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    WORLD HEALTH ORGANIZATION             FOOD AND AGRICULTURE
                                          ORGANIZATION
    ORGANISATION MONDIALE DE LA SANTE     ORGANISATION POUR L'ALIMENTATION
                                          ET L'AGRICULTURE

                                                      VBC/DS/78.33

                                                      ORIGINAL: ENGLISH






    DATA SHEETS ON PESTICIDES No. 33

    CHLORPYRIFOS-METHYL






         It must be noted that the issue of a Data Sheet for a
    particular pesticide does not imply endorsement of the pesticide by
    WHO or FAO for any particular use, or exclude its use for other
    purposes not stated. While the information provided is believed to
    be accurate according to data available at the time when the sheet
    was compiled, neither WHO nor FAO are responsible for any errors or
    omissions, or any consequences therefrom.

    The issue of this document does    Ce document ne constitue pas une
    not constitute formal              publication. Il ne doit faire
    publication. It should not be      l'objet d'aucun compte rendu ou
    reviewed, abstracted or quoted     résumé ni d'aucune citation sans
    without the agreement of the       l'autorisation de l'Organisation
    Food  and Agriculture              des Nations Unies pour
    Organization of the United         l'Alimentation et l'Agriculture
    Nations or of the World Health     ou de l'Organisation Mondiale de
    Organization.                      la Santé.

                             CLASSIFICATION:

                             Primary Use: Insecticide

                             Secondary Use:

                             Chemical Group: Organophosphorus compound

                             Date issued:

    1.  GENERAL INFORMATION

    1.1  COMMON NAME:

    Chlorpyrifos-methyl

    1.1.1  Identity:

    O,O-dimethyl O-(3,5,6-trichloro-2-pyridinyl) phosphorothioate

    CHEMICAL STRUCTURE

    1.1.2  Synonyms:

    DOWCO 214
    ENT 27520
    OMS-1155
    Reldan
    Zertell

    Local synonyms:

    1.2  SYNOPSIS

    An organophosphorus insecticide of low mammalian toxicity.

    1.3  SELECTED PROPERTIES

    1.3.1  Physical characteristics

    White crystalline solid with a mild mercaptan odour melting point
    45.5-46.5°C.

    1.3.2  Solubility

    Poorly soluble in water (4 mg/l). Moderately soluble in hexane and
    alcohols, and readily soluble in other organic solvents such as
    acetone, benzene and chloroform.

    1.3.3  Stability

    Stable under normal storage conditions. Half-life in water at pH 8
    is less than nine days at 25°C and three days at 35°C. It is
    hydrolysed more rapidly at higher pH. Undergoes rapid
    photodecomposition in UV light.

    1.3.4  Vapour pressure

    (volatility) - 4.2 x 10-5 mm Hg at 25°C, 1.8 x 10-4 mm Hg at
    35°C.

    1.4  AGRICULTURE, HORTICULTURE AND FORESTRY

    1.4.1  Common formulations

    25% emulsifiable concentrate: 25% wettable powder: granules 3%, 5%
    and 10%: dusts 3%; microfine granules 3%.

    1.4.2  Pests mainly controlled

    Effective against rice stem borer, aphids, cutworms, plant and leaf
    hoppers, mole crickets and some moths; stored grain pests.

    1.4.3  Use pattern

    Up to four applications per season depending on formulation and pest
    on rice, cotton, tobacco and on vegetables up to 2 kg a.i./ha.

    1.4.4  Unintended effects

    Not phytotoxic at recommended rates.

    1.5  PUBLIC HEALTH PROGRAMMES:

    Considered as a larvicide for onchocerciasis control and as a
    general mosquito larvicide for outdoor surface water that is liable
    to be used for human and animal consumption.

    1.6  HOUSEHOLD USE:

    Not used at present.

    2.  TOXICOLOGY AND RISKS

    2.1  TOXICOLOGY - MAMMALS

    2.1.1  Absorption route

    Absorbed from the gastrointestinal tract and to a lesser extent
    through intact skin.

    2.1.2  Mode of action

    Cholinesterase inhibition.

    2.1.3  Excretion

    Principal excretory route for unchanged chlorpyrifos-methyl is by
    way of faeces. The metabolite, 3,5,6-trichloro-2-pyridinol is
    excreted mainly in the urine as its glucoronide conjugate.

    2.1.4  Toxicity, single dose

    Oral: LD50 rat (M) about 2000 mg/kg
                   (F) about 3000 mg/kg
             mouse (M) greater than 1000 mg/kg
        guinea pig (M) 2250 mg/kg

    Dermal: LD50 rabbits > 2000 mg/kg
                 rats (M,F) > 3700 mg/kg

    Most susceptible species: No appreciable species variation.

    2.1.5  Toxicity, repeated doses

    Oral: Rat - 14 daily doses of 20, 100 and 500 mg/kg body weight by
    gavage produced no mortality. At 500 mg/kg/day a slight body weight
    decrease, some hypertrophy of the liver and a tendency for cardiac
    hypertrophy occurred. In another study, rats were dosed 0.2, 1.0 or
    5.0 mg/kg daily for six weeks. Only effect at the highest dose level
    was a trend for reduced erythrocyte cholinesterase activity. The
    no-effect level for plasma and erythrocyte cholinesterase activity
    was 1.0 mg/kg/day.

    Mouse - 14 daily doses of 150, 250, 500 and 1000 mg/kg/day: at
    1000 mg/kg all mice were dead after four doses; at 500 mg/kg, 40%
    mortality occurred in 14 days and there was a noticeable decrease in
    body weight of survivors. No mortality or significant changes in
    body weight were seen at lower doses.

    Rhesus monkeys - were dosed orally daily with either 1.0 or
    5.0 mg/kg for six months. No reduction of brain cholinesterase or
    changes in many parameters studied were seen. A no-effect level for
    plasma and erythrocyte cholinesterase activity was estimated as
    0.2 mg/kg.

    Cumulation of compound: Metabolized rapidly - not cumulative.

    Cumulation of effect: Repeated exposure may produce a cumulative
    inhibitory effect on cholinesterase.

    2.1.6  Dietary studies

    Short-term: Female rats were fed dietary concentrations between 20
    and 20 000 mg/kg equivalent to 1.6-2.130 mg/kg/day for 14 days. Two
    out of six rats died and significant loss in body weight of the
    survivors occurred at the highest dose level. Cholinesterase
    activity in plasma erythrocyte was significantly reduced at 80 mg/kg
    and in brain at 1250 mg/kg. The no-effect level based on
    cholinesterase inhibition was between 80 and 20 mg/kg diet.

    Rats - both sexes were fed at doses from 0.08 to 160 mg/kg/day for
    90 days. The no-effect level based on plasma cholinesterase activity
    was between 8 and 0.8 mg/kg/day, in males and between 0.8 and 0.08
    mg/kg/day in females. The no-effect level based on brain
    cholinesterase activity was between 40 and 8 mg/kg/day. There was no
    significant differences in frequency and rates of lesions between
    treated and untreated in the main tissues tested.

    Rats - both sexes were fed at levels from 0.5 to 100 mg/kg diet
    for six months. Plasma and erythrocyte cholinesterase activity of
    the groups given more than 20 mg/kg diet showed statistically
    significant decreases after one, three and six months of dosing. The
    maximum no-effect level using plasma and erythrocyte cholinesterase
    activity as the index, was 10 mg/kg diet.

    Mice - both sexes were fed the 5-100 mg/kg diet for six months.
    Using cholinesterase activity as the index the maximum no-effect
    level corresponded to 5 mg/kg diet.

    Dogs were fed from 0.3 to 10 mg/kg diet for 92 days. Brain
    cholinesterase was not depressed even at highest level. However,
    plasma cholinesterase was significantly depressed at all levels
    after 1, 4 and 12 weeks' treatment.

    Cows were fed silage corn previously treated with
    chlorpyrifos-methyl equivalent to a dietary residue intake of up to
    0.054 mg of chlorpyrifos-methyl and 0.01 mg of the pyridinol
    respectively. No effect was found on food intake, milk production or
    blood cholinesterase activity.

    Dietary studies

    Long-term: Rats were fed at levels from 0.03 mg/kg/day, in the
    diet for two years. Rats receiving 3 mg/kg/day showed depression of
    erythrocyte and plasma cholinesterase levels. No-effect level was
    0.1 mg/kg/day.

    Dogs - were fed from 0.03 to 3.0 mg/kg/day for a period of two
    years. Brain cholinesterase levels were not affected but the mean
    level of plasma cholinesterase as a percentage of the mean control
    level was 63 at 3 mg/kg/day. The no-effect level in dogs is
    0.01 mg/kg/day and even at 1 mg/kg/day there was only a slight
    decrease in plasma cholinesterase levels.

    2.1.7  Supplementary studies of toxicity

    Carcinogenicity: Rats were fed 0.1 and 1.0 mg/kg/day for two
    years. No spontaneous rumour incidence observed and it was concluded
    that chlorpyrifos-methyl is not carcinogenic.

    Teratogenicity: Rats were fed dose levels of 50, 100 and
    200 mg/kg/day on days 6-15 of gestation. No teratogenic effects were
    observed. A study on mice with doses up to 250 mg/kg/day for seven
    days on days 7-13 of gestation showed effects at highest dose level
    associated with decreased weight growth or maturation of the mouse.

    Neurotoxicity: Hens surviving an oral dose of 4455 mg
    chlorpyrifos-methyl/kg were given both atropine, 10 mg/kg and PAM,
    50 mg/kg intramuscularly as well as a second oral dose of 4555 mg
    chlorpyrifos-methyl/kg on the twenty-first day after first dose. The
    birds were held for a further 21 days during which no clinical signs
    of ataxia were observed.

    Reproduction: Prolonged dietary administration of
    chlorpyrifos-methyl at levels of 1 or 3 mg/kg/day had no adverse
    effect on the reproduction capacity of either male or female rat.

    2.1.8  Modification of toxicity

    No information

    2.2  TOXICOLOGY - MAN

    2.2.1  Absorption

    Ingestion is likely to be the only significant route of absorption.

    2.2.2  Dangerous doses

    Single: Not known.

    Repeated: Not known.

    2.2.3  Observations on occupationally exposed workers

    No information available.

    2.2.4  Observations on exposure of the general population

    No information available.

    2.2.5  Observation of volunteers

    Human - 28 single daily doses were administered to two groups of
    five adult males each at either 0.1 or 0.03 mg/kg/day. These
    treatments were without effect and produced no measurable
    cholinesterase changes.

    Chlorpyrifos-methyl was given orally three times a day to three male
    and three female humans at either 0.1 or 0.3 mg/kg/day. At a dose
    rate of 0.3 mg/kg/day for 14 days there was no effect on erythrocyte
    cholinesterase activity but plasma cholinesterase depression greater
    than two standard deviations below the mean pretreatment level was
    noted. At the dose rate of 0.1 mg/kg for 21 days there was no change
    in plasma or erythrocyte cholinesterase activity. There were no
    other changes or adverse clinical symptoms at any dose level.

    2.2.6  Reported mishaps

    No information.

    2.3  TOXICITY TO NON-MAMMALIAN SPECIES

    2.3.1  Fish - Toxic to shrimps, crabs and fish.

    2.3.2  Birds

    Chicken LD50 > 2000 mg/kg
    Bob white quail LD50 1835 mg/kg in diet
    Japanese quail LC50 > 5000 mg/kg in diet
    Mallard duck LC50 2500-5000 mg/kg in diet

    2.3.3  Other species

    No information.

    3.  FOR REGULATORY AUTHORITIES - RECOMMENDATIONS ON REGULATIONS OF
        COMPOUND

    3.1  RECOMMENDED RESTRICTIONS ON AVAILABILITY

    (for definition of categories, see introduction)

    Liquid formulations 25% and over, category 4. All other
    formulations, category 5.

    3.2  TRANSPORATION AND STORAGE

    All formulations - Should be transported or stored in clearly
    labelled leak-proof containers out of reach of children, away from
    food or drink.

    3.3  HANDLING

    Formulations in category 4 - Adequate washing facilities should be
    provided at all times during handling and should be close to the
    site of the handling. Eating, drinking and smoking should be
    prohibited during handling and before washing after handling.

    Formulations in category 5 - No facilities other than those needed
    for the handling of any chemical may be required.

    3.4  DISPOSAL AND/OR DECONTAMINATION OF CONTAINER

    Containers may be decontaminated (for method see paragraph 4.3 in
    Part 4). Decontaminated containers should not be used for food and
    drink. Containers that are not decontaminated should be burned or
    should be crushed and buried below topsoil. Care must be taken to
    avoid subsequent contamination of water sources.

    3.5  SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS

    Formulations in category 4 - Pre-employment medical examination
    and periodic cholinesterase test for workers desirable. Warning of
    workers to avoid contact essential.

    3.6  ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT

    All formulations - No special regulations recommended.

    3.7  LABELLING

    Formulations in category 4 - Minimum cautionary statement

    "Chlorpyrifos-methyl is an organophosphorus compound which inhibits
    cholinesterase. It is of low toxicity but may be poisonous if
    swallowed. Keep the material out of reach of children and well away

    from foodstuffs, animal feed and their containers. If poisoning
    occurs call a physician. Atropine and atropine with pralidoxime are
    specific antidotes; artificial respiration may be needed."

    Formulations in category 5 - Minimum cautionary statement

    This formulation contains chlorpyrifos-methyl. Keep the material out
    of reach of children and well away from foodstuffs, animal feed and
    their containers.

    3.8  RESIDUES IN FOOD

    Maximum residue limits have been recommended by the Joint FAO/WHO
    Meeting on Pesticide Residues.

    4.  PREVENTION OF POISONING IN MAN AND EMERGENCY AID

    4.1  PRECAUTIONS IN USE

    4.1.1

    Chlorpyrifos-methyl is an organophosphorus insecticide of low
    toxicity. It can be absorbed by mouth, and to some extent through
    the intact skin. In dilute liquid formulations the vehicle (solvent)
    may be more toxic than the insecticide.

    4.1.2  Manufacture and formulation

    T.L.V. - No information. Although volatility is low, vapour and
    dust should be controlled.  Protective equipment for skin and
    respiratory protection may be desirable.

    4.1.3  Mixers and applicators

    When opening the container and when mixing, care should be taken to
    avoid contact with the mouth and eyes. If necessary a facial visor
    and gloves should be worn. Mixing, if not mechanical, should always
    be carried out with a paddle of appropriate length.

    Splashes should be washed immediately from the skin or eyes with
    large quantities of water. Before eating, drinking or smoking, hands
    and other exposed skin should be washed.

    4.1.4  Other associated workers (including flagmen in aerial
           operations)

    Persons exposed to chlorpyrifos-methyl and associated with its
    application should observe the precautions described above in 4.1.3
    under "mixers and applicators".

    4.1.5  Other populations likely to be affected

    With good agricultural practice, other populations should not be
    exposed to hazardous amounts of chlorpyrifos-methyl.

    4.2  ENTRY OF PERSONS INTO TREATED AREAS

    Persons may enter treated areas as soon as the spray has dried
    without being exposed to hazardous amounts of chlorpyrifos-methyl.

    4.3  DECONTAMINATION OF SPILLAGE AND CONTAINERS

    Residues in containers should be emptied in a diluted form into a
    deep pit taking care to avoid ground waters. The empty container may
    be decontaminated by rinsing two or three times with water and
    scrubbing the sides. An additional rinse should be carried out with

    5% sodium hydroxide solution which should remain in the container
    overnight. Impermeable gauntlets should be worn during this work and
    a soakage pit should be provided for the rinsings. Decontaminated
    containers should not be used for food and drink. Spillage of
    chlorpyrifos-methyl and its formulations should be removed by
    washing with 5% sodium hydroxide solution and then rinsing with
    large quantities of water.

    4.4  EMERGENCY AID

    4.4.1  Early symptoms of poisoning

    Early symptoms of poisoning following the ingestion of
    chlorpyrifos-methyl may include excessive sweating, headache,
    weakness, giddiness, nausea, vomiting, stomach pains, blurred
    vision, slurred speech, and muscle twitching. If a massive dose has
    been swallowed there may be convulsion, coma, loss of reflexes and
    loss of sphincter control. Symptoms of poisoning are unlikely to
    occur following dermal contact.

    4.4.2  Treatment before person is seen by a physician, if these
           symptoms appear following exposure

    If swallowed, vomiting should be induced if the person is conscious. 
    In the event of a collapse, artifical respiration should be given.

    5.  FOR MEDICAL AND LABORATORY PERSONNEL

    5.1  MEDICAL DIAGNOSIS AND TREATMENT OF CASES OF POISONING

    5.1.1  General information

    An organophosphorus insecticide of low toxicity which can be
    absorbed by the mouth and by inhalation. Absorption may occur slowly
    through the dermal route. It is a weak inhibitor of acetyl
    cholinesterase. It is metabolized and excreted rapidly from the
    body. Poisoning in man has not been reported. In dilute liquid
    formulations the vehicle may be more toxic than the insecticide.

    5.1.2  Symptoms and signs

    Based upon studies and upon symptoms of poisoning from other
    organophosphorus pesticides, initial symptoms of poisoning may
    include excessive sweating, headache, weakness, giddiness, nausea,
    vomiting, stomach pains, blurred vision, slurred speech and muscle
    twitching. In the event of ingestion of an excessive dose more
    advanced symptoms of poisoning may be convulsions, coma, loss of
    reflexes and loss of sphincter control.

    5.1.3  Laboratory

    The most important finding is reduction in activity of blood
    cholinesterase. Urinary levels of the main metabolite
    3,5,6-trichloro-2-pyridinol could be used as a measure of exposure.

    5.1.4  Treatment

    If pesticide has been ingested, unless the patient is vomiting,
    rapid gastic lavage should be performed using 5% sodium bicarbonate,
    if available. In spite of the low dermal toxicity after skin
    contact, it is advisable to wash the skin with soap and water. If
    the compound has entered the eyes, they should be washed with
    isotonic saline. Persons without signs of respiratory inefficiency
    but with manifest peripheral symptoms should be treated with 2-4 mg
    of atropine sulfate and 1000-2000 mg of pralidoxime chloride or
    250 mg of toxogonin (adult dose) by slow intravenous injection. More
    atropine may be given as needed. Persons with severe intoxication
    with respiratory difficulties, convulsions and unconsciousness
    should immediately be given atropine and a reactivator. In such
    severe cases 4-6 mg of atropine sulfate should be given initially
    followed by repeated doses of 2 mg at 5-10 minute intervals. The
    patient's condition including respiration, blood pressure, pulse
    frequency, salivation and convulsions should be carefully observed

    as a guide to further administration of atropine. If the patient is
    cyanotic, artificial respiration should be given at the same time as
    atropine sulfate. The airways should be kept free and artificial
    respiration, if necessary, should be applied, preferably by
    mechanical means. If necessary intubation should be performed.

    Contraindicated are morphine, barbiturates, phenothiazine
    tranquillizers and central stimulants of all kinds.

    5.1.5  Prognosis

    As there have been no reports of poisoning of man with
    chlorpyrifos-methyl the prognosis is not known. By analogy with
    other moderately toxic organophosphorus compounds it may be assumed
    that if the acute toxic effect is survived the chances of complete
    recovery are good. In very severe cases following the ingestion of a
    massive dose of chlorpyrifos-methyl it is possible that without
    adequate artificial respiration prolonged hypoxia could give rise to
    permanent brain damage.

    5.1.6  References of previously reported cases

    None.

    5.2  SURVEILLANCE TESTS

    
         Test                     Normal level   Action level   Symptomatic level

    Plasma cholinesterase            100%*          50%            variable

    Erythrocyte cholinesterase       100%           70%           usually < 40%

    *Percentage of pre-exposure activity by any test.

    
    5.3  LABORATORY METHODS

    References are given only.

    5.3.1  Detection and assay of compound

    It is unlikely the unchanged chlorpyriphos-methyl will be measurable
    in human tissues after exposure. Determination of the level of blood
    cholinesterase is probably the most suitable method in cases of
    suspected poisoning. Levels of unchanged chlorpyrifos-methyl and its
    major metabolite, 3,5,6-trichloro-2-pyridinol can be measured in
    faeces and urine by methods using gas-liquid chromatography.

    Johnson, J. C. et al. (1974) J. Dairy Sci., 57(1), 467-73

    McKellar, R. L. & Dishburger, H. J. (1970) The Dow Chemical Company
    Method ACR 70.19

    5.3.2.  Other tests of cases of poisoning

    Levels of cholinesterase in blood provide the most useful diagnosis
    of poisoning.


    Michel, N. O. (1949) J. Lab. Clin. Med., 34, 1564-1568

    Ellman, G. L., Courtney, K. D., Andreas, V. jr, & Featherstone, R.
    M. (1961) Biochem. Pharmacol., 7, 88-95

See Also:
        Chlorpyrifos methyl (PIM 753)