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Section B
Exposure Assessment of POPs and Dioxins
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Dioxin: Chemical Structure
! 2,3,7,8 - Tetrachlorodibenzo - p - dioxin (TCDD)
! CAS number: 1746-01-6
9
Cl
8
10
O
1
3
7
Cl
Cl
2
6
O
5
4
Cl
3
Physiochemical Properties of TCDD
! Molecular weight: 321.96
! Molecular formula: C12H4C14O2
! Vapor pressure: 7.4 X 10-10 torr
! Solubility in water: 19.3 ng/l
! Solubility in benzene: 570 mg/l
! Partition coefficient (octanol/water): 1.4 x 106 – 3.0 x 108
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Risk Characterization Sources
! Waste incineration
! High-temperature industrial processes
! By-product in herbicide production (Agent Orange/Vietnam )
! The pulp and paper industry (paper bleaching)
! Traffic exhaust
! Cigarette smoke
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Dioxin Example
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Routes of Human Exposure
! Ingestion of contaminated foods
- Milk
- Fat of meats
! Inhalation of contaminated air
- POP adsorbed onto particle
! Skin contact with contaminated soil
! Occupational exposure to chlorinated pesticides
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Relative Potency Ranges for 2,3,7,8-Substituted PCDDs
Congener
2,3,7,8-TCDD
1,2,3,7,8-PentaCDD
OCDD
a
TEF values NATO
In vivo toxicities
In vitro resultsa
1
—
—
0.5
0.59–0.053
0.64–0.07
0.001
> 0.0013
0.0006
Does not include receptor binding data
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Factors that Affect the Dose-Response Relationship
Biological Half-Life (Years) of Dioxins in Humans
Varies with Number of Chlorine Substitutions
Chemical
Blood
Fat
Whole Body
7.1–11.3
9.7
5.8
2,3,4,7,8-PCDF
7.2
4.7
1,2,3,4,7,8-HCDF
4.4
2.9
1,2,3,6,7,8-HCDF
4.3
3.5
2,3,7,8-TCDD
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Values for PCDD and PCDF
Values for PCDD and PCDF
From 30 Samples of Human Milk (ppt/Fat)
Isomer
Minimum
Maximum
Mean
2,3,7,8-TCDF
1.1
5.8
2.5
2,3,7,8-TCDD
1.6
6.9
3.4
OCDD
120
1,300
530
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Toxic Equivalency Factors (TEFs)
! Data used to define relative potencies of dioxin-like compounds
versus 2,3,7,8-TCDD
- Acute toxicity studies
- Subchronic studies of receptor-meditated toxicities:
! Thymic atrophy
Body weight loss
! Immunotoxicity
! - Reproductive and carcinogenicity studies
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The Toxic Equivalency Concept (TEQ)
! Criteria defined by WHO and IPCS
- A compound must show a structure relationship to the PCDDs
and PCDFs
- A compound must bind to the aryl hydrocarbon receptor (AhR)
- A compound must elicit AhR-mediated biochemical and toxic
- responses
A compound must be persistent and accumulate in the food
chain
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TEQs
! TEQs used to assess risk of mixes of PCDDs, PCDFs, and PCBs
! TEQ = ∑i-n (congener i x TEF i ) + …… (congener n x TEF n)
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Five Congeners Contribute ~ 80% Total TEQ in Humans
! 2,3,7,8 – TCDD
! 1,2,3,7,8 – PCDD
! 1,2,3,6,7,8 – HxCDD
! 2,3,4,7,8-PCDF
! PCB 126 (non-ortho substituted)
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Levels of Dioxin TEQ in Breast Milk
Levels of Dioxin TEQ in Breast Milk
Associated with Health Effects in Infants
Health effects
Breast milk levels
Neurologic delay
836 ± 388 ng/ml
Thyroid hormone disturbances
31–76 pg/g fat
Altered immune function
67 pg/g fat
Late form of HND*
30–93 pg/g fat
*Hemorrhagic disease of the newborn
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Dioxin Exposure Assessment
ADI (industrial countries)
1–3 pg TEQ/kg/d
Nursing infant
35–53 pg TEQ kgd
TDI (WHO, 1998)
1–4 pg TEQ/kg/d
ADI = average daily intake
TDI = tolerable daily intake
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