FINAL DRAFT
FRAMEWORK GUIDELINE FOR THE TOXICOLOGCAL
EVALUATION OF PESTICIDES IN SOUTH AFRICA
February 2014
1
TABLE OF CONTENTS
Page
ACKNOWLEDGEMENTS
4
GLOSSARY
5
1. BACKGROUND AND PURPOSE
9
1.1 Background
9
1.2 Purpose
11
2. CURRENT PROCEDURE OF TOXICOLOGICAL EVALUATION
OF PESTICIDES BY DEPARTMENT OF HEALTH
11
3. INFORMATION ON TOXICOLOGICAL HEALTH EFFECTS
12
4. INFORMATION ON ECOLOGICAL EFFECTS
13
4.1 Toxicity
13
4.2 Persistence and degradability
14
4.3 Bioaccumulative potential
14
4.4 Mobility in soil
14
4.5 Results of PBT and vPvB assessment
14
4.6 Other adverse effects
14
5. SAFETY DATA SHEET
15
6. LINKAGE TO OTHER DATA SOURCES
15
REFERENCES
16
ANNEXURE A:
ANNEXURE B:
Data requirements for the active ingredient and
formulated product in the dossier index
Criteria relating to the proposed recommendations /
restrictions to Department of Agriculture, Forestry
2
17
ANNEXURE C:
and Fisheries
21
Data requirements for persistent, bioaccumulative
and toxic substances and very persistent and very
bioaccumulative substances
22
3
ACKNOWLEDGEMENTS
The Department of Health would like to acknowledge the support and assistance
provided by the following role players in finalization of the framework guideline:

Officials from the Department of Health

Swedish Chemicals Agency (KEMI)

Department of Agriculture, Forestry and Fisheries

Department of Environmental Affairs

Department of Labour

Department of Water Affairs

University of Cape Town
4
GLOSSARY
Acute toxicity
adverse effects occurring after oral or
dermal administration of a single dose of
a substance, or multiple doses given
within 24 h, or an inhalation exposure of 4
h.
ADI
Acceptable daily intake
a.i.
Active ingredient
Active ingredient
means the biologically active part of the
pesticide
Bioaccumulation
net result of uptake, transformation and
elimination of a substance in an organism
due to all routes of exposure (air, water,
sediment/soil and food).
Biocentration
net result of uptake, transformation and
elimination of a substance in an organism
due to waterborne exposure.
BCF
Bioconcentration factor
Bioconcentration factor
ratio of the concentration of a test
substance in a test organism to the
concentration of the test substance in the
test water at equilibrium.
DAFF
Department of Agriculture, Forestry &
Fisheries
DoH
Department of Health
DTƽo
is the measure of the amount of time it
takes for 50% of the parent compound to
disappear from soil or water by
transformation.
ECƽo
concentration of a substance, in milligram
per litre of water, that causes the
maximum response to 50% of a
population of daphnia (water flea) and
crustacean.
5
Environment
means surroundings, including water, air,
soil and their inter-relationship as well as
their relationship with any living
organisms.
Eye irritation
production of changes in the eye
following the application of a test
substance to the anterior surface of the
eye, which are fully reversible within 21 d
of application.
FAO
Food and Agriculture Organization of the
United Nations
GHS
Globally Harmonized System
Hazard
means the inherent property of a
substance, agent or situation having the
potential
to
cause
undesirable
consequences (e.g. properties that can
cause adverse effects or damage to
health, the environment or property).
ISO
International standards organization Kow
Octanol-water partition coefficient
IUPAC
International Union for pure and applied
chemistry
LCƽo
Lethal concentration of a substance in air
or in water which causes the death of
50% of a group of test animals.
LDƽo
Lethal dose/concentration of a substance,
expressed in milligram per kilogram of
body mass which causes the death of
50% of a group of test animals when
ingested or exposure to the bare skin all
at once.
Liquid
liquid which, while in itself not necessarily
combustible can, generally by yielding
oxygen, cause, or contribute to, the
combustion of other material.
6
Mixture
solid or a solution composed of two or
more substances that do not react with
each other.
MRL
Maximum residue limit
Maximum residue limit
means the maximum concentration of a
residue that is legally permitted or
recognized as acceptable in or on a food
or agricultural commodity or animal
feedstuff.
NOEL
No observed exposure level
Octanol-water partition coefficient
(log Kow)
measure of the transfer of a substance
from the aquatic environment to an
organism, for example, fish and the
potential
bioaccumulation
of
the
substance at equilibrium concentration.
Pesticide
means any substance or mixture of
substances intended to prevent, destroy
or control any pest, including vectors of
human or animal disease, unwanted
species of plants or animals causing
harm during or otherwise interfering with
the production, processing, storage,
transport or marketing of food, agricultural
commodities, wood and wood products,
or animal feedstuffs or which may be
administered to animals for the control of
insects, arachnids or other pests in or on
their
bodies.
The
term
includes
substances intended for use as a plant
growth regulator, defoliant, desiccant, or
agent for thinning fruit or preventing the
premature fall of fruit, and substances
applied to crops either before or after
harvest to protect the commodity from
deterioration
during
storage
and
transport.
PBT
Persistent, bioaccumulative and toxicity
7
Product (or pesticide / formulated
product)
means the pesticide active ingredient(s)
and other components, in the form in
which it is packaged and sold.
Risk
is a function of the probability of an
adverse health or environmental effect
and the severity of that effect following
exposure.
Respiratory sensitizer
substance that induces hypersensitivity of
the airways following inhalation of the
substance.
Reproductive toxicity
adverse effects on sexual functions and
fertility in adult males and females as well
as adverse effects on the development of
offspring.
SDS
Safety Data Sheet
Serious eye damage
production of tissue damage in the eye or
serious physical decay of vision following
application of a test substance to the
anterior surface of the eye which is not
fully reversible within 21 d of application.
Skin corrosion
production of irreversible damage to the
skin following the application of a test
substance for up to 4 h.
Skin sensitizer
substance that will include an allergic
response following skin contact.
Solid
solid which, while in itself not necessarily
combustible may generally by yielding
oxygen, cause, or contribute to, the
combustion of other material.
STOT
Specific target organ toxicity
Substance
chemical elements and their compounds
in the natural state or obtained by any
production process, including any additive
necessary to preserve the stability of the
product and any impurities deriving from
the process used but excluding any
solvent which may be separated without
8
affecting the stability of the substance or
changing its composition.
Toxicity
means a physiological or biological
property which determines the capacity of
a chemical to do harm or produce injury
to a living organism by other than
mechanical means.
vPvB
Very persistent, very bioaccumulative
WHO
World Health Organization
9
1.
BACKGROUND AND PURPOSE
1.1
Background
One of the key performance areas of the sub-programme at the Ministry of Health,
Directorate: Environmental Health is the toxicological evaluation of pesticides. The
Department of Health (DoH) has to assess and evaluate the health and
environmental risks and hazards associated with the pesticide applications
together with the dossiers / data information on the active ingredient and
formulated product as indicated in Lists I and II under the “Regulations relating to
Agricultural Remedies”, 2006 under Fertilizer, Farm Feeds, Agricultural Remedies
and Stock Remedies Act, 1947 (Act No.
36 of 1947) received from the
Department of Agriculture, Forestry and
Fisheries (DAFF). These data
requirements are listed in Annexure A. In the review process each pesticide has to
be evaluated as to whether it could be used safely with regard to human health
(consumers, farmers, local residents and passers-by) and the environment, in
particular groundwater and non-target organisms such as birds, bees, mammals,
earthworms and micro-organisms. Although the Department has a guideline in
place it is not comprehensive in nature and does not cover all aspects of
toxicology on human health and the environment. There are gaps that have been
identified due to the guideline being outdated. This has resulted in not providing a
true reflection of the toxicological evaluations of pesticides conducted by the
Department of Health.
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1.2
Purpose
The toxicological evaluations of pesticides are currently not done in an effective
and efficient manner at the Ministry of Health in South Africa. This has resulted in
the unnecessary delay of approval and authorization of pesticides in the country.
Extensive time (months) are consumed in reviewing of literature and gathering
relevant information in order to make an informed decision and recommendations
on the pesticides evaluated. The need for a framework guideline to toxicologically
evaluate the level and extent of pesticides using secondary data is critical. This
framework guideline will improve the efficacy and quality of the proposed
recommendations / restrictions made to the Department of Agriculture, Fisheries
and Forestry. The criteria for the proposed recommendations / restrictions are
included in Annexure B. In addition, it will establish a network of relevant experts
and credible databases on toxicological evaluations conducted on pesticides on a
global level.
2.
CURRENT PROCEDURE OF TOXICOLOGICAL EVALUATION
OF PESTICIDES BY DEPARTMENT OF HEALTH
Application
and
dossier
forwarded by DAFF to DoH
Evaluation by Department of
Health
11
Proposed recommendations /
restrictions generated by DoH
Proposed recommendations /
restrictions officially forwarded
to DAFF
3.
INFORMATION ON TOXICOLOGICAL HEALTH EFFECTS
A concise but complete and comprehensible description of the various
toxicological health effects and the available data used to identify those effects
shall be provided, including, where appropriate, information on toxicokinetics,
metabolism and distribution. The information on toxicological health effects shall
include, amongst others, the following:
√ Information shall be provided for the following hazard classes:
a. acute toxicity;
b. chronic toxicity;
c. skin corrosion;
d. serious eye damage / irritation;
e. respiratory or skin sensitization;
f. germ cell mutagenicity;
g. carcinogenicity;
h. reproductive toxicity and endocrine disrupting properties;
i. STOT- single exposure (not for mixtures);
j. STOT- repeated exposure (not for mixtures); and
k. aspiration hazard.
√ If available, the relevant toxicological properties of the hazardous substances in
a mixture shall also be provided (LDƽo, acute toxicity estimates or LCƽo).
√ An assessment related to the Globally Harmonized System (GHS) criteria shall
be provided.
12
√ Information shall be provided on likely routes of exposure and the effects of the
substance or mixture via each possible route (ingestion, inhalation or skin / eye
exposure).
√ The first symptoms at low exposures through to the consequences of severe
exposure shall be described.
√ Information shall be provided on whether delayed or immediate effects can be
expected after short or long-term exposure.
√ Information on interactions shall be included if relevant and available.
√ Where specific data are not used, or where data are not available, this shall be
clearly stated.
√ Other relevant information on adverse health effects shall be included even
when not required by the classification criteria.
INFORMATION ON ECOLOGICAL EFFECTS
4.
Information shall be provided to evaluate the environmental impact of the
substance or mixture when released to the environment. Data shall be provided
including, where available, relevant test data and clearly indicating species, media,
units, test duration and test conditions. Information on bioaccumulation,
persistence and degradability shall be given, where available and appropriate, for
each relevant substance in the mixture. Information shall also be provided for
hazardous transformation products arising from the degradation of substances and
mixtures. Information on environmental hazard classification should be provided.
4.1
Toxicity

Information on toxicity shall include relevant available data on aquatic
toxicity, both acute and chronic.
13
4.2
Persistence and degradability

Test results relevant to assess persistence and degradability shall be given
where available.

If degradation half lives are quoted it must be indicated whether these half
lives refer to mineralization or to primary degradation.

The potential of the substance or certain substances in a mixture to
degrade in sewage treatment plants shall also be mentioned.
4.3
Bioaccumulative potential

Test results relevant to assess the bioaccumulative potential shall be
given.

This shall include reference to the octanol-water partition coefficient (Kow)
and

4.4
Bioconcentration factor (BCF), if available.
Mobility in soil

4.5
The potential for mobility in soil shall be given where available.
Results of PBT and vPvB assessment

Where a chemical safety report is required, the results of the PBT and vPvB
assessment as set out in the chemical safety report shall be given.

The data requirements for fulfilling the PBT and vPvB criterion are set out in
Annexure C.
4.6
Other adverse effects:

Information on any other adverse effects in the environment shall be
included where available, such as
: environmental fate (exposure)
: photochemical ozone creation potential
: ozone depletion potential
: endocrine disrupting potential
: global warming potential
14
5.
SAFETY DATA SHEET
The applicant shall provide a comprehensive safety data sheet (SDS) for the
pesticide to be evaluated in terms of the information contained in the Globally
Harmonized System of Classification and Labelling of Chemicals (SANS, 2008).
6.
LINKAGE TO OTHER DATA SOURCES
It is imperative that linkages to other data sources are made use of in terms of
evaluation of the pesticide concerned. These data sources include, but are not
limited to the following:
- http://comtrade.un.org/db/
- http://madb.europa.eu/mkaccdb2/indexPubli.htm
- http://www.chem.cn/info/ImpExp/IEStat.aspx
- http://www.echemportal.org/echemportal/participant/page.action?pageID=0
- http://esis.jrc.ec.europa.eu/
- http://www.chem.unep.ch/irptc/sids/OECDSIDS/INDEXCHEMIC.htm
- www.efsa.europa.eu/efsajournal
- http://www.kemi.se/en/Content/Statistics/Statistics-in-brief/Statistics-in-briefProducts-and-sectors/Solvents/
- http://ozone.unep.org/
- http://www.chem.unep.ch/gmn/01 intregpro.htm
- http://www.epa.gov/tri/tridata/index.htm#pdr
- http://prtr.ec.europa.eu/Home.aspx
- http://echa.europa.eu/information-on-chemicals
- http://www.oecd-ilibrary.org/environment/oecd-guidelines-for-the-testing-ofchemicals-section-4-health-effects 20745788
15
REFERENCES
1. Fertilizer, Farm Feeds, Agricultural Remedies and Stock Remedies Act, 1947
(Act No. 36 of 1947)
2. Pesticide Management Policy for South Africa, 2010. Department of Agriculture,
Forestry and Fisheries.
3. Regulations Relating to Agricultural Remedies, No. R. 935 of 22 September
2006. Department of Agriculture.
4. Regulations (EC) No. 1907/2006 of the European Parliament and of the Council
of 18 December 2006. Registration, Evaluation, Authorization and Restriction of
Chemicals (REACH).
5. South African National Standard. Globally Harmonized System of classification
and labelling of chemicals (GHS), SANS 10234:2008.
6. WHO Recommended Classification of Pesticides by Hazard and Guidelines to
Classification. 2009. World Health Organization.
16
ANNEXURE A
DATA REQUIREMENTS FOR THE ACTIVE INGREDIENT AND
FORMULATED PRODUCT IN THE DOSSIER INDEX
ACTIVE INGREDIENT: DOSSIER INDEX
ACTIVE INGREDIENT (a.i.)
(Technical Grade)
1. DESIGNATION
a. Common name (ISO)
b. Manufacturer or development code
c. Chemical name (IUPAC)
d. Chemical group
e. Structural formula
f. Empirical formula
g. Patent status
Is the a.i. under patent?
Who is patent holder?
Expiry date
2. PHYSICAL AND CHEMICAL PROPERTIES
(Active ingredient-technical grade)
a. Physical state
b. Colour
c. Odour
d. Density at 20°C
e. Vapour pressure at 20/25°C
f. Volatility
g. Hydrolysis DTƽo.........Days........°C......pH
h. Photolysis
i. Solubility in water......°C................pH
j. Solubility organic solvents
k. n-octanol/water partition coefficient
l. Boiling point °C
m. Melting point °C
n. Decomposition temperature °C
o. Method of analysis and impurities
3. TOXICOLOGY
(Active ingredient-technical grade)
a. ADI
b. Acute oral LDƽo mg/kg rat/rabbit
c. Acute dermal LDƽo mg/kg rat
d. Inhalation LCƽo mg/l/hour (rat)
e. Skin irritation (rabbit)
f. Eye irritation (rabbit)
g. Sensitization (guinea pig)
17
LIST I
h. Reproduction (specify species)
i. Subchronic toxicity 90 day NOEL mg/kg/day
j. Chronic toxicity NOEL mg/kg/day
k. Carcinogenicity (life time) NOEL mg/kg/day
l. Neurotoxicity NOEL mg/kg/day
m. Teratogenicity NOEL mg/kg/day
n. Mutagenicity NOEL mg/kg/day
o. Metabolism (rat)
p. Other issues:
4. ECOTOXICOLOGY
(Active ingredient-technical grade)
a. Birds (2 species)
LDƽo mg/kg
NOEL
LDƽo mg/kg
NOEL
Reproduction
b. Fish (2 species)
LDƽo mg/kg
NOEL
LDƽo mg/kg
NOEL
Reproduction
BCF
c. Daphnia
LCƽo mg/l
NOEL
d. Algae
LCƽo mg/l
NOEL
e. Bees
LDƽo ug/bees
NOEL
f. Earthworms
LCƽo mg/kg
g. Soil micro-organisms
EC/LCƽo mg/kg
5. BEHAVIOUR IN ENVIRONMENT
(Active ingredient-technical grade)
Behaviour, ways of degradation, degradation products in soil:
a. Metabolites
b. DTƽo (days)
c. Mobility
d. Absorption
e. Mobility of metabolites
Behaviour, ways of degradation, degradation products in water:
f. Major metabolites
g. DTƽo (days)
h. Surface
i. Ground
6. MODE OF ACTION
7. PLANT RESIDUES
a. Major metabolites
b. Metabolism
c. Behaviour of residues
18
d. Crop
e. MRL codex
f. MRL country
g. PHI & MRL proposed
h. Method of residue analysis
8. COUNTRY SPECIFIC REQUIREMENTS
a.
b.
c.
d.
e.
f.
FORMULATED PRODUCT: DOSSIER INDEX
FORMULATED PRODUCT
1. PHYSICAL AND CHEMICAL PROPERTIES
a. Physical state / formulation type
b. Colour
c. Odour
d. Storage stability
e. Shell life
f. Density
g. Bulk Density
h. Flammability
i. Flash Point
j. Compatibility with other pesticides
k. pH
l. pH of 1% aqueous dilution
m. Oxidizing properties
n. Corrosiveness
o. Water content
p. Wettability
q. Solubility in water
r. Foaming
s. Particle size
t. Suspensibility
u. Emulsion
v. Volatility
w. Viscosity
x. Other properties (where applicable)
y. Method of Analysis
2. TOXICOLOGY
a. Rat
Acute dermal LDƽo mg/kg
b. Acute dermal LDƽo mg/kg
19
LIST II
c. Inhalation LCƽo mg/l/hour
d. Rabbit
Skin irritation
e. Eye irritation
f. Sensitization in guinea pig
g. WHO classification
p. Other studies
3. EMERGENCY PROCEDURES IN CASE OF ACCIDENTAL EXPOSURE OR
POISONING
a. Symptoms of human poisoning
b. First aid treatment
c. Skin contact
d. Eye contact
e. Inhalation
f. Ingestion
g. Antidote
h. Note to physician
4. EMERGENCY PROCEDURES IN CASE OF FIRES/SPILLAGES
a. Fire fighting measures
b. Procedures in case of spillage
5. USES (New label claims with this application)
a. Crop/area of use
b. Target organism
c. Rate
d. Stage of treatment
e. Directions for use
f. Residue data and pre-harvest interval
g. Phytotoxicity
h. Contraindications
6. MINIMUM LABEL REQUIREMENTS
a. Product identification
b. Warnings and use restrictions
c. Safety precautions
d. First aid/note to physician (as applicable)
e. Pictograms (if applicable)
f. FAO colour code (if applicable) / group
g. Directions for use
7. COUNTRY SPECIFIC REQUIREMENTS
a.
b.
c.
d.
e.
f.
20
ANNEXURE B
CRITERIA RELATING TO THE PROPOSED RECOMMENDATIONS /
RESTRICTIONS TO DEPARTMENT OF AGRICULTURE,
FORESTRY AND FISHERIES
The following criteria are required when proposing recommendations / restrictions
to the Department of Agriculture, Forestry and Fisheries:
1.
Persistence
2.
Bioaccumulation
3.
Biodegradability
4.
Toxicity
5.
Hazard classification (WHO and GHS)
6.
Registration in other country/ies
7.
Application rates/concentrations/dosages of the product
8.
Mode of action
9.
Intended use / application of product
10.
Carcinogenicity
11.
Mutagenicity
12.
Teratogenicity
13.
Reproductive toxicity
14.
Neurotoxicity
21
ANNEXURE C
DATA REQUIREMENTS FOR PERSISTENT, BIOACCUMULATIVE
AND TOXIC SUBSTANCES AND VERY PERSISTENCE AND VERY
BIOACCUMULATION SUBSTANCES
A substance is identified as a PBT substance if it fulfils the data requirements in
sections 1.1, 1.2 and 1.3.
A substance is identified as a vPvB if it fulfils the data requirements in sections 2.1
and 2.2.
This annexure shall not apply to inorganic substances but shall apply to organometals.
1.
PBT substances
A substance that fulfils all three of the criteria of the sections below is a PBT
substance.
1.1.
Persistence
A substance fulfils the persistence criterion (P) when:
-
the half-life in marine water is higher than 60 days, or
-
the half-life in fresh or estuarine water is higher than 40 days, or
-
the half-life in marine sediment is higher than 180 days, or
-
the half-life in fresh or estuarine water sediment is higher than 120 days,
or
-
the half-life in soil is higher than 120 days.
22
The assessment of the persistency in the environment shall be based on
available data collected under the adequate conditions which shall be
described by the registrant.
1.2.
Bioacumulation
A substance fulfils the bioaccumulation criterion (B) when:
-
the bioconcentration factor (BCF) is higher than 2 000.
The assessment of bioaccumulation shall be based on measured data on
bioconcentration in the aquatic species. Data from freshwater as well as
marine water species can be used.
1.3.
Toxicity
A substance fulfils the toxicity (T) criterion when:
-
the long-term no-observed effect concentration (Noec) for marine or
freshwater organisms is less than 0,01mg/l, or
-
the substance is classified as carcinogenic (category 1 or 2), mutagenic
(category 1 or 2) or toxic for reproduction (category 1,2 or 3), or
-
2.
there is other evidence of chronic toxicity.
vPvB substances
A substance that fulfils the criteria of the sections below is a vPvB
substance.
2.1.
Persistence
A substance fulfils the very persistene criterion (vP) when:
-
the half-life in marine, fresh or estuarine water is higher than 60 days, or
23
-
the half-life in marine, fresh or estuarine water sediment is higher than
180 days, or
-
2.2.
the half-life in soil is higher than 180.
Bioaccumulation
A substance fulfils the very bioaccumulative criterion (vB) when:
-
the bioconcentration factor is greater than 5000.
24