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    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. 
    Applications and enquiries should be addressed to the Office of
    Publications, World Health Organization, Geneva, Switzerland, which
    will be glad to provide the latest information on any changes made
    to the text, plans for new editions, and reprints and translations
    already available.

    (c) World Health Organization 1994

    Publications of the World Health Organization enjoy copyright
    protection in accordance with the provisions of Protocol 2 of the
    Universal Copyright Convention.  All rights reserved.

    The designations employed and the presentation of the material in
    this publication do not imply the expression of any opinion
    whatsoever on the part of the Secretariat of the World Health
    Organization concerning the legal status of any country, territory,
    city or area or of its authorities, or concerning the delimitation
    of its frontiers or boundaries.

    The mention of specific companies or of certain manufacturers'
    products does not imply that they are endorsed or recommended by the
    World Health Organization in preference to others of a similar
    nature that are not mentioned.  Errors and omissions excepted, the
    names of proprietary products are distinguished by initial capital
    letters.

    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 g/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 g/litre, and
    the Canadian interim guideline maximum level for the protection of
    freshwater aquatic life is 0.24 g/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.


    See Also:
       Toxicological Abbreviations
       Tri-allate (ICSC)