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    IPCS INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

    Health and Safety Guide No. 82



    CARBENDAZIM
    HEALTH AND SAFETY GUIDE



    UNITED NATIONS ENVIRONMENT PROGRAMME

    INTERNATIONAL LABOUR ORGANISATION

    WORLD HEALTH ORGANIZATION



    WORLD HEALTH ORGANIZATION, GENEVA 1993


    This is a companion volume to Environmental Health Criteria
    149: Carbendazim

    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

    Carbendazim : health and safety guide.

    (Health and safety guide ; no. 82)

    1.Benzimidazoles - standards 2.Benzimidazoles - toxicity
    3.Fungicides, Industrial - standards 4.Fungicides, Industrial - toxicity
    I.Series

    ISBN 92 4 151082 X          (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 1993

    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.

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    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. Exposure
         2.2. Uptake, metabolism, and excretion
         2.3. Effects on organisms in the environment
         2.4. Effects on experimental animals and  in vitro
              test systems
         2.5. Effects on humans

    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. Advice to physicians
              4.1.2. Health surveillance advice
         4.2. Explosion and fire hazards
         4.3. Storage
         4.4. Transport
         4.5. Spillage
         4.6. Disposal

    5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION

    6. SUMMARY OF CHEMICAL SAFETY INFORMATION

    7. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS
         7.1. Previous evaluations by international bodies
         7.2. Exposure limit values
         7.3. Specific restrictions
         7.4. Labelling, packaging, and transport
         7.5. Waste disposal

    BIBLIOGRAPHY
    

    INTRODUCTION

    The Environmental Health Criteria (EHC) monographs produced by the
    International Programme on Chemical Safety include an assessment of
    the effects on the environment and on human health of exposure to a
    chemical or combination of chemicals, or physical or biological
    agents. They also provide guidelines for setting exposure limits.

    The purpose of a Health and Safety Guide is to facilitate the
    application of these guidelines in national chemical safety
    programmes. The first three sections of a Health and Safety Guide
    highlight the relevant technical information in the corresponding
    EHC. 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. A bibliography has been included for
    readers who require further background information.

    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

    Common name:                  Carbendazim

    Chemical formula:             C9H9N3O2

    Chemical structure:

    CHEMICAL STRUCTURE 1

    Common trade names
    (including formulations):     Carbendazim, Delsene, Bavistin,
                                  Corbel, Konker, Bedazim, Derosal,
                                  Kombat, Kemdazin, Carbendor, Hoe
                                  017411, Cekudazim, Equitdazin,
                                  Aimcozim (some are formulations with
                                  other pesticides)

    CAS chemical name:            Methyl (1H-benzimidazol-2-yl)carbamate

    Synonyms:                     Carbendazol (ZMAF), methyl-2-
                                  benzimidazole carbamate (MBC, MCB,
                                  BCM, BMC)

    CAS registry number:          10605-21-7

    RTECS registry number:        DD 6500000

    Other information:            Carbendazim is a metabolite of other
                                  benzimidazole fungicides

    1.2  Physical and chemical properties

    Carbendazim, a white crystalline solid, is a systemic fungicide of
    the benzimidazole family. It melts at approximately 250 C and has a
    vapour pressure of <1  10-9 mbar at 25 C. Carbendazim is
    essentially insoluble in water (8 mg/litre) at pH 7 and 25 C. It is
    stable under normal storage conditions.

    1.3  Analytical methods

    Analyses of environmental samples and residues are performed by
    extraction with an organic solvent and purification of the extract
    by a liquid-liquid partitioning procedure.  Residue levels may be
    determined by HPLC or immunoassay.

    1.4  Production and uses

    In 1988, the estimated global sale of carbendazim was approximately 
    3600 tonnes. It is the most widely used member of a family of
    fungicides known as the benzimidazoles. Carbendazim is a systemic
    and broad spectrum fungicide that is currently registered for use
    for the control of diseases in fruit trees, nut crops, vegetables,
    cereals, tropical crops and ornamentals, turf, and many field crops.
    It is formulated as an aqueous dispersion, aqueous suspension,
    flowable water dispersible granules, and a wettable powder.

    2.  SUMMARY AND EVALUATION

    2.1  Exposure

    The primary source of carbendazim exposure for the general human
    population is dietary intake. Estimated human exposures, based on
    dietary analysis and crop tolerance values, indicate an expected
    intake substantially below the recommended Acceptable Daily Intake
    (ADI), based on no-observed-effect levels in animal tests.

    Occupational exposure during manufacture or crop application is
    within acceptable levels. Primary routes of exposure are inhalation
    and dermal contact and both are easily reduced and controlled by the
    use of dust masks and protective clothing.

    2.2  Uptake, metabolism, and excretion

    Carbendazim is well absorbed after oral, but not dermal, exposure.
    Absorbed carbendazim is rapidly metabolized and eliminated in the
    urine and faeces.

    2.3  Effects on organisms in the environment

    Because of its stability on plant material, lasting several weeks,
    carbendazim may become accessible to organisms feeding on leaf
    litter. Soil and sediments may contain residues of carbendazim for
    up to 3 years. However, the strong adsorption of carbendazim on soil
    and sediment particles reduces the exposure of terrestrial and
    aquatic organisms.

    Carbendazim applied at recommended application rates has little
    effect on soil microbial activity. Some adverse effects have been
    reported in groups of fungi.

    Carbendazim is algicidal and was toxic for aquatic organisms and
    fish in laboratory studies.

    Carbendazim was toxic for earthworms in laboratory studies, when
    applied at realistic exposure concentrations, and, in the field, at
    recommended levels of use. Its toxicity for birds is low and it is
    relatively non-toxic for honey bees.

    2.4  Effects on experimental animals and in vitro test systems

    The toxicity of carbendazim through ingestion is low, with an LD50
    in rats of 10 000 mg/kg. Inhalation toxicity is very low (4-h LC50
    >50 mg/litre) and toxicity through dermal contact, moderate (LD50
    >10 000 mg/kg). Carbendazim is not a skin irritant or sensitizer in
    guinea-pigs, but it may cause eye irritation.

    In long-term feeding studies on rats, hepatotoxicity and testicular
    toxicity were observed at dose levels greater than 500 mg/kg
    (equivalent to 25 mg/kg body weight per day). Hepatotoxicity was
    observed in dogs at dose levels greater than 300 mg/kg. Decreases in
    sperm counts and reduced fertility were found in rats at dose levels
    of 50 mg/kg body weight per day or more. No effect on the male
    reproductive system was found at a dose level of 500 mg/kg (25 mg/kg
    body weight per day) in the rat.

    Carbendazim caused increases in malformations and anomalies in the
    rat at dose levels greater than 10 mg/kg. Decreases in fetal weight
    and increases in fetal lethality were also found in the rat at dose
    levels of 20 mg/kg body weight per day or more.

    Carbendazim resulted in an increased incidence of hepatocellular
    tumours in certain strains of mice known to have a high background
    rate for these tumours. No carcinogenic effect was observed in rats.

    Carbendazim is not a heritable gene mutagen. However, it produced
    numerous chromosome aberrations or aneuploidy, caused by the same
    mechanism that is responsible for its fungicidal activity.

    Carbendazim was found to bind to fungal tubulin but to have a low
    affinity for mammalian tubulin.

    2.5  Effects on humans

    No inadvertent poisoning of agricultural or factory workers has been
    documented.

    3.  CONCLUSIONS AND RECOMMENDATIONS

    Estimated human exposures, based on dietary analysis and crop
    tolerance values, indicate the expected intake to be below the
    recommended Acceptable Daily Intake (ADI), based on
    no-observed-effect levels in animal tests. Given the toxicity levels
    of carbendazim and the low dietary exposure levels, it is unlikely
    that it poses a significant health risk for the general population.

    Occupational exposures during manufacture or crop application are
    below the established Threshold Limit Values.

    Carbendazim is strongly adsorbed on soil organic matter and persists
    in the soil for up to 3 years. Carbendazim persists on leaf surfaces
    and, therefore, in leaf litter. Earthworms have been shown to be
    adversely affected (population and reproductive effects) at
    recommended rates of application. There is no information on other
    soil or litter arthropods that would be similarly exposed.

    The high toxicity for aquatic organisms in laboratory tests is
    unlikely to be seen in the field, because of the low bioavailability
    of sediment-bound residues of carbendazim. However, no information
    is available on sediment-living species, which would receive high
    exposure.

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

    4.1  Human health hazards, prevention and protection, first aid

    4.1.1  Advice to physicians

    The acute toxicity of carbendazim for humans is believed to be very
    low. There is no specific antidote. In case of skin contact,
    immediately wash skin with soap and water. In case of eye contact,
    immediately flush eyes with plenty of water for at least 15 min.

    4.1.2  Health surveillance advice

    No specific health surveillance information is available.

    4.2  Explosion and fire hazards

    4.2.1  Explosion hazards

    Like most organic powders or crystals, under severe dust conditions,
    this material may form explosive mixtures in air.

    4.2.2  Fire hazards

    Evacuate personnel to a safe area, keeping them away from, and
    upwind of, the fire. Wear self-contained breathing apparatus. Use
    water or dry chemical to extinguish the fire and water spray to cool
    the tank/container.

    4.3  Storage

    Store in well ventilated area. Keep container tightly closed. Do not
    store or consume food, drink, or tobacco in areas where they may
    become contaminated with this material.

    4.4  Transport

    All products should be transported in secure vehicles according to
    local regulations. Containers should be sound, adequately labelled,
    and kept dry.

    4.5  Spillage

    Sections 4.1 and 4.2 of this Guide should be reviewed before
    proceeding with clean up. Use appropriate personnel protective
    equipment during clean up.

    Prevent liquid from entering sewers, waterways, or low areas.
    Shovel, or sweep, up.

    4.6  Disposal

    Treatment, storage, transportation, and disposal must be in
    accordance with applicable local regulations. Remove nonusable solid
    materials and/or contaminated soil for disposal in an approved and
    permitted landfill. Do not flush into surface water or sanitary
    sewer systems.

    Do not reuse container; dispose of according to approved local
    procedures.

    5.  HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION

    The strong adsorption of benomyl and its degradation product
    carbendazim on particulates in soil and aquatic sediment reduces its
    bioavailability. However, earthworm populations have been reduced at
    recommended application rates. There is no information on toxicity
    to other soil invertebrates or aquatic invertebrates living in
    sediments. Residues on particulates may persist for years.

    Excessive application of benomyl to the same area should be avoided
    to prevent build up of residues. Disposal should avoid contamination
    of both soil and surface water sediments.

    6.  SUMMARY OF CHEMICAL SAFETY INFORMATION

    This summary should be easily available to all health workers
    concerned with, and users of, carbendazim. It should be displayed
    at, or near, entrances to areas where there is potential exposure to
    carbendazim, and on processing equipment and containers. The summary
    should be translated into the appropriate language(s). All persons
    potentially exposed to the chemical should also have the
    instructions in the summary clearly explained.

    Space is available for insertion of the National Occupational
    Exposure Limit, the address and telephone number of the National
    Poison Control Centre, and local trade names.

    
    SUMMARY OF CHEMICAL SAFETY INFORMATION

    CARBENDAZIM

    Methyl (1H-benzimidazol-2-yl)carbamate

    C9H9N3O2

                                                                                                                             
    PHYSICAL PROPERTIES                                         OTHER CHARACTERISTICS
                                                                                                                             

    Relative molecular mass                   191.2             White, crystalline solid
    Melting point (C)                        250
    Water solubility (mg/litre, pH 7, 25 C)  8.0
    Specific density                          0.27
    Relative vapour pressure (Pa, 20 C)      <1 x 10-7
    Explosion limit (LEL, g/litre in air)     0.13

                                                                                                                             
    HAZARD/SYMPTOM                        PREVENTION AND PROTECTION              FIRST AID
                                                                                                                             

    SKIN: Irritation                      Wear long-sleeved shirt and long       Remove contaminated clothing, wash with 
                                          trousers, chemical resistant gloves,   soap and water, and obtain medical
                                          shoes or boots                         treatment

    EYE: Irritation                       Wear safety goggles or face shield     Flush with plenty of water for at least 
                                                                                 15 min and obtain medical treatment

    INHALATION: Irritation                Avoid breathing dust or spray mist     Remove from exposure; obtain medical
                                                                                 attention

    INGESTION:                            Do not eat, drink, chew or smoke       Obtain medical attention
                                          during use; keep out of reach of
                                          children
                                                                                                                             

                                                                                                                             
    HAZARD/SYMPTOM                        PREVENTION AND PROTECTION              FIRST AID
                                                                                                                             

    ENVIRONMENT: Presents a risk          Contamination of water and soil
    for aquatic and soil organisms        should be avoided by proper methods
                                          of application, storage, transport, and
                                          waste disposal

                                                                                                                             
    SPILLAGE                              STORAGE                                FIRE AND EXPLOSION
                                                                                                                             
    Wear appropriate protective           Store in well ventilated area; keep    Under severe dust conditions, carbendazim 
    equipment during clean up; prevent    container tightly closed; store in     may form explosive mixtures in air;
    liquid from entering sewers,          original container only, away from     in case of fire, evacuate personnel 
    waterways, or low areas; shovel,      other pesticides, fertilizer, food,    to a safe area, wear self-contained 
    or sweep, up                          or  animal feed; do not allow to       breathing apparatus, use water or dry 
                                          become wet during storage              chemical to extinguish fire, and cool
                                                                                 tank/container with water spray

                                                                                                                             
    WASTE DISPOSAL
                                                                                                                             
    Treatment, storage, transportation,   National occupational exposure
    and disposal must be in accordance    limit:
    with applicable local regulations;
    waste disposal must be in an 
    approved and permitted landfill or
    by incineration; do not flush to      National Poison Control Centre:
    surface water or sanitary sewer 
    system
                                                                                                                             
    

    7.  CURRENT REGULATIONS, GUIDELINES AND STANDARDS

    7.1  Previous evaluations by international bodies

    Carbendazim was evaluated by the Joint FAO/WHO Meeting on Pesticide
    Residues (JMPR) in 1973, 1975, 1978, 1983, and 1988. The 1978
    meeting agreed that the Maximum Residue Limits for benomyl,
    carbendazim, and thiophanate-methyl should be combined and expressed
    as carbendazim. The 1983 meeting evaluated benomyl toxicology and
    set the following carbendazim no-observed-effect levels (NOELs) and
    ADI:

         Rat                 500 mg/kg diet, equivalent to 25 mg/kg body
                             weight

         Dog                 100 mg/kg diet, equivalent to 2.5 mg/kg
                             body weight

         Rat (teratology)    30 mg/kg body weight per day (benomyl).

    The estimated ADI for carbendazim was established at 0-0.01 mg/kg
    body weight.

    7.2  Exposure limit values

    Exposure limit values are presented in the table on p. 20.

    7.3  Specific restrictions

    There are no specific restrictions on the use of carbendazim.

    7.4  Labelling, packaging, and transport

    European Economic Community legislation requires labelling as a
    dangerous substance using the symbol Xn.

    FIGURE 1

    
    Table 1. Exposure limit values

                                                                                                                              

    Medium         Specification       Country/           Exposure limit                            Values
                                       organization       description
                                                                                                                              

    Food           plant (specified)   Brazil             Acceptable limit (AL)                     0.1-0.5 mg/kg
    Food           plant (specified)   Germany            Maximum residue limit (MRL)               0.2-7.0 mg/kg
    Food           plant (specified)   India              Maximum tolerable concentration (MTC)     0.1-5.0 mg/kg
    Food           plant (specified)   Russian            Maximum residue limit (MRL)               0.1 mg/kg
                                         Federation
    Food           cereals             Sweden             Maximum tolerable concentration (MTC)     0.1 mg/kg
    Food           plant (specified)   United             Maximum residue limit (MRL)               0.1-10.0 mg/kg
                                         Kingdom
    Food                               FAO                Acceptable daily intake (ADI)             0.02 mg/kg body weight
    Food           plant (specified)   FAO                Maximum residue limit (MRL)               0.1-50 mg/kg
    Air            occupational        Russian            Maximum allowable concentration (MAC)     0.1 mg/m3
                   (aerosol)             Federation
    Water          surface water       Russian            Maximum allowable concentration (MAC)     0.1 mg/litre
                                         Federation
                                                                                                                              


            
    a From: IRPTC Legal File (1992).
    

    The following label statements are required:

         R40 - Possible risk of irreversible effects

         S36/37 - Wear suitable protective clothing and gloves

    Carbendazim has been classified as a Marine Pollutant and a
    Flammable Solid by the International Maritime Organization.

    7.5  Waste disposal

    European Economic Community regulations require that carbendazim
    and/or its container must be disposed of as hazardous waste.

    BIBLIOGRAPHY

    FAO/WHO (1985a) Benomyl. In:  Pesticide residues in food - 1983:
     evaluations 1983. Rome, Food and Agriculture Organization of the
    United Nations, pp. 7-46.

    FAO/WHO (1985b) Carbendazim. In:  Pesticide residues in food - 1983:
     evaluations 1983. Rome, Food and Agriculture Organization of the
    United Nations, pp. 89-121.

    FAO/WHO (1988a) Benomyl. In:  Pesticide residues in food - 1988:
     evaluations 1988. Rome, Food and Agriculture Organization of the
    United Nations, pp. 5-15.

    FAO/WHO (1988b) Carbendazim. In:  Pesticide residues in food - 1988:
     evaluations 1988. Rome, Food and Agriculture Organization of the
    United Nations, pp. 41-54.

    ILO (1991)  Occupational exposure limits for airborne toxic
     substances. Geneva, International Labour Organisation
    (Occupational Safety and Health Series, No. 37).

    UNEP IRPTC (1992)  IRPTC legal file 1992. Geneva, International
    Register of Potentially Toxic Chemicals, United Nations Environment
    Programme.

    WHO (1993)  Environmental Health Criteria 148: Benomyl. Geneva,
    World Health Organization.

    WHO (1993)  Environmental Health Criteria 149: Carbendazim. Geneva,
    World Health Organization.


    See Also:
       Toxicological Abbreviations
       Carbendazim (EHC 149, 1993)
       Carbendazim (ICSC)
       Carbendazim (PDS)
       Carbendazim (WHO Pesticide Residues Series 3)
       Carbendazim (Pesticide residues in food: 1976 evaluations)
       Carbendazim (Pesticide residues in food: 1977 evaluations)
       Carbendazim (Pesticide residues in food: 1978 evaluations)
       Carbendazim (Pesticide residues in food: 1983 evaluations)
       Carbendazim (Pesticide residues in food: 1985 evaluations Part II Toxicology)
       Carbendazim (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental)
       Carbendazim (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental)
       Carbendazim (JMPR Evaluations 2005 Part II Toxicological)