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    IPCS INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
    Health and Safety Guide No. 80




    MONOCROTOPHOS
    HEALTH AND SAFETY GUIDE



    UNITED NATIONS ENVIRONMENT PROGRAMME

    INTERNATIONAL LABOUR ORGANISATION

    WORLD HEALTH ORGANIZATION



    WORLD HEALTH ORGANIZATION, GENEVA 1993


    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

    Monocrotophos : health and safety guide.

    (Health and safety guide ; no. 80)

    1.Hazardous substances - standards 2.Monocrotophos - standards
    3.Monocrotophos - toxicity    I.Series

    ISBN 92 4 151080 3          (NLM Classification: WA 240)
    ISSN 0259-7268

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    CONTENTS

    INTRODUCTION

    1. PRODUCT IDENTITY AND USES
         1.1. Identity
         1.2. Physical and chemical properties
         1.3. Analytical methods
         1.4. Uses

    2. SUMMARY AND EVALUATION
         2.1. Exposure
         2.2. Effects on experimental animals and  in vitro
              test systems
         2.3. Effetcs on humans
         2.4. Evaluation of the effects on the environment

    3. CONCLUSIONS AND RECOMMENDATIONS
         3.1. Conclusions
         3.2. 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
                        4.1.1.1   Symptoms of poisoning
                        4.1.1.2   Medical treatment
              4.1.2. Health surveillance advice
         4.2. Explosion and fire hazards
         4.3. Storage
         4.4. Transport
         4.5. Spillage and disposal
              4.5.1. Spillage
              4.5.2. Disposal

    5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION

    6. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS
         6.1. Previous evaluations by international bodies
         6.2. Exposure limit values
         6.3. Specific restrictions
         6.4. Labelling, packaging, and transport
         6.5. Waste disposal

    BIBLIOGRAPHY

    ANNEX     Treatment of organophosphate isecticide poisoning
              in man
    

    INTRODUCTION

    This Health and Safety Guide is not based on an existing
    Environmental Health Criteria monograph, but on evaluations by the
    Joint FAO/WHO Meeting on Pesticide Residues and on critical national
    reviews.

    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 structure:

    CHEMICAL STRUCTURE 1

    Molecular formula:       C7H14NO5P

    Common names:            Monocrotophos, (Approved by BSI, E-ISO,
                             F-ISO, JMAF)

    IUPAC name:              Dimethyl (E)1-methyl-2- (methylcarbamoyl)
                             vinylphosphate; 3-(dimethoxyphosphinyl-
                             oxy)- N-methylisocrotonamide

    CAS chemical name:       (E)-dimethyl-1-methyl-3-(methylamino)-
                             3-oxo-1-propenyl phosphate (9Cl); dimethyl
                             phosphate ester with
                             (E)-3-hydroxy- N-methylcrotonamide
                             (8 Cl)

    Trade names:             Nuvacron(R), Azodrin(R)

    CAS registry number:     6923-22-4

    RTECS registry number:   TC4375000

    OMS number:              834

    Technical monocrotophos is at least 75% pure.

    1.2  Physical and chemical properties

     Pure monocrotophos is in the form of colourless crystals. It is
    soluble in water, acetone, and aliphatic alcohols, but only slightly
    soluble in mineral oils. Monocrotophos is fairly resistant to
    hydrolysis.

     Technical monocrotophos is a reddish brown mixture of solid and
    liquid, melting at 25-35 C. It has a mild ester odour.

    Some other relevant physical properties of monocrotophos are given
    in Table 1.

    Table 1. Physical properties of monocrotophos

                                                                  
    Relative molecular mass             223.2
    Melting point (C)                  54-55
    Boiling point (C)                  125 (at 0.0005 mmHg)
    Vapour pressure (20 C)             0.29 mPa
    Solubility in water (20 C)         1 kg/litre
    Half-life in aqueous solution
      at pH 5.0                         96 days
      at pH 7.0                         66 days
      at pH 9                           17 days
                                                                  

    Monocrotophos is unstable in short-chain alcohols and glycols.
    However, it is stable when stored in glass or polyethylene
    containers. In solution at 2 mg/litre (2 ppm), the half-life at
    pH 7.0 and 38 C is 23 days; at pH 4.6 and 100 C, it is 80 min.

    Monocrotophos is corrosive to black iron, drum steel, stainless
    steel, and brass.

    1.3  Analytical methods

    Gas chromatography or HPLC are the analytical methods of choice for
    both formulated products and residues. Recommendations for the
    methods of analysis of monocrotophos residues have been given by the
    Codex Alimentarius Commission (FAO/WHO, 1989).

    1.4  Uses

    Monocrotophos is a broad-spectrum, fast-acting insecticide with both
    systemic and residual contact actions. It is particularly effective
    against Lepidoptera, Homoptera, and certain Coleoptera. The main use
    of monocrotophos is for foliar application to cotton. To a certain
    extent, monocrotophos is also effective against mites.

    When applied under cool conditions, monocrotophos has been known to
    cause phytotoxic effects in apples, cherries, peaches, and sorghum.

    Monocrotophos is available in a variety of formulations. There are
    the 200, 400, and 600 g a.i./litre concentrates, the 400, 500, and
    600 g a.i./litre water-soluble concentrates, and the 250 g
    a.i./litre ULV formulation. Monocrotophos is also available in
    mixtures with other pesticides.

    2.  SUMMARY AND EVALUATION

    The information in this section is largely based on evaluations of
    the Joint FAO/WHO Meeting on Pesticide Residues.

    2.1  Exposure

    In the environment, monocrotophos is rapidly degraded (half-life in
    soil 1-7 days) but hydrolysis in solutions is rather slow, even at
    high pH. Using the recommended pre-harvest intervals (see section
    6.3) monocrotophos residues are low.

    The general population is not generally exposed to monocrotophos
    from the air or water. It is not usually detected as residues in
    food in total diet studies.

    Occupational exposure to monocrotophos may occur during
    manufacturing, formulation, application, and storage. This exposure
    is mainly through inhalation and dermal absorption. Higher
    occupational exposures may be observed in cases of accident or as a
    result of incorrect handling. With correct usage, there should not
    be exposure to hazardous amounts.

    2.2  Effects on experimental animals and  in vitro test systems

    Monocrotophos is highly toxic via the oral route. The acute oral
    LD50 for rats is 14 mg/kg. The acute dermal LD50 for rats is at
    least 135 mg/kg. It is slightly irritating to the skin and mildly
    irritating to the eyes.

    Monocrotophos can be absorbed following ingestion, inhalation, and
    skin contact. In rats, monocrotophos was rapidly eliminated in the
    urine. Within 6 h, the excreted materials were primarily hydrolysis
    products (70%), unchanged monocrotophos (25%), and traces of the
     N-hydroxymethyl and desmethyl metabolites. The elimination rate
    then diminished substantially, indicating rapid absorption and
    elimination.

    In mammals, the primary conversion products of monocrotophos are
    dimethyl phosphate,  O-desmethyl monocrotophos and  N-desmethyl
    monocrotophos.  N-desmethyl monocrotophos is more toxic than
    monocrotophos via the oral and intraperitoneal routes.

    Signs of intoxication from exposure to monocrotophos are those
    typical of exposure to organophosphorus pesticides. Inhibition of
    cholinesterase is the most sensitive indicator of exposure to
    monocrotophos and may indicate toxicity. A dietary level of 0.1
    mg/kg, equivalent to 0.005 mg/kg body weight per day, is considered
    to be the no-adverse-effect level in rats; in dogs, it is 0.5 mg/kg
    diet, equivalent to 0.0125 mg/kg per day.

    The Joint FAO/WHO Meeting on Pesticide Residues (JMPR) has estimated
    the acceptable daily intake in man to be 0-0.00005 mg/kg body
    weight.

    In a 2-year study on mice at dietary concentrations of 0, 1, 2, 5 or
    10 mg/kg, a NOAEL could not be established, because brain
    acetylcholinesterase inhibition was detected at the lowest dietary
    concentration (approximately 20% inhibition). There was no evidence
    of any treatment-related carcinogenic effects.

    In a 2-year study on rats at dietary concentrations of 0, 0.01,
    0.03, 0.1, 1.0, or 10 mg/kg, the NOAEL was 0.1 mg/kg, equivalent to
    0.005 mg/kg body weight per day, based on brain acetylcholinesterase
    inhibition at the highest dose. Again, there was no evidence of
    carcinogenicity.

    Monocrotophos did not cause delayed neuropathy in hens.

    In a multigeneration reproduction study on rats at dietary
    concentrations of 0, 0.1, 1, 3, or 10 mg/kg, the NOAEL was 1 mg/kg,
    equivalent to 0.05 mg/kg body weight per day, based on toxicity in
    pups seen in the F2 generation at 3 mg/kg.

    In a teratology study on rats at doses of 0, 0.3, 1, or 2 mg/kg body
    weight per day, the NOAEL was 0.3 mg/kg body weight per day for both
    maternal toxicity and teratogenicity. There was a slightly increased
    incidence of malformed and/or misshapen brain at all dose levels,
    including the lowest dose level of 0.3 mg/kg body weight per day. A
    dose-effect relationship for this uncommon malformation was lacking
    and historical control data were not available. It may have been an
    artefact. A repeat study is in progress. In a rabbit teratology
    study, no teratogenic potential was demonstrated and the maternal
    NOEL was 1 mg/kg per day.

    An extensive data base showed a weak mutagenic activity  in vitro.
     In vivo assays gave mostly negative or, rarely, equivocal results.

    2.3  Effects on humans

    In a 30-day trial with human volunteers, a daily oral dose of 0.006
    mg/kg was without effect.

    Several cases of monocrotophos poisoning in humans have been
    reported.

    2.4  Evaluation of the effects on the environment

    In the environment, monocrotophos is degraded mainly via hydrolysis
    and oxidation. The products of these degradation pathways are
    non-cholinesterase inhibiting and of low toxicity. Volatilization
    appears to be the major factor in the rapid loss of residues
    following application.

    Monocrotophos and its metabolites are rapidly degraded in soil,
    mainly biologically, to complete mineralization. They will not
    accumulate in the environment under normal use conditions.

    Monocrotophos is highly toxic for birds, bees, aquatic
    invertebrates, and mammals, including wild species. It is moderately
    toxic for fish and non-toxic for microorganisms. The acute LD50
    for birds is 1.0-6.5 mg/kg, for rainbow trout, 12 mg/litre, and for
    honey bees, 33-84 g/bee.

    3.  CONCLUSIONS AND RECOMMENDATIONS

    3.1  Conclusions

    *    Under proper conditions of use, exposure of the general
         population to monocrotophos is negligible.

    *    Monocrotophos is highly toxic. Using appropriate safety
         precautions, exposure to monocrotophos during manufacture,
         formulation, application, and disposal should not pose an
         unacceptable human health hazard.

    *    Monocrotophos is rapidly degraded and is not persistent in the
         environment. Care should be taken not to expose aquatic
         invertebrates, bees, birds, fish, and mammals to this
         insecticide.

    3.2  Recommendations

    *    Cleaning and disposal of contaminated equipment, clothing, and
         containers should be in accordance with recommended procedures.

    *    Pretreatment of effluent waters from formulation plants should
         be required.

    *    Monocrotophos should be used only with proper precautions and
         under proper supervision, in order to avoid overexposure.

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

    4.1  Human health hazards, prevention and protection, first aid

    Monocrotophos has a high acute oral toxicity and a moderate acute
    dermal toxicity and can be hazardous for human beings if incorrectly
    handled. On overexposure, typical signs and symptoms of
    organophosphorus poisoning may occur rapidly. The human health
    hazards associated with certain types of exposure to monocrotophos,
    together with preventive and protective measures and first aid, are
    listed in Table 2.

    4.1.1  Advice to physicians

    For a more complete treatise on the effects of organophosphorus
    insecticides, especially their short- and long-term effects on the
    nervous system, please refer to EHC 63:  Organophosphorus
     insecticides - a general introduction (WHO, 1986). The section on
    treatment from the above monograph is reprinted in the Annex to this
    publication.

    4.1.1.1  Symptoms of poisoning

    Signs and symptoms may include a feeling of exhaustion, headache,
    blurred vision, weakness, and confusion. Vomiting, abdominal pain,
    excessive sweating, and salivating may develop. The pupils are
    constricted. Difficulty in breathing may be experienced, due to
    congestion of the lungs and weakness of the respiratory muscles.
    Arrhythmias and cardiac failure have been reported. On severe
    poisoning, there will be muscle spasms, unconsciousness, and
    convulsion. Breathing may stop, followed by death.

    4.1.1.2  Medical treatment

    If ingested and the formulation does not contain petroleum
    distillates, induce vomiting, or preferably perform gastric lavage
    using 5% sodium bicarbonate. In the case of ingestion of liquid
    formulations containing hydrocarbon solvents, vomiting involves a
    risk of aspiration pneumonia. Instead, the stomach should be
    emptied, as soon as possible, by careful gastric lavage (using a
    cuffed endotracheal tube). If possible, identify the solvents
    present in the formulation and observe the victim for additional
    toxic effects. As early as possible, administer 2 mg of atropine
    sulfate iv and 1000-2000 mg of pralidoxime chloride or 250 mg of
    obidoxime chloride (adult dose) iv to patients suffering from severe
    respiratory difficulties, convulsions, and unconsciousness. Repeated
    doses of 2 mg of atropine sulfate should be given, as required,
    based on the respiration, blood pressure, pulse frequency,
    salivation, and convulsion conditions. Diazepam should be given in
    all but the mildest cases in doses of 10 mg, sc or iv, which may be

    repeated as required. For children, the doses are 0.04-0.08 mg of
    atropine/kg body weight, 250 mg of pralidoxime chloride per child or
    4-8 mg of obidoxime chloride per kg body weight.

    Artificial respiration should be applied if required.

    Morphine, barbiturates, phenothiazine derivatives,
    tranquillizers, and all kinds of central stimulants
    are contraindicated in the absence of artificial
    respiration

    The diagnosis of intoxication should be confirmed, as soon as
    possible, by determination of the cholinesterase activity in venous
    blood.

    In all cases of clinical poisoning with monocrotophos and other
    organophosphorus insecticides, it is essential to maintain general
    surveillance and cholinesterase (ChE) and cardiac monitoring for at
    least 14 days, and longer if necessary, and to adopt general
    supportive and specific therapy in accordance with the findings.

    As stated earlier, more information on the treatment of
    organophosphorus insecticide poisoning can be obtained from EHC 63:
     Organophosphorus insecticides - a general introduction (WHO, 1986)
    and also from the Annex to this Guide.

    4.1.2  Health surveillance advice

    In human beings exposed to monocrotophos, the cholinesterase
    activity of the blood should be monitored regularly. Measurement of
    whole blood acetylcholinesterase (AChE) is the most widely adopted
    method. Because physiological variations of blood-ChE levels occur
    in a healthy person and amongst populations, it is preferable to
    compare results with pre-exposure ChE levels.


        Table 2. Human health hazards, prevention and protection, first aid

                                                                                                                                      
    HAZARD/SYMPTOM                          PREVENTION AND PROTECTION                  FIRST AID
                                                                                                                                      

    GENERAL: Cholinesterase                 Avoid exposure
    inhibition


    SKIN: Contamination may cause           Wear PVC or neoprene gloves and            Remove and wash contaminated
    poisoning                               rubber boots                               clothing; wash contaminated skin
                                                                                       with water and soap

    EYES: Redness; irritation               Wear safety goggles or face shield         Flush eyes with clean water for at
                                                                                       least 15 min; if irritation persists,
                                                                                       obtain medical attention

    INHALATION: Excessive                   Avoid breathing the mist, aerosol, or      In case of signs and symptoms of
    inhalation may cause poisoning          dust; use proper (exhaust) ventilation     organophosphorus poisoning, remove
                                            or suitable mask                           from contaminated area and obtain
                                                                                       medical attention immediately

    INGESTION: An unlikely                  Wash hands before eating, drinking,        -
    occupational hazard                     using the toilet, and after work;
                                            do not keep food in areas with
                                            potential exposure

    Accidental or intentional swallowing    -                                          Obtain medical attention immediately;
    may rapidly cause typical signs and                                                induce vomiting if subject is conscious;a
    symptoms of organophosphorus                                                       if breathing has stopped, apply
    poisoning, leading to respiratory                                                  artificial respiration
    arrest and death
                                                                                                                                      

                                                                                                                                      
    HAZARD/SYMPTOM                          PREVENTION AND PROTECTION                  FIRST AID
                                                                                                                                      

    REPEATED EXPOSURE VIA                   Wash hands before eating, drinking,        Obtain medical attention immediately;
    INGESTION, INHALATION, OR               using the toilet, and after work           induce vomiting if subject is conscious;a
    THROUGH THE SKIN                                                                   if breathing has stopped, apply
    may gradually lead to signs,                                                       artificial respiration
    symptoms, and poisoning;
    sensitization may occur
                                                                                                                                      

    a  Caution: if monocrotophos is dissolved in solvents, e.g., petroleum solvents, vomiting may cause pulmonary aspiration.
    

    Depressions of AChE or ChE levels of 20-25% are considered
    diagnostic of exposure, but not necessarily indicative of hazard.
    Depressions of 30-50% or more are considered indicators for removal
    of an exposed individual from further contact with pesticides, until
    levels return to normal. Work procedures and hygiene should also be
    checked.

    4.2  Explosion and fire hazards

    Liquid formulations may be flammable. With sufficient burning or
    external heat, monocrotophos will decompose, emitting toxic fumes.
    Fire-fighters must wear protective clothing and a self-contained
    breathing apparatus. Extinguish fires with alcohol-resistant foam or
    powder. Confine the use of water spray to the cooling of unaffected
    stock, thus avoiding polluted run-off from the site.

    4.3  Storage

    Technical monocrotophos and its formulations should be stored in the
    original labelled containers in locked, well-ventilated storage
    areas, preferably dedicated to insecticides. Do not expose to direct
    sunlight. Keep products out of reach of children and unauthorized
    personnel. Do not store near animal feed or foodstuffs.

    4.4  Transport

    Comply with any local regulations regarding the movement of
    hazardous goods. Do not transport with animal feed or foodstuffs.
    Food and animal feed should not be transported in vehicles that have
    been used for the transport of pesticides. Before dispatch, make
    sure that containers are in good condition and that the labels are
    undamaged.

    4.5  Spillage and disposal

    4.5.1  Spillage

    Avoid skin contamination and inhalation of vapour. Cover
    contaminated areas and absorb spilled liquid with a 1:3 mixture of
    sodium carbonate crystals and damp sawdust, lime, sand, or earth.
    Sweep up and place in an impervious container. Ensure that container
    is tightly closed and labelled before transfer to a safe place for
    disposal.

    Spills of powders should be cleaned up using a dustless method
    (e.g., by a vacuum cleaner suitable for use with toxic dusts).
    Alternatively, mix with damp saw-dust and place in separate
    container for subsequent disposal. Dry brushing should not be
    carried out, as this creates dust clouds.

    Prevent liquid from spreading and contaminating other cargo,
    vegetation, or waterways by using a barrier of the most suitable and
    readily available material, e.g., earth or sand.

    Empty any of the product remaining in the damaged/leaking container
    into a clean empty container, which should then be tightly closed
    and suitably labelled. Decontaminate emptied leaking containers with
    a 10% sodium carbonate (washing soda) solution, added at a rate of
    at least 1 litre/20-litre drum. Swirl round to rinse walls, empty,
    and add rinsings to sawdust. Do not reuse containers for any other
    purpose. Puncture and crush the container to prevent reuse.

    4.5.2  Disposal

    Large amounts should be incinerated at high temperature in a unit
    with effluent gas scrubbing. When no incinerator is available, bury
    in an approved dump, or in an area where there is no risk of
    contamination of surface or groundwater. Before burying, liberally
    mix with sodium carbonate (washing soda) crystals to help neutralize
    the product, and with soil rich in organic matter. Comply with any
    local legislation.

    5.  HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION

    Monocrotophos is rather resistant to hydrolysis, but is rapidly
    degraded in the soil and in aquatic systems (ponds, rivers), mainly
    biologically, to complete mineralization. With normal usage,
    monocrotophos will not accumulate.

    The insecticide is highly toxic for aquatic invertebrates, birds,
    bees, and mammals. It is moderately toxic for fish and earthworms
    and non-toxic for microorganisms and algae.

    Avoid contamination of the soil, water, and atmosphere by proper
    methods of use, storage, transport, handling and waste disposal. In
    case of spillage, use the methods advised in section 4.5.1.

    6.  CURRENT REGULATIONS, GUIDELINES AND STANDARDS

    The information given in this section has been extracted from the
    International Register of Potentially Toxic Chemicals (IRPTC) legal
    file and other United Nations sources. A full reference to the
    original national document from which the information was extracted
    can be obtained from IRPTC.

    The reader should be aware that regulatory decisions about chemicals
    taken in a certain country can only be fully understood in the
    framework of the legislation of that country. Furthermore, the
    regulations and guidelines of all countries are subject to change
    and should always be verified with the appropriate regulatory
    authorities before application.

    6.1  Previous evaluations by international bodies

    The Joint FAO/WHO Meeting on Pesticide Residues (JMPR) evaluated
    monocrotophos in 1972, 1975, and 1991. The acceptable daily intake
    (ADI) was estimated at 0-0.00005 mg/kg body weight in 1991. This was
    based on levels causing no toxicological effects of:

         -    <1 mg/kg diet, equivalent to <0.15 mg/kg body weight per
              day in the mouse; and 

         -    0.1 mg/kg diet, equivalent to 0.005 mg/kg body weight per
              day in the rat.

    The FAO/WHO Codex Alimentarius Commission (FAO/WHO, 1986)
    recommended Maximum Residue Limits (MRLs) in several food
    commodities, ranging from 0.002 to 1 mg/kg (see Table 3).

    WHO (1992) classified technical monocrotophos as "highly hazardous"
    in normal use, based on an oral LD50 in the rat of 14 mg/kg.

    6.2  Exposure limit values

    Some exposure limit values are given in Table 3.


        Table 3.  Exposure limit values

                                                                                                                                      
    Medium     Specification     Country/         Exposure limit description                         Value               Effective
                                 organization                                                                            date
                                                                                                                                      

    AIR        Workplace         Argentina        Maximum permissible concentration
                                                  - Time-weighted average (TWA)a                     0.25 mg/m3          1979

                                 USA (OSHA)       Permissible exposure limit (PEL)
                                                  - Time-weighted average (TWA)a                     0.25 mg/m3          1989


                                 USA (NIOSH)      Recommended exposure limit (REL)
                                                  - up to 10-h TWA                                   0.25 mg/m3          1989

                                 USA (ACGIH)      Threshold limit value (TLV)
                                                  - Time-weighted average (TWA)a                     0.25 mg/m3          1989
                                                  - Short-term exposure limit (STEL)                 deleted

    FOOD       Uptake from       FAO/WHO          Acceptable daily intake (ADI)                      0-0.00005 mg/kg     1991
                                                                                                     body weight

    FOOD       Residues          FAO/WHO          Maximum residue limit (MRL)
                                                  specified as follows:                              0.002-1 mg/kg       1986

                                                  - milk                                             0.002 mg/kg

                                                  - cattle, goats, pigs, poultry, sheep (edible
                                                    offal and carcass meat in all cases), eggs
                                                    (shell-free basis), milk products, poultry       0.02 mg/kg

                                                  - carrots, cotton seed oil, maize (grain),
                                                    potatoes, soya beans, sugar beets, turnips       0.05 mg/kg
                                                                                                                                      

    Table 3.  (continued)

                                                                                                                                      
    Medium     Specification     Country/         Exposure limit description                         Value               Effective
                                 organization                                                                            date
                                                                                                                                      

                                                  - coffee (raw beans), cotton seed,
                                                    onions, peas                                     0.1 mg/kg

                                                  - beans, brussels sprouts, cabbage,
                                                    cauliflower, citrus fruit                        0.2 mg/kg

                                                  - apples, pears, tomatoes                          1 mg/kg
                                                                                                                                      

              

    a  TWA usually 8 h.
    

    6.3  Specific restrictions

    Monocrotophos is approved as a pesticide in many countries. Specific
    uses, limitations, and precautions are listed in national regulatory
    documents.

    In the USA, monocrotophos and its preparations may only be handled
    by certified operators. A field sprayed with monocrotophos may not
    be entered without protective clothing within 48 h of application.
    The registration has, however, been cancelled voluntarily.

    In Germany, it may not be handled by adolescents and pregnant and
    nursing women.

    Preharvest intervals have been set in several countries and are
    generally of the order of 7-15 days for vegetables and potatoes, 14
    days for cotton, 21 days for tomatoes, maize, and citrus, and 28-30
    days for other crops.

    6.4  Labelling, packaging, and transport

    The United Nations Committee of Experts on the Transportation of
    Dangerous Goods classifies monocrotophos in:

    -    Hazard Class 6.1:   poisonous substance;

    -    Packing Group 2:    substances and preparations presenting a
                             serious risk of poisoning, for formulations
                             containing 25-100% monocrotophos.

    -    Packing Group 3:    harmful substances and preparations
                             presenting a relatively low risk of
                             poisoning, for solid formulations
                             containing 7-25% active material and liquid
                             formulations containing 2.5-25% active
                             material.

    The label should appear as follows:

    In Packaging Group II

    FIGURE 1

    In Packaging Group III

    FIGURE 2

    In the International Maritime Dangerous Goods (IMDG) Code,
    monocrotophos is classified as a marine pollutant. It should bear
    the following mark on the label:

    FIGURE 3

    For flammable formulations, the following subsidiary label is
    required when the flash-point of the solution is below or equal to
    61 C (closed cup):

    FIGURE 4

    There is no WHO specification for monocrotophos, as the material is
    not used in public health. However, specifications for technical
    material and some formulations (ULV and SLs) have been agreed
    between FAO and the manufacturer.

    All packages should bear, durably and legibly marked on the
    container, the following:

         -    manufacturer's name;
         -    technical monocrotophos to specification;
         -    batch or reference number, and date of test;
         -    net weight of contents;
         -    date of manufacture.

    and, in the case of the formulated products:

         -    manufacturer's name;
         -    monocrotophos to specification;
         -    monocrotophos ... g/kg;
         -    batch or reference number, and date of test;
         -    net weight of contents;
         -    instructions for dilution;
         -    date of formulation.

    and the following minimum cautionary notice:

          Monocrotophos is an organophosphorus compound that inhibits
          cholinesterase. It is poisonous if swallowed or inhaled. It
          may be absorbed through the skin. Avoid skin contact: wear
          protective gloves, clean protective clothing, and a respirator
          when handling the material. Wash thoroughly with soap and
          water after using.

          Keep the material out of the reach of children and well away
          from foodstuffs and animal feed and their containers.

          If poisoning occurs, call a physician. Atropine and
          pralidoxime are specific antidotes, and artificial respiration
          may be needed.

    The monocrotophos content should be declared (minimum 75% for the
    technical products) and should not differ from the declared
    percentage more than 2% for the technical products and 5-10% for its
    formulations.

    Containers should be suitable, clean, dry and as specified in the
    order and should not adversely affect, or be affected by, the
    product, but should adequately protect it from external conditions.
    They should comply with pertinent national and international
    transport and safety regulations.

    Specifications for storage stability are given.

    The European Community Legislation requires labelling as dangerous
    substance using the symbol:

    FIGURE 5

    The label must read:

          Very toxic by inhalation, in contact with skin and if
          swallowed; keep locked up; keep away from food, drink and
          animal feeding stuffs; after contact with skin, wash
          immediately with plenty of ...... (to be specified by the
          manufacturer); in case of accident or if you feel unwell, seek
          medical advice (show the label where possible).

    The European Community legislation on the labelling of pesticide
    preparations classifies pesticide preparations that contain
    monocrotophos into Class 1A as toxic at concentrations >1% and as
    harmful at >0.05-1%. Member States should ensure that pesticides
    cannot be placed on the market unless their packaging, fastenings,
    and labels comply with the requirements laid down.

    6.5  Waste disposal

    In the USA, any non-domestic waste containing monocrotophos is
    considered a hazardous waste and should be notified. Permits are
    required for its handling, transport, treatment, storage, or
    disposal. Waste incinerators must achieve 99.99% destruction and
    removal of this substance.

    BIBLIOGRAPHY

    CEC (1987)  Legislation on dangerous substances - Classification and
     labelling in the European Communities. Vol. 1 and 2. Commission of
    the European Communities, London, Graham & Trotman, Ltd.

    FAO (1985a)  Guidelines for the packaging and storage of pesticides.
    Rome, Food and Agriculture Organization of the United Nations.

    FAO (1985b)  Guidelines for the disposal of waste pesticides and
     pesticide containers on the farm. Rome, Food and Agriculture
    Organization of the United Nations.

    FAO (1985c)  Guidelines on good labelling practice for pesticides.
    Rome, Food and Agriculture Organization of the United Nations.

    FAO (1986)  International code of conduct on the distribution and
     use of pesticides. Rome, Food and Agriculture Organization of the
    United Nations.

    FAO/WHO (1964-present)  Evaluations of pesticide residues in food.
    Rome, Food and Agriculture Organization of the United Nations.

    FAO/WHO (1986)  Codex Maximum Limits for pesticide residues. Codex
    Alimentarius Commission, CAC/Vol. XIII., Supplement 1 & 2, 3rd ed.
    Rome, Food and Agriculture Organization of the United Nations.

    FAO/WHO (1989)  Guide to Codex recommendations concerning pesticide
     residues. Part 8. Recommendations for methods of analysis of
     pesticide residues. 4th ed. Rome, Codex Committee on Pesticide
    Residues.

    GIFAP (1982)  Guidelines for the safe handling of pesticides during
     their formulation, packaging, storage and transport. Brussels,
    Groupement International des Associations Nationales des Fabricants
    de Produits Agrochimiques.

    GIFAP (1983)  Guidelines for the safe and effective use of
     pesticides. Brussels, Groupement International des Associations
    Nationales des Fabricants de Produits Agrochimiques.

    GIFAP (1984)  Guidelines for emergency measures in cases of
     pesticides poisoning. Brussels, Groupement International des
    Associations Nationales des Fabricants de Produits Agrochimiques.

    GIFAP (1987)  Guidelines for the safe transport of pesticides.
    Brussels, Groupement International des Associations Nationales des
    Fabricants de Produits Agrochimiques.

    HAYES, W.J., Jr & LAWS, E.R., Jr. (1991)  Handbook of pesticide
     toxicology. 3 vol. New York, Academic Press.

    IARC (1972-present)  IARC monographs on the evaluation of
     carcinogenic risk of chemicals to man. Lyon, International Agency
    for Research on Cancer.

    ILO (1991)  Safety and health in the use of agro-chemicals - a
     guide. Geneva, International Labour Office.

    IRPTC (1985)  IRPTC file on treatment and disposal methods for waste
     chemicals. Geneva, International Register of Potentially Toxic
    Chemicals, United Nations Environment Programme.

    IRPTC (1987)  IRPTC legal file 1986. Geneva, International Register
    of Potentially Toxic Chemicals, United Nations Environment
    Programme.

    PLESTINA, R. (1984)  Prevention, diagnosis, and treatment of
     insecticide poisoning. Geneva, World Health Organization
    (Unpublished WHO document VBC/84.889).

    SAX, N.I. (1984)  Dangerous properties of industrial materials. New
    York, van Nostrand Reinhold Company, Inc.

    UNEP/IEO (1990)  Storage of hazardous materials: a technical guide
     for safe warehousing of hazardous materials. Paris, United Nations
    Environment Programme, Industry and Environment Office, 80 pp.

    UNITED NATIONS (1989)  Recommendations on the transport of dangerous
     goods. 6th ed. New York, United Nations.

    UNITED NATIONS (1991)  Consolidated list of products whose
     consumption and/or sale have been banned, withdrawn, severely
     restricted or not approved by Governments. 4th ed. New York,
    United Nations.

    US NIOSH/OSHA (1981)  Occupational health guidelines for chemical
     hazards. 3 vol. Washington DC, US Department of Health and Human
    Services, US Department of Labor (Publication No. DHHS(NIOSH)
    01-123).

    WHO (1986)  Environmental Health Criteria 63: Organophosphorus
     insecticides - a general introduction. Geneva, World Health
    Organization, 181 pp.

    WHO (1992)  The WHO recommended classification of pesticides by
     hazard and guidelines to classification, 1992-93. Geneva, World
    Health Organization (Unpublished document WHO/PCS/92.14).

    WORTHING, C.R. & HANCE, R.J. (1991)  The pesticide manual. 9th ed.
    Unwin Brothers, Ltd., Old Woking, Surrey, UK.

    ANNEX

    TREATMENT OF ORGANOPHOSPHATE INSECTICIDE POISONING IN MAN1

    All cases of organophosphorus poisoning should be dealt with as an
    emergency and the patient sent to hospital as quickly as possible.
    Although symptoms may develop rapidly, delay in onset or a steady
    increase in severity may be seen up to 48 h after ingestion of some
    formulated organophosphorus insecticides.

    Extensive descriptions of treatment of poisoning by organophosphorus
    insecticides are given in several major references (Kagan, 1977;
    Taylor, 1980; UK DHSS, 1983; Plestina, 1984) and will also be
    included in the IPCS Health and Safety Guides to be prepared for
    selected organophosphorus insecticides.

    The treatment is based on:

    (a) minimizing the absorption;
    (b) general supportive treatment; and
    (c) specific pharmacological treatment.

    A.1  Minimizing the absorption

    When dermal exposure occurs, decontamination procedures include
    removal of contaminated clothes and washing of the skin with
    alkaline soap or with a sodium bicarbonate solution. Particular care
    should be taken in cleaning the skin area where venepuncture is
    performed. Blood might be contaminated with direct-acting
    organophosphorus esters and, therefore, inaccurate measures of ChE
    inhibition might result. Extensive eye irrigation with water or
    saline should also be performed. In the case of ingestion, vomiting
    might be induced, if the patient is conscious, by the administration
    of ipecacuanha syrup (10-30 ml) followed by 200 ml water. 

    This treatment is, however, contraindicated in the case of
    pesticides dissolved in hydrocarbon solvents. Gastric lavage (with
    addition of bicarbonate solution or activated charcoal) can also be
    performed, particularly in unconscious patients, taking care to
    prevent aspiration of fluids into the lungs (i.e., only after a
    tracheal tube has been put into place).

    The volume of fluid introduced into the stomach should be recorded
    and samples of gastric lavage frozen and stored for subsequent
    chemical analysis. If the formulation of the pesticide involved is
    available, it should also be stored for further analysis (i.e.,
    detection of toxicologically relevant impurities). A purgative can
    be administered to remove the ingested compound.

              

    1  From EHC 63:  Organophosphorus insecticides - a general
     introduction. Geneva, World Heralth Organization, 1986.

    A.2  General supportive treatment

    Artificial respiration (via a tracheal tube) should be started at
    the first sign of respiratory failure and maintained for as long as
    necessary.

    Cautious administration of fluids is advised, as well as general
    supportive and symptomatic pharmacological treatment and absolute
    rest.

    A.3  Specific pharmacological treatment

    A.3.1  Atropine

    Atropine should be given, beginning with 2 mg iv and given at
    15-30-min intervals. The dose and the frequency of atropine
    treatment varies from case to case, but should maintain the patient
    fully atropinized (dilated pupils, dry mouth, skin flushing, etc.).
    Continuous infusion of atropine may be necessary in extreme cases
    and total daily doses up to several hundred mg may be necessary
    during the first few days of treatment.

    A.3.2  Oxime reactivators

    Cholinesterase reactivators (e.g., pralidoxime, obidoxime)
    specifically restore AChE activity inhibited by organophosphates.
    This is not the case with enzymes inhibited by carbamates. The
    treatment should begin as soon as possible, because oximes are not
    effective on "aged" phosphorylated ChEs. However, if absorption,
    distribution, and metabolism are thought to be delayed for any
    reasons, oximes can be administered for several days after
    intoxication. Effective treatment with oximes reduces the required
    dose of atropine. Pralidoxime is the most widely available oxime. A
    dose of 1 g pralidoxime can be given either im or iv and repeated
    2-3 times per day or, in extreme cases, more often. If possible,
    blood samples should be taken for AChE determinations before and
    during treatment. Skin should be carefully cleansed before sampling.
    Results of the assays should influence the decision whether to
    continue oxime therapy after the first 2 days.

    There are indications that oxime therapy may possibly have
    beneficial effects on CNS-derived symptoms.

    A.3.3  Diazepam

    Diazepam should be included in the therapy of all but the mildest
    cases. Besides relieving anxiety, it appears to counteract some
    aspects of CNS-derived symptoms that are not affected by atropine.
    Doses of 10 mg sc or iv are appropriate and may be repeated as
    required (Vale & Scott, 1974). Other centrally acting drugs and

    drugs that may depress respiration are not recommended in the
    absence of artificial respiration procedures.

    A.3.4  Notes on the recommended treatment

    A.3.4.1  Effects of atropine and oxime

    The combined effect far exceeds the benefit of either drug singly.

    A.3.4.2  Response to atropine

    The response of the eye pupil may be unreliable in cases of
    organophosphorus poisoning. A flushed skin and drying of secretions
    are the best guide to the effectiveness of atropinization. Although
    repeated dosing may well be necessary, excessive doses at any one
    time may cause toxic side-effects. Pulse-rate should not exceed
    120/min.

    A.3.4.3  Persistence of treatment

    Some organophosphorus pesticides are very lipophilic and may be
    taken into, and then released from, fat depots over a period of many
    days. It is therefore quite incorrect to abandon oxime treatment
    after 1-2 days on the supposition that all inhibited enzyme will be
    aged. Ecobichon et al. (1977) noted prompt improvement in both
    condition and blood-ChEs in response to pralidoxime given on the
    11th-15th days after major symptoms of poisoning appeared due to
    extended exposure to fenitrothion (a dimethyl phosphate with a short
    half-life for aging of inhibited AChE).

    A.3.4.4  Dosage of atropine and oxime

    The recommended doses above pertain to exposures, usually for an
    occupational setting, but, in the case of very severe exposure or
    massive ingestion (accidental or deliberate), the therapeutic doses
    may be extended considerably. Warriner et al. (1977) reported the
    case of a patient who drank a large quantity of dicrotophos, in
    error, while drunk. Therapeutic dosages were progressively increased
    up to 6 mg atropine iv every 15 min together with continuous iv
    infusion of pralidoxime chloride at 0.5 g/h for 72 h, from days 3 to
    6 after intoxication. After considerable improvement, the patient
    relapsed and further aggressive therapy was given at a declining
    rate from days 10 to 16 (atropine) and to day 23 (oxime),
    respectively. In total, 92 g of pralidoxime chloride and 3912 mg of
    atropine were given and the patient was discharged on the
    thirty-third day with no apparent sequelae.

    References to Annex

    ECOBICHON, D.J., OZERE, R.L., REID, E., & CROCKER, J.F.S (1977)
    Acute fenitrothion poisoning.  Can. Med. Assoc. J., 116: 377-379.

    KAGAN, JU.S. (1977)  [Toxicology of organophosphorus pesticides],
    Moscow, Meditsina, pp. 111-121, 219-233, 260-269 (in Russian).

    PLESTINA, R. (1984)  Prevention, diagnosis, and treatment of
     insecticide poisoning. Geneva, World Health Organization
    (Unpublished document VBC/84.889).

    TAYLOR, P. (1980) Anticholinesterase agents. In: Goodman, L.S. &
    Gilman, A., ed.  The pharmacological basis of therapeutics. 6th
    ed., New York, Macmillan Publishing Company, pp. 100-119.

    UK DHSS (1983)  Pesticide poisoning: notes for the guidance of
     medical practitioners. London, United Kingdom Department of Health
    and Social Security, pp. 41-47.

    VALE, J.A. & SCOTT, G.W. (1974) Organophosphorus poisoning.  Guy's
     Hosp. Rep., 123: 13-25.

    WARRINER, R.A., III, NIES, A.S., & HAYES, W.J., Jr (1977) Severe
    organophosphate poisoning complicated by alcohol and terpentine
    ingestion.  Arch. environ. Health, 32: 203-205.


    See Also:
       Toxicological Abbreviations
       Monocrotophos (ICSC)
       Monocrotophos (WHO Pesticide Residues Series 2)
       Monocrotophos (WHO Pesticide Residues Series 5)
       Monocrotophos (Pesticide residues in food: 1991 evaluations Part II Toxicology)
       Monocrotophos (Pesticide residues in food: 1993 evaluations Part II Toxicology)
       Monocrotophos (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental)