IPCS INCHEM Home


    IPCS INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
    Health and Safety Guide No. 72



    FOLPET
    HEALTH AND SAFETY GUIDE







    UNITED NATIONS ENVIRONMENT PROGRAMME

    INTERNATIONAL LABOUR ORGANISATION

    WORLD HEALTH ORGANIZATION



    WORLD HEALTH ORGANIZATION, GENEVA 1992


    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

    Folpet : health and safety guide.

    (Health and safety guide ; no. 72)

    1.Fungicides, Industrial - standards 2.Fungicides, Industrial - toxicity
    3.Phthalimides - standards 4.Phthalimides - toxicity
    5.Environmental exposure  I.Series

    ISBN 92 4 151072 2          (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 1992

    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. Analytical methods
         1.4. Production and uses

    2. SUMMARY AND EVALUATION
         2.1. Human exposure to folpet
         2.2. Effects on the environment
         2.3. Uptake, metabolism, and excretion
         2.4. Effects on animals
         2.5. Effects on human beings

    3. CONCLUSIONS AND RECOMMENDATIONS
         3.1. Conclusions
         3.2. Recommendations

    4. HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY ACTION

         4.1. Main 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
         4.6. Disposal

    5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION

    6. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS
         6.1. Exposure limit values
         6.2. Specific restrictions
         6.3. 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 Director 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

    1.  PRODUCT IDENTITY AND USES

    1.1  Identity

    Chemical formula:               C9H4CL3NO2S

    Chemical structure:

    CHEMICAL STRUCTURE 1

    Relative molecular mass:        296.58

    Common trade names:             Acryptan; Folpan; Folpet; Ftalan;
                                    Orthophaltan; Phaltan; Phthaltan;
                                    Thiophal; Troysan anti-mildew 0;
                                    Splacid; Folnit; Fungitrol-II;
                                    Vinicoll; Intercide-TMP; Cosan-I

                                     Mixtures include: Acylon Super F;
                                    Ridomil Combi (folpet + metalaxyl);
                                    Caltan (folpet + ofurace); Caltam C
                                    (folpet + captafol + ofurace);
                                    Galben F, WP (folpet + benalaxyl);
                                    Mycodifol, Mycodifol F
                                    (folpet + captafol); Sandofan F
                                    (folpet + oxadixyl)

    CAS chemical name:              1H-isoindole-1,3 (2H)-dione,
                                    2-((trichloromethyl)thio)-;

    Synonyms:                        N-(trichloromethylmercapto)
                                    phthalimide;
                                     N-(trichlormethylthio)-
                                    phthalimide;
                                    2-((trichloromethyl)-thio)-
                                    1H-isoindole-1,3(2H)-dione;
                                     N-(trichloromethylthio)phthalimide;
                                     N-(trichlor-methylthio)-phthalamid
                                    (German)

    CAS registry number:            133-07-3

    RTECS registry number:          TI1575000

    Technical folpet is usually 90% pure. The main impurities are
    phthalimide (up to 4.0%) and sodium chloride (up to 5%).

    1.2  Physical and chemical properties

    Pure folpet is a white crystalline solid with a reported melting
    point of 177 C. At 20 C, the vapour pressure of the pure compound
    is very low. Its solubility in water is 1 mg/litre at room
    temperature and it is slightly soluble in organic solvents (ethanol,
    acetone).

    In the dry state, it is stable at room temperature, but it is
    hydrolysed in an aqueous solution at a rate that depends on the pH.
    In alkaline solution, this breakdown is rapid, occurring within
    minutes. The hydrolysis products are carbon dioxide, hydrochloric
    acid, hydrogen sulfide, phthalamic acid, and phthalic acid.

    1.3  Analytical methods

    Capillary gas-liquid chromatography with an electron-capture
    detector is a suitable method for the routine determination of
    folpet residues in the presence of captan, captafol, vinclozolin,
    and iprodione.

    1.4  Production and uses

    Folpet was first marketed in the early 1950s. The world production
    in 1989 is believed to have been in excess of 5000 tonnes. Folpet is
    a broad spectrum phthalimide fungicide that is used in the
    cultivation of both food and non-food crops, as well as in the
    manufacture of oil-based interior and exterior paints and coatings,
    and in the manufacture of plastics. Methods of application include
    dusting, spraying, or direct incorporation into paints, coatings,
    and plastic formulations.

    In agriculture and horticulture, it is mainly applied, as a
    protective fungicide, to the foliage of grapes, apples, avocados,
    citrus, cucumbers, soft fruit, lettuces, melons, onions, flowering
    ornamentals, and tomatoes. It is generally available as a wettable
    powder, dust, flowable concentrate, and as water-soluble pellets.

    2.  SUMMARY AND EVALUATION

    2.1  Human exposure to folpet

    The heaviest occupational exposure to folpet is associated with its
    use in agriculture; other occupational exposures, for example in the
    production of paints, are negligible. Owing to its widespread use,
    the general population may be exposed to this pesticide through
    residues in food. However, folpet is extensively hydrolysed by
    cooking, and as a result of the maceration of plant materials.
    Because of the nature of the folpet residues, they are readily
    removed by washing, blanching, peeling, etc. 

    2.2  Effects on the environment

    The acute toxicity of folpet for birds is extremely low and it is
    relatively non-toxic for honey bees. On the other hand, it is highly
    toxic for fish; 96-h LC50s in the range of 0.04-0.3 mg/litre have
    been reported for various species of fish. It is also toxic for
    freshwater invertebrates, such as daphnids (water fleas).

    Folpet is not persistent, and its use is not considered to
    constitute a threat to terrestrial wildlife. The environmental
    impact of the pesticide is likely to be limited by its high rate of
    biodegradation. It does not bioaccumulate.

    2.3  Uptake, metabolism, and excretion

    Folpet may be absorbed by ingestion as well as by inhalation, and to
    a very limited extent by skin exposure. It is rapidly hydrolysed in
    the blood and gives rise to phthalamic acid and phthalimide, and to
    derivatives of the trichloromethylthioside chain. Neither folpet nor
    its metabolites appear to accumulate in the tissues of mammals, but
    are rapidly excreted in the urine (95% within 24 hours). Degradation
    in the gut appears to play a major role in the metabolism of folpet.
    Here, the reactive intermediate thiophosgene is generated, and
    further metabolized.

    2.4  Effects on animals

    The acute toxicity of folpet following ingestion or dermal contact
    is low, the acute oral LD50 in rats being greater than 5000 mg/kg
    body weight. There are indications that folpet is more toxic when
    inhaled.

    Folpet is irritating to the eyes and has been found to cause
    sensitization in the guinea-pig.

    The no-observed-adverse-effect level (NOAEL) in the dog, with oral
    administration for 1 year,was about 10 mg/kg body weight per day.
    The main adverse effects were related to organ weight changes,
    mainly of the testes, adrenals, and liver. None of these findings
    were associated with macro- or microscopic pathological findings. A
    reduction in the rate of body weight gain in the high- and
    intermediate-dose groups was noted. A decrease in food intake was
    found only in the high-dose group. Dose-related increases in benign
    and malignant tumours of the gastrointestinal tract were noted in
    two strains of mice after life-long administration. However, the
    results of long-term studies on rats have been negative. Folpet has
    been proved to be genotoxic in several  in vitro systems; however,
     in vivo, it has not been possible to demonstrate any mutagenic
    effects in mammals.

    Several studies to evaluate the teratogenic potential of folpet have
    been carried out on rabbits and rats. In none of these
    investigations could teratogenic effects be demonstrated at levels
    below a maternal toxic dose. The NOAEL for fetotoxic effects in the
    rat was 10 mg/kg body weight per day in these studies.

    2.5  Effects on human beings

    No serious adverse health effects have been reported for this
    pesticide. It is an irritant to the eyes and skin.

    3. CONCLUSIONS AND RECOMMENDATIONS

    3.1  Conclusions

    No serious adverse health effects have been demonstrated in humans
    It is a compound of low acute mammalian toxicity. It is irritant to
    the eyes and skin, and might cause sensitization. At high exposure
    levels, folpet induces general toxic effects. Tumours were found in
    mice following long-term, high-dose, oral administration. Tumours
    were not observed in similar studies on rats, and therefore the
    evidence for the carcinogenicity of this compound in experimental
    animals is inadequate. It seems that the potential for causing
    heritable effects in mammals is very low.

    If good agricultural practices are observed, particularly as regards
    the recommended pre-harvest application interval, the exposure of
    the public is unlikely to exceed the recommended maximum residue
    limits for folpet.

    Folpet is highly toxic for freshwater fish and toxic for freshwater
    invertebrates. It is not a hazard for terrestrial organisms in
    normal usage.

    3.2  Recommendations

    Occupational exposure to folpet should be kept to a minimum,
    particularly in view of its irritant effects.

    Because of the high aquatic toxicity of folpet, adequate precautions
    should be taken to prevent contamination of surface waters.

    In order to avoid high levels of residue in fresh fruits and
    vegetables, the recommended pre-harvest intervals for the
    application of folpet to these crops should be strictly enforced.

    4.  HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY ACTION

    4.1  Main human health hazards, prevention and protection, first aid

    4.1.1  Prevention and protection

    The acute oral toxicity of technical folpet is low, but the compound
    may be more toxic by inhalation, may cause eye irritation, and may
    induce allergic dermatitis.

    The main goal of preventive measures is to ensure a safe work
    environment and proper work practices. 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.

    *    Do not smoke, drink, or eat while handling folpet. Wash the
         hands and any exposed skin before eating, drinking, smoking,
         and after work.

    *    Avoid breathing folpet dust or spray mist, and wear disposable
         dust masks wherever appropriate.

    *    When unloading and handling containers of concentrates, wear
         protective PVC or neoprene gloves.

    *    When handling any leaking containers, or when dealing with
         leaks and spills, wear overalls and PVC or neoprene aprons,
         gloves, and boots. If overalls become contaminated, change and
         wash them thoroughly before re-use.

    *    Store products in closed, original, labelled containers, out of
         the reach of children and away from food and animal feed.

    4.1.2  First aid

    Acute poisoning by folpet is unlikely unless large amounts have been
    ingested. In cases of overexposure, apply routine first aid
    measures. If material has been spilled on the skin, immediately
    remove the patient from the source of contamination, remove all
    contaminated clothing, and wash the affected areas with soap and
    water. If the material is in the eyes, flush with clean water for at
    least 5-10 minutes. In case of ingestion of significant quantities,
    if the patient is conscious give water to drink and induce vomiting.
    In serious cases, medical attention should be sought.

    4.2  Advice to physicians

    The acute toxicity of folpet for humans is believed to be low. There
    is no specific antidote. Treat symptomatically as required. In cases
    of ingestion, gastric lavage may be indicated.

    4.3  Explosion and fire hazards

    Folpet itself is not flammable, but when heated it may produce toxic
    fumes, such as sulfur dioxide, hydrochloric acid, and phosgene. If
    folpet is involved in a fire, extinguishers that dispense
    alcohol-resistant foam, carbon dioxide, or dry powder should be
    used. Confine the use of water sprays to the cooling of unaffected
    stock only, thus avoiding polluted run-off from the site. Fire
    service personnel should be advised that self-contained breathing
    apparatus may be necessary, because of the generation of noxious
    fumes.

    4.4  Storage and transport

    All products should be stored in secure buildings, out of the reach
    of children and animals, and local regulations should be complied
    with. Containers should be sound and adequately labelled.

    Folpet should be transported in a separate compartment to prevent
    the contamination of any food or animal feed.

    4.5  Spillage

    Avoid direct personal contact with solids or liquids containg folpet
    and keep spectators away from any leakage. This pesticide is highly
    toxic for fish. Prevent contamination of other goods or cargo, or
    surface waters.

    Absorb spillage of liquid products with sawdust, earth, or sand,
    sweep up and place in separate container. Empty any product
    remaining in damaged or leaking containers into a clean empty
    container, and ensure that it is suitably labelled. Sweep up any
    spilt powder with damp sawdust, taking care not to raise a dust
    cloud. Remove trapped material with suction hoses. Place in a
    separate container for subsequent disposal.

    4.6  Disposal

    Do not deposit unwanted folpet or folpet waste in a landfill, or in
    sewers or surface waters. Wastes should be incinerated in plants
    with an effluent-gas scrubbing device.

    Folpet may be also disposed of by mixing with excess calcium oxide
    or sodium hydroxide and sand or other absorbents, in a pit or trench
    at least 0.5 m deep, in damp soil.

    Folpet containers made of permanent materials may be decontaminated
    and used for purposes other than the storage of food, water, and
    animal feed, provided that the following procedure is strictly
    followed:

         The container should be rinsed by filling with water up to at
         least half its volume, and emptied. The container should then
         be soaked by being entirely filled with water and allowed to
         stand for 24 hours. The rinsing water and the first soaking
         water must be disposed of in a dry pit, in order not to
         contaminate surface waters. The soaking procedure must be
         repeated for at least two more periods of 24 hours. The
         original pesticide label must be obliterated. The container
         must be clearly re-labelled, "Not to be used for food, drink,
         or animal feed".

    Arrangements for decontamination will vary in different countries,
    and centralized decontamination centres might be established in some
    cases.

    5.  HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION

    Folpet is not persistent and small quantities of the compound are
    readily hydrolysed in soil and surface waters. However, it is highly
    toxic for aquatic organisms. Contamination of ponds, waterways, and
    ditches with folpet, or with equipment used for dispersing the
    chemical or used containers, should therefore be avoided. In case of
    spills, and for decontamination of equipment and containers, apply
    the methods recommended in section 4.6. Empty containers made of
    permanent materials must be decontaminated as indicated in section
    4.6.

    6.  CURRENT REGULATIONS, GUIDELINES, AND STANDARDS

    6.1  Exposure limit values

    No threshold limit values (TWA) have been set for folpet.

    In 1990, the Joint FAO/WHO Meeting on Pesticide Residues in Food
    (JMPR) established a temporary ADI of 0-0.01 mg/kg body weight. Some
    tolerances for food products are given in the table opposite.

    6.2  Specific restrictions

    The use of folpet is banned in Finland and Sweden. All registrations
    for the use of folpet on food crops were voluntarily withdrawn in
    the United States of America in 1987.

    6.3  Transport and labelling

    Conveyance labelling should be as follows:

    FIGURE 1


        Tolerances and maximum residue limits for food products

                                                                                                                              
    Country/       Food product                                              Exposure limit               Value      Effective
    organization                                                             description                  (mg/kg)    date
                                                                                                                              
    Brazil         Onions, cucumbers, melons                                 Acceptable limit             2.0        1985
                   Other fruits and vegetables                                                            10-20 

    Canada         Fruits and vegetables                                     Tolerance                    15-30      1990

    Codex          Cucumber, melons except water melon, onion, bulb,
    Alimentarius   tomato                                                    Maximum residue limit        2-5        1991
    Commission     Apple, citrus fruits, cherries, lettuce head,
                   strawberry, grapes                                                                     10-25

    European       Pome fruit, berries and small fruit, grapes, tomatoes     Maximum residue limit a      3          1988
    Community
    legislation    Beans, broad-leaved endives, peas, endives, leeks,
                   stone-fruit, lettuce                                                                   2

    Germany        Fruits and vegetables                                     Maximum residue limit a      0.1-3.0    1989

    Sweden         Fruits and vegetables                                     Maximum acceptable           0.1-3.0    1989
                                                                             concentrationa

    USA            Fruits and vegetables                                     Tolerance                    15-50      1987

              
    a Sum of captan and folpet.

    

     Supply and use labelling. European Economic Community legislation
    requires labelling as a dangerous substance, using the symbol:

    FIGURE 2

    The label must read:

         Irritating to eyes; possible risks of irreversible effects: may
         cause sensitization by skin contact; wear suitable protective
         clothing and gloves.

    BIBLIOGRAPHY

    ACGIH (1988) TLV's, threshold limit values and biological exposure
    indices for 1987-1988.

    FAO/WHO (1991) Joint FAO/WHO Meeting of Pesticide Residues in Food
    (JMPR), 1990 Evaluations. Part II - Toxicology. Rome, Food and
    Agriculture Organization of the United Nations, 1990, pp. 69-80.

    WHO (1992) The WHO recommended classification of pesticides by
    hazard and guidelines to classification 1992-1993. Geneva, World
    Health Organization (unpublished document, WHO/PCS/92.14).

    IRPTC (1989) IRPTC legal file 1988. Geneva, International Register
    of Potentially Toxic Chemicals, United Nations Environment
    Programme.

    Reiter A (1986) Folpet exposure assessment. Report to the Hazard
    Assessment Branch from the Exposure Assessment Branch, Office of
    Pesticides and Toxic Substances, US EPA, Washington, DC.

    Rinde E (1986) Peer review of folpet. Toxicology Assessment Branch,
    Office of Pesticides and Toxic Substances, US EPA, Washington, DC.
    US EPA (1986) Registration standard for folpet - ecological effects
    chapter. Office of Pesticides and Toxic Substances, June 9, 1986,
    Washington, DC.

    Worthing CR & Hance RJ (1991) The pesticide manual. Farnham, British
    Crop Protection Council, 9th ed., pp. 431-432.


    See Also:
       Toxicological Abbreviations
       Folpet (ICSC)
       Folpet (FAO/PL:1969/M/17/1)
       Folpet (WHO Pesticide Residues Series 3)
       Folpet (WHO Pesticide Residues Series 4)
       Folpet (Pesticide residues in food: 1984 evaluations)
       Folpet (Pesticide residues in food: 1986 evaluations Part II Toxicology)
       Folpet (Pesticide residues in food: 1990 evaluations Toxicology)
       Folpet (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental)