IPCS INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
Health and Safety Guide No. 89
TRI-ALLATE
HEALTH AND SAFETY GUIDE
UNITED NATIONS ENVIRONMENT PROGRAMME
INTERNATIONAL LABOUR ORGANISATION
WORLD HEALTH ORGANIZATION
WORLD HEALTH ORGANIZATION, GENEVA 1994
Published by the World Health Organization for the International
Programme on Chemical Safety (a collaborative programme of the
United Nations Environment Programme, the International Labour
Organisation, and the World Health Organization)
This report contains the collective views of an international group
of experts and does not necessarily represent the decisions or the
stated policy of the United Nations Environment Programme, the
International Labour Organisation, or the World Health Organization
WHO Library Cataloguing in Publication Data
Tri-allate : health and safety guide.
(Health and safety guide ; no. 89)
1. Tri-allate - toxicity 2. Herbicides
3. Environmental exposure I.Series
ISBN 92 4 151089 7 (NLM Classification: WA 240)
ISSN 0259-7268
The World Health Organization welcomes requests for permission to
reproduce or translate its publications, in part or in full.
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(c) World Health Organization 1994
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CONTENTS
INTRODUCTION
1. PRODUCT IDENTITY AND USES
1.1. Identity
1.2. Physical and chemical properties
1.3. Composition
1.4. Uses
1.5. Analytical methods
2. SUMMARY AND EVALUATION
2.1. Human exposure
2.2. Effects on the environment
2.3. Uptake, metabolism, and excretion
2.4. Effects on experimental animals
2.5. Effects on human beings
3. CONCLUSIONS AND RECOMMENDATIONS
4. HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY
ACTION
4.1. Human health hazards, prevention and
protection, first aid
4.1.1. Prevention and protection
4.1.2. First aid
4.2. Advice to physicians
4.3. Explosion and fire hazards
4.4. Storage and transport
4.5. Spillage and disposal
5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION
6. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS
6.1. Exposure limit values
6.2. Transport and labelling
BIBLIOGRAPHY
INTRODUCTION
This Health and Safety Guide is not based on an existing
Environmental Health Criteria document, but on critical national
reviews. The hazard evaluation in the Health and Safety Guide was
made on the basis of carefully selected studies, after scrutiny of
the original publications.
In order to assist the peer-review process of the present Health and
Safety Guide, a background companion document was prepared by the
IPCS and can be obtained from the Manager on request; the IPCS does
not intend that the background document should be published.
The first three sections of this Health and Safety Guide present
essential technical information and the hazard evaluation. Section 4
includes advice on preventive and protective measures and emergency
action; health workers should be thoroughly familiar with the
medical information to ensure that they can act efficiently in an
emergency. The section on regulatory information has been extracted
from the legal file of the International Register of Potentially
Toxic Chemicals (IRPTC) and from other United Nations sources.
The target readership includes occupational health services, those
in ministries, governmental agencies, industry, and trade unions who
are involved in the safe use of chemicals and the avoidance of
environmental health hazards, and those wanting more information on
this topic. An attempt has been made to use only terms that will be
familiar to the intended user. However, sections 1 and 2 inevitably
contain some technical terms.
Revision of the information in this Guide will take place in due
course, and the eventual aim is to use standardized terminology.
Comments on any difficulties encountered in using the Guide would be
very helpful and should be addressed to:
The Director
International Programme on Chemical Safety
World Health Organization
1211 Geneva 27
Switzerland
THE INFORMATION IN THIS GUIDE SHOULD BE CONSIDERED AS A STARTING
POINT TO A COMPREHENSIVE HEALTH AND SAFETY PROGRAMME
1. PRODUCT IDENTITY AND USES
1.1 Identity
Common name: tri-allate
Chemical formula: C10H16Cl3NOS
Chemical structure:
C
'
[(CH3)2CH]2N.CO.SCH2C = CCl2
Relative molecular mass: 304.7
Trade names: Avadex BW; Buckle (with trifluralin); CP
23426; Dipthal; Far-go; Riflex (with
metoxuron); Trigger (with isoproturon)
CAS chemical name: S-(2,3,3-trichloro-2-propenyl)
bis(1-methylethyl)carbamothioate
IUPAC chemical name: S-2,3,3-trichloroallyl
di-isopropylthiocarbamate
Synonyms: carbamic acid, diisopropylthio-,
S-(2,3,3-trichloroallyl)ester;
diisopropyltrichloroallylthiocarbamate;
N-diisopropylthiocarbamic acid
S-2,3,3-trichloro-2-propenyl ester;
N,N-diisopropyl-2,3,3-trichloroallylthiol
carbamat; 2-propene-1-thiol,
2,3,3-trichloro-, diisopropylcarbamate
triallat; S-2,3,3-trichloroallyl
N,N-diisopropylthiocarbamate;
thiocarbamic acid,
N-diisopropyl- S-2,3,3-trichloroallyl
ester; 2,3,3-trichloroallyl
N,N-diisopropylthiocarbamate; triallate;
triamyl
CAS registry number: 2303-17-5
RTECS registry number: EZ8575000
1.2 Physical and Chemical Properties
Pure tri-allate is an amber, oily, non-corrosive liquid with a
melting point of 29-30 °C and a boiling point of 117 °C. It
decomposes above 200 °C. At 25 °C, the vapour pressure of the pure
compound is 16 mPa. Tri-allate is soluble in organic solvents and in
water at 4 mg/litre (25 °C). It is stable on storage and resistant
to decomposition by UVR. The log Kow is 4.54.
Like other thiocarbamates, tri-allate is relatively resistant to
hydrolysis. Tri-allate is also stable to UV irradiation in distilled
water, but may be decomposed by UVR in the presence of certain
organic compounds.
1.3 Composition
Technical tri-allate is usually 95-97 % pure. Main impurities are
bis-(2,3,3-trichloroallyl) sulfide (CAS No. 25647-79-4; <1.5%),
1,1,1,2,2,3-hexachloropropane (CAS No. 24425-97-6; <1%);
bis-(2,3,3-tri-chloro-allyl) disulfide (CAS No. 82709-38-4; <1%),
S-(3,3-dichloroallyl)- N,N-diisopropylthiocarbamate (<0.7%), and
S-(2,3,3-trichloroallyl)- N-ethyl- N-isopropylthiocarbamate
(<0.7%).
1.4 Uses
Tri-allate is mainly used as a pre- or post-plant soil-incorporated
herbicide to control wild oats in barley, lentils, peas, and spring
and winter wheat at rates of 1.1-2.3 kg a.i./ha. It was introduced
in 1962 by Monsanto Co. In some formulations, it is used together
with trifluralin, metoxuron, or isoproturon.
It is commonly available as an emulsifiable concentrate (44-46%) or
as granules (10%).
1.5 Analytical Methods
Tri-allate and the major metabolite in plants,
2,3,3-trichloro-2-propene-sulfonic acid, can be determined using
HPLC. Gas-liquid chromatography with an electron-capture detector is
suitable for the determination of residues in soil or crops.
2. SUMMARY AND EVALUATION
2.1 Human Exposure
Production volumes for various uses give an indication of areas of
expected human exposure. The world production of tri-allate has been
estimated to be about 5000 tonnes. Exposure of the general
population occurs by ingestion of certain agricultural commodities;
farm workers are exposed both dermally and via inhalation during the
application of the pesticide.
2.2 Effects on the Environment
Available evidence points to a low-level contamination of non-target
land and water courses, when tri-allate is used under field
conditions. Uptake of the residues in soil by plants results in
residues in crops, and trichloro-propene-sulfonic acid (TCPSA) as
well as diisopropylamine have been identified as the main plant
metabolites.
Most temperate agricultural soils contain microbial systems that can
degrade tri-allate. However, because of its relatively high vapour
pressure, the loss of tri-allate through volatilization may become
an important factor under certain conditions, e.g., after surface
application. Apart from the fact that TCPSA and CO2 appear to be
the main decomposition products, little information seems to be
available concerning the metabolic pathways of tri-allate
degradation in soil and and the metabolites formed. The half-life of
tri-allate varies widely, depending on factors such as temperature,
humidity, and organic matter content. Values from 3 to 195 days have
been cited. Because of its strong tendency to be adsorbed on soil
particles, tri-allate has a low leachability and partitioning to
sediments represents a major sink in the environment.
Tri-allate bioaccumulates in fish under static as well as dynamic
conditions. However, when the fish is placed in clean water
following exposure, tri-allate is eliminated from the organism
within about two weeks. Tri-allate will not accumulate appreciably
in rotated crops planted after application to soils. Therefore,
little inadvertent human dietary exposure should occur via carryover
to crops other than those treated directly with tri-allate.
Under normal conditions, tri-allate does not seem to affect soil
micro-organisms adversely. Because of its herbicidal activity, it
inhibits algal growth at low concentrations, and is highly toxic for
several aquatic invertebrate and vertebrate species. Toxic effects
on the reproduction of aquatic invertebrates have been recorded at
concentrations as low as 2.4 µg/litre. Exposure of aquatic organisms
to tri-allate through the direct exposure of surface waters may,
therefore, be a cause for concern under certain conditions. The
toxicity of tri-allate for earthworms and honey bees is low, and the
acute and short-term toxicities for birds also appear to be low.
2.3 Uptake, Metabolism, and Excretion
Tri-allate is readily taken up through ingestion and inhalation, and
dermal penetration is sufficient to evoke toxic reactions in animals
at high doses. After a single exposure, radiolabelled tri-allate and
its metabolites are eliminated with the urine and faeces. The
kinetics for the whole-body elimination of radioactivity were
consistent with a two-compartment open model. The small amount of
radioactivity excreted with milk in goats given labelled tri-allate,
was recently shown to be mainly due to the metabolic incorporation
of breakdown products into natural lactose. Similarly, the activity
detected in egg yolk in eggs from laying hens receiving the labelled
pesticide was found to be mostly due to the metabolic incorporation
of such fragments into natural constituents, such as cholesterol and
fatty acids. Tissue residues remaining in rats 10 days after oral
administration accounted for less than 5% of the total dose.
Information is limited with respect to the pharmacokinetics of
tri-allate and/or its metabolites after repeated exposure.
2.4 Effects on Experimental Animals
In experimental animals, tri-allate was moderately toxic following
acute oral exposure (LD50 was 1100 mg/kg in rats and 930 mg/kg in
mice) as well as inhalation exposure (4-h LC50 in rats > 5.3
mg/litre). The acute dermal toxicity was also low (LD50 in rat
>5000 mg/kg). Signs of neurotoxicity were observed after acute
intoxication by various routes of administration, in several animal
species (rat, mouse, dog, rabbit, hamster, hen, and quail) including
behavioural changes, decreased forelimb grip strength, and lack of
muscular coordination. Tri-allate did not inhibit blood or brain
cholinesterase in the rat. It was moderately irritating to the eyes
and skin of the rabbit, but there was no evidence that it caused
dermal sensitization in guinea-pigs or humans.
In rats, mice, hamsters, rabbits, and dogs, the liver and kidneys
appear to be the main target organs after repeated and long-term
exposure. Clinical chemistry parameters related to liver function
(triglyceride levels in hamsters and elevation of serum alkaline
phosphatases in dogs), splenic haematopoiesis in male mice, as well
as increased relative liver and kidney weights in dogs seem to be
the most sensitive toxic end-points.
Tri-allate appears to cause two distinct neurotoxic effects in rats.
One is caused by either a single or repeated doses and is
characterized by a variety of abnormal behaviours indicative of a
central nervous system effect. These effects have not been shown to
be associated with histopathological changes in the central nervous
system and persisted for one month after the end of exposure. It
cannot be ascertained whether these signs are irreversible at higher
doses or whether they reflect the pharmacokinetics of tri-allate
and/or its metabolites. The second type of neurotoxicity is a
central-peripheral axonopathy with accompanying myelin loss that
occurred in one of the dorsal sensory tracts of the spinal cord
(fasciculus gracilis) and in some peripheral nerves. These effects
were observed in rats with short-term exposure to tri-allate and
occurred at the same, or lower, doses as those causing CNS toxicity.
The histopathological findings may be correlated with changes such
as decreased grip strength and increased landing foot splay. The
lesions in the spinal cord are considered to be irreversible.
Adequately performed long-term studies on rodents do not indicate
that tri-allate possesses carcinogenic properties. Tri-allate has
not been shown to be teratogenic, but it is toxic for the fetus
(reduced birth weight and disturbances of ossification) at doses
causing maternal toxicity. In rats, certain adverse effects on
reproduction (pregnancy rate, gestation length, survival) have been
noted, but only at doses that were maternally toxic. In prokaryotes
with metabolic activation, tri-allate was consistently shown to have
mutagenic potential. With the exception of sister chromatid
exchanges and equivocal results from the mouse lymphoma test, the
results from other assays, conducted both in vitro and in vivo,
were negative.
For the most sensitive toxic end-points, the no-observed-effect
levels (NOELs) in long-term studies on rats, mice, hamsters, and
dogs were in the range of 1-5 mg/kg per day. In short-term, oral
studies, neurotoxic effects were observed at doses down to about 30
mg/kg per day in rats, and 50 mg/kg per day in rabbits. In the rat,
the NOEL for the induction of acute neurobehaviourial effects was
approximately 300 mg/kg, whereas with short-term exposures, this
level was as low as 8 mg/kg body weight per day. In rats exposed via
inhalation for 7 weeks, the NOEL was 10 mg/m3, and, in a 3-week
dermal study on rabbits, the NOEL was 300 mg/kg per day.
2.5 Effects on Human Beings
No case reports, or epidemiological studies, have been identified
that indicate that systemic toxicity in humans can be attributed to
exposure to tri-allate.
3. CONCLUSIONS AND RECOMMENDATIONS
The data base available for tri-allate is sufficient to permit an
adequate toxicological evaluation in mammals with respect to the
most important toxicological end-points. Although certain data gaps
remain, the ecotoxicological properties of tri-allate have been
relatively well investigated.
Acute exposure to technical tri-allate resulted in moderate toxicity
in mammals. However, the toxocity of most formulations is likely to
be slight. Tri-allate is irritating to the eyes and skin. The
toxicity of tri-allate is considerably higher with repeated and
long-term oral administration, and particularly with inhalation
exposure. Tri-allate induces toxicity in the liver, kidney, and
nervous system. There have not been any indications of
teratogenicity or evidence of carcinogenic effects in long-term
studies on rodents. Adverse effects on reproduction have been found
only at dose levels that were maternally toxic.
Provided that good agricultural practices are observed, exposure of
the general population to tri-allate via food and drinking-water is
negligible and does not constitute a health hazard. Occupational
exposure to tri-allate through skin contact and inhalation should be
kept to a feasible minimum.
Tri-allate is highly toxic for aquatic organisms, but does not pose
a hazard for terrestrial organisms with normal usage. Because of its
high aquatic toxicity, it is recommended that adequate precautions
should be taken to prevent contamination of surface waters.
4. HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY
ACTION
4.1 Human Health Hazards, Prevention and Protection, First Aid
The acute oral toxicity of technical tri-allate for humans is
thought to be moderate. Most formulations are likely to be only
slightly toxic.
4.1.1 Prevention and protection
The following precautions should be observed during handling and
use, in order to reduce the risk of accidental contamination:
* Avoid contact with the skin and eyes. If eyes become
contaminated, flush with water for at least 15 min.
* Do not smoke, drink, or eat in the workplace. Wash hands and
any exposed skin before eating, drinking, or smoking, and after
work.
* Avoid raising and breathing dust when handling granular
formulations.
* When unloading and handling containers, wear protective
neoprene gloves.
* When spraying, handling leaking containers, or when dealing
with leaks and spills, wear goggles, overalls, and neoprene
gloves and boots. If overalls become contaminated, change and
wash them thoroughly before re-use.
* Store products in closed original containers, out of reach of
children, and away from food and animal feed.
4.1.2 First aid
In cases of overexposure, apply routine first aid measures. If
material has been spilled on the skin, remove the person from the
source of contamination, remove all contaminated clothing, and wash
affected areas with soap and running water. If the material is in
the eyes, flush with clean water for at least 15 min. In case of
ingestion, give large quantities of water and induce vomiting, if
the patient is conscious (except in the case of the EC formulation,
which contains hydrocarbon solvents). If the patient is unconscious,
do not try to induce vomiting or give anything by mouth. Seek
medical advice.
4.2 Advice to Physicians
The acute toxicity of technical tri-allate for humans is believed to
be moderate. There is no specific antidote. Treat symptomatically,
when required. In cases of ingestion, gastric lavage may be
indicated.
4.3 Explosion and Fire Hazards
Tri-allate, as such, is not flammable, but produces toxic fumes,
such as carbon disulfide, hydrochloric acid, and phosgene, upon
heating. However, the emulsifiable concentrate does contain
flammable solvents.
Fight small fires with carbon dioxide, dry powder, or
alcohol-resistant foam. Confine the use of water sprays to the
cooling of unaffected stock only, thus avoiding the accumulation of
polluted run-off from the site. Fire service personnel should be
advised that self-contained breathing apparatus may be required,
because of the generation of noxious fumes.
4.4 Storage and Transport
All products should be stored in secure buildings, out of reach of
children and animals, and local regulations should be complied with.
Containers should be sound and adequately labelled.
4.5 Spillage and Disposal
Avoid contact with solid or dust. Keep spectators away from any
leakage. This pesticide is highly toxic for fish and other aquatic
organisms. Prevent contamination of other goods or cargo, or nearby
vegetation and waterways.
Absorb spillage of liquid products with sawdust, peat moss, straw,
or sand, sweep up and place in separate container. Activated carbon
can also be used to absorb tri-allate. Empty any product remaining
in damaged or leaking containers into a clean empty container, which
should be suitably labelled. Sweep up any spilt powder with damp
sawdust taking care not to raise a dust cloud (vacuum cleaner).
Remove trapped material with suction hoses. Place in separate
container for subsequent disposal.
Destroy wastes by incineration.
5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION
Technical tri-allate is highly toxic for aquatic organisms.
Contamination of ponds, waterways, and ditches with tri-allate
during the rinsing of application equipment or of empty containers
should therefore be avoided. Empty containers should be punctured to
prevent re-use. In case of spills, apply methods recommended in
section 4.5.
6. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS
6.1 Exposure Limit Values
The maximum acceptable concentration of tri-allate in drinking-water
recommended by the Health and Welfare, Canada, is 230 µg/litre, and
the Canadian interim guideline maximum level for the protection of
freshwater aquatic life is 0.24 µg/litre (on the basis of adverse
reproductive effects in the invertebrate Ceriodaphnia dubia).
The maximum daily intake in the USA is based on data from the 2-year
feeding study in dogs, where an LOEL of 4.3 mg/kg per day and an
NOEL of 1.3 mg/kg per day were found. Using an uncertainty factor of
100, an RfD (ADI) of 0.013 mg/kg per day was established. Some
selected tolerances for food and animal feed are given in the table
on page 19 (Health and Welfare Canada, 1990).
6.2 Transport and Labelling
Recommended precautionary statement:
DANGER. Toxic if swallowed, or inhaled, or upon repeated or
prolonged skin contact. Use adequate protective equipment in
case there is a potential for repeated inhalation of dust or
aerosols. Do not get in eyes. Avoid contact with skin and
clothing.
This pesticide is highly toxic for fish and other aquatic organisms.
Do not apply directly to water or wetlands. Drift and run-off from
treated areas may be hazardous for aquatic organisms in neighbouring
areas. Do not contaminate water by cleaning of equipment or disposal
of wastes.
CURRENT REGULATIONS, GUIDELINES, AND STANDARDS
Tolerances for food products in different countries
Country Food Product Exposure limit description Value Effective
(mg/kg) date
Australia kidney, meat fat maximum residue 0.2 November
meat, milk, poultry meat 0.1 1987
cereal grains, oilseeds 0.05
vegetables
Canada barley, flax, peas, mustard, acceptable residue limit negligible May 1990
rapeseed, sugar beets (sugar), residues
wheat
Germany, all foods of plant origin maximum residue limit 0.1 (diallate March 1990
Federal +tri-allate)
Republic of
United States grain, lentils, peas, forage acceptable residue limit 0.05 May 1990
of America (negligible
residues)
BIBLIOGRAPHY
Fisher SW & Metcalf RL (1983) Production of delayed ataxia by
carbamate acid esters. Pest biochem Physiol, 19, 213-253.
Hackett AG, Kotyk JJ, Fujiwara H, & Logusch EW (1993) Metabolism of
triallate in Sprague-Dawley rats. 3. In vitro metabolic pathways.
J agric food Chem, 41, 141-147.
Ridley WP, Warren JA, & Nadeau RG (1993) Metabolism of triallate in
Sprague-Dawley rats. 1. Material balance, tissue distribution and
elimination kinetics. J agric food Chem, 41, 128-131.
Stevens JT & Sumner DD (1991) Herbicides. 20.8. Carbamate
herbicides. In: Hayes WJ & Laws ER, ed. Handbook of pesticide
toxicology. New York, Academic Press, Inc.
WHO (1988) Environmental Health Criteria 76: Thiocarbamate
pesticides: a general introduction. Geneva, World Health
Organization.
Worthing CR & Hance RJ, ed. (1991) The pesticide manual. A world
compendium, 9th ed. Thornton Heath, England, British Crop Protection
Council.