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    IPCS INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
    Health and Safety Guide No. 79

    METHAMIDOPHOS
    HEALTH AND SAFETY GUIDE






    UNITED NATIONS INTERNATIONAL

    ENVIRONMENT PROGRAMME 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

    Methamidophos: health and safety guide.

    (Health and safety guide ; no. 79)

    1.Hazardous substances - standards
    2.Insecticides, Organothiophosphate - standards
    3.Insecticides, Organothiophosphate - toxicity  I.Series

    ISBN 92 4 151079 X          (NLM Classification: WA 240)
    ISSN 0259-7268

    The World Health Organization welcomes requests for permission to
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    (c) World Health Organization 1993

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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. Kinetics and metabolism
         2.3. Effects on experimental animals and in vitro test systems
         2.4. Effects on humans
         2.5. 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 poisoning14
                     4.1.1.2  Medical treatment14
              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 insecticide 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

    THE INFORMATION IN THIS GUIDE SHOULD BE CONSIDERED AS A STARTING POINT
    TO A COMPREHENSIVE HEALTH AND SAFETY PROGRAMME

    1.  PRODUCT IDENTITY AND USES

    1.1  Identity

    Chemical structure:
                                 O
                                 "
                             CH3OPSCH3
                                 '
                                 NH2

    Molecular formula:       C2H8O2NPS

    Common names:            Methamidophos, (BSI, E-ISO, F-ISO, ANSI)

    IUPAC name:               O,S,-dimethyl phosphoramidothioate

    CAS chemical name:        O,S,-dimethyl phosphoramidothioate

    Trade names:             Monitor(R), Tamaron(R), Nitosol(R)

    CAS registry number:     10265-92-6

    RTECS registry number:   TB4970000

    1.2  Physical and chemical properties

    Pure methamidophos is a colourless crystalline solid with a melting
    point of 44.5 C.  Technical methamidophos, which is about 73% pure,
    is in the form of yellowish to colourless crystals.  Some physical
    properties are given in Table 1.

    Table 1.  Physical properties of methamidophos

                                                                         

    Relative molecular mass                141.1
    Melting point (C)                     44.5 (pure)
                                           37-39 (technical)
    Boiling point (C)                     thermally unstable
    Vapour pressure (30 C)                40 mPa
    Solubility in water (kg/litre)         2
    Density (20 C)                        1.31
    Half-life in aqueous solution
      at pH 2.0 (40 C)                    140 h
      at pH 9 (37 C)                      120 h

                                                                         

    Methamidophos, which is readily soluble in water (>2 kg/litre),
    alcohols, ketones, and aliphatic chlorinated hydrocarbons, is
    sparingly soluble in ether and practically insoluble in petroleum
    ether. This insecticide is stable at ambient temperatures. 
    Methamidophos decomposes before its boiling point is reached.

    Technical methamidophos and concentrated formulated products are
    corrosive to mild steel and copper-containing alloys.  This
    insecticide is not compatible with alkaline pesticides.

    1.3  Analytical methods

    The active ingredient contents of the formulated products are
    determined using infrared spectrometry or high-pressure liquid
    chromatography.  Residues can be determined by gas-liquid
    chromatography using a flame ionization detector or a flame thermionic
    detector after clean-up in silica gel columns.

    Recommendations for methods of determination of methamidophos residues
    have been made by the Codex Alimentarius Commission (FAO/WHO, 1989).

    1.4  Uses

    Methamidophos is an acaricide-insecticide with systemic properties. 
    It has been shown to be effective against a broad range of insect
    pests (sucking, biting, and mining insects) on such crops as brassica,
    cotton, tobacco, sugar beet, head lettuce, and potatoes.  It is used
    as a preharvest spray at 0.5-1.5 kg/ha.  At these rates, control is
    obtained for 7-21 days.

    Methamidophos is marketed mainly as the water-soluble concentrate in
    various concentrations.

    2.  SUMMARY AND EVALUATION

    The following information is largely based on the evaluations of the
    Joint FAO/WHO Meeting on Pesticide Residues (JMPR).

    2.1  Exposure

    The general population is not generally exposed to methamidophos in
    air or water.  Use of methamidophos in edible commodities may result
    in low-level residues in some that reach the market place.  If the
    recommended preharvest intervals are observed, there should not be any
    health hazards.  The use of the related insecticide, acephate, may
    give rise to methamidophos as a residue.

    Degradation of methamidophos in soils and natural waters has been
    found to be fairly rapid.  The final degradation product is usually
    phosphoric acid.  The same has been observed when methamidophos is
    applied to crops.

    Occupational exposure to methamidophos, which may occur during
    manufacturing, formulation, application, and storage, is mainly
    through inhalation and dermal absorption.  Higher occupational
    exposures may occur in the case of accidents or as a result of
    incorrect handling.  With correct usage, there should not be any
    exposure to hazardous amounts.

    2.2  Kinetics and metabolism

    Methamidophos, an anticholinesterase organophosphorus ester, is also a
    metabolite of acephate.  It is rapidly absorbed, distributed,
    metabolized, and excreted in mammals.  Excretion is mainly via the
    urine in the form of acid metabolites and through expired air as
    carbon dioxide.

    On the basis of data on the solubility of methamidophos,
    bioaccumulation would not be expected to occur.  Biotransformation in
    mammals results in the formation of metabolites that are
    toxicologically insignificant.

    2.3  Effects on experimental animals and in vitro test systems

    Methamidophos is an acutely toxic pesticide with an acute oral LD50
    of 15-30 mg/kg in the male rat, 30 mg/kg in the mouse, 30-50 mg/kg in
    the guinea-pig, and 10-30 mg/kg in the rabbit.  The acute dermal
    LD50 in the male rat is 50-110 mg/kg.  The inhalation LC50 in the
    male rat is 525 mg/m3 for a 1-h exposure and 162 mg/m3 for a 4-h
    exposure.

    Animals poisoned with methamidophos show typical signs of
    anticholinesterase poisoning.  The signs appear rapidly (5-20 min) and
    disappear in 4-6 days.  The acute signs of poisoning can be relieved
    with the aid of atropine and reactivators, such as 2-PAM. 
    Methamidophos exerts its primary effects on the red blood cell (and
    presumably brain) cholinesterase in animal models.  In humans, plasma
    cholinesterase appears to be the more sensitive enzyme parameter.

    Moderate erythema and oedema were observed in skin tests on the rabbit
    ear.  The chemical is also irritating to the eye.

    In short- and long-term studies, no significant somatic effects were
    noted.  Cholinesterase depression was manifested in short-term
    studies.  In 90-day  studies on dogs, cholinesterase depression was
    observed at 5 mg/kg while a dietary level of 1.5 mg/kg (equivalent to
    0.04 mg/kg body weight per day) did not cause any observable effects. 
    In a 2-year study on dogs, somatic effects were not noted at a level
    of 0.75 mg/kg per day, but cholinesterase activity was not determined. 
    Depression of cholinesterase activity was observed in rat feeding
    studies at dietary levels of 6 mg/kg or more, but a level of 2 mg/kg
    did not induce any depression of cholinesterase activity. Maximum
    tolerated doses in hens failed to cause delayed neuropathy.

    In reproductive studies, several parameters were affected at
    relatively low levels (the levels were, however, sufficient to cause
    cholinesterase depression in the parents).  No terata were induced in
    the reproductive study or in special teratological studies on rabbits,
    though the dose levels used in the latter studies were extremely low.

    Methamidophos was found to be non-mutagenic in bacterial and  in vivo
    assays.  There were no indications of oncogenicity in a mouse
    oncogenicity study or in a long-term toxicity/oncogenicity study on
    rats.

    The following levels have been found not to cause any toxicological
    effect (FAO/WHO, 1990):

          Rat          2 mg/kg in the diet, equal to 0.1 mg/kg 
                       body weight per day

          Dog          2 mg/kg in the diet equal to 0.06 mg/kg 
                       body weight per day)

          Chicken      0.3 mg/kg body weight per day

          Human        0.04 mg/kg body weight per day

    2.4  Effects on humans

    Several cases of methamidophos poisoning in humans have been reported. 
    In a controlled study in which a combined dose of methamidophos and
    acephate was administered to groups of male and female volunteers,
    cholinesterase depression was observed predominantly in those
    receiving a higher methamidophos: acephate ratio (1:4 rather than
    1:9).  A higher total concentration (0.2 mg/kg), administered at the
    lower ratio (1:9), did not result in any depression of enzyme
    activity.

    Excessive human exposure (among others, Senanayake & Johnson, 1982) to
    methamidophos caused delayed polyneuropathy.

    2.5  Effects on the environment

    In mildly acidic or neutral aqueous solutions, methamidophos is stable
    at temperatures up to 80 C. Methamidophos is degraded in outdoor
    natural water systems with half-lives of 15.9 days in water and 7.5
    days in silt.  Although methamidophos was leached from soils, it also
    degraded rapidly in natural water systems.

    It is degraded relatively rapidly in soils.  Within 1 week, the
    residue dropped to 10% of the level measured on the day of
    application.  Furthermore, there was no accumulation of the
    insecticide, even after several applications.

    Methamidophos is moderately toxic for fish as evidenced by 96-h
    LC50s of 25 mg/litre for rainbow trout  (Oncorhynchus mykiss), and
    approximately 100 mg/litre for goldfish  (Carassius auratus) and carp
     (Cyprinus carpio).  The LD50s for the mallard duck  (Anas
     platyrhynchos), Japanese quail  (Coturnix coturnix Japonica), and
    the hen  (Gallus domesticus) are 29.5, 10, and 25 mg/kg,
    respectively.  This insecticide can also be harmful to bees.

    3.  CONCLUSIONS AND RECOMMENDATIONS

    3.1  Conclusions

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

    *     Methamidophos is highly toxic, but, using appropriate safety
          precautions, exposure to methamidophos during manufacture,
          formulation, application, and disposal should not pose an
          unacceptable human health hazard.

    *     Methamidophos is rapidly degraded to non-toxic products in the
          environment. However, care should be taken not to expose aquatic
          invertebrates, bees, birds, fish, and wild mammals to this
          insecticide.

    3.2  Recommendations

    *     Safe re-entry periods under different conditions of use should
          be determined.

    *     Effluent water from formulation plants should be treated.

    *     Methamidophos 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

    The acute oral and dermal toxicities of methamidophos are high and it
    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 methamidophos, 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 reproduced as an Annex to this Guide.

    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 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 pralidoxime chloride or 250 mg 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 methamidophos and other
    organophosphorus insecticides, it is essential to maintain general
    surveillance and cholinesterase 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 No.
    63:  Organophosphorus insecticides - a general introduction (WHO,
    1986) and also the Annex to this Guide.

    4.1.2  Health surveillance advice

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


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

                                                                                                                                         

    HAZARDS/SYMPTOMS                            PREVENTION AND PROTECTION                FIRST AID
                                                                                                                                         

    GENERAL: Readily absorbed via skin,
    ingestion, and inhalation; may cause
    organophosphate poisoning: weakness,
    headache, vomiting, excessive sweating
    and salivation, pinpoint pupils; in
    severe cases: convulsions, 
    unconsciousness, and death due to
    respiratory paralysis

    SKIN: Irritation; redness; extensive        Wear PVC or neoprene gloves and          Remove and wash contaminated
    contamination may cause poisoning           apron; rubber boots                      clothing; wash contaminated skin
                                                                                         with water and soap; obtain medical
                                                                                         attention immediately

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

    INHALATION: Overexposure may                Avoid breathing the vapour; use          In case of signs and symptoms, remove
    cause poisoning                             proper (exhaust) ventilation or a        from contaminated area and obtain
                                                respirator or mask approved for toxic    medical attention immediately
                                                dust and organic vapours

    INGESTION: An unlikely occupational         Wash hands before eating, drinking,      -
    hazard                                      using the toilet, and after work

    Accidental or intentional ingestion         -                                        Obtain medical attention immediately;
    may rapidly lead to severe poisoning                                                 induce vomiting, if subject is consciousa;
                                                                                         if breathing has stopped, apply
                                                                                         artificial respiration

                                                                                                                                         

    HAZARDS/SYMPTOMS                            PREVENTION AND PROTECTION                FIRST AID
                                                                                                                                         

    REPEATED EXPOSURE THROUGH                   As above                                 As above
    INHALATION OR INGESTION, OR 
    THROUGH SKIN: may gradually lead
    to signs and symptoms of inhibition of
    cholinesterase activity

                                                                                                                                         

    a Caution: If methamidophos 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, methamidophos 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 methamidophos 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 the container is tightly
    closed and labelled before transfer to a safe place for disposal.

    Spills and 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 a 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 re-use 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

    As it is readily degraded, methamidophos is non-persistent in the
    environment.  Under normal conditions of usage, it will not
    accumulate.  However, it is toxic for aquatic invertebrates, birds,
    bees, fish, and wild mammals.

    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

    Methamidophos was evaluated by the Joint FAO/WHO Meeting on Pesticide
    Residues (JMPR) in 1976, 1982, 1985, and 1990.  An acceptable daily
    intake (ADI) for man of 0-0.004 mg/kg body weight was estimated in
    1990.

    In the  WHO recommended classification of pesticides by hazard and
     guidelines to classification, 1992-93 (WHO 1992), technical
    methamidophos is classified as highly hazardous (Class 1b), when
    handled in accordance with instructions.

    The FAO/WHO Codex Alimentarius Commission (FAO/WHO, 1986, 1989, 1990)
    recommended Maximum  Residue Limits (MRLs) in several food
    commodities, ranging from 0.01 to 5 mg/kg as follows:

         Commodity                                   MRL (mg/kg)

         Carcass meat and fat of cattle,
           goats and sheep, milk, tree tomato        0.01a
         Soya bean (dry), sugar beet                 0.05
         Rapeseed                                    0.1
         Brussels sprouts, cucumber, lettuce
           (head), sugar beet (leaves or tops)       1
         Alfalfa forage (green)                      2
         Hops (dry)                                  5

              

    a Approximate limit of determination.

    6.2  Exposure limit values

    Pre-harvest intervals (the time between the last application of
    methamidophos and the harvest of the treated plants) have been set in
    many countries.  These intervals vary from 3 to 90 days (most of them
    14-21 days), depending on the crop, harvesting technique, and the
    country, and should be verified with the competent national authority.

    The FAO/WHO Maximum Residue Limits (MRLs) for methamidophos are shown
    in section 6.1.

    The MRL in fruits and vegetables in Finland is 0.2 mg/kg.

    6.3  Specific restrictions

    Methamidophos is approved as a pesticide in many countries.  Specific
    uses, limitations, and precautions are listed in national regulatory
    documents.  In the USA, methamidophos is classified for restricted
    use, and its preparations may only be handled by certified operators.

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

    6.4  Labelling, packaging, and transport

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

    -  Hazard Class 6.1:     poisonous substance;

    -  Packing Group 2:      substances and preparations presenting a
                             serious risk of poisoning, for formulations
                             containing 15-100% active material;

    -  Packing Group 3:      harmful substances and preparations
                             presenting a relatively low risk of
                             poisoning, for solid formulations containing
                             3-15% active material and liquid formulations
                             containing 1.5-15% active material.

    The label should be as follows:

    FIGURE 1

    FIGURE 2

    In the International Maritime Dangerous Goods (IMDG) Code,
    methamidophos 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 methamidophos, as the material is
    not used in public health. However, proposals for FAO specifications
    for methamidophos are under preparation.  These include the following:

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

         -    manufacturer's name;
         -    technical methamidophos 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;
         -    methamidophos to specification;
         -    methamidophos ... 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:

          Methamidophos 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 methamidophos content should be declared (minimum 73% for the
    technical products) and should not differ from the declared percentage
    by more than 2% for the technical product 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.

    Containers 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 Economic Community legislation on the labelling of
    pesticide preparations classifies pesticide preparations that contain
    methamidophos in 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 methamidophos 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 & 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.

    FAO/WHO (1990)  Pesticide residues in food - 1990. Report of the
    Joint Meeting of the FAO Panel of Experts on Pesticide Residues in
    Food and the Environment and a WHO Expert Group on Pesticide Residues.
    Rome, Food and Agriculture Organization of the United Nations (FAO
    Plant Production and Protection Paper 102).

    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 document VBC/84.889).

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

    SENANAYAKE, N. & JOHNSON, M.K.  (1982)   Acute polyneuropathy
     following poisoning by a new organophosphate insecticide: A
     preliminary report. New Eng. J. Med., 306: 155-157.

    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.
    Old Woking, Surrey, England, Unwin Brothers, Ltd..

    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).


              

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

    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.

    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
       Methamidophos (ICSC)
       Methamidophos (JMPR Evaluations 2002 Part II Toxicological)
       Methamidophos (Pesticide residues in food: 1976 evaluations)
       Methamidophos (Pesticide residues in food: 1979 evaluations)
       Methamidophos (Pesticide residues in food: 1981 evaluations)
       Methamidophos (Pesticide residues in food: 1982 evaluations)
       Methamidophos (Pesticide residues in food: 1984 evaluations)
       Methamidophos (Pesticide residues in food: 1985 evaluations Part II Toxicology)
       Methamidophos (Pesticide residues in food: 1990 evaluations Toxicology)