered in this assessment without correcting for
background values. That is, no correction for background was applied to measured concentrations which were
used together with nominal concentrations to derive the PNEC. Highly reliable data supported by nominal
concentrations were regarded as Q2 data. If it is not mentioned whether the NOEC/L(E)C 10 values are based on
measured or nominal concentrations, they were considered as nominal concentrations.
Control data
Tests were rated as not reliable if control data was not provided. Effect levels derived from toxicity tests using
only one test concentration always result in unbounded values and therefore not assignable data. Therefore, only
the results from toxicity tests using one control and at least two cadmium concentrations were retained for this
evaluation.
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Data reporting mortality rates higher than 20% in the control were not used in this assessment.
Test statistics
Because effect concentrations are statistically derived values, information concerning the statistics was used as a
criterion for data selection. Studies that do not report test statistics but present trust-worthy data are rated as
reliable with restrictions (Q2). Studies that do not report test statistics and do not present a dose-response
analysis are rated as unreliable (Q3).
Test design
Data without treatment replication or with pseudo-replication were not used (Q3).
Type of test (duration, endpoints covered)
Only reliable endpoints from properly conducted chronic tests were considered. Toxicological (sub)lethal
endpoints which affect the species at population level were taken into account (i.e. survival, development,
reproduction and growth). Historically, chronic exposure has been defined as > 4 days for all invertebrates and
fish. With respect to this assessment, the arbitrary selection of this exposure period has been reviewed in light of
the sensitivity of the endpoint and the duration of the life stage under assessment. For example, early life stages
tests (embryos, larvae) of 24-48 hours have been included in this assessment because of their expected higher
sensitivity towards pollutants. Sperm cells and fertilized eggs tests of a few hours were also considered as
chronic data. Indeed, abnormal development can be observed within this time frame (e.g. in molluscs,
echinoderms), and the continuation of these tests would derive no additional information which could provide
protection for the environment. For algae, and according to ASTM guidelines, data reporting growth rates < 1 in
the control were not used.
Origin of test species:
The culture and test conditions are considered more relevant than the geographical origin of the species and the
OECD guidelines recommend the use of a number of “standard” species which do not have a world-wide
distribution. Moreover, using the origin of species as criterion would considerably reduce the dataset and limit
the data to only a few species / taxa, which may obscure variation in sensitivity. Therefore, the geographical
origin of the test species has not been used as selection criterion. Organisms collected at contaminated sites were
not used in the analysis. Only results from unpolluted test media were used.
Derivation of NOEC/LOEC values (methods)
The toxicological variables are estimated based on NOECs or EC10 values coming from concentration-effect
relationship. In the past, the NOEC was determined directly from the concentration-effect curve by
consideration of the deviation from the control (e.g. 10%) or it was derived on the basis of ANOVA (analysis of
variance) and a subordinate test (e.g. Dunett's). This method to derive the NOEC with the ANOVA is criticized.
Pack et al., 1993 recommends the calculation of the ECX point as a preferable alternative. In older
investigations, it may be difficult to find out how the NOEC was generated unless test reports or raw data are
available. NOEC values without any information about the concentration-dependent response were excluded
from PNEC analysis.
Unbounded NOEC values (i.e. no effect was found at the highest concentration tested) were not used in this
analysis in accordance to previous risk assessments on metals.
In a few cases, no NOEC or LOEC value was provided, but raw data were reported. When possible, the raw data
were used to derive an EC10 using the Toxicity Relationship Analysis Program (TRAP) from the US EPA
National Health and Environmental Effects Research Laboratory (NHEERL) or using a simple linear
interpolation. The recalculated EC10 values were used with restrictions.
In case only a LOEC is given in the report, it was used to derive a NOEC with the following procedure (in
accordance to the approach taken in the EU Risk Assessment Report on Zn metal, ECB 2008):
- LOEC ≥ 10 and < 20% effect: NOEC can be calculated as LOEC/2.
- LOEC ≥ 20 and < 30% effect: NOEC can be calculated as LOEC/3.
- If the effect percentage of the LOEC is higher than 30% or if it is unknown, no NOEC can be
derived.
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CAS number:
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In aquatic toxicity the MATC (maximal acceptable toxicant concentration) is often calculated. This is the
geometric mean of the NOEC and the LOEC. If in the test report only the MATC is presented, the MATC can
be divided by √2 to derive a NOEC.
If for one species, several chronic NOEC values (from different tests) based on the same endpoint are available,
these values are averaged by calculating the geometric mean, resulting in a “species mean NOEC”. If several
toxicity endpoints are reported for the same species, the most sensitive endpoint, so the lowest NOEC value is
selected for PNEC derivation. The lowest value is determined on the basis of the geometric mean if more than
one value for the same endpoint exists.
Chronic toxicity of Cd in saltwater
Aquatic marine ecotoxicity database for cadmium
The marine cadmium database largely fulfils the species and taxonomic requirements for input chronic toxicity
data as explained in the RIP R. 10 guidance (at least 10 species NOECs and 8 taxonomic groups). Indeed, 48
species mean NOECs based on 62 NOEC values, coming from 39 families and from 9 taxonomic groups
covering three trophic levels were found to fulfil the relevancy and reliability requirements as explained by
Klimisch et al. 1997. The marine Cd database includes 1 micro- and 1 macro-algae species, 4 annelid species,
11 crustacean species, 7 echinoderm species, 13 mollusc species, 3 nematod species, 2 cnidarian species, 1
ascidian species and 6 fish species.
The geometric mean values of the species NOECs together with their reliability scoring are presented in Table
below. Most of the effects data are ranked as reliability 2 (Q2). Data are either reported as nominal or measured
concentrations.
Table 40. Endpoints selected for use in SSD for the derivation of marine PNEC for Cd.
Cadmium aquatic marine database (chronic toxicity data)
Taxonomic
Species name
Family
Geomean NOECadd
group
value
(µg Cddiss/L)
Micro-Algae
- Chaetoceros compressum
Chaetocerotacae
18.3
(1)
Macro-Algae
- Ulva pertusa
Ulvaceae
63
(1)
Annelids
- Capitella capitata
Capitellidae
126.5
(4)
- Ctenodrilus serratus
Ctenodrilidae
320.9
- Neanthes arenaceadontata
Nereididae
126.5
- Ophryotrocha diadema
Dorvilleidae
100
Cnidarians
- Eirene viridula
Eirenidae
100
(2)
- Campanularia flexuosa
Campanulariidae
87.7
Crustaceans
- Artemia franciscana
Artemiidae
39.3
(11)
- Artemia parthenogenetica
Artemiidae
106.1
- Artemia persimilis
Artemiidae
99.5
- Artemia salina
Artemiidae
56.7
- Balanus Amphitrite
Balanidae
5
- Elminius modestus
Archaeobalanidae
316
- Mysidopsis bahia
Mysidae
2.2
- Paragraspus
Grapsidae
105
quadridentatus
Penaeidae
33.3
- Penaeus monodon
Harpacticidae
36.7
- Tigriopus brevicornis
Moiniidae
1.8
- Moina monogolica
Echinoderms
- Arbacia lixula
Arbaciidae
357
(7)
- Asterias amurensis
Asteriidae
10000
- Echinometra mathaei
Echinometridae
10
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Reliability
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
1
2
2
2
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Taxonomic
group
Molluscs
(13)
Nematods
(3)
Ascidians (1)
Fish
(6)
TOTAL:
10 Tax. gps
-
CAS number:
10124-36-4
Cadmium aquatic marine database (chronic toxicity data)
Species name
Family
Geomean NOECadd
value
(µg Cddiss/L)
Lytechinus pictus
Toxopneustidae
4.2
Paracentrotus lividus
Echinidae
35.5
Sphaerechinus granularis
Toxopneustidae
623
Strongylocentrotus
Strongylocentrotidae
12.5
droebachiensis
Crassostrea cucullata
Ostreidae
7.1
Crassostrea gigas
Ostreidae
13
Crassostrea margaritacea
Ostreidae
12.6
Haliotis rubra
Haliotidae
520
Ilyanassa obsolete
Nassariidae
112.4
Isognomon californicum
Isognomonidae
0.3
Meretrix lusoria
Veneridae
33.3
Mya arenaria
Myidae
50
Mytilus edulis
Mytilidae
480
Mytilus galloprovincialis
Mytilidae
119.8
Perna viridis
Mytilidae
345.8
Ruditapes decussatus
Veneridae
265
Tresus nuttalli
Mactridae
42
Monhystera disjuncta
Monhysteridae
3333
Monhysteramicrophthalma Monhysteridae
1000
Pellioditis marina
Rhabditidae
25000
Ciona intestinalis
Ascidiaceae
430.5
Atherinops affinis
Atherinidae
10
Epinephelus coioides
Serranidae
33.3
Lates calcarifer
Centropomidae
794
Menidia menidia
Atherinidae
259.8
Mugil cephalus
Mugilidae
20
Pseudopleuronectes
Pleuronectidae
283.7
americanus
48 species
39 families
Reliability
2
2
2
2
2
2
2
2
2
2
2
2
2
2 and 1
2 and 1
2
2
2
2
2
1 and 2
1
2
2
2
2
2
48 species mean
NOECs
Statistics on Species sensitivity distribution
Given the multitude of relevant high quality ecotoxicity data, species mean NOECs were plotted in a species
sensitivity distribution (SSD) and statistical extrapolation was used for PNEC determination. No alternative
method i. e. assessment factor approach was applied for the PNEC determination. Following the RIP R. 10
guidance, different distributions may be used for the SSD. But according to the rules established in previous
Risk Assessments for metals, and given the significance levels are accepted, the use of a log-normal distribution
is preferred over other statistical distributions (Cd RAR 2007).
Based on the 48 species geometric mean NOECs presented in Table above and use of the program ETX 2.0
(Van Vlaardingen et al. 2004) for deriving an SSD (Figure below), the median 5 th percentile value of 2.28 µg/L
is calculated with a lower 95 per cent confidence interval of 0.93 µg/L and an upper 95 per cent confidence
interval of 4.64 µg/L.
The assumption that the input data are normally distributed is accepted at the highest significance level (P =
0.01) using the Anderson-Darling Goodness-of-Fit, the Kolmogorov-Smirnov and the Cramer von Mises tests
for normality.
Other statistical distributions were calculated using the software “@risk” (Palisade Inc.). The Logistic
distribution on the log-transformed data turned out to be the best fit with an HC5-50 value of 2.54 µg Cd/L
(Table below). The difference between both distributions is however minimal. The statistics of the curve-fitting
on the chronic NOEC data are summarized in the table below.
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CAS number:
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Table 41. Summary statistics for the SSD on chronic NOEC values for cadmium in saltwater (n=50).
Distribution
Median
HC5
Median
HC5/lower
95% C. I.
2.45
A-D
statistic
2.28
Lower
estimate
on HC5
0.93
Lognormal
(ETX)
Lognormal
(@risk)
Best
fit
(Logistic;
@risk)
K-S
statistic
0.35
A-D
significance
level
P > 0.1
2.33
/
2.54
/
0.66
K-S
significance
level
P > 0.1
Acceptance
for PNEC
setting
Accepted
/
0.35
P > 0.25
0.09
P > 0.15
Accepted
/
0.21
P > 0.25
0.07
P > 0.1
Accepted
The observed high quality data are presented as log-scale together with their fitted normal distribution curve in
figure below:
Figure 5. Species sensitivity distribution of selected chronic marine Cd endpoints (n=47)
The 5th percentile value of the SSD (the HC5), set at 50% confidence value, using the lognormal distribution
(ETX 2.0) function, results in a value of 2.28 µg cadmium/L. This value is taken forward for the PNEC
derivation.
Mesocosm studies
A study on phytoplankton communities from three different areas was carried out by Wolter et al. (1984).
Influence of metal to carbon fixation rate of phytoplankton and to glucose incorporation by bacteria was
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determined. Water samples coming from Kiel Fjord, North Sea and a coastal area of the North Atlantic Ocean
were investigated after addition of varying concentrations of metals including cadmium. Surface samples were
taken in Kiel Fjord during the spring and autumn plankton bloom. Cadmium was added to subsamples to give
concentrations in the range of 0.08 to 20.08 µg/L. Samples from the North Sea and Atlantic were collected. The
added cadmium concentrations were 0.5 to 2.5 µg/L. The added metal concentrations were lower than in the
Kiel Fjord experiments due to lower concentrations in the water compared to Baltic Sea water. In all cases the
samples contained mixed phytoplankton populations which were dominated by diatoms.
From the graph, cadmium did not reduce plankton activity in the Kiel Fjord samples at a concentration of 1.5
µg/L. However, carbon fixation measurements carried out four and 24 hours after metal addition to the North
Sea and Atlantic samples were not reduced at any test concentration, which then gives unbounded values (see
table below for summary of results). The same was true for bacterial glucose incorporation.
Table 42. Results of field experiments made on phytoplankton communities coming from various natural
sea waters


Location

Endpoint


Kiel Fjord

North Sea

Atlantic


NOEC
(µg  1.5
(from  2.5

2.5

C fixation rate
Cd/L) after 4 or
graph)
(unbounded)
(unbounded)
24
hours
exposure

NOEC
(µg  /

2.5

2.5

Bacterial
Cd/L) after 4 or
(unbounded)
(unbounded)
glucose
24
hours
incorporation
exposure
Although this study has nothing inherently wrong in the design, but some important details are lacking (no
accurate information about test organisms and test conditions, no information on statistics and on control data,
…). The results should thus be handled with care .
7.1.1.1. Fish
7.1.1.1.1. Short-term toxicity to fish
The results are summarised in the following table:
Table 43. Overview of short-term effects on fish
Method
Results
Remarks
Reference
Pimephales promelas
LC50 (4 d): 1500 µg/L
dissolved (nominal)
2 (reliable with
restrictions)
Phipps &
Holcombe (1985)
freshwater
key study
flow-through
read-across based on
grouping of
substances (category
approach)
4 days acute fish test, flow-through
system, natural water
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Carassius auratus
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LC50 (4 d): 748 µg/L
dissolved (nominal)
2 (reliable with
restrictions)
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Holcombe (1985)
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Method
Results
CAS number:
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Remarks
freshwater
key study
flow-through
read-across based on
grouping of
substances (category
approach)
4 days acute fish test, flow-through
system, natural water
Reference
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Ictalurus punctatus
LC50 (4 d): 4480 µg/L
dissolved (nominal)
freshwater
2 (reliable with
restrictions)
Phipps &
Holcombe (1985)
key study
flow-through
read-across based on
grouping of
substances (category
approach)
4 days acute fish test, flow-through
system, natural water
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Lepomis macrochirus
LC50 (4 d): 6470 µg/L
dissolved (nominal)
freshwater
2 (reliable with
restrictions)
Phipps &
Holcombe (1985)
key study
flow-through
read-across based on
grouping of
substances (category
approach)
4 days acute fish test, flow-through
system, natural water
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Jordanella floridae
LC50 (4 d): 2500 µg/L
dissolved (meas. (not
specified))
freshwater
flow-through
American Public Health Association
1971 - Standard methods for the
examination of water and waste waters.
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2 (reliable with
restrictions)
Spehar RL (1976)
key study
read-across based on
grouping of
substances (category
approach)
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Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Salmo salar
freshwater
LC50 (24 d): 2300 µg/L
dissolved (meas. (not
specified))
semi-static
2 (reliable with
restrictions)
Bishop &
McIntosh (1982)
key study
read-across based on
grouping of
substances (category
approach)
fish 24d mortality test in semi-static
system, natural water
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Salmo salar
freshwater
semi-static
24d mortality test on juveniles
LC50 (24 d): 34 µg/L
dissolved (meas. (not
specified))
2 (reliable with
restrictions)
Rombough &
garside (1982)
key study
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Discussion
All good quality short-term data that were available for all Cd-substances were considered together, since the
toxicity of the Cd++ ion is key to the hazard assessment of Cd in water.
Data were available on 7 fish species. The lowest short-term EC50 is observed on Salmo Salar: 34 µg Cd/l
(single measured value). The EC50 values ranged between 34 and 6470 µg Cd/l. Toxicity was generally low
with EC50 in 6 out of 7 species > 700µg Cd/l. The results were obtained in a pH range of 6.5 -7.8. The toxicity
was in general highest at lower hardness.
The following information is taken into account for acute fish toxicity for the derivation of PNEC:
The good quality short-term data that were available for all Cd-substances were considered together, since the
toxicity of the Cd++ ion is key to this analysis.
Data were available on 7 fish species. The lowest short-term EC50 is observed on Salmo Salar: 34 µg Cd/l
(single measured value). The EC50 values ranged between 34 and 6470 µg Cd/l.
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7.1.1.1.2. Long-term toxicity to fish
The results are summarised in the following table:
Table 44. Overview of long-term effects on fish
Method
Results
Remarks
Reference
Salvelinus fontinalis
NOEC (10 d): 8 µg/L
dissolved (meas. (not
specified)) based on:
survival
2 (reliable with
restrictions)
Jop KM, Askew
AM and Foster RB
(1995)
NOEC (10 d): 18 µg/L
dissolved (meas. (not
specified)) based on:
growth rate
read-across based on
grouping of
substances (category
approach)
NOEC (10 d): 62 µg/L
dissolved (meas. (not
specified)) based on:
survival
Test material
(IUPAC name):
cadmium (See
endpoint summary
for justification of
read-across)
freshwater
survival, growth
static with renewal
other
NOEC (10 d): 132 µg/L
dissolved (meas. (not
specified)) based on:
growth rate
key study
LOEC (10 d): 18 µg/L
dissolved (meas. (not
specified)) based on:
survival
LOEC (10 d): 132 µg/L
dissolved (meas. (not
specified)) based on:
survival
Oncorhynchus kisutch
NOEC (27 d): 1.3 µg/L
dissolved (meas. (TWA))
based on: Standing crop
(biomass)
freshwater
embryos, sac-fry stage and juveniles,
standing crop
Embryos: test containers screenbottom glass jars 6 cm diameter - after
hatching, young fish released into glass
larval test chambers (15cm wide, 30
cm deep, 30 cm long) containing ± 10 l
of water.
Estimated replacement time of 90%
water in each chamber is 6 to 7 h
2010-09-07 CSR-PI-5.2.1
key study
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
sac-fry stage incubated before testing
freshwater
Eaton et al. (1978)
read-across based on
grouping of
substances (category
approach)
flow-through
Salvelinus fontinalis
2 (reliable with
restrictions)
NOEC (65 d): 1.1 µg/L
dissolved (meas. (TWA))
based on: standing crop
(biomass)
2 (reliable with
restrictions)
Eaton et al. (1978)
key study
CHEMICAL SAFETY REPORT
131
EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Method
Results
Remarks
embryo & larvae-juveniles
NOEC (126 d): 1.1 µg/L
dissolved (meas. (TWA))
based on: standing crop
(biomass)
read-across based on
grouping of
substances (category
approach)
flow-through
Embryos: test containers screenbottom glass jars 6 cm diameter - after
hatching, young fish released into glass
larval test chambers (15cm wide, 30
cm deep, 30 cm long) containing ± 10 l
of water.
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Estimated replacement time of 90%
water in each chamber is 6 to 7 h
Salmo gairdneri (new name:
Oncorhynchus mykiss)
freshwater
adult fish: (sub)lethal effects
flow-through
NOEC (84 d): 12 µg/L
dissolved (meas. (TWA))
based on: adult mortality
LOEC (84 d): 36 µg/L
dissolved (meas. (TWA))
based on: adult mortality
Fish kept in 300l tanks supplied by
aerated well water at 10°C ± 1°C
freshwater
early-life stage: reproduction,
(sub)lethal effects
flow-through
other method
Salvelinus fontinalis
freshwater
mortality, growth, reproduction
2010-09-07 CSR-PI-5.2.1
Lowe-Jinde &
Niimi (1984)
key study
read-across based on
grouping of
substances (category
approach)
NOEC (100 d): 4.1 µg/L
dissolved (meas. (not
specified)) based on:
reproduction
2 (reliable with
restrictions)
NOEC (100 d): 8.1 µg/L
dissolved (meas. (not
specified)) based on:
growth rate
read-across based on
grouping of
substances (category
approach)
LOEC (100 d): 16 µg/L
dissolved (meas. (not
specified)) based on:
growth rate
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
NOEC (36 mo): 1.7 µg/L
dissolved (meas. (not
specified)) based on:
mortality
2 (reliable with
restrictions)
NOEC (36 mo): 1.7 µg/L
dissolved (meas. (not
specified)) based on:
American Public Health Association et growth rate (of 16 weeks
al. 1971 for chemical measurements
old juveniles)
flow-through
2 (reliable with
restrictions)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Feeding ad libitum every other day
Jordanella floridae
Reference
Spehar (1976)
key study
key study
read-across based on
grouping of
substances (category
approach)
Benoit DA,
Leonard EN,
Christensen GM
and Fiandt JT
(1976b)
Test material
(IUPAC name):
CHEMICAL SAFETY REPORT
132
EC number:
233-331-6
Method
cadmium sulphate
Results
NOEC (36 mo): 0.9 µg/L
dissolved (meas. (not
specified)) based on: weight
(of youngs from second
generation)
CAS number:
10124-36-4
Remarks
Reference
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
NOEC (36 mo): 6.4 µg/L
dissolved (meas. (not
specified)) based on:
reproduction
Salmo salar
freshwater
growth and total biomass
semi-static
long term growth inhibition test of
eggs and alevins
NOEC (46 d): 0.47 µg/L
dissolved (meas. (not
specified)) based on: total
biomass
2 (reliable with
restrictions)
LOEC (46 d): 0.78 µg/L
dissolved (meas. (not
specified)) based on: total
biomass
read-across based on
grouping of
substances (category
approach)
Rombough and
Garside (1982)
key study
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Salvelinus fontinalis
freshwater
survival, growth
static with renewal
other
NOEC (10 d): 8 µg/L
dissolved (meas. (not
specified)) based on:
survival
2 (reliable with
restrictions)
NOEC (10 d): 18 µg/L
dissolved (meas. (not
specified)) based on:
growth rate
read-across based on
grouping of
substances (category
approach)
NOEC (10 d): 62 µg/L
dissolved (meas. (not
specified)) based on:
survival
Test material
(IUPAC name):
cadmium (See
endpoint summary
for justification of
read-across)
NOEC (10 d): 132 µg/L
dissolved (meas. (not
specified)) based on:
growth rate
key study
Jop KM, Askew
AM and Foster RB
(1995)
LOEC (10 d): 18 µg/L
dissolved (meas. (not
specified)) based on:
survival
LOEC (10 d): 132 µg/L
dissolved (meas. (not
specified)) based on:
survival
Pimephales promelas
2010-09-07 CSR-PI-5.2.1
NOEC (60 d): 13 µg/L
dissolved (meas. (not
3 (not reliable)
CHEMICAL SAFETY REPORT
Pickering QH and
Gast MH (1972)
133
EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Method
Results
Remarks
freshwater
specified)) based on:
reproduction (pond fish)
supporting study
life cycle: reproduction, (sub)lethal
effects
NOEC (60 d): 14 µg/L
dissolved (meas. (not
specified)) based on:
static for fish and static and continuous reproduction (laboratory
for fry
fry)
Reference
experimental result
Test material (EC
name): cadmium
sulphate
statis and continuous flow tests on fish
and fry (60d)
Salmo gairdneri (new name:
Oncorhynchus mykiss)
freshwater
NOEC (48 d): 4 µg/L
dissolved (nominal) based
on: median survival time
3 (not reliable)
supporting study
experimental result
median survival time
Test material (EC
name): cadmium
sulphate
semi-static
semi-static 28d survival test
Danio rerio (reported as Brachydanio NOEC (36 d): 1 µg/L
rerio)
dissolved (nominal) based
on: reproduction
freshwater
LOEC (24 d): 10 µg/L
mortality, growth and reproduction
dissolved (nominal) based
on: reproduction
semi-static
3 (not reliable)
other, no details
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Oryzias latipes
freshwater
mortality and abnormal behavior
semi-static
equivalent or similar to Dutch
Standardisation Organisation (NEN
6409, 6502, 6504, 6506, 1980)
Mugil cephalus
saltwater
embryo and sac-fry stage: (sub)lethal
effects
2010-09-07 CSR-PI-5.2.1
Dave G,
Andersson K,
Berglind R and
Hasselrot B (1981)
NOEC (18 d): 6 µg/L
dissolved (meas. (not
specified)) based on:
mortality and abnormal
behaviour in hard water
NOEC (18 d): 3 µg/L
dissolved (meas. (not
specified)) based on:
mortality and abnormal
behavior in soft water
NOEC (8 wk): 20 µg/L
dissolved (nominal) based
on: mortality
Bresch H. (1982)
supporting study
read-across based on
grouping of
substances (category
approach)
3 (not reliable)
supporting study
Canton JH and
Slooff (1982)
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
2 (reliable with
restrictions)
key study
Hilmy, AM, MB
Shabana, AY
Daabees (1985)
read-across based on
CHEMICAL SAFETY REPORT
134
EC number:
233-331-6
cadmium sulphate
Method
Results
8 weeks mortality test on fry of the fish
Mugil cephalus, designed for doseresponse
early-life stage: reproduction,
(sub)lethal effects
7-d immobility test on the spotted
grouper (Epinephelus coioides),
designed for dose-response
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Mugil cephalus
NOEC (8 wk): 20 µg/L
dissolved (nominal) based
on: mortality
saltwater
embryo and sac-fry stage: (sub)lethal
effects
8 weeks mortality test on fry of the fish
Mugil cephalus, designed for doseresponse
semi-static
U.S. EPA. 1995. Short-term methods
for estimating the chronic toxicity of
effluents and receiving waters to West
Coast marine and estuarine organisms,
1st ed. EPA/600/R-95-136. Technical
2010-09-07 CSR-PI-5.2.1
2 (reliable with
restrictions)
key study
Hilmy, AM, MB
Shabana, AY
Daabees (1985)
read-across based on
grouping of
substances (category
approach)
semi-static
early-life stage: reproduction,
(sub)lethal effects
Chien-Min Chen,
Ming-Chao Liu.
(2006a)
read-across based on
grouping of
substances (category
approach)
static
saltwater
Reference
Test material
(IUPAC name):
cadmium metal
(See endpoint
summary for
justification of
read-across)
NOEC (7 d): 33.33 µg/L
2 (reliable with
dissolved (estimated) based restrictions)
on: immobility
key study
saltwater
Atherinopsis affinis
Remarks
grouping of
substances (category
approach)
semi-static
Epinephelus coioides
CAS number:
10124-36-4
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
NOEC (14 d): 10 µg/L
dissolved (nominal) based
on: growth
2 (reliable with
restrictions)
key study
read-across based on
grouping of
substances (category
approach)
Rose WL, Hobbs
JA, Nisbet RM,
Green PG, Cherr
GN, Anderson SL
(2005)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
CHEMICAL SAFETY REPORT
135
EC number:
233-331-6
Method
cadmium sulphate
Results
Report. Cincinnati, OH With
deviations
Lates calcarifer
saltwater
EC10 (7 d): 794 µg/L
dissolved (nominal) based
on: growth
7-d growth test on seabass larvae,
designed for dose-response
embryo and sac-fry stage: (sub)lethal
effects
embryo and sac-fry stage: (sub)lethal
effects
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
EC10 (7 d): 283.7 µg/L
2 (reliable with
dissolved (estimated) based restrictions)
on: development, mortality
key study
read-across based on
grouping of
substances (category
approach)
development and mortality tests on
winter flounder, designed for doseresponse
saltwater
2010-09-07 CSR-PI-5.2.1
Voyer RA,
Heltsche JF &
Kraus RA (1979)
read-across based on
grouping of
substances (category
approach)
static
Mugil cephalus
Thongra-ar W &
Musika C (1997)
key study
EC10 (11 d): 259.8 µg/L
2 (reliable with
dissolved (estimated) based restrictions)
on: mortality
key study
short term chronic mortality test,
designed for dose-response
saltwater
2 (reliable with
restrictions)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
flow-through
Pseudopleuronectes americanus
Reference
read-across based on
grouping of
substances (category
approach)
semi-static
saltwater
Remarks
summary for
justification of
read-across)
early-life stage: reproduction,
(sub)lethal effects
Menidia menidia
CAS number:
10124-36-4
Voyer RA,
Wentworth Jr. CE,
Barry EP &
Hennekey RJ
(1977)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
NOEC (8 wk): 20 µg/L
dissolved (nominal) based
on: mortality
2 (reliable with
restrictions)
key study
CHEMICAL SAFETY REPORT
Hilmy, AM, MB
Shabana, AY
Daabees (1985)
136
EC number:
233-331-6
cadmium sulphate
Method
Results
embryo and sac-fry stage: (sub)lethal
effects
CAS number:
10124-36-4
Remarks
Reference
read-across based on
grouping of
substances (category
approach)
semi-static
8 weeks mortality test on fry of the fish
Mugil cephalus, designed for doseresponse
Test material (EC
name): cadmium
chloride (See
endpoint summary
for justification of
read-across)
Discussion
Freshwaters:
16 reliable studies on 12 different species were considered for chronic toxicity for species sensitivity
distribution.
Fish species NOECs were combined with other marine chronic data in the SSD to give the HC5 from which the
PNEC is derived.
Marine waters:
Relevant and reliable chronic toxicity data on marine fish were found in 6 families: Atherinidae, Serranidae,
Centropomidae, Atherinidae, Mugilidae and Pleuronectidae. The species are equally distributed over the species
sensitivity distribution (SSD). Fish species NOECs were combined with other marine chronic data in the SSD to
give the HC5 from which the PNEC is derived.
The following information is taken into account for long-term fish toxicity for the derivation of PNEC:
Freshwater: Data on 12 fish species: NOECs range between 0.47 and 13.5 µg/l Cd (dissolved concentrations)
Marine waters: Data on 6 fish species belonging to 6 different families are available. Species NOECs range
between 10 and 794 µg Cd/L (dissolved concentrations).
7.1.1.2. Aquatic invertebrates
7.1.1.2.1. Short-term toxicity to aquatic invertebrates
The results are summarised in the following table:
Table 45. Overview of short-term effects on aquatic invertebrates
Method
Results
Remarks
Reference
Daphnia magna
LC50 (48 d): 110 µg/L
dissolved (meas. (initial))
based on: mobility
2 (reliable with
restrictions)
Janssen
Pharmaceutica
(1993a)
freshwater
static
OECD Guideline 202 (Daphnia sp.
Acute Immobilisation Test)
key study
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium (See
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
137
EC number:
233-331-6
Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
endpoint summary
for justification of
read-across)
Daphnia magna
freshwater
flow-through
other - flow through system, 96h
mortality test
Daphnia magna
freshwater
static
LC50 (36 h): 203.8 µg/L
2 (reliable with
Attar EN and Maly
dissolved (meas. (arithm.
restrictions)
EJ (1982)
mean)) based on: mortality
key study
LC50 (48 h): 58.16 µg/L
read-across based on
dissolved (meas. (arithm.
mean)) based on: mortality grouping of
substances (category
approach)
LC50 (60 h): 15.8 µg/L
dissolved (meas. (arithm.
mean)) based on: mortality Test material
(IUPAC name):
LC50 (72 h): 8.88 µg/L
cadmium dichloride
dissolved (meas. (arithm.
(See endpoint
mean)) based on: mortality summary for
justification of
LC50 (96 h): 5 µg/L
read-across)
dissolved (meas. (arithm.
mean)) based on: mortality
LC50 (48 h): 38 µg/L
dissolved (meas. (not
specified)) based on:
mortality
2 (reliable with
restrictions)
key study
Lewis PA and
Horning II WB
(1991)
read-across based on
grouping of
substances (category
approach)
EPA 600/4-78 012
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Daphnia pulex
freshwater
static
LC50 (48 h): 42 µg/L
dissolved (meas. (not
specified)) based on:
mortality
2 (reliable with
restrictions)
key study
Lewis PA and
Horning II WB
(1991)
read-across based on
grouping of
substances (category
approach)
EPA 600/4-78 012
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Daphnia magna
2010-09-07 CSR-PI-5.2.1
LC50 (48 h): 36 µg/L
dissolved (meas. (not
2 (reliable with
restrictions)
CHEMICAL SAFETY REPORT
Schuytema GS,
Nelson PO,
138
EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Method
Results
Remarks
freshwater
specified)) based on:
mortality
key study
static and continuous
E729-80 from American Society for
Testing and Materials
LC50 (48 h): 49 µg/L
dissolved (meas. (not
specified)) based on:
mortality
Reference
Malueg KW,
Nebeker AV,
Krawczyk DF,
read-across based on Ratcliff (1984)
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Daphnia magna
freshwater
semi-static
EC50 (24 h): 1900 µg/L
dissolved (meas. (not
specified)) based on:
mortality
2 (reliable with
restrictions)
key study
Kühn R, Pattard
M, Pernak KD and
Winter A (1989)
read-across based on
grouping of
substances (category
approach)
DIN-Standard 38412, part II - Daphnia
short time test
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
other aquatic crustacea: Barytelphusa LC50 (96 h): 1820 µg/L
guerini
dissolved (nominal) based
on: mortality
freshwater
2 (reliable with
restrictions)
semi-static
read-across based on
grouping of
substances (category
approach)
Short term mortality test
key study
Venugopal NBRK,
Ramesh TVDD,
Reddy DS and
Reddy SLN (1997)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Daphnia magna
freshwater
static
OECD Guideline 202 (Daphnia sp.
Acute Immobilisation Test)
2010-09-07 CSR-PI-5.2.1
LC50 (48 d): 110 µg/L
dissolved (meas. (initial))
based on: mobility
2 (reliable with
restrictions)
key study
Janssen
Pharmaceutica
(1993a)
read-across based on
grouping of
substances (category
approach)
CHEMICAL SAFETY REPORT
139
EC number:
233-331-6
Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
Test material
(IUPAC name):
cadmium (See
endpoint summary
for justification of
read-across)
Daphnia magna
freshwater
LC50 (48 d): 750 µg/L
dissolved (meas. (initial))
based on: mobility
static
2 (reliable with
restrictions)
key study
Janssen
Pharmaceutica
(1993b)
read-across based on
grouping of
substances (category
approach)
OECD Guideline 202 (Daphnia sp.
Acute Immobilisation Test)
Test material
(IUPAC name):
oxocadmium (See
endpoint summary
for justification of
read-across)
Discussion
The good quality short-term data that were available for all Cd-substances were considered together, since the
toxicity of the Cd++ ion is key to this analysis. Data were available on 2 Daphnia species. The lowest short-term
EC50 is observed on Daphnia pulex: 42 µg Cd/l (single measured value). The EC50 values ranged between 38
and 1900 µg Cd/l. Species geomean for Daphnia is 130 µg Cd/l.
The following information is taken into account for short-term toxicity to aquatic invertebrates for the derivation
of PNEC:
The good quality short-term data that were available for all Cd-substances were considered together, since the
toxicity of the Cd++ ion is key to this analysis.
Data were available on 2 Daphnia species and the crab Barythelphusa guerini. The lowest short-term EC50 is
observed on Daphnia pulex: 42 µg Cd/l (single measured value). The EC50 values ranged between 38 and 1900
µg Cd/l. Species geomean for Daphnia is 130 µg Cd/l.
7.1.1.2.2. Long-term toxicity to aquatic invertebrates
The results are summarised in the following table:
Table 46. Overview of long-term effects on aquatic invertebrates
Method
Results
Remarks
Reference
Ceriodaphnia dubia
NOEC (7 d): 19 µg/L
dissolved (meas. (not
specified)) based on:
survival
2 (reliable with
restrictions)
Jop KM, Askew
AM and Foster RB
(1995)
NOEC (7 d): 11 µg/L
dissolved (meas. (not
specified)) based on:
reproduction
read-across based on
grouping of
substances (category
approach)
freshwater
static with renewal
other, survival, reproduction
2010-09-07 CSR-PI-5.2.1
key study
CHEMICAL SAFETY REPORT
140
EC number:
233-331-6
cadmium sulphate
Method
CAS number:
10124-36-4
Results
Remarks
NOEC (7 d): 19 µg/L
dissolved (meas. (not
specified)) based on:
survival
Test material
(IUPAC name):
cadmium (See
endpoint summary
for justification of
read-across)
NOEC (7 d): 10 µg/L
dissolved (meas. (not
specified)) based on:
reproduction
Reference
LOEC (7 d): 41 µg/L
dissolved (meas. (not
specified)) based on:
survival
LOEC (7 d): 19 µg/L
dissolved (meas. (not
specified)) based on:
reproduction
LOEC (7 d): 39 µg/L
dissolved (meas. (not
specified)) based on:
survival
LOEC (7 d): 19 µg/L
dissolved (meas. (not
specified)) based on:
reproduction
other aquatic mollusc: Physa integra
NOEC (21 d): 8.3 µg/L
dissolved (meas. (not
specified)) based on:
mortality
freshwater
semi-static
2 (reliable with
restrictions)
key study
Spehar RL,
Anderson RL and
Fiandt JT (1978b)
read-across based on
grouping of
substances (category
approach)
Intermittent-flow exposure system 28d
survival test
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Daphnia magna
NOEC (21 d): 0.6 µg/L
dissolved (nominal) based
on: reproduction
freshwater
semi-static
equivalent or similar to
Umweltbundeamt - 1984 - Extended
toxicity test using Daphnia magna determination of NOEC for
reproduction rate, mortality and time of
the appearance of the first offspring.
2010-09-07 CSR-PI-5.2.1
2 (reliable with
restrictions)
key study
Kühn R, Pattard
M, Pernak KD and
Winter A (1989)
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
CHEMICAL SAFETY REPORT
141
EC number:
233-331-6
Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Daphnia magna
freshwater
flow-through
NOEC (21 d): 0.8 µg/L
dissolved (meas. (not
specified)) based on:
reproduction
2 (reliable with
restrictions)
Knowles CO and
McKee M.J (1987)
key study
read-across based on
grouping of
substances (category
approach)
ATSM 1985
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
other aquatic mollusc: Aplexa
hypnorum
freshwater
NOEC (26 d): 4.41 µg/L
dissolved (meas. (not
specified)) based on:
growth
flow-through
2 (reliable with
restrictions)
key study
Holcombe GW,
Phipps GL and
Marier JW (1984)
read-across based on
grouping of
substances (category
approach)
other - growth test - shell length
measured after 26d exposure (starting
from hatching)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Ceriodaphnia dubia
freshwater
static with renewal
other, survival, reproduction
NOEC (7 d): 19 µg/L
dissolved (meas. (not
specified)) based on:
survival
2 (reliable with
restrictions)
NOEC (7 d): 11 µg/L
dissolved (meas. (not
specified)) based on:
reproduction
read-across based on
grouping of
substances (category
approach)
NOEC (7 d): 19 µg/L
dissolved (meas. (not
specified)) based on:
survival
Test material
(IUPAC name):
cadmium (See
endpoint summary
for justification of
read-across)
NOEC (7 d): 10 µg/L
dissolved (meas. (not
specified)) based on:
reproduction
2010-09-07 CSR-PI-5.2.1
key study
CHEMICAL SAFETY REPORT
Jop KM, Askew
AM and Foster RB
(1995)
142
EC number:
233-331-6
Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
3 (not reliable)
Winner RW
(1988)
LOEC (7 d): 41 µg/L
dissolved (meas. (not
specified)) based on:
survival
LOEC (7 d): 19 µg/L
dissolved (meas. (not
specified)) based on:
reproduction
LOEC (7 d): 39 µg/L
dissolved (meas. (not
specified)) based on:
survival
LOEC (7 d): 19 µg/L
dissolved (meas. (not
specified)) based on:
reproduction
Ceriodaphnia dubia
freshwater
NOEC (7 d): 1.5 µg/L
dissolved (nominal) based
on: mortality
supporting study
static
experimental result
other - synthetic water, static system
Test material (EC
name): cadmium
sulphate
Daphnia magna
freshwater
NOEC (7 d): 2 µg/L
dissolved (nominal) based
on: reproduction
3 (not reliable)
supporting study
static
experimental result
other - synthetic water, static system
Test material (EC
name): cadmium
sulphate
Daphnia magna
freshwater
semi-static
other - no details
Daphnia magna
freshwater
statis-renewal
equivalent or similar to EPA OPPTS
850.1300 (Daphnid Chronic Toxicity
Test)
2010-09-07 CSR-PI-5.2.1
NOEC (21 d): 3.2 µg/L
dissolved (nominal) based
on: intrinsic rate of natural
increase
NOEC (21 d): 1 µg/L
dissolved (nominal) based
on: mortality
3 (not reliable)
supporting study
experimental result
Winner RW
(1988)
Van Leeuwen CJ,
Luttmer WJ and
Griffioen PS
(1985)
Test material
(IUPAC name):
cadmium dichloride
NOEC (21 d): 0.16 µg/L
3 (not reliable)
Chapman G., Ota,
dissolved (meas. (not
S and Recht, F.
supporting study
specified)) based on:
(1980)
reproduction (hardness 100)
read-across based on
grouping of
NOEC (21 d): 0.21 µg/L
substances (category
dissolved (meas. (not
approach)
specified)) based on:
reproduction (hardness 200)
Test material
(IUPAC name):
cadmium dichloride
CHEMICAL SAFETY REPORT
143
EC number:
233-331-6
Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
(See endpoint
summary for
justification of
read-across)
Daphnia magna
freshwater
semi-static
NOEC (14 d): 2.5 µg/L
dissolved (nominal) based
on: reproduction
impairment
Reproductive impairment defined as
decrease in the average cumulative
number of young per adult.
3 (not reliable)
supporting study
read-across based on
grouping of
substances (category
approach)
Elnabarawy MT,
Welter AN and
Robideau RR
(1986)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Ceriodaphnia dubia
freshwater
semi-static
NOEC (14 d): 0.25 µg/L
dissolved (nominal) based
on: reproduction
impairment
Reproductive impairment defined as
decrease in the average cumulative
number of young per adult.
3 (not reliable)
supporting study
read-across based on
grouping of
substances (category
approach)
Elnabarawy MT,
Welter AN and
Robideau RR
(1986)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Daphnia pulex
freshwater
semi-static
NOEC (14 d): 7.5 µg/L
dissolved (nominal) based
on: reproduction
impairment
Reproductive impairment defined as
decrease in the average cumulative
number of young per adult.
3 (not reliable)
supporting study
read-across based on
grouping of
substances (category
approach)
Elnabarawy MT,
Welter AN and
Robideau RR
(1986)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Daphnia magna
freshwater
Semi-continuous flow
endpoint = biomass production per
2010-09-07 CSR-PI-5.2.1
NOEC (25 d): 2.5 µg/L
dissolved (nominal) based
on: biomass
production/female
3 (not reliable)
supporting study
read-across based on
grouping of
CHEMICAL SAFETY REPORT
Bodar CWM, Van
Leeuwen CJ,
Voogt PA and
Zandee DI (1988)
144
EC number:
233-331-6
Method
cadmium sulphate
Results
female
CAS number:
10124-36-4
Remarks
Reference
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Daphnia magna
freshwater
NOEC (21 d): 1 µg/L
dissolved (nominal) based
on: weight/animal
semi-continuous flow
freshwater
supporting study
Biesinger KE and
Christensen GM
(1972)
read-across based on
grouping of
substances (category
approach)
Weight measurement after exposure: 3
week old animals were collected on
paper toweling, transferred to small
plastic cups and dried to a constant
weight, then weighed.
Daphnia pulex
3 (not reliable)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
NOEC (104 d): 1 µg/L
dissolved (nominal) based
on: longevity
semi-continuous flow
3 (not reliable)
supporting study
Bertram PE and
Hart BA (1979)
read-across based on
grouping of
substances (category
approach)
Determination of average longevity
with exposure to cadmiated water or
food
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Daphnia sp.
freshwater
semi-static
Determination of average longevity
with exposure to cadmiated water
NOEC (154 d): 2 µg/L
dissolved (nominal) based
on: number of individuals
4 (not assignable)
Marshall JS (1978)
supporting study
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
145
EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Method
Results
Remarks
Reference
Ceriodaphnia sp.
NOEC (9 d): 3.4 µg/L
dissolved (meas. (not
specified)) based on:
reproduction
3 (not reliable)
Spehar RL and
Carlson AR (1984)
freshwater
static
Method described by Mount&Norberg
1984 (see reference)
supporting study
Mount DI and
read-across based on Norberg TJ (1984)
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
other aquatic crustacea: Hyalella
azteca
freshwater
NOEC (42 d): 0.51 µg/L
dissolved (meas. (not
specified)) based on:
survival
flow-through
other - no details
3 (not reliable)
supporting study
Ingersoll C and
Kemble N (2000)
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
Cadmium (See
endpoint summary
for justification of
read-across)
other aquatic arthropod: Chironomus
tentans
freshwater
NOEC (20 d): 5.8 µg/L
3 (not reliable)
dissolved (meas. (not
specified)) based on: weight supporting study
Ingersoll C and
Kemble N (2000)
read-across based on
grouping of
substances (category
approach)
flow-through
other - no details
Test material
(IUPAC name):
Cadmium (See
endpoint summary
for justification of
read-across)
Eirene viridula, Cnidaria, Medusa,
Eirenidae
saltwater
NOEC (3 mo): 100 µg/L
dissolved (nominal) based
on: development
2 (reliable with
restrictions)
key study
semi-static
experimental result
3-mo hydroid development test
Test material (EC
name): cadmium
sulphate
other aquatic mollusc: Tresus nuttalli, NOEC (48 h): 42 µg/L
Horse clam, Molluscs
dissolved (nominal) based
on: larval development
2 (reliable with
restrictions)
2010-09-07 CSR-PI-5.2.1
Karbe L (1972)
CHEMICAL SAFETY REPORT
Cardwell, R.D.,
C.E. Woelke, M.I.
Carr, and E.W.
146
EC number:
233-331-6
Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
saltwater
key study
static
experimental result
48h larval development test on the
horse clam Tresus nuttalli
Test material (EC
name): cadmium
sulphate
other aquatic crustacea: Artemia
fransiscana, brine shrimp
saltwater
static
24h mortality test on instar II nauplii,
designed for dose-response
LC10 (24 h): 33 µg/L
dissolved (meas. (not
specified)) based on:
mortality
2 (reliable with
restrictions)
LC10 (24 h): 46.7 µg/L
dissolved (meas. (not
specified)) based on:
mortality
read-across based on
grouping of
substances (category
approach)
key study
Reference
Sanborn (1979)
Raquel Sarabia,
Jose Del Ramo,
Inma Varo, Javier
Di´Az-Mayans,
Amparo (2002)
Test material (EC
name): cadmium
metal (See endpoint
summary for
justification of
read-across)
other aquatic crustacea: Artemia
parthenogenetica, brine shrimp
saltwater
static
24h mortality test on instar II nauplii,
designed for dose-response
other aquatic crustacea: Artemia
persimilis, brine shrimp
saltwater
LC10 (24 h): 111 µg/L
dissolved (meas. (not
specified)) based on:
mortality
2 (reliable with
restrictions)
LC10 (24 h): 66.1 µg/L
dissolved (meas. (not
specified)) based on:
mortality
read-across based on
grouping of
substances (category
approach)
LC10 (24 h): 162.6
dissolved (meas. (not
specified)) based on:
mortality
Test material (EC
name): cadmium
metal (See endpoint
summary for
justification of
read-across)
LC10 (24 h): 99.5 µg/L
dissolved (meas. (not
specified)) based on:
mortality
2 (reliable with
restrictions)
static
key study
key study
read-across based on
grouping of
substances (category
approach)
24h mortality test on instar II nauplii,
designed for dose-response
Raquel Sarabia,
Jose Del Ramo,
Inma Varo, Javier
Di´Az-Mayans,
Amparo (2002)
Raquel Sarabia,
Jose Del Ramo,
Inma Varo, Javier
Di´Az-Mayans,
Amparo (2002)
Test material (EC
name): cadmium
metal (See endpoint
summary for
justification of
read-across)
other aquatic crustacea: Artemia
salina, brine shrimp
2010-09-07 CSR-PI-5.2.1
LC10 (24 h): 58.6 µg/L
dissolved (meas. (not
specified)) based on:
2 (reliable with
restrictions)
CHEMICAL SAFETY REPORT
Raquel Sarabia,
Jose Del Ramo,
Inma Varo, Javier
147
EC number:
233-331-6
Method
saltwater
static
24h mortality test on instar II nauplii,
designed for dose-response
cadmium sulphate
Results
mortality
LC10 (24 h): 54.9 µg/L
dissolved (meas. (not
specified)) based on:
mortality
CAS number:
10124-36-4
Remarks
Reference
key study
Di´Az-Mayans,
Amparo (2002)
read-across based on
grouping of
substances (category
approach)
Test material (EC
name): cadmium
metal (See endpoint
summary for
justification of
read-across)
other aquatic worm: Ctenodrilus
serratus, Annelid, Polychaete,
Ctenodrilidae
saltwater
static
21-d annelid reproduction test
NOEC (21 d): 1000 µg/L
dissolved (zinc) (nominal)
based on: reproduction
2 (reliable with
restrictions)
Reish DJ & Carr
RS (1978)
key study
read-across based on
grouping of
substances (category
approach)
Test material (EC
name): cadmium
chloride (See
endpoint summary
for justification of
read-across)
other aquatic worm: Neanthes
arenaceaodentata, Annelid,
Polychaete, Nereididae
saltwater
semi-static
9-months annelid reproduction test
other aquatic worm: Capitella
capitata, Annelida, Polychaete worm,
Capitellidae
saltwater
semi-static
2 months annelid reproduction test
2010-09-07 CSR-PI-5.2.1
NOEC (9 mo): 50 µg/L
2 (reliable with
Reish DJ &
dissolved (estimated) based restrictions)
Gerlinger TV
on: reproduction
(1984)
key study
NOEC (9 mo): 100 µg/L
dissolved (nominal) based read-across based on
grouping of
on: reproduction
substances (category
approach)
NOEC (6 mo): 320 µg/L
dissolved (nominal) based
Test material (EC
on: reproduction
name): cadmium
LOEC (9 mo): 320 µg/L
chloride (See
dissolved (nominal) based endpoint summary
on: reproduction
for justification of
read-across)
LOEC (6 mo): 1000 µg/L
dissolved (nominal) based
on: reproduction
NOEC (2 mo): 126.5 µg/L 2 (reliable with
dissolved (estimated) based restrictions)
on: reproduction
key study
NOEC (2 mo): 160 µg/L
dissolved (nominal) based read-across based on
grouping of
on: reproduction
substances (category
approach)
NOEC (2 mo): 100 µg/L
dissolved (nominal) based
CHEMICAL SAFETY REPORT
Reish DJ,
Gerlinger TV,
Phillips CA &
Schmidtbauer PD
(1977)
148
EC number:
233-331-6
Method
cadmium sulphate
Results
on: reproduction
other aquatic worm: Ctenodrilus
serratus, Annelida, Polychaeta,
Nereididae
saltwater
semi-static
35-42d annelid reproduction test
other aquatic worm: Ophiotrocha
labronica
saltwater
CAS number:
10124-36-4
Remarks
Reference
Test material (EC
name): cadmium
chloride (See
endpoint summary
for justification of
read-across)
NOEC (35 d): 103 µg/L
2 (reliable with
dissolved (estimated) based restrictions)
on: reproduction
key study
NOEC (35 d): 100 µg/L
dissolved (nominal) based read-across based on
grouping of
on: reproduction
substances (category
approach)
NOEC (35 d): 106 µg/L
dissolved (nominal) based
Test material (EC
on: reproduction
name): cadmium
chloride (See
endpoint summary
for justification of
read-across)
Reish DJ,
Gerlinger TV,
Phillips CA &
Schmidtbauer PD
(1977)
NOEC (30 d): 100 µg/L
2 (reliable with
dissolved (estimated) based restrictions)
on: growth rate, size at
key study
maturity time to maturity
Roed K.H. (1980)
semi-static
read-across based on
grouping of
substances (category
approach)
>30-d exposure test on annelid,
designed for dose-response
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Campanularia flexuosa, Hydroid,
Cnidaria
saltwater
NOEC (11 d): 87.7 µg/L
2 (reliable with
dissolved (estimated) based restrictions)
on: growth
key study
semi-static
Moore, M.N., and
A.R.D. Stebbing
(1976)
read-across based on
grouping of
substances (category
approach)
11-d growth test on the hydroid
Campanularia flexuosa, designed for
dose-response
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
other aquatic crustacea: Paragrapsus
2010-09-07 CSR-PI-5.2.1
NOEC (4 d): 105 µg/L
2 (reliable with
CHEMICAL SAFETY REPORT
Ahsanullah M &
149
EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Method
Results
quadridentatus, Toothed Shore Crab,
Grapsidae
dissolved (zinc) (estimated) restrictions)
based on: mortality
key study
saltwater
Remarks
Reference
Arnott GH (1978)
read-across based on
grouping of
substances (category
approach)
semi-static
4-d survival test on crab larvae
Test material (EC
name): cadmium
chloride (See
endpoint summary
for justification of
read-across)
Mysidopsis bahia (new name:
Americamysis bahia)
saltwater
NOEC (33 d): 2 µg/L
1 (reliable without
dissolved (estimated) based restriction)
on: growth
key study
flow-through
read-across based on
grouping of
substances (category
approach)
33-d growth test on mysids, designed
for dose-response
Carr, R.S., J.W.
Williams, F.I.
Saksa, R.L. Buhl,
and J.M. Neff
(1985)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
other aquatic crustacea: Peneus
monodon, Tiger shrimp
saltwater
NOEC (7 d): 33.33 µg/L
2 (reliable with
dissolved (estimated) based restrictions)
on: immobilisation
key study
static
Chien-Min Chen,
Ming-Chao Liu.
(2006b)
read-across based on
grouping of
substances (category
approach)
ELS tests methods standardized by
EPA Taiwan with modifications
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
other aquatic crustacea: Tigriopus
brevicornis, Copepod, Harpacticidae
saltwater
static
10-d reproductive toxicity and larval
development of copepods test
2010-09-07 CSR-PI-5.2.1
EC10 (10 d): 34.94 µg/L
dissolved (nominal) based
on: reproduction (larval
development)
2 (reliable with
restrictions)
EC10 (10 d): 41.48 µg/L
dissolved (nominal) based
on: reproduction
(prod/female)
read-across based on
grouping of
substances (category
approach)
Le Dean L &
Devineau J (1987)
key study
CHEMICAL SAFETY REPORT
150
EC number:
233-331-6
Method
cadmium sulphate
Results
Remarks
EC10 (10 d): 34.04 µg/L
dissolved (nominal) based
on: reproduction
(copepodites/total larv.
Prod)
Test material (EC
name): cadmium
chloride (See
endpoint summary
for justification of
read-across)
EC10 (10 d): 36.7 µg/L
dissolved (estimated) based
on: reproduction
other aquatic crustacea: Elminius
modestus
saltwater
CAS number:
10124-36-4
NOEC (28 d): 316 µg/L
dissolved (meas. (not
specified)) based on:
mortality
semi-static
2 (reliable with
restrictions)
Reference
Rainbow PS &
White SL (1989)
key study
read-across based on
grouping of
substances (category
approach)
28 days mortality test on the barnacle
Elminius modestus
Test material (EC
name): cadmium
chloride (See
endpoint summary
for justification of
read-across)
Mysidopsis bahia (new name:
Americamysis bahia)
saltwater
EC10 (28 d): 6.3 µg/L
dissolved (meas. (not
specified)) based on:
mortality
flow-through
2 (reliable with
restrictions)
key study
EC10 (28 d): 1.6 µg/L
dissolved (meas. (not
28d mortality test on mysids, designed specified)) based on:
for dose-response
mortality
read-across based on
grouping of
substances (category
approach)
EC10 (28 d): 1.1 µg/L
dissolved (meas. (not
specified)) based on:
mortality
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
other aquatic crustacea: Balanus
amphitrite
saltwater
static
6d settlement behaviour test on the
barnacle Balanus amphitrite, designed
for dose-response
NOEC (6 d): 5 µg/L
2 (reliable with
dissolved (estimated) based restrictions)
on: behaviour, settlement
key study
Voyer, R.A., and
D.G. McGovern
(1991)
Wu, R.S.S., P.K.S.
Lam, and B. Zhou
(1997)
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
151
EC number:
233-331-6
Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
read-across)
Arbacia lixula, Sea Urchin, Arbaciidae NOEC (38 h): 357 µg/L
2 (reliable with
Cesar A, Maríndissolved (estimated) based restrictions)
Guirao L, Vita R
saltwater
on: development
& Marín A (2002)
key study
static
read-across based on
equivalent or similar to EPA/600/ Rgrouping of
95-136,
substances (category
approach)
equivalent or similar to Environment
Canada EPS 1/RM/27
Test material (EC
name): cadmium
equivalent or similar to CETESB
chloride (See
L5.250
endpoint summary
for justification of
read-across)
Spherechinus granularis, Sea Urchin,
Arbaciidae
saltwater
static
equivalent or similar to EPA/600/ R95-136,
equivalent or similar to Environment
Canada EPS 1/RM/27
equivalent or similar to CETESB
L5.250
NOEC (38 h): 623 µg/L
2 (reliable with
dissolved (estimated) based restrictions)
on: development
key study
Cesar A, MarínGuirao L, Vita R
& Marín A (2002)
read-across based on
grouping of
substances (category
approach)
Test material (EC
name): cadmium
chloride (See
endpoint summary
for justification of
read-across)
Lytechinus pictus, sea urchin,
Echinodermata
NOEC (80 min): 12.5 µg/L 2 (reliable with
dissolved (nominal) based restrictions)
on: fertilization
saltwater
key study
NOEC (80 min): 4.2 µg/L
static
dissolved (estimated) based read-across based on
grouping of
on: fertilization
ASTM (1987) Sea Urchin Fertilization
substances (category
Test method 1008. US EPA (1988)
approach)
Short-Term method for estimating
chronic toxicity of effluents and
Test material
receiving waters to marine and
(IUPAC name):
estuarine organisms. 600/4-87/028.
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Jonczyk, E., K.G.
Doe, P.C. Wells,
and S.G. Yee
(1991)
Strongylocentrotus droebachiensis, sea NOEC (80 min): 12.5 µg/L 2 (reliable with
urchin, Echinodermata
dissolved (nominal) based restrictions)
on: fertilization
saltwater
key study
Jonczyk, E., K.G.
Doe, P.C. Wells,
and S.G. Yee
(1991)
static
ASTM (1987) Sea Urchin Fertilization
Test method 1008. US EPA (1988)
2010-09-07 CSR-PI-5.2.1
read-across based on
grouping of
substances (category
CHEMICAL SAFETY REPORT
152
EC number:
233-331-6
Method
cadmium sulphate
Results
Short-Term method for estimating
chronic toxicity of effluents and
receiving waters to marine and
estuarine organisms. 600/4-87/028.
Asterias amurensis, Northern Pacific
Seastar, Asteriidae
saltwater
static
equivalent or similar to EPA/600/ R95-136
CAS number:
10124-36-4
Remarks
Reference
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
NOEC (80 min): 10000
µg/L dissolved (estimated)
based on: fertilization
LOEC (80 min): 80000
µg/L dissolved (nominal)
based on: fertilization:
presence of fertilization
membrane
2 (reliable with
restrictions)
key study
Lee CH, Ryu TK,
Chang M & Choi
JW (2004)
read-across based on
grouping of
substances (category
approach)
Test material (EC
name): cadmium
chloride (See
endpoint summary
for justification of
read-across)
Paracentrotus lividus, sea urchin,
Echinodermata
saltwater
static
60 min fertilization test on
Paracentrotus lividus, designed for
dose-response
NOEC (60 min): 11.2 µg/L 2 (reliable with
dissolved (nominal) based restrictions)
on: fertilization
key study
Pagano G,
Esposito A,
Giordano GG
(1982)
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
other aquatic mollusc: Isognomon
californicum, bivalve, molluscs
saltwater
semi-static
4d growth test on bivalves Isognomon
californicum, designed for doseresponse
NOEC (4 d): 0.3 µg/L
2 (reliable with
dissolved (estimated) based restrictions)
on: larval growth
key study
Ringwood, A.H.
(1992)
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
153
EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Method
Results
Remarks
Paracentrotus lividus, echinoid,
Echinodermata
NOEC (75 min): 112.4
µg/L dissolved (nominal)
based on: fertilization
2 (reliable with
restrictions)
other aquatic mollusc: Mytilus
galloprovincialis, Blue mussel,
Mytilidae
NOEC (2 d): 250 µg/L
dissolved (nominal) based
on: embryogenesis
2 (reliable with
restrictions)
Reference
Warnau M,
Iaccarino M, De
Biase A, Temara
saltwater
key study
A, Jangoux M,
NOEC (72 h): 112.4 µg/L
Dubois P &
static
dissolved (nominal) based read-across based on Pagano G (1996)
on: embryonic development grouping of
85 min fertilization test on sperm cells
substances (category
of the echinoid Paracentrotus lividus,
approach)
designed for dose-response
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
saltwater
key study
Beiras R &
Albentosa M
(2004)
read-across based on
grouping of
substances (category
approach)
static
2-d larval development of marine
mollusks, dose-response designed test
Test material (EC
name): cadmium
chloride (See
endpoint summary
for justification of
read-across)
other aquatic mollusc: Ruditapes
decussatus, Grooved Carpet shell
clam, Veneridae
saltwater
static
2-d larval development of marine
mollusks, dose-response designed test
EC10 (2 d): 265 µg/L
dissolved (nominal) based
on: development
2 (reliable with
restrictions)
key study
Beiras R &
Albentosa M
(2004)
read-across based on
grouping of
substances (category
approach)
Test material (EC
name): cadmium
chloride (See
endpoint summary
for justification of
read-across)
other aquatic mollusc: Meretrix
lusoria, Hard clam
saltwater
static
ELS tests methods standardized by
EPA Taiwan with modifications
2010-09-07 CSR-PI-5.2.1
NOEC (7 d): 33.33 µg/L
2 (reliable with
dissolved (estimated) based restrictions)
on: immobilisation
key study
Chien-Min Chen,
Ming-Chao Liu.
(2006b)
read-across based on
grouping of
substances (category
approach)
CHEMICAL SAFETY REPORT
154
EC number:
233-331-6
Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
other aquatic mollusc: Ilyanassa
obsoleta
saltwater
NOEC (142 min): 112.4
µg/L dissolved (nominal)
based on: development
static
2 (reliable with
restrictions)
Conrad, GW
(1988)
key study
read-across based on
grouping of
substances (category
approach)
142 min development test on the
mudsnail, Ilyanassa obsoleta, Molluscs
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Mya arenaria
saltwater
NOEC (7 d): 50 µg/L
dissolved (nominal) based
on: mortality
static
2 (reliable with
restrictions)
Eisler R (1977)
key study
read-across based on
grouping of
substances (category
approach)
lab designed test for dose-response
Test material (EC
name): cadmium
chloride (See
endpoint summary
for justification of
read-across)
other aquatic mollusc: Haliotis rubra, EC10 (2 d): 520 µg/L
Blacklip Abalone, Haliotidae
dissolved (nominal) based
on: development
saltwater
2 (reliable with
restrictions)
static
read-across based on
grouping of
substances (category
approach)
Similar to: Hunt JW, Anderson BS.
1990. Abalone larval development:
Short-term toxicity test protocol. In:
Anderson BW, Hunt JW, Turpen SL,
Coulon AR, Martin M, McKeown DL,
Palmer FH, eds, Procedures Manual
for Conducting Toxicity Tests
Developed by the Marine Bioassay
Project. 90-10WQ. California State
Water Resources Control Board,
Sacramento, CA, USA, pp 17–48.
2010-09-07 CSR-PI-5.2.1
key study
Gorski J &
Nugegoda D
(2006)
Test material (EC
name): cadmium
chloride (See
endpoint summary
for justification of
read-across)
CHEMICAL SAFETY REPORT
155
EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Method
Results
Remarks
Reference
other aquatic mollusc: Mytilus edulis
LC5 (96 h): 480 µg/L
dissolved (nominal) based
on: mortality
2 (reliable with
restrictions)
Nelson DA, Miller
JE & Calabrese A
(1988)
saltwater
static renewal
key study
read-across based on
grouping of
substances (category
approach)
lab designed test for dose-response
Test material (EC
name): cadmium
chloride (See
endpoint summary
for justification of
read-across)
other aquatic mollusc: Perna viridis,
Green mussel, Molluscs
saltwater
NOEC (24 h): 140 µg/L
1 (reliable without
dissolved (meas. (not
restriction)
specified)) based on: larval
key study
development
static
read-across based on
grouping of
substances (category
approach)
ASTM 1993. Standard guide for
conducting static acute toxicity test
starting with embryos of four species
of saltwater bivalve molluscs. Method
E724-89.
other aquatic mollusc: Mytilus
galloprovincialis, Blue mussel,
Mytilidae
saltwater
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
NOEC (2 d): 1100 µg/L
dissolved (nominal) based
on: development (shell
length)
2-d larval development of marine
mollusks, lad designed test for doseresponse
saltwater
static
3h fertilization test on sea urchin
echinometra mathaei, designed for
dose-response
2010-09-07 CSR-PI-5.2.1
2 (reliable with
restrictions)
key study
read-across based on
grouping of
substances (category
approach)
static
Echinometra mathaei, sea urchin,
Echinodermata
Panggabean LMG
(1997)
Pavicic J, Skreblin
M, Kregar I,
Tusekznidaric M
& Stegnar P
(1994)
Test material (EC
name): cadmium
chloride (See
endpoint summary
for justification of
read-across)
NOEC (3 h): 10 µg/L
dissolved (nominal) based
on: fertilization
2 (reliable with
restrictions)
Ringwood, A.H.
(1992)
key study
read-across based on
grouping of
substances (category
approach)
CHEMICAL SAFETY REPORT
156
EC number:
233-331-6
Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
Test material (EC
name): cadmium
chloride (See
endpoint summary
for justification of
read-across)
other aquatic mollusc: Crassostrea
gigas, Oyster, Ostreidae
saltwater
semi-static
4-d growth inhibition test of oyster
larvae, test designed for dose-response
EC10 (4 d): 13 µg/L
2 (reliable with
dissolved (estimated) based restrictions)
on: growth (valve width)
key study
Watling HR
(1982)
read-across based on
grouping of
substances (category
approach)
Test material (EC
name): cadmium
chloride (See
endpoint summary
for justification of
read-across)
other aquatic mollusc: Crassostrea
cucullata, Oyster, Ostreidae
saltwater
semi-static
4-d growth inhibition test of oyster
larvae, tests designed for doseresponse
NOEC (4 d): 5 µg/L
2 (reliable with
dissolved (estimated) based restrictions)
on: growth (valve width)
key study
Watling HR
(1982)
read-across based on
grouping of
substances (category
approach)
Test material (EC
name): cadmium
chloride (See
endpoint summary
for justification of
read-across)
other aquatic mollusc: Crassostrea
margaritacea , Oyster, Ostreidae
saltwater
semi-static
4-d growth inhibition test of oyster
larvae, test designed for dose-response
EC10 (4 d): 12.6 µg/L
2 (reliable with
dissolved (estimated) based restrictions)
on: growth (valve width)
key study
Watling HR
(1982)
read-across based on
grouping of
substances (category
approach)
Test material (EC
name): cadmium
chloride (See
endpoint summary
for justification of
read-across)
Monhystera disjuncta
saltwater
2010-09-07 CSR-PI-5.2.1
NOEC (11 d): 3333 µg/L
2 (reliable with
dissolved (estimated) based restrictions)
on: mortality
CHEMICAL SAFETY REPORT
Vranken, G., R.
Vanderhaeghen,
and C. Heip
157
EC number:
233-331-6
Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
static
key study
chronic toxicity test for mortality on
nematods, designed for dose-response
read-across based on
grouping of
substances (category
approach)
Reference
(1985)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Monhystera microphtalma
saltwater
EC6 (13 d): 1000 µg/L
dissolved (nominal) based
on: mortality
static
2 (reliable with
restrictions)
key study
Vranken, G., R.
Vanderhaeghen,
and C. Heip
(1985)
read-across based on
grouping of
substances (category
approach)
chronic toxicity test for mortality on
nematods, designed for dose-response
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Pellioditis marina
saltwater
static
NOEC (8 d): 25000 µg/L
2 (reliable with
dissolved (estimated) based restrictions)
on: mortality
key study
Vranken, G., R.
Vanderhaeghen,
and C. Heip
(1985)
read-across based on
grouping of
substances (category
approach)
chronic toxicity test for mortality on
nematods, designed for dose-response
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
other aquatic crustacea: Moina
monogolica
saltwater
semi-static
ASTM (2004)
2010-09-07 CSR-PI-5.2.1
EC10 (21 d): 1.78 µg/L
dissolved (meas. (not
specified)) based on:
reproduction (net
reproductive rate)
1 (reliable without
restriction)
key study
Wang Z., C. Yan
and X. Zhang
(2009)
read-across based on
grouping of
substances (category
approach)
CHEMICAL SAFETY REPORT
158
EC number:
233-331-6
Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
other aquatic mollusc: Mytilus
galloprovincialis
saltwater
NOEC (48 h): 6.25 µg/L
dissolved (nominal) based
on: larval development
static
1 (reliable without
restriction)
key study
Prato E &
Biandolino F
(2007)
read-across based on
grouping of
substances (category
approach)
ASTM, E1563-98 Standard guide for
conducting static acute toxicity tests
with echinoid embryos (2004) EPA
/600/R95/136 Short-term methods for
estimating the chronic toxicity of
effluents and receiving waters to west
coast marine and estuarine Organisms
Test material
(IUPAC name):
cadmium dinitrate
(See endpoint
summary for
justification of
read-across)
Discussion
Freshwater: 22 studies on 8 invertebrate species (Crustaceans, Insect and Gastropods) were selected in the EU
RA to derive the PNEC freshwater. NOECs range between 0.16 and 11 µg/l Cd in dissolved concentrations.
Marine: Relevant and reliable marine chronic toxicity data on invertebrates were found in 6 taxonomic groups
including Annelids (4 families), Cnidarians (2 families), Crustaceans (8 families), Echinoderms (7 families),
Molluscs (9 families) and Nematods (2 families). The invertebrate dataset covers a large range of NOEC values
going from 0.3 µg/L up to 25000 µg/L. Data on the 6 invertebrate taxonomic groups are combined together with
the other marine chronic data in the species sensitivity distribution to give the HC5 from which the PNEC is
derived.
The following information is taken into account for long-term toxicity to aquatic invertebrates for the derivation
of PNEC:
freshwater: 22 studies on 8 invertebrate species were selected in the EU RA to derive the PNEC freshwater.
NOECs range between 0.16 and 11 µg/l Cd in dissolved concentrations.
marine waters: Data on 40 invertebrate species are available. Species NOECs range between 0.3 µg Cd/L
(Isognomon californicum, Isognomonidae, Molluscs) up to 25000 µg Cd/L (Pellioditis marina, Rhabditidae,
Nematods). Concentrations are expressed as dissolved ones.
7.1.1.3. Algae and aquatic plants
The results are summarised in the following table:
Table 47. Overview of effects on algae and aquatic plants
Method
Results
Remarks
Reference
Coelastrum proboscideum (algae)
NOEC (1 d): 6.3 µg/L
dissolved (meas. (not
specified)) based on:
2 (reliable with
restrictions)
Müller KW and
Payer HD (1979)
freshwater
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
159
EC number:
233-331-6
Method
static
24h growth test
cadmium sulphate
Results
biomass
NOEC (1 d): 27 µg/L
dissolved (meas. (not
specified)) based on:
biomass
Selenastrum capricornutum (new
EC50 (72 h): 23 µg/L
name: Pseudokirchnerella subcapitata) dissolved (meas. (not
(algae)
specified)) based on:
biomass
freshwater
NOEC (3 d): 2.4 µg/L
static
dissolved (meas. (not
specified)) based on: cell
OECD Guideline 201 (Alga, Growth
number
Inhibition Test)
CAS number:
10124-36-4
Remarks
Reference
key study
experimental result
Test material (EC
name): cadmium
sulphate
1 (reliable without
restriction)
K. Van der Kerken
(1998)
key study
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium (See
endpoint summary
for justification of
read-across)
Selenastrum capricornutum (new
EC50 (72 h): 70 µg/L
name: Pseudokirchnerella subcapitata) dissolved (meas. (TWA))
(algae)
based on: growth rate
freshwater
1 (reliable without
restriction)
key study
Janssen
Pharmaceutica
(1993c)
read-across based on
grouping of
substances (category
approach)
static
OECD Guideline 201 (Alga, Growth
Inhibition Test)
Test material
(IUPAC name):
cadmium (See
endpoint summary
for justification of
read-across)
Asterionella formosa (algae)
freshwater
static
1-d growth rate test
NOEC (1 d): 0.85 µg/L
dissolved (meas. (not
specified)) based on:
biomass
2 (reliable with
restrictions)
LOEC (1 d): 1.9 µg/L
dissolved (meas. (not
specified)) based on:
biomass
read-across based on
grouping of
substances (category
approach)
key study
Conway HL and
Williams SC
(1979)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Selenastrum capricornutum (new
EC50 (72 h): 23 µg/L
name: Pseudokirchnerella subcapitata) dissolved (meas. (not
2010-09-07 CSR-PI-5.2.1
1 (reliable without
restriction)
CHEMICAL SAFETY REPORT
K. Van der Kerken
(1998)
160
EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Method
Results
Remarks
(algae)
specified)) based on:
biomass
key study
NOEC (3 d): 2.4 µg/L
dissolved (meas. (not
specified)) based on: cell
number
read-across based on
grouping of
substances (category
approach)
freshwater
static
OECD Guideline 201 (Alga, Growth
Inhibition Test)
Reference
Test material
(IUPAC name):
cadmium (See
endpoint summary
for justification of
read-across)
Selenastrum capricornutum (new
EC50 (72 h): 70 µg/L
name: Pseudokirchnerella subcapitata) dissolved (meas. (TWA))
(algae)
based on: growth rate
freshwater
1 (reliable without
restriction)
key study
Janssen
Pharmaceutica
(1993c)
read-across based on
grouping of
substances (category
approach)
static
OECD Guideline 201 (Alga, Growth
Inhibition Test)
Test material
(IUPAC name):
cadmium (See
endpoint summary
for justification of
read-across)
Selenastrum capricornutum (new
EC50 (72 h): 120 µg/L
name: Pseudokirchnerella subcapitata) dissolved (meas. (TWA))
(algae)
based on: growth rate
freshwater
1 (reliable without
restriction)
key study
Janssen
Pharmaceutica
(1993d)
read-across based on
grouping of
substances (category
approach)
static
OECD Guideline 201 (Alga, Growth
Inhibition Test)
Test material
(IUPAC name):
oxocadmium (See
endpoint summary
for justification of
read-across)
Selenastrum capricornutum (new
EC50 (72 h): 18 µg/L
name: Pseudokirchnerella subcapitata) dissolved (meas. (not
(algae)
specified)) based on:
growth rate
freshwater
static
OECD Guideline 201 (Alga, Growth
Inhibition Test)
1 (reliable without
restriction)
LISEC (1998a)
key study
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
oxocadmium (See
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
161
EC number:
233-331-6
Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
endpoint summary
for justification of
read-across)
Coelastrum proboscideum (algae)
freshwater
static
24h growth test
Chlamydomonas reinhardtii (algae)
freshwater
NOEC (1 d): 6.3 µg/L
dissolved (meas. (not
specified)) based on:
biomass
2 (reliable with
restrictions)
NOEC (1 d): 27 µg/L
dissolved (meas. (not
specified)) based on:
biomass
experimental result
NOEC (7 d): 7.5 µg/L
dissolved (nominal) based
on: cell number
3 (not reliable)
Müller KW and
Payer HD (1979)
key study
Test material
(IUPAC name):
cadmium sulfate
supporting study
Lawrence SG,
Holoka MH and
Hamilton RD
(1989)
flow-through
LOEC (7 d): 10 µg/L
dissolved (nominal) based
two-stage, nitrogen-limited chemostat - on: cell number
7d experiment with endpoint = steady
state cell number
read-across based on
grouping of
Lawrence SG and
substances (category Holoka MH
approach)
(1979)
Two-stage chemostat apparatus
described by Lawrence & Holoka
(1979), see reference above
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Lemna paucicostata (algae)
freshwater
static
7d growth experiment (number of
fronds)
NOEC (7 d): 5 µg/L
dissolved (nominal) based
on: number of fronds
3 (not reliable)
NOEC (7 d): 10 µg/L
dissolved (nominal) based
on: number of fronds
read-across based on
grouping of
substances (category
approach)
supporting study
Nasu Y and
Kugimoto M
(1989)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Scenedesmus quadricauda (algae)
freshwater
static
7d static test with endpoint = biomass
NOEC (7 d): 31 µg/L
dissolved (nominal) based
on: biomass
3 (not reliable)
supporting study
Bringmann G and
Kühn R (1980)
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dinitrate
(See endpoint
summary for
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
162
EC number:
233-331-6
Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
justification of
read-across)
Chaetoceros compressum (algae)
saltwater
static
EC10 (3 d): 18.3 µg/L
2 (reliable with
dissolved (estimated) based restrictions)
on: growth rate
key study
Fisher NS & Frood
D (1980)
read-across based on
grouping of
substances (category
approach)
3-d growth inhibition test with marine
diatom, designed for dose-response
Test material (EC
name): cadmium
chloride (See
endpoint summary
for justification of
read-across)
Ulva pertusa (algae)
saltwater
static
5-d sporulation test with marine
macroalga, designed for dose-response
NOEC (5 d): 63 µg/L
dissolved (nominal) based
on: reproduction,
sporulation
2 (reliable with
restrictions)
Taejun Han, GyeWoon Choi (2005)
key study
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Discussion
Effects on algae / cyanobacteria
The good quality data that were available for all Cd-substances were considered together, since the toxicity of
the Cd++ ion is key to this analysis.
freshwater short-term:
Data were available on 1 species. The lowest short-term EC50 is observed on Selenastrum caprocornutum: 18
µg Cd/l (single measured value). This value is used as the reference value for short-term toxicity to aquatic
organisms, used for classification. The EC50 values on this species ranged between 18 and 120 µg Cd/l. Results
were obtained at neutral/high pH where toxicity is expected to be highest.
Long-term toxicity: 8 reliable studies were considered for algae on 6 differents species. The NOECs, ranging
from 0.85 to 31 µg/l Cd dissolved) were conbined to the other chronic data in the SSD to determine HC5 and
further the PNEC.
Marine toxicity:
Relevant and reliable chronic toxicity data were found for one species of micro-algae (family Chaetocerotacae)
and one species of macro-algae (family Ulvacae). Those two species are not among the most sensitive endpoints
in the species sensitivity distribution (SSD) but they are situated in the first half of the fraction affected (NOEC
range: 18.3 -63 µg Cd/L).
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Algae species NOECs were combined together with other marine chronic data in the SSD to give the HC5 from
which the PNEC is derived.
The following information is taken into account for effects on algae / cyanobacteria for the derivation of PNEC:
freshwater short-term:
The good quality short-term data that were available for all Cd-substances were considered together, since the
toxicity of the Cd++ ion is key to this analysis.
Data were available on 1 species. The lowest short-term EC50 is observed on Selenastrum capricornutum: 18 µg
Cd/l (single measured value). The EC50 values on this species ranged between 18 and 120 µg Cd/l.
marine waters: Data on 2 algae species available. Species NOECs values are of 18.3 µg Cd/L for the microalgae Chaetoceros compressum and of 63 µg Cd/L for the macro-algae Ulva pertusa.
Value used for CSA:
EC50/LC50 for freshwater algae: 0.018 mg/L
7.1.1.4. Sediment organisms
The results are summarised in the following table:
Table 48. Overview of long-term effects on sediment organisms
Method
Results
Remarks
Leptocheirus plumulosus
NOEC (28 d): 1370 mg/kg
sediment dw (meas. (not
specified)) based on:
survival, growth (length)
and reproduction
(offspring/female)
1 (reliable without
restriction)
saltwater
long-term toxicity (laboratory study)
semi-static
28 d chronic sediment toxicity test on
the amphipod Leptocheirus plumulosus
Reference
DEWITT T,
SWARTZ RC,
HANSEN DJ,
weight of evidence MCGOVERN D,
BERRY WJ.
read-across based on (1996)
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium (See
endpoint summary
for justification of
read-across)
Caenorhabditis elegans
freshwater
short-term toxicity (laboratory study)
static
analysis of contaminants performed
according to DIN, ISO and EN.
NOEC (72 h): 1226.4
1 (reliable without
mg/kg sediment dw (meas. restriction)
(geom. mean)) based on:
weight of evidence
growth (body length)
HOSS S., T
HENSCHEL, M
HAITZER, W
TRAUNSPURGE
R, CEW
read-across based on STEINBERG
grouping of
(2001)
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Chironomus sp.
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NOEC (56 wk): 115 mg/kg 2 (reliable with
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Method
Results
Remarks
Reference
freshwater
sediment dw (nominal)
based on: abundance
restrictions)
Carignan and M.
A. Huerta-Diaz
(1994)
long-term toxicity (field study)
field
field test
weight of evidence
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dinitrate
(See endpoint
summary for
justification of
read-across)
Annelids, molluscs, arthropods,
nematods, sipuncula, cniderians,
rhinocaelians, chordates
saltwater
long-term toxicity (field study)
flow-through
118d in situ colonization study (field
study) looking at taxa richeness and
abundance of benthic invertebrates
NOEC (117 d): 1.3 µmol/g 2 (reliable with
measured SEM (meas. (not restrictions)
specified)) based on: taxa
supporting study
richeness, abundance
Hansen DJ,
Mahony JD, Berry
WJ, Benyi SJ,
Pratt SD, Di Toro
DM and Abel MB
read-across based on (1996)
grouping of
substances (category
approach)
Test material (EC
name): Cadmium
chloride (See
endpoint summary
for justification of
read-across)
Discussion
Freshwater PNECsediment: Conclusion
The assessment of the freshwater PNECsedimentfor cadmium identified only two long-term ecotoxicity studies
from the scientific literature. However, both the “Added” EqP (using partitioning coefficients and a robust
aquatic toxicity database from the Cd RAR) and AF (using the lowest NOEC from a field colonization study)
approaches produced consistent derivations for the freshwater benthic compartment. The resulting value is
considered protective for EU freshwater ecosystems: freshwaterPNECadd, sedimentof 1.80 mg/kg d. w.
(equivalent to 0.40 mg/kg w. w.). It is emphasized that this is an added PNEC, i. e. natural background
needs to be taken into account when characterising the risk from monitored data.
Marine PNECsediment: Conclusion
The assessment of the marinePNECsedimentfor cadmium identified only two long-term ecotoxicity studies from
the scientific literature. However, an “Added” EqP (using partitioning coefficients and a robust aquatic toxicity
database) approach provided a reliable derivation for the marine benthic compartment. The resulting value is
considered protective for EU marine ecosystems: marinePNECsediment, addedof 0.64 mg/kg d. w. (equivalent to
0.14 mg/kg w. w.). It is emphasised that this is an added PNEC, i. e. natural Bg needs to be taken into
account when characterising the risk from monitored data.
The following information is taken into account for sediment toxicity for the derivation of PNEC:
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Freshwater: chronic sediment data are available for one species of benthic nematode (Caenorhabditis elegans)
with a reported NOEC growth of 1225 mg/kg d. w. (geometric mean of three NOECs from same study). The test
was performed in unpolluted sediment with a background cadmium concentration of <1 mg/kg d. w. In addition,
an in-situ recolonization study is also available for freshwater systems with a NOEC abundance reported of 115
mg/kg d. w. The test was performed in unpolluted sediment with a background cadmium concentration of 2.8
mg/kg d. w.
Marine water: chronic sediment data are available for one species of benthic marine crustacean (Leptocheirus
plumulosus) with a reported NOEC growth, survival and reproduction of 1370 mg/kg d. w. The test was
performed in unpolluted sediment with a background cadmium concentration of <0.001 mg/kg d. w. In addition,
a field colonization study is also available for marine systems with a reported NOEC abundance and taxa
richeness of 169 mg added Cd/kg d. w.
7.1.1.5. Other aquatic organisms
The results are summarised in the following table:
Table 49. Overview of short-term effects on other aquatic organisms
Method
Results
Remarks
Reference
Xenopus laevis
NOEC (100 d): 9 µg/L
dissolved (meas. (not
specified)) based on:
inhibition of larval
development
3 (not reliable)
Canton JH and
Slooff (1982)
freshwater
semi-static
other - no details
supporting study
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Ciona intestinalis, vase tunicate,
Ascidiacea, Chordata
saltwater
static
Bellas J, Beiras R, Vazquez E (2003)
A standardisation of Ciona intestinalis
(Chordata, Ascidiacea) embryo-larval
bioassay for ecotoxicological studies.
Water Research 37 4613–4622
Ciona intestinalis, vase tunicate,
Ascidiacea, Chordata
saltwater
static
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NOEC (20 h): 512 µg/L
2 (reliable with
dissolved (estimated) based restrictions)
on: development
key study
Juan Bellas, Elsa
Vazquez, Ricardo
Beiras (2001)
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
NOEC (20 h): 362 µg/L
2 (reliable with
dissolved (estimated) based restrictions)
on: development
key study
Bellas J, Beiras R,
Vazquez E (2004)
read-across based on
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Method
Bellas J, Beiras R, Vazquez E (2003)
A standardisation of Ciona intestinalis
(Chordata, Ascidiacea) embryo-larval
bioassay for ecotoxicological studies.
Water Research 37 4613–4622
cadmium sulphate
Results
CAS number:
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Remarks
Reference
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
natural phytoplancton communities
from field
NOEC (4 h): > 1.5 µg/L
2 (reliable with
dissolved (estimated) based restrictions)
on: C fixation rate
saltwater
supporting study
NOEC (24 h): 2.5 µg/L
static
read-across based on
dissolved (meas. (not
grouping of
specified)) based on: C
Field experiment on natural
substances (category
fixation rate
phytoplancton communities looking at
approach)
C fixation rates as the endpoint,
designed for dose-response
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Wolter K, U.
Rabsch, P.
Krischker and A.
G. Davies (1984)
Discussion
In this section, we report chronic toxicity data on organims that do not belong to the invertebrate, algae or fish
groups. Indeed, reliable and relevant chronic cadmium toxicity data were found for one species of marine
ascidians (Ciona intestinalis, Ascidiacae, Urochordata). The datapoint was added to the aquatic marine SSD.
Field data are also reported in this section. They are important as PNECs for dissolved metals are primarily
based on single species data determined in the laboratory. It is important to check their capacity for protecting
the environment through field data, making the relationship between measured metal levels and observed
ecosystem effects in the field.
Freshwater:
Marine waters:
A study on phytoplankton communities dominated by diatoms was conducted at three different locations (Kiel
Fjord in Baltic Sea, North Sea and Atlantic ocean off Portugal). The lower NOEC carbon fixation rate was
recorded in Kiel Fjord with a value of 1.5 µg/L (Wolter et al. 1984).
The following information is taken into account for any hazard / risk assessment:
Toxicity to other aquatic organims: Marine waters: One ascidian species NOEC available (species mean NOEC
value for Ciona intestinalis of 430.5 µg Cd/L).
Field data on freshwater:
Field data on marine water: A field study on phytoplancton assemblages dominated by diatoms conducted in
Kiel Fjord, Baltic Sea presents a NOEC carbon fixation rate of 1.5 µg Cd/L (Wolter et al. 1984).
7.1.2. Calculation of Predicted No Effect Concentration (PNEC)
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7.1.2.1. PNEC freshwater
In the EU RA, it was concluded that the conditions for using a statistical extrapolation method to derive the
PNEC for Cd in freshwater were met. Accordingly, this approach is also used for the present analysis. All
chronic data mentioned in table above are used in a species sensitivity distribution (SSD), and the PNEC is
derived based on the HC5 concentration.
The EU RA discussed the differences between using RI 1 and 2 data only, or using these data combined with RI
3 data
Further, several ways of using the data were also discussed, i.e. using all NOECs as such (no species geomean),
using the species geomean, using the lowest NOEC by species, or using a “case-by-case” geomean value.
Selection on data quality does affect the value of the HC5: when all the data as such were used, there was a
difference in HC5 between using RI 1 and RI 2 data only, or combining them with RI 3 data: 0.39 µg Cd/l
versus 0.35 µg Cd/l, resp. (RA Cd, table 3.2.10.). Including less reliable data thus decreases the HC5. However,
by using all the distinct data (and not using the species geomean) for the species sensitivity distribution, the
more documented species were over-represented.
Using one geomean value per species or using the lowest NOEC per species was considered not appropriate for
the generic PNEC, because information from the database was lost with these approaches.
Finally, species geomean values were calculated on the RI 1, RI 2, RI 3 data combined, on a “case-by-case”
basis: NOECs were only averaged when obtained in similar medium. If this was not the case, or different
endpoints were mentioned, no geomean was calculated, and the distinct data were included as such in the SSD.
These NOECs were used in the species sensitivity distribution (ECB 2008), presented in figure below. There
was no difference between the log-normal and the log-logistic distribution. The HC5 calculated out of this SSD
is 0,38 µg Cd/l.
Cumulative frequency distribution (%)
100
80
60
-1
HC5 = 0.38 µg L
40
fish/amphibians
aquatic invertebrates
20
primary producers
distribution curve
0
0.1
1
10
100
-1
Cd in solution (µg L )
Figure 6. The cumulative frequency distribution of the NOEC values of Cd toxicity tests of data quality
group and RI 1-3 used to calculate the HC5 (case-by-case geometric mean calculation; n = 44). Selected
data and logistic distribution curve fitted on the data (figure taken from the RA Cd/CdO, ECB 2008).
Discussion on the species sensitivity distribution.
The diversity of the data used for the SSD (44 NOEC values on 28 species) is large enough to use the statistical
extrapolation method for PNEC derivation.
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The uncertainty on the SSD and derived HC5 can further be checked according to set criteria to assign the
additional assessment factor to the HC5 in order to calculate the PNEC:

The taxonomic diversity meets the requirements: it covers 28 species from 16 different families,
including warm and cold water fish, amphibians, crustaceans, insects, algae and higher plants. So,
according to this criterion, there is no need for an additional safety factor on the HC5.

All NOEC data are from real chronic studies; test durations are between 7 days and 3 years except for
the unicellular algae, where different life stages are covered. So, according to this criterion, there is no
need for an additional safety factor on the HC5.

The SSD is statistically significant: the species sensitivity distribution (lognormal) is statistically
accepted (calculation with the ETX programme) at all levels (0.1-0.01 significance level) following
both the Anderson-Darling test ((A-D statistic 0.42) and the Kolmogorov-Smirnov test (K-S statistic
0.69). So, according to this criterion, there is no need for an additional safety factor on the HC5.

Many tests included in the SSD database are performed in synthetic water resulting in a lower degree
of Cd-complexation than under natural water conditions. This means that the test results were in
general conservative, with regard to the aquatic toxicity of Cd in the real environment. So, according to
this criterion, there is no need for an additional safety factor on the HC5.

The RA discussed some data from microcosm model ecosystems. The data were checked for reliability
like the single species tests. Nine multi-species (MS) studies were discussed (for detail see RA
Cd/CdO, table 3.2.11.), and the NOECs and LOECs from these studies were compared with HC5
values corrected for the specific hardness of the microcosm test according to the US-EPA hardness
correction (see below). This revealed that in 8 out of 9 cases, the hardness corrected HC5 values were
within the range of the reported MS-NOECs and below the MS-LOEC values. The one MS-LOEC
below the HC5 may be an argument to apply an additional assessment factor of 2 on the HC5 to derive
the PNEC.

The whole of the single-species database, containing 168 reliable single species test results, contained 3
reliable LOECs below the HC5. This was also used in the RA as an argument to apply the additional
assessment factor 2 on the HC5 to derive the PNEC.
Following the argumentation summarised above, the RA applied an additional safety factor 2 to set the generic
PNEC freshwater at HC5/2 = 0.19µg/l (ECB 2008). This value is also applied in the current analysis.
It is emphasised that this value is very conservative, given the richness of the available dataset.
Bioavailability considerations
Expression of the PNEC freshwater as a function of hardness
Hardness is the main determining factor for Cd toxicity to aquatic organisms (RAR 2008). Cd-toxicity is more
important under conditions of low hardness. The effect of water hardness on Cd toxicity has been quantified by
the US-EPA (US-EPA 2001). Based on data for e.g. Daphnia magna, Pimephales promelas and Salmo trutta, a
quantitative relationship between hardness and chronic toxicity could be derived. US-EPA derived a hardness
correction formula that was used in the RA to express PNECs as a function of hardness (H) in the following
way:
a)
all NOEC values of the SSD were converted to NOEC values at the reference hardness of 50 mg
CaCO3/l (=NOECH=50) by applying the formula NOECH=50 =NOECHx (50/Hx)0.7409 (US-EPA 2001).
b) The normalised NOECs were again put into the SSD and the reference HC5 (at hardness 50) was
calculated
c)
the assessment factor 2 was then applied to give the PNEC for waters of hardness 50 (0.09µg/l).
d) Finally, the equation from EPA was again used to calculate PNECs for different hardnesses:
PNECHx= 0.09 (50/Hx)0.7409
By this procedure, the following hardness-dependent PNECs were calculated in the EU risk assessment report
(ECB 2008):
Hardness 40 mg CaCO3/l: 0.08, H50: 0.09, H100: 0.15, H200: 0.25. These calculations in the RA were
interpreted later in the setting of the Cd-water quality standard in the EU water framework directive as follows:
o
H ≤ 40 mg CaCO3/l: 0.08 µg/l;
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o
H = 40 - <50 mg CaCO3/l: 0.08 µg/l;
o
H = 50 - <100 mg CaCO3/l: 0.09 µg/l;
o
H = 100 - <200 mg CaCO3/l: 0.15 µg/l.
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o H = ≥ 200 mg CaCO3/l: 0.25 µg/l
For water assessment, bioavailability correction can be thus applied by using a hardness-specific PNEC when
hardness or Ca-concentration are documented for the receiving water. When the local values of water hardness
are unknown, the generic PNEC value (0.19 µg dissolved Cd/l) should generally be used. Regional data on
hardness can be used as an alternative, but always with caution.
The possible mitigating effect of dissolved organic carbon (DOC), and other water parameters on the
bioavailability of Cd in water needs further study.
7.1.2.2. PNEC water Marine
Discussion on the assessment factor to apply on the HC5 for PNEC derivation
Based on uncertainty considerations, an assessment factor (AF) between 1 and 5 should be applied to the 5 th
percentile value of the species sensitivity distribution curve at 50% confidence value (thus PNEC = 5th
percentile value / AF). The AF is to be judged on a case by case basis.
According to the ECHA Guidance (2008), the following points have to be considered when determining the size
of the assessment factor:
1. the overall quality of the database and the endpoints covered, e.g., if all the data are generated from
“true” chronic studies (e.g., covering all sensitive life stages);
2.
the diversity and representativity of the taxonomic groups covered by the database, and the extent to
which differences in the life forms, feeding strategies and trophic levels of the organisms are
represented;
3.
knowledge on presumed mode of action of the chemical (covering also long-term exposure). Details on
justification could be referenced from structurally similar substances with established mode of action;
4.
statistical uncertainties around the 5th percentile estimate, e.g., reflected in the goodness of fit or the
size of confidence interval around the 5th percentile, and consideration of different levels of confidence
(e.g. by a comparison between the 5% of the SSD (50%) with the 5% of the SSD (lower confidence
interval);
comparisons between field and mesocosm studies, where available, and the 5th percentile to evaluate
the laboratory to field extrapolation.
5.
Based on the available chronic NOEC data for the marine environment, the following points were considered
when determining the size of the assessment factor:
1.
The overall quality of the database and the end-points covered, e.g., if all the data are generated from
“true” chronic studies (e.g. covering all sensitive life stages);
The marine Cd-database covered lethal and sub-lethal endpoints that are all relevant for potential effects at
population level: mortality/immobilization, reproduction, development of early life stages including e.g. fertility
of sperm cells, behaviour (i.e. settlement of pelagic larvae) and growth including time to maturity.
‘Chronic’ exposure times or relevant exposure periods for sensitive life-stages are also achieved for the
nine taxonomic groups covered in the Cd database reporting accepted data. The exposure times for algae were
of 3 days on diatoms and of 5 days on the macro-algae Ulva pertusa. Regarding the invertebrates, exposure
times went from a few hours on very sensitive life-stages (e.g. sperm cell toxicity tests on echinoderms) up to 9
months (reproduction tests on annelids), and for fish, exposure times varied from 7 days up to 8 weeks on
fertilized eggs or larvae. An additional group belonging to the Chordata that is the Ascidian group could also be
included in the database with early life stage data (embryos).
Sensitive life stages were covered at all trophic levels. Fertilized eggs or newly fertilized embryos were
used in the following groups: echinoderms, molluscs, ascidians and fish. Echinoderms (seastars and sea urchins)
sperm cell experiments were also retained in the Cd marine database. Larvae were extensively used and
represented in the group of annelids, crustaceans (including nauplii and cyprid stages), and molluscs. Juveniles
and young adults were finally found in the group of annelids, molluscs and nematods. Experiments made with
adults deal with long-term chronic experiments, i.e. from 10 d with the crustacean Tigriopus brevicornis up to 9
months with the annelid Neanthes arenaceodentata..
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2. The diversity and representativeness of the taxonomic groups covered by the database;
The Figure below illustrates the marine biodiversity in terms of percentage of species across the various phyla
(ECETOC, 2001). The Molluscs group is the largest taxonomic group in marine waters, followed by the
Crustaceans group (ECETOC, 2001). These groups are the ones for which a large number of toxicity data are
available for cadmium and so both groups were found to be broadly represented in the database. Among the
various trophic levels, the invertebrates cover the largest part of taxonomic biodiversity. The marine database
also includes typical marine groups such as echinoderms and cnidarians. In addition to the inter-taxonomic
diversity, the cadmium marine database covers in each group a number of families which reflects a high level of
intra-taxonomic diversity and a large range of toxicity-related responses (see e.g. the group of echinoderms and
molluscs which display a large range of no effects levels, from 4.2 µg Cd/L to 10 mg Cd/L and 0.3 to 520 µg
Cd/L, respectively). The most sensitive endpoints come from molluscs and crustaceans. However it is
interesting to note that those two taxonomic groups are homogeneously distributed along the SSD.
Figure 7. Species diversity in the marine environment (from ECETOC 2001). The stars highlight
taxonomic groups represented in the cadmium marine database.
The algae database contains macro and micro-algae data. Only two species passed the relevancy criteria, but
additional toxicity information is available at large in the Q3 dataset. Those data are situated in the 20-50%
fraction affected in the species sensitivity distribution and so do not reflect any particular sensitivity of those
organisms towards cadmium in the single species SSD. As for fish, the 6 species represented in the database are
also scattered along the SSD with the lowest value situated at 25 % of the affected fraction. Therefore, there is
no particular sensitivity to be noted in this trophic level.
From the extracted data, the Cd-database does largely fulfil the requirement of 10-15 different NOEC
values (62 individual NOEC values resulting in 48 species mean NOEC values).
Statistical uncertainties around the 5th percentile estimate, e.g., reflected in the goodness-of-fit or the
size of confidence interval around the 5th percentile;
A log-normal distribution was calculated and accepted at all significance levels. A factor of 2.45 was observed
between the one-sided 95% left and the 50% confidence limit. The log-logistic distribution presented a slightly
lower A-D test value (0.21 instead of 0.35), meaning that there is a slightly better fit to the input toxicity data.
3.
Comparisons between field and mesocosm studies and the 5th percentile and mesocosm/field studies to
evaluate the laboratory to field extrapolation.
The available mesocosm data (Wolter et al. 1984) demonstrate that the no effect concentration level observed
4.
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for phytoplankton in Kiel Fjord water may be lower than the HC5 coming from the single species SSD
calculated from the lognormal distribution. However, experiments made in seawater from the North Sea and
Atlantic Ocean did not reveal any significant effect of Cd neither on carbon fixation rates nor on bacterial
glucose incorporation even at the highest concentration added to subsamples which is 2.5 µg/L. Those results
should be interpreted with care as little information about test organisms and test conditions is provided.
5. NOEC values lower than the HC5-50
There are three NOEC/EC10 values reported in the Cd marine dataset that are slightly lower than the HC5-50.
The 28-d EC10 of the crustacean Mysidopsis bahia (2.2 µg/L) and the 21-d EC10 of the crustacean Moina
monogolica (1.8 µg/L). The lowest value is found for the mollusk Isognomon californicum (4-d NOEC of 0.3
µg/L). However, the other NOEC values within those groups are well scattered in the SSD which means that
mollusks and crustaceans do not specifically show a particular sensitivity towards cadmium in marine waters.
Moreover, if there is a high number of data in the SSD the chance of having values which are similar or below
the HC5 is significant. This surely applies to the marine SSD counting 48 entries.
Conclusion on Assessment Factor (AF)
-
-
-
-
The following considerations are made on the uncertainty around the HC5:
The chronic NOEC database is very extensive and contains 48 species entries that cover much more than the
requirements for taxonomic groups (8) and species (at least 10, preferably more than 15) set out in the guidance;
 no justification to put an AF
Sensitive life stages or long chronic exposure periods (a few months) are represented in each taxonomic group
as set out in the guidance;  no justification to put an AF
The large number of species in the SSD results in a low uncertainty on the HC5 value, as is shown by the small
difference between the 50% confidence level and the 95% confidence limits found for the lognormal
distribution: less than a factor of 2.5;  no justification to put an AF
The lognormal distribution that was used for PNEC derivation resulted in an HC5 of 2.28 µg/l, which is slightly
lower than the HC5 value calculated from the log-logistic distribution (2.54 µg/l), which provided the best fit.
So the HC5 that is used for the PNEC derivation highlights the conservative character of the log-normal
distribution;  no justification to put an AF
comparing to field data, the HC5 value from the log-normal SSD may not be protective  justification to put an
AF higher than 1 (2)
There is no indication for a particular sensitive group in the SSD. In addition, whenever an SSD includes > 20
data points, the chance of having a value below the HC5 is significant. So, having one or more values below the
HC5 is inherent to bigger datasets and is not an issue as such;  no justification to put an AF
Based on these observations, it is proposed to divide the HC5 by an assessment factor of 2 which results in a
PNEC saltwater for cadmium of 1.14 µg/L (HC5/2).
Difference between freshwater and saltwater PNEC
The PNEC for Cd toxicity on saltwater organisms is higher than the PNEC for freshwater organisms. The
mitigating effect of salinity on cadmium uptake and toxicity has been demonstrated for a variety of species (see
e.g. Blust et al. 1992, Bjerregaard and Depledge 1994, Blackmore and Wang 2003). Indeed, for the same total
metal concentration, the free ion activity is generally lower in a saltwater environment (high ionic strength)
compared to a freshwater environment (low ionic strength). This is essentially due to complexation effects with
chlorides and to effects of ionic strength on activity coefficients of the different metal species present. A high
ionic strength also results in an increased protective effect towards cadmium uptake via calcium or other major
cation transporters. This all explains why the Cd PNEC saltwater is higher than the Cd PNEC freshwater. This is
also confirmed in other environmental jurisdictions e.g.: in the Australian and New Zealand guidelines for fresh
and marine water quality where trigger values for Cd in fresh and marine waters are of 0.2 and 5.5 µg/L,
respectively (ANZECC and ARMCANZ 2000).
Table 50. PNEC water
PNEC
Assessment
factor
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PNEC
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Remarks/Justification
PNEC aqua
(freshwater): 0.19
µg/L
2
Extrapolation method: statistical extrapolation
PNEC aqua (marine 2
water): 1.14 µg/L
CAS number:
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The following considerations are made on the uncertainty around the
HC5: The chronic freshwater database covers 28 species from 16
different families, including warm and cold water fish, amphibians,
crustaceans, insects, algae and higher plants --> Based on this there is no
need for an AF • All NOEC data are from real chronic studies; test
durations are between 7 days and 3 years except for the unicellular algae,
where different life stages are covered --> Based on this there is no need
for an AF • The SSD is statistically significant: the species sensitivity
distribution (lognormal) is statistically accepted (calculation with the
ETX programme) at all levels (0.1-0.01 significance level) following
both the Anderson-Darling test ((A-D statistic 0.42) and the
Kolmogorov-Smirnov test (K-S statistic 0.69) --> Based on this there is
no need for an AF • Many tests included in the SSD database are
performed in synthetic water resulting in a lower degree of Cdcomplexation than under natural water conditions. This means that the
test results were in general conservative, with regard to the aquatic
toxicity of Cd in the real environment --> Based on this there is no need
for an AF • The RA discussed some data from microcosm model
ecosystems: one out of 9 multi-species was found below the HC5 --> this
was used as an argument to apply an AF2 on the HC5 to derive the
PNEC • In the database containing 168 reliable single species test
results, 3 reliable LOECs were below the HC5 --> this was also used as
an argument to apply an AF2 on the HC5 to derived the PNEC
Extrapolation method: statistical extrapolation
The following considerations are made on the uncertainty around the
HC5:
- The chronic NOEC database is very extensive and contains 48 species
entries that cover much more than the requirements for taxonomic
groups (8) and species (at least 10, preferably more than 15) set out in
the guidance; --> no justification to put an AF
-Sensitive life stages or long chronic exposure periods (a few months)
are represented in each taxonomic group as set out in the guidance; -->
no justification to put an AF
- The large number of species in the SSD results in a low uncertainty on
the HC5 value, as is shown by the small difference between the 50%
confidence level and the 95% confidence limits found for the lognormal
distribution: less than a factor of 2.5; --> no justification to put an AF
- The lognormal distribution that was used for PNEC derivation resulted
in an HC5 of 2.28 µg/l, which is slightly lower than the HC5 value
calculated from the log-logistic distribution (2.54 µg/l), which provided
the best fit. So the HC5 that is used for the PNEC derivation highlights
the conservative character of the log-normal distribution; --> no
justification to put an AF
- comparing to field data, the HC5 value from the log-normal SSD may
not be protective --> justification to put an AF higher than 1 (2)
- There is no indication for a particular sensitive group in the SSD. In
addition, whenever an SSD includes > 20 data points, the chance of
having a value below the HC5 is significant. So, having one or more
values below the HC5 is inherent to bigger datasets and is not an issue as
such; --> no justification to put an AF
Based on these observations, there is a need to divide the HC5 by an
assessment factor 2 which results in a PNEC saltwater for cadmium of
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Assessment
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Remarks/Justification
1.14 µg/L (HC5/2).
Intermittent releases is not applicable for cadmium.
7.1.2.3. PNEC sediment
Freshwater chronic PNEC - establishing the dataset
In this CSR, the results of the chronic freshwater sediment toxicity studies are expressed as the actual
(measured) concentration of cadmium. Consistent with approved methodology, the reported benthic toxicity
data presented here represent total (bulk)-cadmium concentrations, i.e. the dissolved plus particulate fraction.
The chronic freshwater benthic toxicity literature for cadmium was checked according to the general criteria for
data quality:

Study design preferably conform to OECD guidelines or equivalent

Toxicological endpoints, which may affect the species at the population level, are taken into account.
In general, these endpoints are survival, growth and reproduction.

For PNEC derivation a full life-cycle test, in which all relevant toxicological endpoints are studied, is
normally preferred to a test covering not a full life cycle and/or not all relevant endpoints.

If for one species several chronic NOEC values (from different tests) based on the same toxicological
endpoint are available, these values are averaged by calculating the geometric mean, resulting in the
“species mean” NOEC.

If for one species several chronic NOEC values based on different toxicological endpoints are
available, the lowest value is selected. The lowest value is determined on the basis of the geometric
mean if more than one value for the same endpoint is available.

In some cases, NOEC values for different life stages of a specific organism are available. If from these
data it appeared that a distinct life stage was more sensitive, the result for the most sensitive life stage
is selected.

Only the results of tests in which the organisms were exposed to cadmium alone are used, thus
excluding tests with metal mixtures.

Like in the RAR, unbounded NOEC values (i.e. no effect was found at the highest concentration tested)
are not used.
Ecotoxicity data for freshwater sediment
The EU RA contained 2 studies on chronic cadmium toxicity:

One single-species test in a freshwater-sediment system with cadmium was found (Hoss et al., 2001).
The only available study was for a benthic nematode (Caenorhabditis elegans). Although short in
duration, the available study represents a life-cycle test (72 hours exposure), which sufficiently
provides information on survival, growth and reproduction effects. The test was performed in
unpolluted sediment with a background cadmium concentration (Cb) of <1 mg/kg d.w. The NOEC
value (growth) obtained from this study was 1,226.4 mg/kg d.w., which is the geometric mean of three
NOECs from the same study.

One in-situ recolonisation study evaluated the toxicity and accumulation of cadmium from sediment by
benthic invertebrates along a cadmium gradient created in nature (Hare et al., 1994). The cadmium
concentration of sediments from a shield lake in Quebec was adjusted to obtain Cd : AVS ratios of
from 0.05 to 10 and then subjected to in situ colonization by invertebrates over a 14-month period. The
test was performed in unpolluted sediment with a background cadmium concentration (Cb) of 2.8
mg/kg d.w. The abundance of only one of the insect taxa present, Chironomus, was significantly
related to the Cd : AVS molar ratio. The NOEC value (abundance) obtained from this study was 115
mg/kg d.w., which was equivalent to a Cd : AVS of two. However, a general lack of expected toxicity
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for other taxa at high Cd : AVS molar ratios (up to 10) in the field study suggests that the sensitivities
to cadmium vary considerably among animal species used in the laboratory and in the field.

No further information on cadmium toxicity in freshwater sediments was found.
Deriving the PNEC
The available ecotoxicity database for freshwater sediment is limited to one single-species test and one field
colonization study so a statistical extrapolation approach was not justified for estimating an HC5 (concentration
estimated for the 5th percentile of the distribution). Instead, the Equilibrium Partitioning (EqP) approach, as
described in the Cd RAR (2008) is used to translate the PNEC estimated for the robust aquatic freshwater
dataset (44 species) into a PNECsediment. The estimated PNECsediment value was considered with published studies
regarding world-wide compilation of background concentrations of cadmium in freshwater sediments. In
addition, the Assessment Factor [AF] approach for estimating PNEC sediment values was also evaluated for
comparison.
Deriving the PNEC with the EqP Approach
Aquatic Ecotoxicity Data
The freshwater PNECaquatic is taken from the RAR (2008) freshwater aquatic database for cadmium (28 high
quality species mean NOECs based on 44 species, from 16 taxonomic families covering three trophic levels). A
lognormal distribution of the aquatic dataset resulted in a PNEC, with an AF of 2 included, of 0.19 µg Cd/L (see
section on PNEC water derivation).
EqP Calculation
In conformity with the calculation of the PEC for sediment (RAR 2008), the properties of suspended matter are
used to calculate the PNEC for sediment, i.e., PNECsediment = PNECsusp matter. Studies characterizing the
equilibrium partitioning of cadmium to suspended matter in freshwater systems were complied to determine a
median partitioning constant (Kpsusp) for cadmium (RAR 2008). Briefly, according to the TGD, the K susp-water and
PNECsediment are calculated using the following equations:
1.
Ksusp-water :
Fwatersusp + (Fsolidsusp x Kpsusp x RHOsolid)
2.
PNECsediment = PNECsusp matter : (Ksusp-water / RHOsusp) x PNECaquatic
Where:
Ksusp-water = volumetric suspended matter / water partition coefficient (m3/m3)
Fwatersusp
= volume fraction water in suspended matter (m3/m3)
Fsolidsusp
= volume fraction solids in suspended matter (m3/m3)
Kpsusp
= suspended matter / water partition coefficient (m3/kg)
RHOsolid = density of the solid fraction (kg/m3)
PNECsediment
= Predicted No Effect Concentration in sediment (mg/kg wet sediment)
PNECsusp matter
= Predicted No Effect Concentration in suspended matter (mg/kg wet suspended matter)
RHOsusp = bulk density of wet suspended matter (kg/m3)
PNECaquatic
= Predicted No Effect Concentration in water (mg/m3)
Studies characterizing the equilibrium partitioning of cadmium to suspended matter in freshwater systems were
complied to determine a median partitioning coefficient (Kp susp) for cadmium (RAR 2008). The range in Kpsusp
values from various natural freshwater sediment studies was 17,000-224,000 L/kg (RAR 2007). According to
the RA, a median Kpsusp value was calculated to be 130,000 L/kg. Using this median value, the PNEC would be
calculated with the EqP approach as follows (according to the TGD):
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Ksusp-water :
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Fwatersusp + (Fsolidsusp x Kpsusp x RHOsolid) =
0.9 m3/m3 + (0.1 m3/m3 x 130 m3/kg x 2,500 kg/m3) =
0.9 m3/m3 + 32,500 m3/m3 =
32,501 m3/m3
2.
PNECsediment = PNECsusp matter : (Ksusp-water / RHOsusp) x PNECaquatic =
(32,501 m3/m3 / 1,150 kg/m3) x 0.19 mg/m3 =
5.37 mg/kg wet sediment
The above PNECsediment of 5.37 mg/kg w.w. (22% solids by weight) is equivalent to a PNEC sediment of 24.4 mg/kg
d.w.
As described in the Cd RAR (2008), the TGD stipulates an upper limit of Kp beyond which an additional safety
factor of 10 should be included (either in PNEC or in PEC) to take the risk of direct ingestion into account. This
upper limit is at Kp of about 2,000 L/kg. This situation is certainly the case for cadmium, therefore the PNEC
should be lowered by a factor of 10 in all cases. Using the additional safety factor, the EqP approach results in a
PNECsediment of 0.54 mg/kg w.w. (equivalent to 2.44 mg/kg d.w.).
Comparison of the “Total” PNECsediment with the Natural Background
Cadmium is a natural element that is present in natural background concentration in all sediments. A summary
of measured background cadmium concentrations for freshwater sediments reported in the Cd RAR is provided
below.

For Belgium, in 2001 monitoring data from the Flemish Environment Agency (VMM) reported a
range of 0.02 to 7.4 mg/kg d.w. (n=512).

For France, cadmium data for sediments from the Réseau National de Donnéés sur l’Eau (RNDE)
ranged from 1 to 20 mg/kg d.w. (n=192).

In the Netherlands, data available from the Rijkswaterstaat (RWS; n=12) and the COMMPS
database (n=6) ranged from 0.05 to 4.89 mg/kg d.w. and 0.63 to 4.68 mg/kg d.w., respectively.

For Spain, eight values from the COMMPS database ranged from 0.1 to 0.52 mg/kg d.w.

A Swedish dataset gathered by the Swedish University of Agricultural Sciences (SLU) between
1998-2000 reported a range of cadmium concentrations from 0.12 to 7.64 mg/kg d.w.

The 10P, 50P and 90P values for all EU data (1296 samples) are 2.66, 0.85 and 0.31 mg/kg d.w.,
respectively.

In addition, a publication by Chapman et al. (1999) summarized natural background concentrations
for 22 metals and metalloids from different jurisdictions in the U.S.A., Canada, The Netherlands,
Norway, Australia, New Zealand, and China. For cadmium, site-specific background cadmium
concentrations in freshwater sediments ranged from 0.5 to 2.5 mg/kg d.w. with a median value of
1.0 mg/kg d.w.
When considering the PNECsediment proposed above with information on background cadmium concentrations
measured in freshwater sediments in the EU (90P = 2.7 mg/kg d.w.; see above), it can be argued that a PNEC of
2.4 mg Cd/kg d.w. could not be differentiated from the range of measured background concentrations (0.02-20
mg/kg d.w.). That is, because of the natural variability background cadmium concentrations in sediment
observed throughout Europe, the “total risk” approach does not provide adequate resolution for determining risk
among pristine or potentially contaminated sites. As a result, the PNEC”total” is not useful, and an alternative
approach has to be developed.
EqP Calculation Using “Added” Approach
To reliably differentiate the PNECsediment value from background concentrations, it is proposed to use the EqP
methodology in an “added risk” approach, to account for background. Since the EqP approach translates aquatic
ecotoxicity information to loads for suspended matter, the background correction must be applied to the
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PNECaquatic. However, instead of correcting for each species NOEC in the aquatic freshwater database, the
PNECaquatic (0.19 μg/L dissolved Cd) is corrected using the natural background cadmium concentration (0.05
μg/L dissolved Cd; Cd RAR, 2008). This value was also used as the natural background concentration in the
calculation of PECcontinentalwater (Cd RAR, 2008).
From equation #2 above, the PNECaquatic can be substituted with PNECadd, aquatic using the background corrected
value (i.e., 0.19 – 0.05 = 0.14 μg/L):
2.
PNECadd, sed = PNECadd, susp : (Ksusp-water / RHOsusp) x PNECadd, aquatic =
(32,501 m3/m3 / 1,150 kg/m3) x 0.14 mg/m3 =
3.96 mg/kg wet sediment
The above PNECadd, sediment of 3.96 mg/kg w.w. (22% solids by weight) is equivalent to a PNEC add, sediment of 18.0
mg/kg d.w.
Again, because the applied Kp value exceeds 2,000 L/kg, an additional safety factor of 10 is applied to account
for the potential risk of direct ingestion. Using the additional safety factor, the EqP approach results in a
PNECadd, sediment of 0.40 mg/kg w.w. (equivalent to 1.80 mg/kg d.w.). Although this PNECadd, sediment is in the
same order of magnitude as the background, it can be distinguished from the background.
Discussion on the uncertainty on the PNEC derivation
The following considerations are made on the uncertainty around the PNEC add, sediment and for determining the
size of the assessment factor:

Although only one long-term chronic toxicity test with cadmium was available, the NOEC for
C. elegans (growth; 1,226.4 mg/kg d.w.) is nearly 700-fold higher than the PNECadd, sediment estimated
above (1.8 mg/kg d.w.). This difference suggests that the calculated PNECadd, sediment is sufficiently
conservative to provide adequate protection for benthic organisms in freshwater systems and there is no
need for an additional assessment factor.

In the colonization study (Hare et al., 1994), the NOEC (115 mg/kg d.w.) is nearly 60-fold greater
than the estimated PNECadd, sediment presented here (1.8 mg/kg d.w.). This study provides the best
experimental representation of ecosystem effects from cadmium exposure in nature since mixed metal
pollution is the rule rather than the exception in the field. As such, this study provides additional
confidence that the estimated PNECsediment is sufficiently conservative to provide adequate protection
for benthic organisms in freshwater systems and there is no need for an additional assessment factor.

The freshwater aquatic dataset (PNECaquatic) used for the calculation of the PNECadd, sediment in the
EqP approach is extensive and of high quality and relevancy for the freshwater environment. Similarly, the
Kp dataset used for deriving a median Kp value for use in the EqP approach is extensive and robust, and
taken straight from EU RA. Therefore the freshwater Kp is considered reliable for the derivation of the
PNECadd, sediment in the present exercise.

All currently available natural background data for freshwater sediment are in the same order of
magnitude (average = 1.32 mg/kg d.w.; range 0.02 to 20 mg/kg d.w.). From the available dataset for
freshwater sediments, approximately 10% of the sediments have measured cadmium concentrations
exceeding 2.66 mg/kg d.w. (90P). Given the variability and relatively wide range (two orders of
magnitude) of background cadmium concentrations for sediments, the PNEC sediment must be represented
using the “added risk” approach (PNECadd, sediment) to reliably differentiate environmental exposures
from natural background. The resulting PNECadd, sediment value (1.80 mg/kg d.w.) thus provides a more
conservative estimate than using the “total” approach and there is no need for an additional assessment
factor.
An alternative approach for estimating a PNECsediment value was investigated. Here, the Assessment Factor (AF)
approach, as described in the Cd RAR (2008), was evaluated for comparison to the EqP approach described
above. The following considerations are made on the uncertainty around the PNEC add, sediment:

In the Cd RAR (2008), it was concluded that the PNECsediment be based on the AF approach applied to the
lowest observed NOEC from the field colonization study (115 mg/kg d.w.). As prescribed, this NOEC is
divided by an AF of 50. The choice of an AF of 50 instead of 100 was justified by the number of acute
toxicity data, showing no differences between species. This results in PNEC sediment = 115 mg/kg d.w. /
50 = 2.3 mg/kg d.w. (equivalent to 0.49 mg/kg w.w.). The AF method presented here yields a
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PNECsediment value that is nearly 30% greater than the PNECadd, sediment value derived with the EqP
method (1.8 mg/kg d.w.). This difference suggests that the calculated PNEC add, sediment is sufficiently
conservative to provide adequate protection for benthic organisms in freshwater systems and there is no
need for an additional assessment factor.

The AF approach described above could also be applied to the only long-term single species test
indentified from the literature. Given that there is only one long-term test for freshwater benthic
organisms, the TGD (2003; Table 19) prescribes that an AF = 100 be applied for datasets comprising at
least “One long-term test (NOEC or EC10)”. As such, the lowest NOEC of the chronic dataset (C.
elegans; 1,226.4 mg/kg d.w.) is divided by an AF of 100. This results in a PNEC sediment = 1,226.4 mg/kg
d.w. / 100 = 12.26 mg/kg d.w. (equivalent to 2.70 mg/kg w.w.). Although sufficiently conservative
compared to the lowest NOEC value from the field colonization study, this value is 10-fold higher than the
global average background cadmium concentration (discussed above). As such, the PNECadd, sediment
estimated using the EqP approach provides adequate protection for benthic organisms in freshwater
systems.
Freshwater PNECsediment: Conclusion
The assessment of the freshwater PNECsediment for cadmium identified only two long-term ecotoxicity studies
from the scientific literature. However, both the “Added” EqP (using partitioning coefficients and a robust
aquatic toxicity database from the Cd RAR) and AF (using the lowest NOEC from a field colonization study)
approaches produced consistent derivations for the freshwater benthic compartment. The resulting value is
considered protective for EU freshwater ecosystems: freshwater PNECadd, sediment of 1.80 mg/kg d.w.
(equivalent to 0.40 mg/kg w.w.). It is emphasized that this is an added PNEC, i.e. natural background
needs to be taken into account when characterising the risk from monitored data.
Accounting for bioavailability in freshwater sediment
It should be noted that different approaches for characterizing the bioavailable fraction of metals e.g. cadmium
in sediment have been studied for nearly 20 years. Examples of these approaches include consideration of
organic matter content as well as acid volatile sulfide (AVS) and simultaneous extractable metals (SEM). The
sulfide fraction in sediment, as quantified by the AVS, is a reactive pool that binds metals, e.g. Cd and makes
them unavailable for biota. The affinity for metal binding on the sulfide fraction in the sediment has been well
established for the metals Cu, Cd, Pb, Zn and Ni. In that order, these metals will be bound on the sulfide present
in the sediment and, as a consequence, will not be available anymore for uptake and possible toxicity. If the
molar difference between SEM and AVS (i.e., SEM-AVS) is less than zero, no toxicity is expected, while a
molar difference greater than zero suggests that toxic effects may occur. Although the background and
application of this method was described in detail in the Cd RAR (2008), the approach was not applied in the
EU risk assessment on cadmium. However, it was fully worked out in the subsequent discussions on the Zn RA
(ECB 2008), and applied for the risk characterization. Because of the fact that Cd will bind to sulfide
preferentially over zinc, it can be anticipated that the AVS/SEM concept applies also to cadmium. It is therefore
considered possible to apply the concept on a local site-specific scale (Cd RAR, 2008).
Marine chronic PNEC - establishing the dataset
In this CSR, the results of the chronic marine sediment toxicity studies are expressed as the actual (measured)
concentration of cadmium. Consistent with approved methodology, the reported benthic toxicity data presented
here represent total (bulk)-cadmium concentrations, i.e. the dissolved plus particulate fraction.
The chronic marine benthic toxicity literature for cadmium was checked according to the general criteria for
data quality:

Study design preferably conform to OECD guidelines or equivalent

Toxicological endpoints, which may affect the species at the population level, are taken into account.
In general, these endpoints are survival, growth and reproduction.

For PNEC derivation a full life-cycle test, in which all relevant toxicological endpoints are studied, is
normally preferred to a test covering not a full life cycle and/or not all relevant endpoints.
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
If for one species several chronic NOEC values (from different tests) based on the same toxicological
endpoint are available, these values are averaged by calculating the geometric mean, resulting in the
“species mean” NOEC.

If for one species several chronic NOEC values based on different toxicological endpoints are
available, the lowest value is selected. The lowest value is determined on the basis of the geometric
mean if more than one value for the same endpoint is available.

In some cases, NOEC values for different life stages of a specific organism are available. If from these
data it appeared that a distinct life stage was more sensitive, the result for the most sensitive life stage
is selected.

Only the results of tests in which the organisms were exposed to cadmium alone are used, thus
excluding tests with metal mixtures.

Like in the RAR, unbounded NOEC values (i.e. no effect was found at the highest concentration tested)
are not used.

Like in the RAR, only the results of tests with soluble cadmium salts are used, thus excluding tests with
“insoluble” cadmium salts.
Ecotoxicity data for marine sediment
Most of the studies on marine sediment involve exposure to a mix of substances. Therefore only two studies
were identified in a marine-sediment system with cadmium:

One single-species study was for a benthic crustacean (Leptocheirus plumulosus) represents a longterm chronic test (4 weeks exposure), which sufficiently provides information on survival, growth and
reproduction effects. The test was performed in unpolluted sediment with a background cadmium
concentration (Cb) of <0.001 mg/kg d.w. The lowest NOEC value (survival, growth and reproduction)
obtained from this study was 1,370 mg/kg d.w.

The influence of interstitial cadmium and AVS in controlling the bioavailability of sediment-associated
metal was examined using a chronic saltwater benthic colonization test (Hansen et al., 1996). The
colonization study, reported no observed effects on taxa richness or abundance at added (measured-Cb)
cadmium concentrations of 169 mg/kg d.w. (throughout the 4 months exposure). Authors also concluded
that the EqP-based theories used to predict the acute biological consequences of divalent metals in
sediments may be applicable to chronically exposed benthic organisms.

No further information on cadmium toxicity in marine sediments was found.
Deriving the PNEC
The toxicity of cadmium to marine benthic organisms was evaluated to develop PNEC sediment. The available
ecotoxicity database for marine sediment was limited to one field colonization study and one single-species test
so a statistical extrapolation approach was not justified for estimating an PNEC (concentration estimated for the
5th percentile of the distribution). Instead, the Equilibrium Partitioning (EqP) approach, as described in the Cd
RAR (2008) was used to translate the PNEC estimated for the robust aquatic marine dataset (48 species) into a
PNECsediment. The estimated PNECsediment value is considered with published studies regarding world-wide
compilation of background concentrations of cadmium in marine sediments. In addition, the Assessment Factor
[AF] approach for estimating PNECsediment values was also evaluated for comparison.
Deriving the PNEC with the EqP Approach
Aquatic Ecotoxicity Data
The marine PNECaquatic is derived from the marine aquatic database for cadmium, which largely fulfils the
species and taxonomic requirements for input chronic toxicity data as explained in the RIP R. 10 guidance (at
least 10 species NOECs and 8 taxonomic groups). Indeed, 48 species mean NOECs, from 9 taxonomic groups
covering three trophic levels were found to fulfill the relevancy and reliability requirements as explained by
Klimisch et al. 1997. A lognormal distribution of the aquatic dataset resulted in a PNEC, with an AF of 2, of
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1.14 µg Cd/L (Cd RAR, 2008).
EqP Calculation
In conformity with the calculation of the PEC for sediment (RAR 2008), the properties of suspended matter are
used to calculate the PNEC for sediment, i.e., PNECsediment = PNECsusp matter. Studies characterizing the
equilibrium partitioning of cadmium to suspended matter in estuarine and marine systems were complied to
determine a median partitioning constant (Kpsusp) for cadmium (RAR 2008). Briefly, according to the TGD, the
Ksusp-water and PNECsediment are calculated using the following equations:
1.
Ksusp-water :
Fwatersusp + (Fsolidsusp x Kpsusp x RHOsolid)
2.
PNECsediment = PNECsusp matter : (Ksusp-water / RHOsusp) x PNECaquatic
Where:
Ksusp-water = volumetric suspended matter / water partition coefficient (m3/m3)
Fwatersusp
= volume fraction water in suspended matter (m3/m3)
Fsolidsusp
= volume fraction solids in suspended matter (m3/m3)
Kpsusp
= suspended matter / water partition coefficient (m3/kg)
RHOsolid = density of the solid fraction (kg/m3)
PNECsediment
= Predicted No Effect Concentration in sediment (mg/kg wet sediment)
PNECsusp matter
= Predicted No Effect Concentration in suspended matter (mg/kg wet suspended matter)
RHOsusp = bulk density of wet suspended matter (kg/m3)
PNECaquatic
= Predicted No Effect Concentration in water (mg/m3)
The range in Kpsusp values from 18 separate natural marine sediment studies was 65-5,600 L/kg (Turner 1993,
1996 and 2002). A median Kp susp value was calculated to be 587 L/kg. Using this median value, the EqP
approach would be calculated as follows (according to the TGD):
1.
Ksusp-water :
Fwatersusp + (Fsolidsusp x Kpsusp x RHOsolid) =
0.9 m3/m3 + (0.1 m3/m3 x 0.587 m3/kg x 2,500 kg/m3) =
0.9 m3/m3 + 146.8 m3/m3 =
148 m3/m3
2.
PNECsediment = PNECsusp matter : (Ksusp-water / RHOsusp) x PNECaquatic =
(148 m3/m3 / 1,150 kg/m3) x 1.14 mg/m3 =
0.15 mg/kg wet sediment
The above PNECsediment of 0.15 mg/kg w.w. (22% solids by weight) is equivalent to a PNEC sediment of 0.67 mg/kg
d.w.
Comparison of the “Total” PNECsediment with the Natural Background
Cadmium is a natural element that is present in natural background concentration in all sediments. A summary
of measured background cadmium concentrations for marine sediments is provided below.

An extensive monitoring program in Belgium (Belgian Marine Data Center) reported measured
data for coastal, estuarine and open sea sediment measurements covering years 2000-2008. Results
show that the median cadmium concentrations (10 and 90 P) for coastal, estuarine and open sea
sediments are 0.44 (0.18-0.94), 2.76 (0.50-10.4) and 0.17 (0.02-0.60) mg/kg d.w., respectively.

A publication by Chapman et al. (1999) summarized natural background concentrations for 22
metals and metalloids from different jurisdictions in the U.S.A., Canada, The Netherlands, Norway,
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Australia, New Zealand, and China. For cadmium, site-specific background cadmium concentrations
in marine sediments ranged from 0.05 to 1.2 mg/kg d.w., with a median value of 0.83 mg/kg d.w.
When considering the PNECsediment proposed above with the available background cadmium concentrations
measured in marine sediments (90P = 1.2 mg/kg d.w.; see above), it can be argued that addition of 0.67 mg
Cd/kg d.w. could not be differentiated from the range of measured background concentrations (0.02-10.4 mg/kg
d.w.). That is, because of the natural variability background cadmium concentrations in sediment observed
throughout Europe, the “total risk” approach does not provide adequate resolution for determining risk among
pristine or potentially contaminated sites. As a result, the PNEC”total” is not useful, and an alternative
approach has to be developed.
EqP Calculation Using “Added” Approach
To reliably differentiate the PNECsediment value from background concentrations, it is proposed to use the EqP
methodology in an “added risk” approach, to account for background. Since the EqP approach translates aquatic
ecotoxicity information to loads for suspended matter, the background correction must be applied to the
PNECaquatic. However, instead of correcting for each species NOEC in the aquatic marine database, the
PNECaquatic (1.14 μg/L dissolved Cd) is corrected using the natural background cadmium concentration (0.025
μg/L dissolved Cd; Cd RAR, 2008). This value is the highest reported Background Reference Concentration
(BRC) reported by the UK National Marine Monitoring Programme between 1999 and 2001.
From equation #2 above, the PNECaquatic can be substituted with PNECadd, aquatic using the background corrected
value (i.e., 1.14 – 0.025 = 1.12 μg/L):
2.
PNECadd, sed = PNECadd, susp : (Ksusp-water / RHOsusp) x PNECadd, aquatic =
(148 m3/m3 / 1,150 kg/m3) x 1.12 mg/m3 =
0.14 mg/kg wet sediment
The above PNECadd, sediment of 0.14 mg/kg w.w. (22% solids by weight) is equivalent to a PNEC add, sediment of
0.64 mg/kg d.w. Although this PNECadd, sediment is in the same order of magnitude as the background, it can be
distinguished from the background.
Discussion on the uncertainty on the PNEC derivation
The following considerations are made on the uncertainty around the PNECadd, sediment and for determining the
size of the assessment factor:

Although only one long-term chronic toxicity test with cadmium is available, the sensitivity of
L. plumulosus (survival, growth and reproduction; 1,370 mg/kg d.w.) is nearly 1000-fold higher than
the PNECadd, sediment calculated using the EqP approach (0.64 mg/kg d.w.). This difference suggests that
the calculated PNECadd, sediment is sufficiently conservative to provide adequate protection for benthic
organisms in marine systems and there is no need for an assessment factor higher than 1.

In the colonization study (Hansen et al., 1996), the NOECecosystem (169 mg/kg d.w.) is over 250-fold
greater than the estimated PNECadd, sediment presented here (0.64 mg/kg d.w.). This study provides the
best experimental representation of ecosystem effects from cadmium exposure in nature since mixed
metal pollution is the rule rather than the exception in the field. As such, this study provides additional
confidence that the estimated PNECsediment is sufficiently conservative to provide adequate protection
for benthic organisms in marine systems and there is no need for an additional assessment factor.

The marine aquatic dataset (PNECaquatic) used for the calculation of the PNECadd, sediment in the EqP
approach is extensive and of high quality and relevancy for the marine environment. Similarly, the Kp
dataset used for deriving a median Kp value for use in the EqP approach is extensive and robust, including
data from both EU and N. American waters. As such it is comparable in size and representativity with the
dataset on marine Kp, used in the EU RA. Therefore the marine Kp is considered reliable for the derivation
of the PNECadd, sediment in the present exercise.

All currently available natural background data for marine sediment are in the same order of
magnitude (average = 0.8 mg/kg d.w.; range 0.02 to 10.4 mg/kg d.w.). From the available dataset for
marine sediments, approximately 10% of the sediments have measured cadmium concentrations
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exceeding 1.2 mg/kg d.w. (90P). Given the variability and relatively wide range (two orders of
magnitude) of background cadmium concentrations for sediments, the PNEC sediment must be represented
using the “added risk” approach (PNECadd, sediment) to reliably differentiate environmental exposures
from natural background. The resulting PNECadd, sediment value (0.64 mg/kg d.w.) thus provides a more
conservative estimate than using the “total” approach and there is no need for an additional assessment
factor.
An alternative approach for estimating a PNECsediment value was investigated for comparison to the EqP
approach. Here, the Assessment Factor (AF) approach, as described in the Cd RAR (2008), was evaluated for
comparison to the EqP approach described above. The following considerations are made on the uncertainty
around the PNECadd, sediment:

The RIP guidance prescribes that an AF = 100 be applied for datasets comprising at least “One longterm freshwater and one saltwater sediment test representing different living and feeding conditions”.
As such, a NOECgrowth for a freshwater benthic nematode (Caenorhabditis elegans) was reported as
1,226.4 mg/kg d.w. (Hoss et al., 2001). Given that the freshwater NOEC is slightly lower that the
NOEC obtained for the marine crustacean (1,370 mg/kg d.w.; discussed above), the freshwater NOEC
is divided by an AF of 100. This results in a PNEC sediment = 1,226.4 mg/kg d.w. / 100 = 12.3 mg/kg d.w.
(equivalent to 2.71 mg/kg w.w.). This value is nearly 20-times higher than the recommended PNECadd,
sediment (0.64 mg/kg d.w.) and 10-times higher than the 90P background concentration for marine
sediments (1.2 mg/kg d.w.).
Marine PNECsediment: Conclusion
The assessment of the marine PNECsediment for cadmium identified only two long-term ecotoxicity studies from
the scientific literature. However, an “Added” EqP (using partitioning coefficients and a robust aquatic toxicity
database) approach provided a reliable derivation for the marine benthic compartment. The resulting value is
considered protective for EU marine ecosystems: marine PNECsediment, added of 0.64 mg/kg d.w. (equivalent to
0.14 mg/kg w.w.). It is emphasised that this is an added PNEC, i.e. natural Bg needs to be taken into
account when characterising the risk from monitored data.
Accounting for bioavailability in marine waters
As for the freshwater, it is noted that different approaches for characterizing the bioavailable fraction of metals
e.g. cadmium in sediment have been studied for nearly 20 years. Examples of these approaches include
consideration of organic matter content as well as acid volatile sulfide (AVS) and simultaneous extractable
metals (SEM). The sulfide fraction in sediment, as quantified by the AVS, is a reactive pool that binds metals,
e.g. Cd and makes them unavailable for biota. The affinity for metal binding on the sulfide fraction in the
sediment has been well established for the metals Cu, Cd, Pb, Zn and Ni. In that order, these metals will be
bound on the sulfide present in the sediment and, as a consequence, will not be available anymore for uptake
and possible toxicity. If the molar difference between SEM and AVS (i.e., SEM-AVS) is less than zero, no
toxicity is expected, while a molar difference greater than zero suggests that toxic effects may occur. Although
the background and application of this method was described in detail in the Cd RAR (2008), the approach was
not applied in the EU risk assessment on cadmium. However, it was fully worked out in the subsequent
discussions on the Zn RA (ECB 2008), and applied for the risk characterisation. Because of the fact that Cd will
bind to sulfide preferentially over zinc, it can be anticipated that the AVS/SEM concept applies also to
cadmium. It is therefore considered possible to apply the concept on a local site-specific scale (Cd RAR, 2008),
also in the marine environment.
Table 51. PNEC sediment
PNEC
Assessment
factor
Remarks/Justification
PNEC sediment
(freshwater): 1.8
mg/kg sediment dw
1
Extrapolation method: partition coefficient
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It is emphasized that the reported PNEC for freshwater sediments is an
added PNEC, i.e. natural background needs to be taken into account
when characterizing the risks from monitored data. The following
considerations are made for determining the size of the assessment
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factor: •The proposed EqP-derived PNECadd, sediments is nearly 700
fold lower than the only long-term chronic NOEC (NOEC growth for C.
elegans: 1226.4 mg/kg d.w.) •The AF method presented in this
assessment and based on the lowest NOEC from the field colonization
study/AF50 yields a PNECsediment value that is nearly 30% greater than
the PNEcadd, sediment value derived with the EqP method (115 mg/kg
d.w./AF50 = 2.3 mg/kg d.w.) • The AF approach could also be applied to
the only long-term single species test identified in the literature. An AF
100 would then be applied which would result in a PNEC of 1226.4
mg/kg d.w. /100 = 12.26 mg/kg d.w. As such, the PNEcadd, sediment
based on the EqP approach provides adequate protection for benthic
organisms in freshwater systems.
PNEC sediment
1
(marine water): 0.64
mg/kg sediment dw
Extrapolation method: partition coefficient
It is emphasized that the reported PNEC for saltwater sediments is an
added PNEC, i.e. natural background needs to be taken into account
when characterizing the risks from monitored data. The following
considerations are made for determining the size of the assessment
factor: • The only single species long-term chronic NOEC found is a
thousand times higher than the proposed EqP-derived PNEC (NOEC
survival, growth and reproduction for L. plumulosus: 1370 mg/kg d.w.) •
The proposed EqP PNEC is considered protective for ecosystems,
according to field study (NOEC ecosystem: 169 mg/kg d.w.; Hansen et
al. 1996) •AF approach-derived PNEC based on the lowest NOEC from
both saltwater and freshwater dataset (1226.4 mg/kg d.w. /AF100 = 12.3
mg/kg d.w.) is 10 to 20 times higher than the recommended EqP-derived
PNEC of 0.64 mg/kg d.w.
7.2. Terrestrial compartment
7.2.1. Toxicity test results
1)
Chronic data – establishing the dataset
A significant amount of data is available on Cd toxicity to soil or litter microflora, soil fauna and higher plants
in the EU risk assessment (RA; ECB 2008). The quality and relevancy of those data have been reviewed in
detail during the EU risk assessment process. Reliability indices 1, 2 and 3 (RI 1, RI 2 and RI 3) data were used
in the PNEC derivation, while reliability 4 data were excluded. Because the RI 1 and 2 data group has limited
number of species, the RA has proposed to include the reliability 3 data too as basis for deriving the PNEC. This
is mainly due to plant data that are excluded from the group RI 1-2, whereas plants seem to be the most sensitive
group. For the present analysis, the same approach was followed, to be conform with the EU RA. Moreover,
studies assigned RI 3 are still quite well documented and therefore be considered reliable.
In this assessment, an update of the literature was made and new toxicity data for Cd in soil were found useful to
be added to the dataset. Reliability was reviewed based on the same reliability indices as those in the RA and
using the same criteria. For each test, a RI was given according to the following criteria (RA, ECB 2008):
RI 1: standard test, including the OECD 207 acute toxicity test withEisenia fetidain OECD-soil and the ISO
1994: soil quality effects of soil pollutants on Collembolla (Folsomia candida): method for the determination of
effects on reproduction.
RI 2: no standard test but complete background information is given, i. e. the following information is present:
a)
soil pH
b)
soil organic matter or carbon content
c)
texture (class or texture fractions)
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d)
total Cd content of the soil at zero Cd application if the NOEC or LOEC value is below 2m g/g
e)
equilibration time after soil contamination and prior to the test
f)
statistical analysis of the dose-response relationship
g)
no varying metal contamination along with increasing Cd application
h)
the control soil must be tested along with at least two Cd concentrations above the background
concentration
i)
the soil must be homogeneously mixed with the metal prior to the test
RI 3: no standard test and one or more of the following information from the above-mentioned list is missing as
background information: b), c), e) or f). All other information from that list is present.
RI 4: no standard test and one or more of the following information from the above-mentioned list is missing as
background information: a), d), g), h) or i). The requirement d) is critical since some tests reporting LOEC
values < 2m g/g are considered unreliable. Background Cd concentrations in soil typically range between 0.1
and 0.5m g/g and the lack of reporting the background concentration may underestimate the total Cd
concentration in soil at which the first toxic effects are found. Unbounded NOECs were not used. Tests
performed in substrates that were judged as not representative for soils (e. g. pure quartz sand or farmyard
manure) were not included in this effects assessment.
Additional toxicity literature for cadmium was also checked according to the general criteria for data quality:
·
Toxicological endpoints, which may affect the species at the population level, are taken into account. In
general, these endpoints are survival, growth and reproduction.
·
If for one species, several NOEC values on the same endpoint are available, the geometric mean of the
NOEC values was first calculated and the most sensitive endpoint was taken forward in the SSD for PNEC
derivation.
·
Only the results of tests in which the organisms were exposed to cadmium alone were used, thus
excluding tests with metal mixtures.
·
Like in the RA, unbounded NOEC values were not used in the assessment.
·
Like in the RA, only the results of tests with soluble Cd2+ salts were used.
·
The NOECs used are reported as nominal values and were taken as such for the PNEC derivation. No
correction for natural background was thus applied.
From the present revision of the terrestrial dataset, four new species of macro-organisms were found to respond
to the criteria. Among them, three additional arthropod species and one plant species were included, allowing
for a revision of the invertebrates + plants SSD. New data on species already figuring in the RA – database were
also considered and species geometric mean NOEC values were recalculated based on new information. A new
HC5 “plants and invertebrates” could subsequently be calculated (see Section 3).
2)
Single-species data for Cd toxicity in soil
The available database of chronic terrestrial toxicity tests for single-species with cadmium provides information
on several species of soil micro-organisms, invertebrates and plants. These species are routinely utilized for
assessing the toxicity of substances in spiked soils and standard test protocols exist.
Microflora dataset
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The microflora dataset of the RA contains 21 entries (12 tests on respiration, 4 tests on N-cycle, 4 tests on soil
enzymes and one test on N2fixation). The individual NOEC values varied from 3.6 mg/kg for the N 2fixation
endpoint up to 3000 mg/kg for respiration. No new data on microflora was found in this update and the
microflora dataset from the RA remains thus unchanged. The microflora entries are summarized in the table 55.
Invertebrates dataset
The invertebrates dataset now contains 9 species among which: four species of annelids, one species of nematod
and four species of arthropods. The available data on macroinvertebrate organisms include only long-term tests,
from 21 to 294 days, which cover growth and reproduction effects. Three new species of arthropods
(Onychiurus yodai, Sinella umesaoi and Paronychiurus kimi) were added to the RA-dataset with NOEC values
for reproduction of 50, 25 and 25 mg Cd/kg, respectively. A new NOEC value for growth of 12.5 mg Cd/kg was
also found for the annelid L. rubellus and two new NOEC values of 25 and 80 mg Cd/kg were found for the
reproduction endpoint the collembol Folsomia candida. Considering those new values, the endpoint
reproduction becomes the most sensitive endpoint for F. candida. Overall, the individual NOEC values varied
from 5 mg/kg for the annelid Eisenia foetida up to 320 mg/kg for F. candida. The invertebrates entries are
summarized in the table 53.
Plants dataset
The updated plants dataset provides information on 15 species, including exposure times from 14 to 100 days
and covering growth (length, weight, biomass) and germination effects. As compared to the RA, one new
species was added to the dataset, i. e. Brassica campestris L. cv. Chinensis with a NOEC for growth (biomass)
and NOEC for germination of 25 and 100 mg Cd/kg, respectively. New NOECs were found for the wheat
seedling (Triticum aestivum; NOEC root elongation of 20 mg Cd/kg), for the oat (Avena sativa; NOEC biomass
of 6.3 mg Cd/kg and NOEC germination of 25 mg Cd/kg) and the lettuce (Lactuca sativa; NOEC biomass of 3.1
mg Cd/kg and NOEC germination of 12.5 mg Cd/kg). The individual NOEC values varied from 1.8 mg/kg for
the species Picea sitchensis up to 100 mg/kg for B. campestris var. Chinensis. The plants entries are
summarized in the table 54.
The geometric mean NOEC values calculated for invertebrates and plants on the most sensitive endpoint are
reported in table below. NOECs of soil microbial assays have not been averaged across soils because of the
intrinsic variability of the microbial population between soils.
Table 52. Summary table of species geometric mean NOECs for the most sensitive endpoints of plants
and invertebrates used in the SSD. New species to the ones mentioned in the RA or species for which new
information was found are highlighted in bold. The newly added individual NOECs are underlined in the
last column.
organism
phylum/class Order
family
endpoint
Species
geometric
mean NOEC
(µg g-1)
Dendrobaena Annelida
rubida
Haplotaxida
Lumbricidae
Reproduction 10
Eisenia fetida Annelida
Haplotaxida
Lumbricidae
Reproduction 5
Lumbricus
rubellus
Haplotaxida
Lumbricidae
Growth
43.3
geometric
mean of 150,
12.5
Haplotaxida
Lumbricidae
Growth
13.4
Geometric
Annelida
Eisenia andrei Annelida
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phylum/class Order
family
endpoint
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Species
geometric
mean NOEC
(µg g-1)
mean of 10, 18
Onychiurus
yodai
Arthropoda
Isotonida
Onychiuridae Reproduction 50
Sinella
umesaoi
Arthropoda
Isotonida
Onychiuridae Reproduction 25
Paronychiuru Arthropoda
s kimi
Isotonida
Onychiuridae Reproduction 25
Folsomia
candida
Arthropoda
Collembola
Isotomidae
Plectus
acuminatus
Nematoda
Araeolaimida Plectidae
Avena sativa
Avena sativa Cyperale
Picea
sitchensis
Pinopsida
Triticum
aestivum
Liliopsida
Glycine max
Reproduction 50.5
geometric
mean of 25, 80
Growth
32
Poaceae
Growth
8.6
Pinales
Pinaceae
Growth
1.8
Cyperales
Poaceae
Growth
16.9
geometric
mean of 7.1,
20, 20, 29
Magnoliopsid Fabales
a
Fabaceae
Growth
6.6
geometric
mean of 2.5, 5,
10, 10, 10
Raphanus
sativus
Magnoliopsid Capparales
a
Brassicaceae
Growth
20
geometric
mean of 10 and
40
Lactuca
sativa
Magnoliopsid Asterales
a
Asteraceae
Growth
9
geometric
mean of 2, 2.5,
3.1, 3.2, 5, 5,
10, 10, 20, 20,
32, 40, 40
Lycosperisico Magnoliopsid Solanales
n esculentum a
Solanaceae
Growth
50.6
geometric
mean of 32 and
80
Phaseolus
vulgaris
Fabaceae
Growth
20
Zea mays
Magnoliopsid Fabales
a
Cyperales
Liliopsida
Violales
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10
Cucurbitaceae
80
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geometric
mean of 6.3,
10, 10
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organism
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phylum/class Order
family
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endpoint
Species
geometric
mean NOEC
(µg g-1)
Cucurbita
pepo
Lepidium
sativum
Magnoliopsid Capparales
a
Capparales
Magnoliopsid
Apiales
a
Brassicaceae
5
Brassicaceae
10
Apiaceae
10
Brassica rapa Magnoliopsid
a
Daucus
carota
Magnoliopsid
a
Magnoliopsid Capparales
Brassica
a
campestris
var. chinensis
Brassicaceae
Growth
25
Beta vulgaris Magnoliopsid Caryophyllale Chenopodiacea Growth
a
s
e
34
geometric
mean of 20,
20, 20, 40, ‘40,
40, 40, 80
7.2.1.1. Toxicity to soil macro-organisms
The results are summarised in the following table:
Table 53. Overview of effects on soil macro-organisms
Method
Results
Lumbricus rubellus (annelids)
NOEC (84 d): 150 mg/kg
2 (reliable with
soil dw (nominal) based on: restrictions)
mortality, weight
key study
long-term toxicity (laboratory study)
Substrate: natural soil
84 days exposure mortality and weight
test on the annelid Lumbricus rubellus
Remarks
Reference
Ma W.C. (1982)
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Eisenia andrei (annelids)
long-term toxicity (laboratory study)
Substrate: OECD soil
NOEC (21 d): 10 mg/kg
2 (reliable with
soil dw (nominal) based on: restrictions)
juvenile/adult
key study
read-across based on
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van Gestel CAM,
Dirven-van
Breemen EM and
Baerselman R
(1993)
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Method
Results
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Remarks
Reference
grouping of
substances (category
approach)
21 days growth and number of cocoons
test on annelid Eisenia andrei
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Dendrobaena rubida (annelids)
long-term toxicity (laboratory study)
Substrate: natural soil
110 and 270 days exposure test on
Dendrobaena rubida
NOEC (110 d): 10 mg/kg
2 (reliable with
Bengtsson G,
soil dw (nominal) based on: restrictions)
Gunnarsson T and
cocoon production
Rundgren S (1986)
key study
NOEC (110 d): 10 mg/kg
soil dw (nominal) based on: read-across based on
grouping of
hatching success
substances (category
approach)
Test material
(IUPAC name):
cadmium dinitrate
(See endpoint
summary for
justification of
read-across)
Eisenia fetida (annelids)
long-term toxicity (laboratory study)
Substrate: OECD soil
84 days exposure growth, mortality
and development test on the annelid
Eisenia foetida andrei
NOEC (84 d): 18 mg/kg
soil dw based on: growth
3 (not reliable)
van Gestel CAM,
van Dis WA,
supporting study
Dirven-van
Breemen EM,
read-across based on Sparenburg PM
grouping of
and (1991)
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Plectus acuminatus (nematods)
long-term toxicity (laboratory study)
Substrate: OECD-soil
21d juvenile/adult ratio test on
nematod Plectus acuminatus in an
OECD-soil
NOEC (21 d): 32 mg/kg
3 (not reliable)
soil dw (nominal) based on:
supporting study
juvenile/adult ratio
Kammenga JE,
Van Koert PHG,
Riksen JAG,
Korthals GW and
read-across based on Bakker J (1996)
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
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Method
cadmium sulphate
Results
CAS number:
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Remarks
Reference
read-across)
Lumbricus rubellus (annelids)
long-term toxicity (laboratory study)
NOEC (294 d): 12.5 mg/kg 3 (not reliable)
soil dw (nominal) based on:
supporting study
mean weight
Substrate: artificial soil
read-across based on
grouping of
substances (category
approach)
294d growth ecotoxicity soil tests on
earthworms Lumbricus rubellus
D. J. Spurgeon, C.
Svendsen, P. Kille,
A. J. Morgan, J.
M. Weeks (2004)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Eisenia fetida (annelids)
long-term toxicity (laboratory study)
NOEC (56 d): 5 mg/kg soil 3 (not reliable)
dw (nominal) based on:
supporting study
cocoon production
Substrate: OECD soil
Spurgeon DJ and
Hopkin SP (1995)
read-across based on
grouping of
substances (category
approach)
OECD Guideline 207 (Earthworm,
Acute Toxicity Tests)
Test material
(IUPAC name):
cadmium dinitrate
(See endpoint
summary for
justification of
read-across)
Folsomia candida (Collembola (soildwelling springtail))
long-term toxicity (laboratory study)
ISO 1994: soil quality effects of soil
pollutants on Collembolla (Folsomia
candida): method for the determination
of effects on reproduction
NOEC (42 d): NOEC
(nominal) based on:
reproduction
1 (reliable without
restriction)
key study
van Gestel CAM
and Hensbergen PJ
(1997)
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Folsomia candida (Collembola (soildwelling springtail))
NOEC (35 d): NOEC based 2 (reliable with
on: number of offspring
restrictions)
long-term toxicity (laboratory study)
key study
ISO 1994: soil quality effects of soil
pollutants on Collembolla (Folsomia
candida): method for the determination
read-across based on
grouping of
substances (category
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
Crommentuijn T,
Brils J and van
Straalen NM
(1993)
189
EC number:
233-331-6
Method
cadmium sulphate
Results
of effects on reproduction
CAS number:
10124-36-4
Remarks
Reference
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Folsomia candida (Collembola (soildwelling springtail))
long-term toxicity (laboratory study)
NOEC (4 wk): NOEC
(nominal) based on:
reproduction
ISO 11267 (Inhibition of Reproduction
of Collembola by Soil Pollutants)
1 (reliable without
restriction)
T. Nakamori, S.
Yoshida, Y.
Kubota, T. Bankey study
Nai, N. Kaneko,
M. Hasegawa
read-across based on (2008)
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Onychiurus yodai (Collembola (soildwelling springtail))
long-term toxicity (laboratory study)
NOEC (4 wk): NOEC
(nominal) based on:
reproduction
ISO 11267 (Inhibition of Reproduction
of Collembola by Soil Pollutants)
1 (reliable without
restriction)
T. Nakamori, S.
Yoshida, Y.
Kubota, T. Bankey study
Nai, N. Kaneko,
M. Hasegawa
read-across based on (2008)
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Sinella umesaoi (Collembola (soildwelling springtail))
long-term toxicity (laboratory study)
ISO 11267 (Inhibition of Reproduction
of Collembola by Soil Pollutants)
NOEC (4 wk): NOEC
(nominal) based on:
reproduction
1 (reliable without
restriction)
T. Nakamori, S.
Yoshida, Y.
Kubota, T. Bankey study
Nai, N. Kaneko,
M. Hasegawa
read-across based on (2008)
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
190
EC number:
233-331-6
Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
read-across)
Folsomia candida (Collembola (soildwelling springtail))
long-term toxicity (laboratory study)
NOEC (28 d): NOEC
(nominal) based on:
reproduction
ISO 11267 (Inhibition of Reproduction
of Collembola by Soil Pollutants)
1 (reliable without
restriction)
key study
I. N. Herbert, C.
Svendsen, P. K.
Hankard, D. J.
Spurgeon (2004)
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Paronychiurus kimi (Collembola (soil- NOEC (28 d): NOEC
dwelling springtail))
(nominal) based on:
reproduction
long-term toxicity (laboratory study)
28 days exposure Cd soil test on the
collembol P. kimi; artificial soil
prepared according to ISO (1999)
3 (not reliable)
supporting study
J. Son, M. I. Ryoo,
J. Jung, K. Cho
(2007)
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Discussion of effects on soil macro-organisms except arthropods
Chronic soil data are available for 4 species of annelids and one species of nematod with reported geometric
mean NOECs varying from 5 mg/kg d. w. for Eisenia fetida up to 43.3 mg/kg d. w. for Lumbricus rubellus.
The following information is taken into account for effects on soil macro-organisms except arthropods for the
derivation of PNEC:
chronic soil data are available for 4 species of annelids and one species of nematod with reported geometric
mean NOECs varying from 5 mg/kg d. w. for Eisenia fetida up to 43.3 mg/kg d. w. for Lumbricus rubellus.
Discussion of effects on soil arthropods
Chronic soil data are available for 4 species of arthropods with reported geometric NOECs varying from 25
mg/kg d. w. for Sinella umesaoi and Paronychiurus kimi up to 50.5 mg/kg d. w. for Folsomia candida.
The following information is taken into account for effects on soil arthropods for the derivation of PNEC:
chronic soil data are available for 4 species of arthropods with reported geometric NOECs varying from 25
mg/kg d. w. for Sinella umesaoi and Paronychiurus kimi up to 50.5 mg/kg d. w. for Folsomia candida.
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
191
EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
7.2.1.2. Toxicity to terrestrial plants
The results are summarised in the following table:
Table 54. Overview of effects on terrestrial plants
Method
Results
Lactuca sativa
Avena sativa: NOEC (10
1 (reliable without
d): 25 mg/kg soil dw based restriction)
on: germination
key study
Avena sativa: NOEC (10
read-across based on
d): 6.25 mg/kg soil dw
grouping of
based on: biomass
substances (category
Brassica campestris var.
approach)
chinensis: NOEC (10 d):
Test material
100 mg/kg soil dw based
(IUPAC name):
on: germination
cadmium (See
Brassica campestris var.
endpoint summary
chinensis: NOEC (10 d): 25 for justification of
mg/kg soil dw based on:
read-across)
biomass
Brassica campestris var. chinensis
Avena sativa
long-term toxicity (laboratory study)
germination (%) and biomass
Substrate: natural soil
ISO (1995) guideline
Remarks
Reference
A. X. da Rosa
Corrêa, L. Rubi
Rörig, M. A.
Verdinelli, S.
Cotelle (2006)
Lactuca sativa: NOEC (10
d): 12.5 mg/kg soil dw
based on: germination
Lactuca sativa: NOEC (10
d): 3.12 mg/kg soil dw
based on: biomass
Picea sitchensis (Gymnospermae
(conifers))
long-term toxicity (laboratory study)
Picea sitchensis: NOEC
2 (reliable with
(100 d): 1.8 mg/kg soil dw restrictions)
(nominal) based on: growth
key study
(root length)
seed germination/root elongation
toxicity test
read-across based on
grouping of
substances (category
approach)
Substrate: natural soil
long term growth (root length) test
performed on the stika spruce (Picea
sitchensis)
Triticum aestivum (Dicotyledonae
(dicots))
short-term toxicity (laboratory study)
seed germination/root elongation
toxicity test
Substrate: natural soil
2010-09-07 CSR-PI-5.2.1
Burton KW,
Morgan E and
Roig A (1984)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Triticum aestivum: NOEC
(3 d): 20 mg/kg soil dw
(nominal) based on: root
elongation
2 (reliable with
restrictions)
key study
read-across based on
grouping of
substances (category
approach)
CHEMICAL SAFETY REPORT
Q. Cao, Q-H. Hu,
S. Khan, Z.-J.
Wang, A.-J. Lin,
X. Du, Y-G. Zhu
(2007)
192
EC number:
233-331-6
Method
cadmium sulphate
Results
3d root elongation test on wheat
seedlings of the species Triticum
aestivum in a natural silt loam soil
Triticum aestivum (Dicotyledonae
(dicots))
long-term toxicity (laboratory study)
shoot dry weight test
Substrate: natural soil
28d growth test on Triticum aestivum
CAS number:
10124-36-4
Remarks
Reference
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Triticum aestivum: NOEC 2 (reliable with
(28 d): 7.1 mg/kg soil dw
restrictions)
(nominal) based on: growth
key study
(shoot dry weight)
Triticum aestivum: NOEC
(28 d): 29 mg/kg soil dw
(nominal) based on: growth
(shoot dry weight)
Reber HH (1989)
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
oxocadmium (See
endpoint summary
for justification of
read-across)
Beta vulgaris (Dicotyledonae (dicots)) Lactuca sativa: NOEC (63 3 (not reliable)
d): 40 mg/kg soil dw
Lactuca sativa (Dicotyledonae
(nominal) based on: growth supporting study
(dicots))
(shoot dry weight)
experimental result
long-term toxicity (laboratory study)
Lactuca sativa: NOEC (63
Test material (EC
d): 40 mg/kg soil dw
early seedling growth toxicity test
(nominal) based on: growth name): cadmium
sulphate
(shoot dry weight)
Substrate: natural soil
Lactuca sativa: NOEC (63
63 days exposure growth test on lettuce d): 10 mg/kg soil dw
and chard
(nominal) based on: growth
(shoot dry weight)
Mahler RJ,
Bingham FT and
Page AL (1978)
Lactuca sativa: NOEC (63
d): 20 mg/kg soil dw
(nominal) based on: growth
(shoot dry weight)
Lactuca sativa: NOEC (63
d): 20 mg/kg soil dw
(nominal) based on: growth
(shoot dry weight)
Lactuca sativa: NOEC (63
d): 2.5 mg/kg soil dw
(nominal) based on: growth
(shoot dry weight)
Lactuca sativa: NOEC (63
d): 5 mg/kg soil dw
(nominal) based on: growth
(shoot dry weight)
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CHEMICAL SAFETY REPORT
193
EC number:
233-331-6
Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
Lactuca sativa: NOEC (63
d): 10 mg/kg soil dw
(nominal) based on: growth
(shoot dry weight)
Beta vulgaris: NOEC (63
d): 20 mg/kg soil dw
(nominal) based on: growth
(shoot dry weight)
Beta vulgaris: NOEC (63
d): 20 mg/kg soil dw
(nominal) based on: growth
(shoot dry weight)
Beta vulgaris: NOEC (63
d): 40 mg/kg soil dw
(nominal) based on: growth
(shoot dry weight)
Beta vulgaris: NOEC (63
d): 40 mg/kg soil dw
(nominal) based on: growth
(shoot dry weight)
Beta vulgaris: NOEC (63
d): 40 mg/kg soil dw
(nominal) based on: growth
(shoot dry weight)
Beta vulgaris: NOEC (63
d): 20 mg/kg soil dw
(nominal) based on: growth
(shoot dry weight)
Beta vulgaris: NOEC (63
d): 40 mg/kg soil dw
(nominal) based on: growth
(shoot dry weight)
Beta vulgaris: NOEC (63
d): 80 mg/kg soil dw
(nominal) based on: growth
(shoot dry weight)
Phaseolus vulgaris (Dicotyledonae
(dicots))
Glycine max (G. soja) (Dicotyledonae
(dicots))
Triticum aestivum (Dicotyledonae
(dicots))
Zea mays (Dicotyledonae (dicots))
Lycopersicon esculentum
(Dicotyledonae (dicots))
Cucurbita pepo (Dicotyledonae
2010-09-07 CSR-PI-5.2.1
Phaseolus vulgaris: NOEC 3 (not reliable)
: 20 mg/kg soil dw
(nominal) based on: growth supporting study
(bean dry weight)
experimental result
Glycine max (G. soja):
NOEC : 2.5 mg/kg soil dw Test material (EC
(nominal) based on: growth name): cadmium
sulphate
(bean dry weight)
Bingham FT, Page
AL, Mahler RJ
and Ganje TJ
(1975)
Triticum aestivum: NOEC :
20 mg/kg soil dw (nominal)
based on: growth (grain
weight)
CHEMICAL SAFETY REPORT
194
EC number:
233-331-6
Method
(dicots))
Brassica oleracea var. capitata
(Dicotyledonae (dicots))
Oryza sativa (Dicotyledonae (dicots))
Lactuca sativa (Dicotyledonae
(dicots))
Lepidum sativum (Dicotyledonae
(dicots))
Spinacia oleracea (Dicotyledonae
(dicots))
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
3 (not reliable)
Kádár I (1995)
supporting study
Kádár I, Szabo L
and Sarkadi J
(1998)
Zea mays: NOEC : 10
mg/kg soil dw (nominal)
based on: growth (kernal
weight)
Lycopersicon esculentum:
NOEC : 80 mg/kg soil dw
(nominal) based on: growth
(ripe fruit weight)
Cucurbita pepo: NOEC : 80
mg/kg soil dw (nominal)
based on: growth (fruit
weight)
Brassica rapa (Dicotyledonae (dicots)) Brassica rapa: NOEC : 10
mg/kg soil dw (nominal)
Raphanus sativus (Dicotyledonae
based on: growth (tuber
(dicots))
weight)
Daucus carota (Dicotyledonae
(dicots))
long-term toxicity (laboratory study)
weight of dry bean, grain, kernal, ripe
fruit, fruit head, shoot and tuber
Substrate: natural soil
long term (up to maturity) growth test
on various plants
Lactuca sativa: NOEC : 5
mg/kg soil dw (nominal)
based on: growth (head
weight)
Lepidum sativum: NOEC :
5 mg/kg soil dw (nominal)
based on: growth (shoot
weight)
Spinacia oleracea: NOEC :
1.25 mg/kg soil dw
(nominal) based on: growth
(shoot weight)
Raphanus sativus: NOEC :
40 mg/kg soil dw (nominal)
based on: growth (tuber
weight)
Daucus carota: NOEC : 10
mg/kg soil dw (nominal)
based on: growth (tuber
weight)
Spinacia oleracea (Dicotyledonae
(dicots))
Beta vulgaris (Dicotyledonae (dicots))
long-term toxicity (field study)
biomass
Substrate: natural soil
Beta vulgaris: NOEC (48
mo): 90 kg/ha based on:
biomass
Spinacia oleracea: NOEC experimental result
(72 mo): 90 kg/ha based on:
Test material (EC
biomass
name): cadmium
sulphate
Field experiment on various plants in a
calcareous chernozem soil
Raphanus sativus (Dicotyledonae
(dicots))
2010-09-07 CSR-PI-5.2.1
Raphanus sativus: NOEC
(42 d): 10 mg/kg soil dw
3 (not reliable)
CHEMICAL SAFETY REPORT
Khan DH and
Frankland B
195
EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Method
Results
long-term toxicity (laboratory study)
(nominal) based on: growth
supporting study
(shoot dry weight)
growth (shoot dry weight) test
42 days growth test on the radish plant
Raphanus sativus
long-term toxicity (laboratory study)
growth (shoot dry weight) test
Substrate: natural soil
28d growth test on the soya (Glycine
max)
Lactuca sativa (Dicotyledonae
(dicots))
Lycopersicon esculentum
(Dicotyledonae (dicots))
Avena sativa (Dicotyledonae (dicots))
long-term toxicity (laboratory study)
shoot fresh weight
Substrate: artificial soil
OECD Guideline 208 (Terrestrial
Plants Test: Seedling Emergence and
Seedling Growth Test)
Reference
(1983)
read-across based on
grouping of
substances (category
approach)
Substrate: natural soil
Glycine max (G. soja) (Dicotyledonae
(dicots))
Remarks
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Glycine max (G. soja):
3 (not reliable)
Miller JE, Hassett
NOEC (28 d): 10 mg/kg
JJ and Koeppe DE
soil dw (nominal) based on: supporting study
(1976)
growth (shoot dry weight)
read-across based on
grouping of
Glycine max (G. soja):
substances (category
NOEC (28 d): 10 mg/kg
soil dw (nominal) based on: approach)
growth (shoot dry weight)
Test material
(IUPAC name):
Glycine max (G. soja):
NOEC (28 d): 5 mg/kg soil cadmium dichloride
(See endpoint
dw (nominal) based on:
growth (shoot dry weight) summary for
justification of
Glycine max (G. soja):
read-across)
NOEC (28 d): 10 mg/kg
soil dw (nominal) based on:
growth (shoot dry weight)
Lactuca sativa: NOEC (2
3 (not reliable)
Adema D. M. M.
wk): 32 mg/kg soil dw
and L. Henzen
(nominal) based on: growth supporting study
(1989)
(shoot fresh weight)
read-across based on
grouping of
Lactuca sativa: NOEC (2
substances (category
wk): 3.2 mg/kg soil dw
(nominal) based on: growth approach)
(shoot fresh weight)
Test material
Lycopersicon esculentum: (IUPAC name):
cadmium dichloride
NOEC (2 wk): 32 mg/kg
soil dw (nominal) based on: (See endpoint
growth (shoot fresh weight) summary for
justification of
Avena sativa: NOEC (2
read-across)
wk): 10 mg/kg soil dw
(nominal) based on: growth
(shoot fresh weight)
Avena sativa: NOEC (2
wk): 10 mg/kg soil dw
(nominal) based on: growth
(shoot fresh weight)
Phaseolus vulgaris (Dicotyledonae
2010-09-07 CSR-PI-5.2.1
Phaseolus vulgaris: NOEC 3 (not reliable)
CHEMICAL SAFETY REPORT
Sajwan KS, Ornes
196
EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
Method
Results
(dicots))
(30 d): 6.7 mg/kg soil dw
WH, Youngblood
supporting study
(meas. (not specified))
TV and Alva AK
based on: growth (biomass)
(1996)
read-across based on
grouping of
substances (category
approach)
long-term toxicity (field study)
early seedling growth toxicity test
Substrate: natural soil
30 days field study on the bush beans
Phaseolus vulgaris
Remarks
Reference
Test material (EC
name): cadmium
chloride (See
endpoint summary
for justification of
read-across)
Lactuca sativa (Dicotyledonae
(dicots))
Lactuca sativa: NOEC (42 3 (not reliable)
Jasiewicz C (1994)
d): 2 mg/kg soil dw
(nominal) based on: growth supporting study
(shoot dry weight)
read-across based on
grouping of
substances (category
approach)
long-term toxicity (laboratory study)
growth (shoot dry weight) test
Substrate: natural soil
long term growth test on Lactuca sativa
Test material
(IUPAC name):
cadmium dinitrate
(See endpoint
summary for
justification of
read-across)
Nicotina tabacum (Dicotyledonae
(dicots))
Nicotina tabacum: NOEC 4 (not assignable)
(2 mo): 5.44 mg/kg soil dw
supporting study
(meas. (not specified))
Nicotina rustica (Dicotyledonae
based on: biomass
read-across based on
(dicots))
Nicotina rustica: NOEC (2 grouping of
substances (category
Zea mays (Dicotyledonae (dicots))
mo): 5.44 mg/kg soil dw
approach)
(meas. (not specified))
long-term toxicity (field study)
based on: biomass
Test material (EC
biomass test
Zea mays: NOEC (144 mo): name): Cadmium
nitrate (See
7.2 mg/kg soil dw (meas.
Substrate: natural soil
endpoint summary
(not specified)) based on:
for justification of
biomass
2 months field Cd-enriched natural soil
read-across)
experiment on Nicotina spp. and Zea Zea mays: NOEC (144 mo):
mays
8.3 mg/kg soil dw (meas.
(not specified)) based on:
biomass
Mench M,
Tancogne J,
Gomez A and
Juste C (1989)
Discussion
Chronic soil data are available for 15 plant species with reported NOECs varying from 1.8 mg/kg d. w. for Picea
sitchensis up to 100 mg/kg d. w. for Brassica campestris var. chinensis. In addition, field colonization studies
are also available for terrestrial systems and the NOEC vary from >6.7 up to 50 mg/kg d. w.
The following information is taken into account for toxicity on terrestrial plants for the derivation of PNEC:
chronic soil data are available for 15 plant species with reported NOECs varying from 1.8 mg/kg d. w. for Picea
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
197
EC number:
233-331-6
cadmium sulphate
CAS number:
10124-36-4
sitchensis up to 100 mg/kg d. w. for Brassica campestris var. chinensis. In addition, field colonization studies
are also available for terrestrial systems and the NOEC vary from >6.7 up to 50 mg/kg d. w.
7.2.1.3. Toxicity to soil micro-organisms
The results are summarised in the following table:
Table 55. Overview of effects on soil micro-organisms
Method
Results
Species/Inoculum: native soil
microflora
NOEC (490 d): 150 mg/kg 2 (reliable with
Doelman P and
soil dw (nominal) based on: restrictions)
Haanstra L (1984)
respiration rate
key study
NOEC (301 d): 150 mg/kg
soil dw (nominal) based on: read-across based on
grouping of
respiration rate
substances (category
NOEC (630 d): 150 mg/kg approach)
soil dw (nominal) based on:
Test material
respiration rate
(IUPAC name):
NOEC (560 d): 3000 mg/kg cadmium dichloride
soil dw (nominal) based on: (See endpoint
respiration rate
summary for
justification of
NOEC (574 d): 400 mg/kg read-across)
soil dw (nominal) based on:
respiration rate
>300 days respiration test on native
soil microflora
Species/Inoculum: native soil
microflora
33 days exposure test on nitrification
of native soil microflora
Species/Inoculum: native soil
microflora
Long term (560 days) glutamic acid
decomposition time test on various
soils
Remarks
Reference
NOEC (33 d): 10 mg/kg
2 (reliable with
Dusek (1995)
soil dw (nominal) based on: restrictions)
nitrate formation rate
key study
NOEC (33 d): 50 mg/kg
soil dw (nominal) based on: read-across based on
grouping of
nitrate formation rate
substances (category
NOEC (33 d): 100 mg/kg
approach)
soil dw (nominal) based on:
Test material
nitrate formation rate
(IUPAC name):
NOEC (33 d): 50 mg/kg
cadmium dichloride
soil dw (nominal) based on: (See endpoint
nitrate formation rate
summary for
justification of
read-across)
NOEC (560 d): 55 mg/kg
2 (reliable with
soil dw (nominal) based on: restrictions)
glutamic acid
key study
decomposition time
NOEC (560 d): 150 mg/kg
soil dw (nominal) based on:
glutamic acid
decomposition time
Haanstra L and
Doelman P (1984)
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
2010-09-07 CSR-PI-5.2.1
CHEMICAL SAFETY REPORT
198
EC number:
233-331-6
Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
(See endpoint
summary for
justification of
read-across)
Species/Inoculum: native soil
microflora
Long term respiration and
ammonification tests on loamy sand
soil
NOEC (98 d): 14.3 mg/kg 2 (reliable with
soil dw (nominal) based on: restrictions)
respiration rate
key study
Walter C and
Stadelmann F
(1979)
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dinitrate
(See endpoint
summary for
justification of
read-across)
Species/Inoculum: native soil
microflora
84 min. respiration test on soil
microflora from various soil types
Species/Inoculum: native soil
microflora
56 days respiration test on sandy soil
NOEC (84 min): 3.6 mg/kg 2 (reliable with
Reber H.H. (1989)
soil dw (nominal) based on: restrictions)
respiration rate
key study
NOEC (84 min): 3.6 mg/kg
soil dw (nominal) based on: read-across based on
grouping of
respiration rate
substances (category
approach)
NOEC (84 min): 14.3
mg/kg soil dw (nominal)
Test material
based on: respiration rate
(IUPAC name):
oxocadmium (See
endpoint summary
for justification of
read-across)
NOEC (56 d): 5 mg/kg soil 3 (not reliable)
dw (nominal) based on:
supporting study
respiration rate
Cornfield AH
(1977)
experimental result
Test material (EC
name): cadmium
sulphate
Species/Inoculum: Rhizobium
leguminosarum bv. trifolii
NOEC (90 wk): 4 mg/kg
soil dw (meas. (not
specified)) based on: cell
18 months exposure test on Rhizobium number (survival)
leguminosarum bv. trifolii in sandy
loam
Species/Inoculum: native soil
microflora
2010-09-07 CSR-PI-5.2.1
3 (not reliable)
supporting study
Chaudri AM,
McGrath SP and
Giller KE (1992)
experimental result
Test material (EC
name): cadmium
sulphate
NOEC (30 wk): 112 mg/kg 3 (not reliable)
soil dw (nominal) based on:
supporting study
ATP content
CHEMICAL SAFETY REPORT
Frostegard A,
Tunlid A and
Baath E (1993)
199
EC number:
233-331-6
Method
cadmium sulphate
Results
CAS number:
10124-36-4
Remarks
Reference
6 months exposure test on respiration NOEC (30 wk): 60 mg/kg experimental result
rate and ATP content of forest soil and soil dw (nominal) based on:
Test material (EC
arable soil microflora
respiration rate
name): cadmium
sulphate
Species/Inoculum: native soil
microflora
28 days respiration (substrate induced
CO2 evolution) test on native soil
microflora
NOEC (28 d): 50 mg/kg
3 (not reliable)
soil dw (nominal) based on:
supporting study
respiration (substrate
induced CO2 evolution)
read-across based on
grouping of
substances (category
approach)
Saviozzi A, LeviMinzi R, Cardelli
R and Riffaldi R
(1997)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Species/Inoculum: native soil
microflora
45 days exposurecellulolytic activity
test on native soil microflora
NOEC (45 d): 10 mg/kg
3 (not reliable)
soil dw (nominal) based on:
supporting study
cellulolytic activity
Khan DH and
Frankland B
(1984)
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Discussion
The microflora dataset of the RA contains 21 entries (12 tests on respiration, 4 tests on N-cycle, 4 tests on soil
enzymes and one test on N2fixation). The individual NOEC values varied from 3.6 mg/kg for the N 2fixation
endpoint up to 3000 mg/kg for respiration.
The following information is taken into account for toxicity on soil micro-organisms for the derivation of
PNEC:
The microflora dataset of the RA contains 21 entries (12 tests on respiration, 4 tests on N-cycle, 4 tests on soil
enzymes and one test on N2 fixation). The individual NOEC values varied from 3.6 mg/kg for the N2 fixation
endpoint up to 3000 mg/kg for respiration.
7.2.1.4. Toxicity to other terrestrial organisms
7.2.2. Calculation of Predicted No Effect Concentration (PNEC soil)
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PNEC derivation
a.
Statistics on the species sensitivity distribution (SSD)
As in the RA, the statistical extrapolation approach is proposed in the PNEC derivation. We tested the
lognormal distribution in the statistical approach as default option using the RIVM program ETX version 2.0.
As in the RA (ECB, 2008), the HC5 is calculated for three different scenarios of data selection. The first
scenario is by using microflora NOEC values only. The values were taken as such from the Cd RA, as no new
data were added to the dataset. The second scenario is based on the use of the revised database for invertebrates
and plants, (going from 20 to 24 species). The third scenario is making use of the whole terrestrial toxicity
database, i. e. using data on microflora, plants and invertebrate organisms, as applied to other RA on metals (Cu,
Ni) and recommended by the Scientific Committee for Health and Environmental Risks (SCHER) for the zinc
RA. The statistics of the curve-fitting on the chronic NOEC data are summarized in Table below.
Table 56. Summary statistics for the SSD on chronic NOEC values for cadmium in soil
Scenario
N
HC5 at 50%
A-D test and
(Lower estimate significance
on HC5) mg
level
Cd/kg
K-S test and
Statistical
significance level acceptance
Microflora
21
2.3 (0.7)
0.50
0.74
(P>0.1)
(P>0.1)
0.29
0.63
(P>0.1)
(P>0.1)
0.46
0.69
(P>0.1)
(P>0.1)
Plants+Invertebr 24
ates
3.6 (2.0)
Microflora+plan 45
ts+invertebrates
2.4 (1.0)
Accepted
Accepted
Accepted
Using both the Anderson-Darling (A-D) and the Kolmogorov-Smirnov (K-S) tests for normality, the lognormal
distribution fits significantly at a level of 1% for all tested scenarios.
The terrestrial data set is split in two groups: microbial processes and soil invertebrates + higher plants. The
endpoints for microbial processes are relevant at the ecosystem functioning level, while the endpoints for soil
fauna and plants are relevant at the species level. The principle of splitting the terrestrial data in two groups is
open to criticism: there is no scientific argument (e. g. field validation) for either option. However, this approach
was taken forward in the Cd RA (ECB, 2008) and is therefore also applied in the present assessment. It is
however noted that recently, this split has not been applied in more recent metal RAs, e.g. on Ni, Cu.
As in the RA, the lowest NOEC selection approach was not performed because such a selection would not yield
a representative data set for the terrestrial ecosystem (e. g. all clay soils would be excluded). The HC5 for the
microflora is lower than the HC5 for soil fauna and plants. In conclusion, we propose to use the HC5 based on
the microflora data set for the PNEC derivation i. e. HC5microflora= 2.3 μg Cd/g d. w. This approach is in
accordance with the Cd RA (ECB, 2008) and results in the lowest of the three HC5 values following from the
three tested scenarios.
For the sake of comparison, if the assessment factor approach would be applied, using the lowest NOEC divided
by an assessment factor (AF) 10, this would yield a PNEC soil of 1.8 µg g -1/AF10 or 0.18 µg/g. This value is
within the range of cadmium background concentrations in soils which typically range between 0.1 and 0.5 µg/g
(Cd RA, 2008).
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b.
cadmium sulphate
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Discussion on the uncertainty on the HC5 for PNEC soil derivation
Based on the uncertainty considerations, an assessment factor between 1 and 5 should be applied to the HC5 at
50% confidence levels (thus PNEC=HC5/AF). The AF is to be judged on a case by case basis.
The following considerations are made on the uncertainty around the HC5 and for determining the size of the
AF:
Species diversity The HC5 value of the terrestrial ecosystem is derived from 21 individual NOECs covering 5
different microbial processes. The plants belong to 9 different families and 9 different taxonomic orders and the
invertebrates belong to 4 different families and 3 different taxonomic orders. This diversity meets the
recommendation for deriving a PNEC for soil using statistical extrapolation method, i.e. the data set contains
more than 8 different taxa. Based on this criterion, there is no need for an AF.
Types of soils
The data should be based on a diversity of soil properties. The tests on which the HC5 value is
based are performed in soils with pH 3.1-7.9 % carbon 0.6-47 and % clay 2-70. This range in soil properties
covers most of the European topsoils. Based on this criterion, there is no need for an AF.
Field studies
There are field data that allow deriving threshold concentrations of Cd in soil at the field scale.
Cadmium is usually associated with other metals in the field and these other metals can be more readily toxic
than Cd itself. In most cases, Cd pollution is associated with Zn pollution. Effects of smelter contamination on
plants or on earthworms are often attributed to Zn and not to Cd (Tiller, 1989; Spurgeon and Hopkin, 1995).




Field observations (Sajwan et al. 1996) In this field test, effect of Cd was measured in bush beans
grown on a loamy sand located on the Savannah River Site, near Aiken in South Carolina, US. No
growth effects were noted at the highest tested concentration i.e. up to 6.7 µg Cd/g soil d.w (measured
concentration). The Cd level in the control treatment was of 0.6 µg/g Cd (Sajwan et al., 1996).
Field trials (Kádár, 1995; Kádár et al., 1998) A long term field trial was performed in Nagyhörcsök,
Hungary on a calcareous chernozem, characterised by a high cation exchange capacity, high pH and
high base saturation. Cationic metals are strongly sorbed into this soil. Cadmium (as CdSO4) was
applied to the soil at 4 concentrations above control with three fold replication. No toxic effect of Cd
on plant growth was detected up to the highest test concentration (810 kg/ha.y) during the first 4 years.
Toxic effects (significantly different from control) were observed at 270 kg/ha loading in 1995 and
1996, in spinach and red beet, i.e. 162 mg Cd/kg soil (Table 54). The resulting NOECs values for those
species in the field were both 50 mg Cd/kg soil, i.e. well above the HC5 values calculated in the
present analysis. No effects were observed for wheat grain (Table 54).
Field trials (Mench et al. 1989) Another long-term field trial took place in 1988-1990 in Bordeaux (F).
Three nominal Cd concentrations were tested: 10, 20 and 40 g Cd/g. The field has plots with pH 5.35.6 and plots with pH 6.7-7.0. The corn shoot yield data of 2000 are given in Table 54. Cadmium was
more toxic in the most acid plots and had no significant effect on corn shoot yield up to 7-8 g Cd/g.
The LOECs at 15 g Cd/g were associated with a 50 % (high pH) and 61 % (low pH) lower shoot yield
than the control.
Bingham et al. 1975 This paper refers to pot trial experiments on various plant species grown to
commercial harvest stage on a soil pre-treated with municipal sewage sludge (1%). Effects levels
(EC25s) are reported for 14 species. The lowest reported EC25 is for the spinach Spinacia oleracea
with a value of 4 µg Cd/g. This value is 4-fold lower than in the field where 25% yield reduction is
observed at 18 µg Cd/g (see Table 54, Kadar 1995). The phytotoxic effects of Cd were then observed
at higher concentrations in the field trials compared to pot trials. This is also the case for wheat grain.
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Table 57. Phytotoxicity of Cd salts in field trials (from Cd RA, 2008)
test
substance
CdSO4
Cd(NO3)2
Cd(NO3)2
soil properties
Results*
Nagyhörcsök (Hungary):
calcareous Chernozem;
pH (CaCl2) = 7.3; 3%
org. matter; 5%CaCO3;
CEC 22 cmolc/kg
1991: 1single Cd application
(kg Cd/ha)
1994: soil Cd (g)
Kádár et al., 1998
0
0.3
30
18
90
50
270
162
810
not meas.
yield (ton FW/ha)
1991: corn
1992: carrot
1993: potato
1994: pea
1995: red beet
1996: spinach
1997: wheat grain
14.6a
16.3a
6.8a
n.s.
n.s.
n.s.
n.s.
7.4a
12.1a
n.d.
n.s.
n.s.
n.s.
n.s.
9.5a
11.4a
7.3a
n.s.
n.s.
n.s.
n.s.
3.7b
9.8b
6.4a
n.s.
n.s.
n.s.
n.s.
0.7b
3.7b
5.4a
Borde aux (France)
pH (CaCl2) = 5.3-5.6;
CEC 10 cmolc/k g
1988-1990 Cd applications
2000:soil Cd (mg Cd/kg)
2000: corn (g FW/plant)
1.3
59.9a
7.2
39.9a
15
23.3b
35
18.6b
Bordeaux (France)
pH (CaCl2) = 6.7-7.0;
CEC 15 cmolc/kg
1988-1990 Cd applications
2000:soil Cd (mg Cd/kg)
2000: corn (g FW/plant)
1.2
35.6a
8.3
44.0a
15
17.9b
32
16.4b
Mench, pers. com.
(2000)
Mench, pers. com.
(2000)
*values in the same row with the same superscript do not differ significantly
n. s. Not specified
n. d. Not determined
The table below summarizes the chronic long term field NOEC values together with the exposure period and
soil type that are taken from the various studies discussed in this chapter.
Table 58. Chronic long term field NOEC values taken from table 54.
Species
Soil type
Exposure
period
NOEC growth
(mg/kg)
Phaseolus vulgaris
(bush bean)
References
Natural loamy sand
30 days
>6.7 (unbounded)
Spinacia oleracea
(Spinach)
Natural calcareous
chernozem
4 years
50
Kadar 1995, Kadar et al.
1998
Beta vulgaris (Red beet)
Natural calcareous
chernozem
5 years
50
Kadar 1995, Kadar et al.
1998
Triticum aestivum
(Wheat grain)
Natural calcareous
chernozem
6 years
>162
Kadar 1995, Kadar et al.
1998
Zea mays (Corn)
Sandy-clay soil (low
pH)
12 years
7.2
Mench et al. Pers.
Comm.. 2000
Zea mays (Corn)
Sandy-clay soil (high
pH)
12 years
8.3
Mench et al. Pers.
Comm.. 2000
Various plant species
including Spinach
which was the most
sensitive tested species
Silt loam, xerollic
calciorthid soil enriched
with 1% sewage sludge
Up to
maturity
EC25 range: 4>640
Sajwan et al. 1996
Bingham et al. 1975
To conclude, field data yield NOECs that are well above the HC5 of 2.3 g Cd/g (see summary table). There is
currently no indication of higher toxicity of Cd salts in the field than in the laboratory. Given this, there is no
need for an assessment factor higher than one.
Goodness-of-fit of the SSD
The goodness-of-fit of the SSD's is tested with the Anderson-Darling and
Kolmogorov-Smirnov tests. The log-normal distribution is accepted at the 1-10% significance levels when
applied on the microbial data set on which the HC5 is based. A factor of 3.4 is observed between the 95% lower
confidence level and the HC5 microflora. This factor goes down to 1.9 with the combined dataset, which is
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showing that the statistical uncertainty is strongly reduced. Based on this, there is no need for an AF higher than
1.
Toxicity values below the HC5
In the soil dataset, two NOEC values are reported to be below the lowest
HC5. One is from the species Picea sitchensis, a conifer species, and the other one comes from the lettuce
Lactuca sativa, for which a range of NOECs are available. It must be recalled that there is no single test in the
entire database (including tests with RI 4) at which a toxic effect of Cd was found at or below the PNEC soil from
the RA = 2.3 g Cd/g.
Setting the PNEC soil
The PNEC soil is set based on the lowest observed HC5 derived by statistical extrapolation from the microflora
data, i. e. 2.3 µg Cd/kg d. w. In the Cd RA, an AF 1 or 2 was considered. The current analysis rather suggests
using an AF1 on the HC5 to derive the PNEC. It is noted that thePNEC soil based on secondary poisoning is 0.9
µg Cd/g dw which is below the proposed value. The latter value is therefore proposed and used for PNECsoil in
this assessment. This is in accordance with the approach followed in the Cd RA (ECB 2008).
Table 59. PNEC soil
PNEC
Assessment
factor
Remarks/Justification
PNEC soil: 0.9
mg/kg soil dw
1
Extrapolation method: statistical extrapolation
A PNECsoil was derived by statistical extrapolation of the extensive soil
microflora data, as in the EU risk assessment. This resulted in a HC5 of
2.3 mg Cd/kg d.w. (AF1). However, a PNEC for soil based on secondary
poisoning was also derived, effectively suggesting that biotransfer of Cd
from soil to higher trophic levels is the most critical pathway for Cd.
This PNECsoil secondary poisoning is based on the HC5-50% value of a
distribution of soil concentrations leading to critical kidney concentration
of 400µg/g d.w. measured in 8 mammal species. This HC5-50% is 0.9
µg Cd/g d.w. soil and, since it is lower than the value derived for
microflora sensitivity, is used as the PNECsoil. This approach is in
accordance with the one applied in the EU risk assessment on Cd/CdO
(ECB 2008).
7.3. Atmospheric compartment
The EU RA indicated for this scenario: “A quantitative risk characterisation for exposure of organisms to
airborne cadmium is not done because there are no useful data on the effects of airborne cadmium in
environmental organisms and thus no PNEC air could be derived. The PECs in air are used for the risk
assessment of man indirectly exposed via the environment (chapter 4). Inorganic cadmium air emissions are
primarily associated with particulates in the air. Emission to air will settle out to soil. The impact of industrial
air emissions at local scale is therefore included in the conclusions on the terrestrial compartment.”
The same approach is followed in the present analysis.
7.4. Microbiological activity in sewage treatment systems
The EU risk assessment discussed available data for Cd toxicity to micro-organisms. There were 2 high quality
studies available, both performed according to OECD protocol (OECD 209) for testing effect on sludge
respiration, showing similar NOEC values when Cd was expressed as the dissolved fraction.
The LOEC values observed on the dissolved Cd fraction were high as compared to LOEC values for aquatic
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species. This suggested low sensitivity of bacteria to Cd was confirmed by results on bacterial cultures of
Pseudomonas putida, Zoogloea ramigera and Escherichia coli, which also showed LOECs in the 1mg/l range
(RA Cd/Cd0 table 3.2.32.).
The PNEC for STP was derived in the EU risk assessment by applying an assessment factor of 10 on the lowest
observed NOEC (200 µg Cd/l) which yielded a PNECSTP of 20 µg Cd/l. The same PNEC is used for the present
exercise.
This concentration refers to the Cd in the ionic form (dissolved fraction).
7.4.1. Toxicity to aquatic micro-organisms
The results are summarised in the following table:
Table 60. Overview of effects on micro-organisms
Method
Results
Remarks
Reference
activated sludge of a predominantly
domestic sewage
NOEC (3 h): 200 µg/L
dissolved (meas. (arithm.
mean)) based on:
respiration rate
1 (reliable without
restriction)
LISEC (1998b)
NOEC (3 h): 32600 µg/L
test mat. (meas. (arithm.
mean)) based on:
respiration rate
read-across based on
grouping of
substances (category
approach)
LOEC (3 h): 800 µg/L
dissolved (meas. (arithm.
mean)) based on:
respiration rate
Test material
(IUPAC name):
cadmium (See
endpoint summary
for justification of
read-across)
freshwater
static
OECD Guideline 209 (Activated
Sludge, Respiration Inhibition Test)
LOEC (3 h): 100000 µg/L
test mat. (meas. (arithm.
mean)) based on:
respiration rate
key study
Discussion
Lowest NOEC is of high quality study.
The following information is taken into account for effects on aquatic micro-organisms for the derivation of
PNEC:
Lowest NOEC of high quality study: 0.2mg Cd/l
Value used for CSA:
EC10/LC10 or NOEC for aquatic micro-organisms: 0.2 mg/L
7.4.2. PNEC for sewage treatment plant
Table 61. PNEC sewage treatment plant
Value
Assessment
factor
PNEC STP: 20 µg/L 10
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Remarks/Justification
Extrapolation method: assessment factor
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The PNEC for STP was derived in the EU Cd risk assessment by
applying an assessment factor of 10 on the lowest observed NOEC (200
µg Cd/l) from the two available studies on Cd toxicity to microorganisms, testing effects on sludge respiration, which yielded a
PNECSTP of 20 µg Cd/l. The same PNEC is used for the present
exercise.
7.5. Non compartment specific effects relevant for the food chain
(secondary poisoning)
7.5.1. Toxicity to birds
The EU risk assessment on cadmium identified 4 good quality feeding studies on birds, using Cd-spiked diets.
According to the RA, the PNEC oral secondary poisoning is derived from the lowest NOEC on Mallard ducks
(1.6 mg Cd/kg diet; White et al 1978).
The PNEC oral can be calculated applying an assessment factor of 10 on this long-term feeding study, i.e.
0.16mg Cd/kg diet.
The dataset allows to derive a PNEC from statistical extrapolation. This PNEC would be higher than the one
obtained with the assessment factor method (RA, ECB 2008). However, following the approach of the RA, it is
decided to use the more conservative value from the assessment factor approach as the PNEC.
The results are summarised in the following table:
Table 62. Overview of effects on birds
Method
Results
Gallus domesticus
NOEC (28 d): 12 mg/kg
2 (reliable with
diet based on: reproductive restrictions)
parameters (egg production)
weight of evidence
LOEC (28 d): 48 mg/kg
diet based on: reproductive experimental result
parameters (egg production)
Test material (EC
name): cadmium
sulphate
Leach RM, Wang
KWL and Baker
DE (1978)
NOEC (90 d): 1.6 mg/kg
2 (reliable with
diet based on: reproductive restrictions)
parameters
weight of evidence
(spermatogenesis)
White DH, Finley
MT and Ferrell JF
(1978)
repeated dose toxicity test (feed)
Doses: 0-3-12-48 µg/g of basal diet.
Repeated dose toxicity test with
laboratory feeding of Cd-containing
food
Anas platyrhynchos
Repeated dose toxicity test (feed)
Doses: O-2-20-200 mg Cd/kg Wet
weight
Repeated dose toxicity test with
laboratory feeding of Cd-containing
food
LOEC (90 d): 15.2 mg/kg
diet based on: reproductive
parameters
(spermatogenesis)
Remarks
Reference
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Anas platyrhynchos
repeated dose toxicity test (feed)
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NOEC (84 d): 10 mg/kg
diet based on: kidney
lesions
2 (reliable with
restrictions)
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Moore J (1983)
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CAS number:
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Method
Results
Doses: 0-5-10-20 mg/kg of basal diet
NOEC (84 d): 10 mg/kg
weight of evidence
diet based on: haemoglobin
read-across based on
concentrations
grouping of
substances (category
LOEC (84 d): 20 mg/kg
diet based on: kidney
approach)
lesions
Test material
LOEC (84 d): 20 mg/kg
(IUPAC name):
diet based on: haemoglobin cadmium dichloride
concentration
(See endpoint
summary for
justification of
read-across)
Repeated dose toxicity test with
laboratory feeding of Cd-containing
food
Coturnix coturnix japonica
chronic repeated dose toxicity test
(feed)
Doses: 0-75 mg/kg of basal diet
repeated dose test with adminstration
of Cd through the diet.
Remarks
NOEC (42 d): 38 mg/kg
diet based on: growth
2 (reliable with
restrictions)
LOEC (42 d): 75 mg/kg
diet based on: growth
weight of evidence
Reference
Richardson ME,
Spivey Fox MR
and Fry BE (1974)
read-across based on
grouping of
substances (category
approach)
Test material
(IUPAC name):
cadmium dichloride
(See endpoint
summary for
justification of
read-across)
Gallus domesticus
repeated dose toxicity test (feed)
Doses: 0-3-12-48 µg/g of basal diet.
Repeated dose toxicity test with
laboratory feeding of Cd-containing
food
NOEC (28 d): 12 mg/kg
2 (reliable with
Leach RM, Wang
diet based on: reproductive restrictions)
KWL and Baker
parameters (egg production)
DE (1978)
weight of evidence
LOEC (28 d): 48 mg/kg
diet based on: reproductive read-across based on
parameters (egg production) grouping of
substances (category
approach)
Test material:
(IUPAC name):
cadmium sulphate
Discussion
Results from 4 studies were available. The results obtained on mallard ducks give the lowest NOEC of 5 values.
It is used for calculating the PNEC oral for birds.
The following information is taken into account for effects on birds for the derivation of PNEC:
Repeated dose toxicity of Cd administered through the diet was studied on several species. The NOEC ranged
from 1.6mg Cd/kg FW food to 38 mg Cd/kg FW food. The LOEC ranged between 15.2mg Cd/kg FW food and
75 mg Cd/kg FW food.
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7.5.2. Toxicity to mammals
The EU risk assessment on cadmium identified 5 good quality feeding studies on mammals, using Cd-spiked
diets. According to the RA, the PNEC oral secondary poisoning is derived from the lowest NOEC on monkey (3
mg Cd/kg diet; Masoaka et al 1994).
According to the RA, the PNEC oral is calculated applying an assessment factor of 10 on this long-term feeding
study, i.e. 0.3mg Cd/kg diet.
The dataset allows to derive a PNEC from statistical extrapolation. This PNEC would be higher than the one
obtained with the assessment factor method (RA, ECB 2008). However, following the approach of the RA, it is
decided to use the more conservative value from the assessment factor approach as the PNEC.
7.5.3. Calculation of PNECoral (secondary poisoning)
The 4 studies on bird toxicity and 5 studies on mammals allow for the calculation of a PNEC oral for birds and
mammals exposed through the diet. The lowest value of the two is used as PNEC oral.
Table 63. PNEC oral
PNEC
Assessment
factor
Remarks/Justification
PNEC oral: 0.16
mg/kg food
10
The EU risk assessment on cadmium identified 4 and 5 good quality
feeding studies on birds and mammals, respectively, using Cd-spiked
diets. According to the RA, the PNEC oral secondary poisoning is
derived from the lowest NOEC of the 9 chronic studies (NOEC for
Mallard ducks of 1.6 mg Cd/kg diet; White et al 1978) divided by an
AF10.
7.6. Conclusion on the environmental hazard assessment and on
classification and labelling
Environmental classification justification
Cadmium and soluble Cd-compounds are classified based on the Cd++ ion. The substance releases sufficient
Cd-ions at 1 mg/l loading to exceed the reference acute aquatic toxicity value of 18 µg Cd /l. Consequently, it is
classified as
-N, R50/53 (very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment;
cfr Annex 1 dangerous substances directive 67/548/EEC)
-H410 (very toxic to aquatic life with long lasting effects; cfr GHS)
General discussion
A basic assumption made in this hazard assessment and throughout this CSR, (in accordance to the same
assumption made in the EU RA process) is that the ecotoxicity of cadmium and cadmium compounds is due to
the Cd++ion. As a consequence, all aquatic, sediment and terrestrial toxicity data in this report are expressed as
“cadmium”, not as the test compound as such, because ionic cadmium is considered to be the causative factor
for toxicity. A further consequence of this is that all ecotoxicity data obtained on different cadmium compounds,
are mutually relevant for each other. For that reason, the available ecotoxicity databases related to cadmium and
the different cadmium compounds are combined before calculating the PNECs. The only way cadmium
compounds can differ in this respect is in their capacity to release cadmium ions into (environmental) solution.
That effect is checked eventually in the transformation/dissolution tests and may result in different
classifications.
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8. PBT AND VPVB ASSESSMENT
8.1. Assessment of PBT/vPvB Properties
Persistence
Cadmium is an element and as such, the criterion “persistence” is not applicable to Cd and Cd-compounds.
As an alternative for persistency (for organic substances), the concept of “removal from the water column” has
been developed for inorganic elements.
This characteristic has not yet been studied for cadmium.
Bio-accumulation
Data on bioaccumulation of cadmium are presented and discuused under section 4.3. From this analysis, the
following was concluded:
The available evidence makes it difficult to decide whether or not Cd is to be considered as a bioaccumulative
substance in the environment. The high BCF /BAF factors observed in the lower levels of the food chain (algae
notably) would suggest Cd is to be considered as bioaccumulative. However, there are some uncertainties with
the data: the high BCF/BAF factors observed in the algae are (at least partly) due to external absorption, not to
uptake; the higher levels in invertebrates maybe related to lack of gut clearance of the organisms studied. BCF
in fish are generally below the criterion for considering a substance bioaccumulative.
In terms of hazard identification/classification, several considerations speak against a conclusion of considering
Cd as bioaccumulative substance:
-the BCF/BAF values observed with Cd consistently decrease with increasing exposure, which clearly shows
some level of physiological regulation of uptake. One of the key theoretical conditions of the BCF model in
terms of its relevance for chronic toxicity and applicability to the hazard identification/classification of
chemicals is that the BCF/BAF should be independent of exposure. BCF/BAF values should in other words
remain fairly constant over a range of exposures, which is clearly not the case for Cd.
-Evidence related to biomagnification in the aquatic food chain consistently shows that Cd is not biomagnifying.
Based on an extensive review of evidence on a wide variability of taxonomic groups, McGeer et al (2003)
concluded that the BCF/BAF criteria, as conceived for organic substances, are inappropriate for the hazard
identification and classification of metals, including Cd. They highlighted the inconsistency between BCF/BAF
values and toxicological data, as BCF values are highest (suggesting hazard) at low exposure concentrations and
are lowest (indicating no hazard) at the highest exposure concentrations, were toxicity is likely.
So the case on Cd bioaccumulation for hazard identification/classification is inconclusive. In any case, the main
question to pose in this respect is on secondary poisoning. This aspect is discussed below.
Related to secondary poisoning , the following was concluded from the analysis in section 4.4.:
In the freshwater compartment, the risk of secondary poisoning of fish eating birds by Cd is predicted to be
smaller than the direct effects of Cd in the aquatic environment. The RA demonstrated, using BCF’s of fish
(mentioned in section 4.3) that the Cd concentration in whole fish at the PNEC water of 0.19 µg Cd/l (section 7.)
could be predicted to range between 0.0001 and 0.13 mg Cd/kg fresh weight using the whole range of BCF’s
(0.5-684 l/kg fresh weight). It was concluded that these Cd concentrations were below the PNEC oral for birds or
birds+mammals (ECB 2008).
In the terrestrial compartment, a PNEC for secondary poisoning was calculated from the lowest observed
PNECoral for mammals and birds, which was derived from feeding studies with Cd salt spiked diets. Nine
feeding studies were selected (sub-chronic and chronic studies), four studies with birds and 5 studies with
mammals. The PNECoral of 0.9 µg Cd/g DW soil was calculated from the lowest NOEC using an assessment
factor (see section 7). It follows from the risk characterisation under section 10.2.2. (Environment (combined for
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all emission sources)), that the PNEC secondary poisoning is in general not reached in soil.
Toxicity
The reference values for aquatic toxicity following from section 7 are 18µg/l for acute toxicity, and 0.21 µg Cd/l
for chronic aquatic toxicity.
8.1.1. Summary and overall conclusions on PBT or vPvB properties
Considering the elements mentioned above, the case on PBT and vPvB properities of cadmium and its
compounds is inconclusive.
9. EXPOSURE ASSESSMENT
9.1. GES CdSO4 solution-0: Industrial isolation of the Intermediate
Cadmium Sulphate solution (273-721-3) from Cadmium and/or
Cadmium compounds leaching, refining or extraction steps, by settling,
filtering and other hydrometallurgical processes
9.1.1. Exposure scenario
Table 64. GES CdSO4 solution-0
Exposure Scenario Format (1) addressing uses carried out by workers
Title of Exposure Scenario number GES CdSO4 solution -0: Industrial isolation of the
Intermediate Cadmium Sulphate solution (273-721-3) from Cadmium and/or Cadmium
compounds leaching, refining or extraction steps, by settling, filtering and other
hydrometallurgical processes.
List of all use descriptors related to the life cycle stage and all the uses under it; include market sector (by PC), if relevant;
SU: 3, 8, 14
PROC: 2, 3, 4, 5, 8b, 9, 13, 26
PC: 19
AC: not applicable
ERC: 1
Further explanations (if needed)
Cadmium metal cake or cadmium compound bearing scrap is grinded and leached in order to produce cadmium
sulphate solution. Process is carried out in semi-closed leaching tanks, settlers and filter units, with occasional
controlled exposure and transfer of the solution for further extraction of cadmium metal or production of
cadmium compounds.
Exposure Scenario
9.1.1.1 Contributing scenario (1) controlling environmental exposure for the Industrial isolation
of the Intermediate Cadmium Sulphate solution (273-721-3) from Cadmium bearing material
leaching, refining or extraction steps, by settling, filtering and other hydrometallurgical
processes.
Further specification:

Stockpiling of the primary Cd-material (Cd-metal cake and Cd-bearing recycled scrap) in closed and
well ventilated buildings.
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
Feeding of the primary materials into the mixing tank. The leaching reaction with sulphuric acid
solutions is kept at the proper temperature and proper pH (~4.2).

Filtration of the leach-residue occurs on pressfilters, under ventilated hood

Oxidation of some of the present elements may be necessary (i.e. Te > TeO2 or others), followed by
another filtration step, if necessary

Further transfer of the Cadmium sulphate solution occurs by pipes or in specially designed transfer
units that prevent any exposure

Maintenance activities
Product characteristics
Product related conditions:
The Intermediate Cadmium Sulphate solution has a Cadmium-concentration that can vary between 70 g/L (
acidic solution) and 200 g/L (neutral solution – pH 4.5)
Amounts used
Daily and annual amount per site:
Up to 50 t/month of Cadmium contained
Frequency and duration of use
Continuous production
Environment factors not influenced by risk management
Flow rate of receiving surface water:
Default is used unless specified otherwise
Other given operational conditions affecting environmental exposure
Other given operational conditions: e.g. technology or process techniques determining the initial release of substance from
process (via air and waste water); dry or water based processes; conditions related to temperature and pressure; indoor or
outdoor use of products; work in confined area or open air;

Most of the operations are in wet phase.

All steps involving any potential exposure to CdSO4 are conducted in a controlled environment
protected by efficient and performance-monitored filters with verified removal efficiency for submicron particles in excess of 99.9%. The efficiency, flow rate and pressure drop in the filters is
continually monitored.

The manufacturing environment is fully fire protected by automated fire detection and extinguishing
systems.

Chemical storage is within a controlled, isolated area having monitored secondary containment.

Air emissions are processed through efficient filters prior to discharge into the atmosphere.

Waste water is being treated by state-of-the-art technology through precipitation, filtration, ionexchange, neutralization and fully monitored batch discharge system.

All residues containing Cd are recycled.
Technical conditions and measures at process level (source) to prevent release
Process design aiming to prevent releases and hence exposure to the environment; this includes in particular conditions
ensuring rigorous containment; performance of the containment to be specified (e.g. by quantification of a release factor in
section 9.x.2 of the CSR);
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Process enclosures and closed circuits whenever technically possible.
Containment of liquid volumes in sumps to collect/prevent accidental spillage, acid solutions are
treated appropriately.
Technical onsite conditions and measures to reduce or limit discharges, air emissions and releases to soil
Technical measures, e.g. on-site waste water and waste treatment techniques, scrubbers, filters and other technical measures
aiming at reducing releases to air, sewage system, surface water or soil; this includes strictly controlled conditions (procedural
and control technology) to minimise emissions; specify effectiveness of measures;
specify the size of industrial sewage treatment plant (m3/d), degradation effectiveness and sludge treatment (if applicable);

On-site waste water treatment techniques can be applied to prevent releases to water (if applicable)
e.g.: chemical precipitation, sedimentation and filtration (efficiency 90-99.98%).

Containment of liquid volumes in sumps to collect/prevent accidental spillage

Air emissions are controlled by use of scrubbers, filters, demisters.
Organizational measures to prevent/limit release from site
Specific organisational measures or measures needed to support the functioning of particular technical measures. Those
measures need to be reported in particular for demonstrating strictly controlled conditions.

In general, emissions are controlled and prevented by implementing an integrated management system
e.g. ISO 9000, ISO 1400X series, or alike, and, when applicable, by being IPPC-compliant (cf. NFMBREF).
Such management system, aiming at ensuring ‘strictly controlled conditions’, should include general
industrial practice like e.g.:
⁰ The substance is rigorously contained by technical means during the whole lifecycle including
manufacture, purification, cleaning/maintenance of equipment, sampling, analysis, loading
and unloading of equipment or vessels, waste disposal or purification and storage
⁰
Procedural and control technologies shall be used that minimise emission and any resulting
exposure
⁰
Only properly trained and authorised personnel handles the substance
⁰
For cleaning/maintenance, special procedures such as system purging and washing before
opening devices
⁰
Procedures, control technologies for accidents and waste
⁰
Substance-handling procedures well documented and strictly supervised
•
Treatment and monitoring of releases to outside air, and exhaust gas streams (process & hygiene),
according to national regulation.

SEVESO 2 compliance, if applicable
Conditions and measures related to municipal sewage treatment plant
Size of municipal sewage system/treatment plant (m3/d); specify degradation effectiveness; sludge treatment technique
(disposal or recovery); measures to limit air emissions from sewage treatment (if applicable); please note: the default size of the
municipal STP (2000 m3/d) will be rarely changeable for downstream uses.
In cases where applicable: default size, unless specified otherwise.
Conditions and measures related to external treatment of waste for disposal
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Fraction of used amount transferred to external waste treatment for disposal; type of suitable treatment for waste generated by
work-ers uses, e.g. hazardous waste incineration, chemical-physical treatment for emulsions, chemical oxidation of aqueous
waste; specify effectiveness of treatment;

If any, all hazardous wastes are collected, transported, treated and finally disposed by
authorized/certified contractors according to EU and national legislation.
Conditions and measures related to external recovery of waste
Fraction of used amount transferred to external waste treatment for recovery: specify type of suitable recovery operations for
waste generated by workers uses, e.g. re-distillation of solvents, refinery process for lubricant waste, recovery of slags, heat
recovery out-side waste incinerators; specify effectiveness of measure;

All residues formed during the leaching process, are recovered and either further treated in the system
or handled according to the waste legislation.

Users of Cd and Cd-compounds have to favour the recycling channels of the end-of-life products

Users of Cd and Cd-compounds have to minimize Cd-containing waste, promote recycling routes and,
for the remaining, dispose the waste streams according the Waste regulation.
9.1.1.2 Contributing scenario (2) controlling worker exposure for Industrial isolation of the
Intermediate Cadmium Sulphate solution (273-721-3) from Cadmium and/or Cadmiumcompounds leaching, refining or extraction steps, by settling, filtering and other
hydrometallurgical processes.
Name of contributing scenario 2:
Cadmium metal cake or cadmium compound bearing scrap is grinded and leached in order to produce cadmium
sulphate solution. Process is carried out in semi-closed leaching tanks, settlers and filter units, with occasional
controlled exposure and transfer of the solution for further extraction of cadmium metal or production of
cadmium compounds.
Further specification
Product characteristic
Product related conditions, e.g. the concentration of the substance in a mixture, the physical state of that mixture (solid, liquid;
if solid: level of dustiness), package design affecting exposure)
•
The isolated substance is a Cadmium sulphate rich solution (concentration TBC)
Amounts used
Amounts used at a workplace (per task or per shift); note: sometimes this information is not needed for assessment of worker’s
expo-sure
Maximum 50 t/month, 1t/shift of cadmium contained
Frequency and duration of use/exposure
Duration per task/activity (e.g. hours per shift) and frequency (e.g. single events or repeated) of exposure
8hrs shift
Human factors not influenced by risk management
Particular conditions of use, e.g. body parts potentially exposed as a result of the nature of the activity
Uncovered body parts: (potentially) face
Other given operational conditions affecting workers exposure
Other given operational conditions: e.g. technology or process techniques determining the initial release of substance from
process into workers environment; room volume, whether the work is carried out outdoors/indoors, process conditions related
to temperature and pressure.
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
All processes are carried out in confined areas with a minimum of operators

The process is managed and controlled from a separate control-room.
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Technical conditions and measures at process level (source) to prevent release
Process design aiming to prevent releases and hence exposure of workers; this in particular includes conditions ensuring
rigorous containment; performance of containment to be specified (e.g. by quantification of residual losses or exposure)

Process enclosures or semi-enclosures are applied whenever technically feasible.

Local exhaust ventilation on furnaces and other work areas with potential dust generation, dust
capturing and high-efficiency capturing/removal techniques (filters with > 99.9% efficiency)

If applicable, liquid volumes are handled/stored in secondary containments to collect/prevent
accidental spillage
Technical conditions and measures to control dispersion from source towards the worker
Engineering controls, e.g. exhaust ventilation, general ventilation; specify effectiveness of measure

Local exhaust ventilation systems (high efficiency 90-99.9%),

Scrubbers/ demisters (for minimizing air emissions): efficiency: 85-95% (Scrubbers, Absorbers,
demisters...)

Cd in dust/aerosols needs to be measured in the workplace air (static or individual) according to
national regulations.

Special care for the general establishment and maintenance of a clean working environment by e.g.:
1.
Cleaning of process equipment and workshop
o
Storage of solutions in covered vessels and thickeners
Organisational measures to prevent /limit releases, dispersion and exposure
Specific organisational measures or measures needed to support the functioning of particular technical measures (e.g. training
and supervision). Those measures need to be reported in particular for demonstrating strictly controlled conditions (to justify
exposure based waiving).

The protection of workers in the Cd-related industry is achieved by the systematic implementation of a
carefully designed stepwise risk management system, outlining measures to control worker exposure
and combining measurements of both exposure and effect. The system is aimed at prevention of
exposure and protection against early manifestation of (subclinical) effect at the level of the critical
organ, the kidney. The system is described in detail in the industry guidance document “Management
of the risk related to the chronic occupational exposure to cadmium and its compounds” (ICdA 2006).
It involves essentially 2 phases of action:
1) Controlling the Cd-concentration in the workplace air
Firstly, technical measures are taken to comply with the indicative EU (i-)OEL of 4 µg respirable
Cd/m3 proposed by SCOEL in compliance with art. 3 of directive 98/24/EC (2009). This i-OEL is
taken forward as a DNEL; compliance with the i-OEL is mandatory if no other measurements of
Cd-exposure and effect (as described below) are performed. The OEL of 4µg Cd/m3 is applicable
to Cd and Cd-compounds in general, unless the limited solubility of a given Cd-compound is
documented. The total/inhalable fraction corresponding to the respirable fraction is function of the
particle size of the inhaled particles.
2) Individual medical follow up of parameters of exposure and effect

In general when working with cadmium, and, notably, if compliance with the i-OEL cannot be ensured
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in a consistent way, protection of the worker is ensured by complementary risk reduction measures and
compliance with biological indicator limit values at the individual level. These measures include:

Personal respiratory protection and hygiene measures if appropriate (see below, section “Conditions
and measures related to personal protection, hygiene and health evaluation” for detail), in combination
with

Medical follow-up of the worker involving regular measurement of biological indicators of both
exposure and effect:
o exposure: measurement of Cd in urine (µg Cd/g Creatinine) and /or Cd in blood (µg Cd/l) to
assess integrated systemic exposure of the individual
o effect: measurement of early (subclinical) indicators of tubular (kidney) dysfunction. Wellestablished biological indicators (BI) for Cd-effect are e.g. β-microglobuline (β2-MG) and
retinol binding protein (RPB).
The specific medical supervision (for details see ICdA 2006 – part II, section 4) is complementary to the
technical and hygiene measures taken. It integrates exposure through all possible routes by assessing the Cdbody burden and assesses early biological indicators (BI’s) of (subclinical) renal effect. It ensures as such that
the risk to Cd-exposed workers is fully controlled.
The results of the medical supervision are applied as follows (see also Figure below):
Figure: Illustration of Eurometaux/ICdA medical supervision guidance (2006) (BI: biological indicators; C:
creatinine)
General medical follow-up level

Cd-U ≤ 2 µg Cd/g creatinine (C). This is a conservative threshold based on general population studies,
as described in Section 5.6.2. In this situation, the worker is followed by general medical follow-up
(complementary indicator: Cd-B ≤ 5 µg Cd/L). No further special action is required beyond proper
implementation of the general hygiene procedures and medical surveillance.
Action level

2 < Cd-U ≤ 5 µg Cd /g creatinine: Action level zone. This zone is defined by the threshold based on
studies at the workplace, as described in Section 5.6.2. Observation of Cd-U (or Cd-B) values in this “
action” zone triggers (complementary trigger: 5 µg Cd/l < Cd-B ≤ 8 µg Cd/l) an individual follow up
of the worker characterized by:
o
Systematic and frequent follow up of exposure by measuring Cd-U (complementary analysis:
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Cd-B), combined with individual analysis and follow-up of hygiene behaviour
o
Measurement of biological indicators (BI’s) of early renal dysfunction (e.g. beta-2
microglobuline (B2-M) or retinol-binding protein (RBP) on a regular basis;
When the worker moves into this action level zone, the occupational doctor and plant hygiene team will check
for the reason for the increased exposure (analysis of the workplace, with a view to identify possible substance
releases, analysis of compliance with hygienic procedures, and interview with the worker to assess possible
other causes, e.g. due to current or previous exposure, due to personal hygiene behaviour?).
Based on the results of the individual medical surveillance programme, the following management decisions are
taken:

The worker remains in the action zone: If the Cd-U (Cd-B) values do not progress further towards the
threshold and the BI’s remain stable and below the reference value (e.g. 300 µg/g creatinine for β2MG and RBP), the worker is kept at the workplace. Additional hygiene measures are taken as
appropriate, and medical follow-up is strictly continued.

The worker is removed from exposure:
o
If Cd-U > 5 µg Cd/g creatinine (or Cd-B > 8 µg/l) and/or
o
If the BI’s are exceeding the reference values or showing a consistent pattern of increase
which may lead to approaching the reference values

The management scheme as outlined above is applicable to workers that entered the Cd industry rather
recently. Workers that have been working in the Cd-industry for long may have been historically
exposed to elevated Cd -levels, and may show e.g. Cd-U levels exceeding 5 µg/gC due to historical
exposure. The supervising medical doctor will evaluate these individuals carefully, focusing on the
BI’s. In any case, when BI values exceed the BI-reference values or approach them, the worker will be
removed from Cd-exposure.

In addition to the above, general industrial hygiene programmes are to be implemented , as required by
EU Directive 98/24/EC on protection of workers from chemical agents and other referenced systems
on best practice : IPPC-BREF notes, BIMSCH or equivalent, ICH-Q7, FAMI-QS, ISO9000, ISO
13.100 or alike:
1.
General industrial hygiene practice
2.
Collective protection measures and use of warning & safety signs
3.
Minimizing the number of workers exposed or likely to be exposed
4.
Workplace cleanliness: ensure procedures are designed, written and implemented so as to
make sure cleanliness is obtained at workstations, work sections, traffic and storage areas,
upper areas, building structures and various horizontal surfaces, air suction ducts.
5.
Procedures for process control
Conditions and measures related to personal protection, hygiene and health evaluation
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Personal protection, e.g. wearing of gloves, face protection, full body dermal protection, goggles, respirator; specify
effectiveness of measure; specify the suitable material for the PPE (where relevant) and advise how long the protective
equipment can be used before replacement (if relevant)
Wearing of gloves and protective clothing is compulsory (efficiency >=90%).
With normal handling, no respiratory personal protection (breathing apparatus) is necessary. If risk for
exceedance of OEL/DNEL, use e.g.:
-dust filter-half mask P1 (efficiency 75%)
-dust filter-half mask P2 (efficiency 90%)
-dust filter-half mask P3 (efficiency 95%)
-dust filter-full mask P1 (efficiency 75%)
-dust filter-full mask P2 (efficiency 90 %)
-dust filter-full mask P3 (efficiency 97.5%)
Eyes: safety glasses are optional but recommended
9.1.2. Exposure estimation
9.2. GES CdSO4 solution-2: Industrial use of the Intermediate Cadmium
Sulphate solution (273-721-3) in the ultimate manufacturing of
Cadmium or Cadmium compounds by several metallurgical processes.
9.2.1. Exposure scenario
Table 65. GES CdSO4 solution-2
Exposure Scenario Format (1) addressing uses carried out by workers
Title of Exposure Scenario number GES CdSO4 solution-2: Industrial use of the Intermediate
Cadmium Sulphate solution (273-721-3) in the ultimate manufacturing of Cadmium or Cadmium
compounds by several metallurgical processes.
List of all use descriptors related to the life cycle stage and all the uses under it; include market sector (by PC), if relevant;
SU: 3, 8, 14
PROC: 2, 3, 4, 5, 8b, 9, 13, 26
PC: 19
AC: not applicable
ERC: 6a
Further explanations (if needed)
The Intermediate Cadmium Sulphate solution is unloaded, potentially blended with other material streams and
loaded in vessels for further use, reaction and production of Cadmium metal or Cadmium compounds.
Exposure Scenario
9.2.1.1 Contributing scenario (1) controlling environmental exposure for the Industrial use of
the Intermediate Cadmium Sulphate solution (273-721-3) in the ultimate manufacturing of
Cadmium or Cadmium compounds by several metallurgical processes.
Further specification:

The Cadmium sulphate solution is unloaded, potentially mixed with other solutions or reagents and
transferred to the reaction vessels through especially designed transfer launders,
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
This Intermediate is typically used in production units of Cadmium metal or Cadmium compounds.

Maintenance activities
Product characteristics
Product related conditions:
The Intermediate Cadmium Sulphate solution has a Cadmium-concentration that can vary between 70 g/L (
acidic solution) and 200 g/L (neutral solution – pH 4.5)
Amounts used
Daily and annual amount per site:
Up to 50 t/month of Cadmium contained
Frequency and duration of use
Continuous production
Environment factors not influenced by risk management
Flow rate of receiving surface water:
Default is used unless specified otherwise
Other given operational conditions affecting environmental exposure
Other given operational conditions: e.g. technology or process techniques determining the initial release of substance from
process (via air and waste water); dry or water based processes; conditions related to temperature and pressure; indoor or
outdoor use of products; work in confined area or open air;

Most of the operations are in wet phase.

All steps involving any potential exposure to CdSO4 are conducted in a controlled environment
protected by efficient and performance-monitored filters with verified removal efficiency for submicron particles in excess of 99.9%. The efficiency, flow rate and pressure drop in the filters is
continually monitored.

The manufacturing environment is fully fire protected by automated fire detection and extinguishing
systems.

Chemical storage is within a controlled, isolated area having monitored secondary containment.

Air emissions are processed through efficient filters prior to discharge into the atmosphere.

Waste water is being treated by state-of-the-art technology through precipitation, filtration, ionexchange, neutralization and fully monitored batch discharge system.

All residues containing Cd are recycled.
Technical conditions and measures at process level (source) to prevent release
Process design aiming to prevent releases and hence exposure to the environment; this includes in particular conditions
ensuring rigorous containment; performance of the containment to be specified (e.g. by quantification of a release factor in
section 9.x.2 of the CSR);

Process enclosures and closed circuits where relevant and possible.

Containment of liquid volumes in sumps to collect/prevent accidental spillage, acid solutions are
treated appropriately.
Technical onsite conditions and measures to reduce or limit discharges, air emissions and releases to soil
Technical measures, e.g. on-site waste water and waste treatment techniques, scrubbers, filters and other technical measures
aiming at reducing releases to air, sewage system, surface water or soil; this includes strictly controlled conditions (procedural
and control technology) to minimise emissions; specify effectiveness of measures;
specify the size of industrial sewage treatment plant (m3/d), degradation effectiveness and sludge treatment (if applicable);
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
On-site waste water treatment techniques can be applied to prevent releases to water (if applicable)
e.g.: chemical precipitation, sedimentation and filtration (efficiency 90-99.98%).

Containment of liquid volumes in sumps to collect/prevent accidental spillage

Air emissions are controlled by use of scrubbers, filters, demisters.
Organizational measures to prevent/limit release from site
Specific organisational measures or measures needed to support the functioning of particular technical measures. Those
measures need to be reported in particular for demonstrating strictly controlled conditions.

In general, emissions are controlled and prevented by implementing an integrated management system
e.g. ISO 9000, ISO 1400X series, or alike, and, when applicable, by being IPPC-compliant (cf. NFMBREF).
Such management system, aiming at ensuring ‘strictly controlled conditions’, should include general
industrial practice like e.g.:
⁰ The substance/ UVCB is rigorously contained by technical means during the whole lifecycle
including manufacture, purification, cleaning/maintenance of equipment, sampling, analysis,
loading and unloading of equipment or vessels, waste disposal or purification and storage
⁰
Procedural and control technologies shall be used that minimise emission and any resulting
exposure
⁰
Only properly trained and authorised personnel handles the substance
⁰
For cleaning/maintenance, special procedures such as system purging and washing before
opening devices
⁰
Procedures, control technologies for accidents and waste
⁰
Substance-handling procedures well documented and strictly supervised
•
Treatment and monitoring of releases to outside air, and exhaust gas streams (process & hygiene),
according to national regulation.

SEVESO 2 compliance, if applicable
Conditions and measures related to municipal sewage treatment plant
Size of municipal sewage system/treatment plant (m3/d); specify degradation effectiveness; sludge treatment technique
(disposal or recovery); measures to limit air emissions from sewage treatment (if applicable); please note: the default size of the
municipal STP (2000 m3/d) will be rarely changeable for downstream uses.
In cases where applicable: default size, unless specified otherwise.
Conditions and measures related to external treatment of waste for disposal
Fraction of used amount transferred to external waste treatment for disposal; type of suitable treatment for waste generated by
work-ers uses, e.g. hazardous waste incineration, chemical-physical treatment for emulsions, chemical oxidation of aqueous
waste; specify effectiveness of treatment;

If any, all hazardous wastes are collected, transported, treated and finally disposed by
authorized/certified contractors according to EU and national legislation.
Conditions and measures related to external recovery of waste
Fraction of used amount transferred to external waste treatment for recovery: specify type of suitable recovery operations for
waste generated by workers uses, e.g. re-distillation of solvents, refinery process for lubricant waste, recovery of slags, heat
recovery out-side waste incinerators; specify effectiveness of measure;
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
All residues formed during the leaching process, are recovered and either further treated in the system
or handled according the waste legislation.

Users of Cd and Cd-compounds have to favour the recycling channels of the end-of-life products

Users of Cd and Cd-compounds have to minimize Cd-containing waste, promote recycling routes and,
for the remaining, dispose the waste streams according the Waste regulation.
9.2.1.2 Contributing scenario (2) controlling worker exposure for Industrial use of the
Intermediate Cadmium Sulphate solution (273-721-3) in the ultimate manufacturing of Cadmium
or Cadmium compounds by several metallurgical processes.
Name of contributing scenario 2:
The Intermediate Cadmium Sulphate solution is unloaded, potentially blended with other material streams and
loaded in vessels for further use, reaction and production of Cadmium metal or Cadmium compounds.
Further specification
Product characteristic
Product related conditions, e.g. the concentration of the substance in a mixture, the physical state of that mixture (solid, liquid;
if solid: level of dustiness), package design affecting exposure)
•
The isolated substance/ UVCB is a Cadmium sulphate rich solution
•
With occasional (sampling, cleaning, maintenance) and minimized exposure for workers
•
The average Cadmium content of the solution lies between 70 - 200 g/L
Amounts used
Amounts used at a workplace (per task or per shift); note: sometimes this information is not needed for assessment of worker’s
expo-sure
Maximum 50 t/month, 1t/shift of Cadmium contained
Frequency and duration of use/exposure
Duration per task/activity (e.g. hours per shift) and frequency (e.g. single events or repeated) of exposure
8hrs shift
Human factors not influenced by risk management
Particular conditions of use, e.g. body parts potentially exposed as a result of the nature of the activity
Uncovered body parts: (potentially) face
Other given operational conditions affecting workers exposure
Other given operational conditions: e.g. technology or process techniques determining the initial release of substance from
process into workers environment; room volume, whether the work is carried out outdoors/indoors, process conditions related
to temperature and pressure.

All processes are carried out in confined areas with a minimum of operators

The process is managed and controlled from a separate control-room.
Technical conditions and measures at process level (source) to prevent release
Process design aiming to prevent releases and hence exposure of workers; this in particular includes conditions ensuring
rigorous containment; performance of containment to be specified (e.g. by quantification of residual losses or exposure)

Local exhaust ventilation on work areas with potential dust generation, dust capturing and removal
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techniques

Process enclosures closed circuits or semi-enclosures where appropriate.

Containment of liquid volumes in sumps to collect/prevent accidental spillage
Technical conditions and measures to control dispersion from source towards the worker
Engineering controls, e.g. exhaust ventilation, general ventilation; specify effectiveness of measure

Local exhaust ventilation systems (generic LEV (84%)),

Scrubbers/ demisters (for minimizing air emissions): efficiency: 85-95% (Scrubbers, Absorbers,
demisters...)

Cd in dust/aerosols needs to be measured in the workplace air (static or individual) according to
national regulations.

Special care for the general establishment and maintenance of a clean working environment by e.g.:
1.
Cleaning of process equipment and workshop
o
Storage of solutions in covered vessels and thickeners
Organisational measures to prevent /limit releases, dispersion and exposure
Specific organisational measures or measures needed to support the functioning of particular technical measures (e.g. training
and supervision). Those measures need to be reported in particular for demonstrating strictly controlled conditions (to justify
exposure based waiving).

The protection of workers in the Cd-related industry is achieved by the systematic implementation of a
carefully designed stepwise risk management system, outlining measures to control worker exposure
and combining measurements of both exposure and effect. The system is aimed at prevention of
exposure and protection against early manifestation of (subclinical) effect at the level of the critical
organ, the kidney. The system is described in detail in the industry guidance document “Management
of the risk related to the chronic occupational exposure to cadmium and its compounds” (ICdA 2006).
It involves essentially 2 phases of action:
3) Controlling the Cd-concentration in the workplace air
Firstly, technical measures are taken to comply with the indicative EU (i-)OEL of 4 µg respirable
Cd/m3 proposed by SCOEL in compliance with art. 3 of directive 98/24/EC (2009). This i-OEL is
taken forward as a DNEL; compliance with the i-OEL is mandatory if no other measurements of
Cd-exposure and effect (as described below) are performed. The OEL of 4µg Cd/m3 is applicable
to Cd and Cd-compounds in general, unless the limited solubility of a given Cd-compound is
documented. The total/inhalable fraction corresponding to the respirable fraction is function of the
particle size of the inhaled particles.
4) Individual medical follow up of parameters of exposure and effect

In general when working with cadmium, and, notably, if compliance with the i-OEL cannot be ensured
in a consistent way, protection of the worker is ensured by complementary risk reduction measures and
compliance with biological indicator limit values at the individual level. These measures include:

Personal respiratory protection and hygiene measures if appropriate (see below, section “Conditions
and measures related to personal protection, hygiene and health evaluation” for detail), in combination
with

Medical follow-up of the worker involving regular measurement of biological indicators of both
exposure and effect:
o exposure: measurement of Cd in urine (µg Cd/g Creatinine) and /or Cd in blood (µg Cd/l) to
assess integrated systemic exposure of the individual
o effect: measurement of early (subclinical) indicators of tubular (kidney) dysfunction. Well-
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established biological indicators (BI) for Cd-effect are e.g. β-microglobuline (β2-MG) and
retinol binding protein (RPB).
The specific medical supervision (for details see ICdA 2006 – part II, section 4) is complementary to the
technical and hygiene measures taken. It integrates exposure through all possible routes by assessing the Cdbody burden and assesses early biological indicators (BI’s) of (subclinical) renal effect. It ensures as such that
the risk to Cd-exposed workers is fully controlled.
The results of the medical supervision are applied as follows (see also Figure below):
Figure: Illustration of Eurométaux/ICdA medical supervision guidance (2006) (BI: biological indicators; C:
creatinine)
General medical follow-up level

Cd-U ≤ 2 µg Cd/g creatinine (C). This is a conservative threshold based on general population studies,
as described in Section 5.6.2. In this situation, the worker is followed by general medical follow-up
(complementary indicator: Cd-B ≤ 5 µg Cd/L). No further special action is required beyond proper
implementation of the general hygiene procedures and medical surveillance.
Action level

2 < Cd-U ≤ 5 µg Cd /g creatinine: Action level zone. This zone is defined by the threshold based on
studies at the workplace, as described in Section 5.6.2. Observation of Cd-U (or Cd-B) values in this “
action” zone triggers (complementary trigger: 5 µg Cd/l < Cd-B ≤ 8 µg Cd/l) an individual follow up
of the worker characterized by:
o
Systematic and frequent follow up of exposure by measuring Cd-U (complementary analysis:
Cd-B), combined with individual analysis and follow-up of hygiene behaviour
o
Measurement of biological indicators (BI’s) of early renal dysfunction (e.g. beta-2
microglobuline (B2-M) or retinol-binding protein (RBP) on a regular basis;
When the worker moves into this action level zone, the occupational doctor and plant hygiene team will check
for the reason for the increased exposure (analysis of the workplace, with a view to identify possible substance
releases, analysis of compliance with hygienic procedures, and interview with the worker to assess possible
other causes, e.g. due to current or previous exposure, due to personal hygiene behaviour?).
Based on the results of the individual medical surveillance programme, the following management decisions are
taken:
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
The worker remains in the action zone: If the Cd-U (Cd-B) values do not progress further towards the
threshold and the BI’s remain stable and below the reference value (e.g. 300 µg/g creatinine for β2MG and RBP), the worker is kept at the workplace. Additional hygiene measures are taken as
appropriate, and medical follow-up is strictly continued.

The worker is removed from exposure:
o
If Cd-U > 5 µg Cd/g creatinine (or Cd-B > 8 µg/l) and/or
o
If the BI’s are exceeding the reference values or showing a consistent pattern of increase
which may lead to approaching the reference values

The management scheme as outlined above is applicable to workers that entered the Cd industry rather
recently. Workers that have been working in the Cd-industry for long may have been historically
exposed to elevated Cd -levels, and may show e.g. Cd-U levels exceeding 5 µg/gC due to historical
exposure. The supervising medical doctor will evaluate these individuals carefully, focusing on the
BI’s. In any case, when BI values exceed the BI-reference values or approach them, the worker will be
removed from Cd-exposure.

In addition to the above, general industrial hygiene programmes are to be implemented , as required by
EU Directive 98/24/EC on protection of workers from chemical agents and other referenced systems
on best practice : IPPC-BREF notes, BIMSCH or equivalent, ICH-Q7, FAMI-QS, ISO9000, ISO
13.100 or alike:
1.
General industrial hygiene practice
2.
Collective protection measures and use of warning & safety signs
3.
Minimizing the number of workers exposed or likely to be exposed
4.
Workplace cleanliness: ensure procedures are designed, written and implemented so as to
make sure cleanliness is obtained at workstations, work sections, traffic and storage areas,
upper areas, building structures and various horizontal surfaces, air suction ducts.
5.
Procedures for process control
Conditions and measures related to personal protection, hygiene and health evaluation
Personal protection, e.g. wearing of gloves, face protection, full body dermal protection, goggles, respirator; specify
effectiveness of measure; specify the suitable material for the PPE (where relevant) and advise how long the protective
equipment can be used before replacement (if relevant)
Wearing of gloves and protective clothing is compulsory (efficiency >=90%).
With normal handling, no respiratory personal protection (breathing apparatus) is necessary. If risk for
exceedance of OEL/DNEL, use e.g.:
-dust filter-half mask P1 (efficiency 75%)
-dust filter-half mask P2 (efficiency 90%)
-dust filter-half mask P3 (efficiency 95%)
-dust filter-full mask P1 (efficiency 75%)
-dust filter-full mask P2 (efficiency 90 %)
-dust filter-full mask P3 (efficiency 97.5%)
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Eyes: safety glasses are optional but recommended
9.2.2. Exposure estimation
10. RISK CHARACTERISATION
10.1. (Title of exposure scenario 1)
10.1.1. Human health
10.1.1.1. Workers
10.1.1.2. Consumers
10.1.1.3. Indirect exposure of humans via the environment
10.1.2. Environment
10.1.2.1. Aquatic compartment (incl. sediment)
10.1.2.2. Terrestrial compartment
10.1.2.3. Atmospheric compartment
10.1.2.4. Microbiological activity in sewage treatment systems
10.2. (Title of exposure scenario 2)
10.3. Overall exposure (combined for all relevant emission/release
sources)
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10.3.1. Human health (combined for all exposure routes)
10.3.2. Environment (combined for all emission sources)
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