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                                          ET L'AGRICULTURE


                                                      ORIGINAL: ENGLISH


    July 1975


         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.

    Part 1 - General information


                               Primary use: insecticide

                               Secondary use: acaricide

                               Chemical group: organophosphorus compound

                               Data Sheet No. 18

                               Date issued: July 1975

    1.1  COMMON NAME:

    chlorpyrifos (proposed ISO common name).

    Identity:  0,0-diethyl 0-(3,5,6-trichloro-2-pyridyl)


    Synonyms                          Local Synonyms




    ENT 27311

    OMS 971

    1.2  SYNOPSIS

    An organophosphorus pesticide of moderate mammalian toxicity which
    is active against a wide variety of agricultural and public health
    arthropod pests.


    1.3.1  Physical characteristics:

    A white granular crystalline solid with a mild mercaptan-like odour
    mp 42-43.5°C.

    1.3.2  Solubility:

    Water at 25% practically insoluble (2 ppm.), soluble in most organic
    solvents (e.g. methyl alcohol, 45%, iso-octane, 79%).

    1.3.3  Stability:

    Stable under normal storage conditions. Half-life in aqueous
    methanolic solution 1930 days at pH 6.0; 7.2 days at pH 9.96.
    Hydrolysed by water with similar dependence on pH. Decomposition is
    rapid above pH 8.0. Compatible with non-alkaline pesticides.
    Corrosive to copper and brass.

    1.3.4  Vapour pressure (volatility):

    1.87 x 10-5 mm Hg at 25°C.


    1.4.1  Common formulations

    Wettable powder, 25%; emulsifiable concentrates, 25 and 50%;
    granules, 1-10%.

    1.4.2  Pests mainly controlled

    Broad spectrum insecticide and acaricide. Active against mosquitos
    (larvae and adults), soil and household pests, ectoparasites of
    cattle, sheep and poultry, foliar and fruit feeding pests of various
    field, tree fruit and vegetable crops.

    1.4.3  Use pattern

    Used as dip or spray to control ticks, lice and horseflies on beef
    and non-lactating dairy cattle, and blowflies, ticks, lice and keds
    on sheep.

    Used as a soil spray in turkey pens, before the turkeys are penned,
    to control chiggers.

    Used as pre- and post-planting soil treatment to control insects
    attacking maize, spring cereals, beans, onions, carrots, turnips,
    lettuce, bulb flowers and tobacco.

    Used as foliar treatment against insect pests of rape, cereals,
    potatoes, fodder crops, legumes, brassicas, rice, cotton, tobacco
    and deciduous fruits, and as a spray on lawns.

    Used on agricultural and household premises.

    Chlorpyrifos has a short residual life on plant foliage, but is
    effective for several weeks on soil, polluted water, wood, concrete,
    etc. Very resistant to leaching from soils.

    1.4.4  Unintended effects

    Toxic to shrimps, crabs, and fish. Not phytotoxic at concentrations
    recommended for use. Its persistence in soil (1-2 months) and on
    various surfaces, although not hazardous in itself, could lead to
    undesirable effects by accumulation, depending on the frequency of
    applications and amount applied.


    Widely used in mosquito control, mainly as a larvicide. Also used as
    ULV concentrate for control of adult mosquitos as space spray.


    Used for control of most common household insects, particularly

    Part 2 - Toxicology and risks


    2.1.1  Absorption route:

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

    2.1.2  Mode of action:

    cholinsterase inhibition.

    2.1.3  Excretion products:

    The main excretion products which occur largely in the urine and to
    a lesser extent in the faeces are: 3,5,6-trichloro-2-pyridyl
    phosphate, 3,5,6-trichloro-2-pyridinol and traces of unchanged

    2.1.4  Toxicity, single dose

    Oral: LD50 rat (M) 155 mg/kg  Dermal: LD50 rat (M) 202 mg/kg
                 rat (F) 135 mg/kg

    Dermal:  LD50 rabbit 2000 mg/kg

    2.1.5  Toxicity, repeated doses

    Oral:  There was no inhibition of plasma or erythrocyte
    cholinesterase when dogs were given 0.01 mg/kg daily by capsule for
    32 days. At 0.03 mg/kg for 90 days, there was marginal reduction of
    cholinesterase activity. At 0.1, 0.3 and 1 mg/kg for 90 days, there
    was significant decrease in plasma and erythrocyte cholinesterase
    activity, but there were no other abnormalities. Recovery of both
    plasma and erythrocyte cholinesterase occurred within 14 days after
    discontinuing feeding the compound.

    Rhesus monkeys received 0.08, 0.4 or 2.0 mg/kg of chlorpyrifos by
    gavage daily for six months. There were no abnormalities except
    decrease in erythrocyte and plasma cholinesterase activity at 0.4
    and 2.0 mg/kg and a slight decrease only in plasma cholinesterase
    activity at 0.08 mg/kg.

    Inhalation:  Rats exposed for 7 h/day to an atmosphere of
    chlorpyrifos (0.007 g/m3 air) for 16 exposures over a 21 day
    interval, showed no effects on growth, appearance, behaviour or
    plasma and erythrocyte cholinesterase activity.

    Dermal:  Rabbits were exposed dermally to it varying schedule of
    dosages and number of exposures. At both ends of the schedule,
    5 mg/kg applied for 12 h on 20 occasions and 50 mg/kg applied for
    12 h once only, significant: plasma and erythrocyte cholinesterase
    inhibition occurred without any other abnormalities.

    Cumulation of compound: There is some persistence of chlorpyrifos
    in fatty tissues, the half-life being about 62 h.

    2.1.6  Dietary studies

    Short-term:  In a 90-day feeding study with rats, cholinesterase
    inhibition in plasma and erythrocytes was evident at dietary levels
    of 10 ppm (0.5 mg/kg/day) and above. No symptoms of toxicity were,
    however, evident at 100 ppm (5 mg/kg/day) and below. At 300 ppm and
    1000 pp (15 and 50 mg/kg/day) there were marked cholinergic symptoms
    with high mortality at the top dose level. In another 90-day study,
    the no-effect level with respect to cholinesterase inhibition was a
    dietary level equivalent to 0.1 mg/kg per day.

    Gross cholinergic effects were evident in dogs fed 600 and 200 ppm
    (15 and 5 mg/kg/day) for 16 and 45 days respectively. At 60 and 20
    ppm (1.5 and 0.5 mg/kg/day) for 88 and 77 days respectively,
    retardation in growth and reduction of cholinesterase activity were
    the only abnormalities.

    Long-term:  Groups of dogs were fed chlorpyrifos in the diet for
    up to two years at dose levels of 0, 6.01, 0.03, 0.1, 1.0 and
    3.0 mg/kg/day. Inhibition of erythrocyte cholinesterase in males and
    females was evident at 1.0 and 3.0 mg/kg. Marginal reduction in
    brain cholinesterase activity was shown at the highest level of
    feeding. Plasma cholinesterase was inhibited at 0.1 mg/kg/day in
    both males and females. Occasional reduction at 0.03 mg/kg was
    noted. Gross examination showed an increase in liver weight and
    ratio at 3.0 mg/kg. All other tissues were normal. Inhibition of
    cholinesterase activity was the only abnormality detected.

    Groups of rats were fed dietary levels of chlorpyrifos of 0, 0.01,
    0.03, 0.1, 1.0 and 3.0 mg/kg/day for two years. Blood cholinesterase
    activity primarily in plasma was reduced in females at 0.1. mg/kg
    and above. Brain cholinesterase was inhibited at 3.0 mg/kg and
    slightly reduced at 1.0 mg/kg. Chlorpyrifos at all dosage levels had
    no significant effect on behaviour, appearance, growth, mortality,
    haematology, urinalysis, clinical biochemistry, gross or
    histopathology of tissues and organs or the incidence of neoplasms.

    2.1.7  Supplementary studies of toxicity

    Reproduction and teratogenicity

    In a three generation reproduction study, prolonged exposure to
    dietary levels up to and including 1.0 mg/kg/day had no Adverse
    effect on the reproductive capacity of either sex. No terata were
    observed in the offspring of rats orally administered 1.0 mg/kg/day
    on days 6-15 of gestation.

    Delayed neurotoxicity

    A maximum dose of 150 mg/kg of chlorpyrifos has been administered
    orally to hens which were protected by pralidoxime. Surviving birds
    did not display delayed ataxia or paralysis.

    Studies on the metabolite 3,5,6-trichloro-2-pyridinol

        Oral  LD50 rat (M) 794 mg/kg
                   rat (F) 870 mg/kg

    Studies in rats and dogs reveal that the no-effect level for the
    metabolite 3,5,6-trichloro-2-pyridinol is 1000 ppm. in the diet of
    rats (50 mg/kg/day) and 400 ppm in the diet of dogs (10 mg/kg/day).
    Levels up to 1000 ppm of 3,5,6-trichloro-2-pyridinol for three weeks
    did not produce mortality or cataracts in ducklings,

    2.1.8  Modification of toxicity


    The toxicity of chlorpyrifos was significantly moderated in rats by
    treatment with atropine sulfate either alone or in combination with
    pralidoxime. The following gives the LD50 values following
    subcutaneous injection:

    Chlorpyrifos (alone)                              147 mg/kg
    Chlorpyrifos (+ atropine sulfate - 17.4 mg/kg)    205 mg/kg
    Chlorpyrifos (+ atropine sulfate - 17.4 mg/kg
                  + pralidoxime 50 mg/kg)             540 mg/kg


    2.2.1  Dangerous doses

    Single:  Not known.

    Repeated:  Not known.

    2.2.2  Observations of occupationally exposed workers

    Three studies have been conducted on spraymen applying chlorpyrifos
    in public health programme. In all studies reduced cholinesterase
    activity was recorded. In one study five of seven spraymen showed
    more than 50% reduction of plasma cholinesterase activity within two
    weeks after the beginning of the spraying. No clinical
    manifestations of organophosphorus poisoning were noted in any of
    the spraymen; no inhibition of erythrocyte cholinesterase activity
    was observed at any time.

    2.2.3  Observations on exposure of the general population

    No information.

    2.2.4  Observations on volunteers

    In human volunteers given daily oral doses of 0, (control), 0.014,
    0.03 or 0.1 mg/kg of chlorpyrifos, the threshold level for reduction
    of plasma or cholinesterase activity was judged to be 0.03 mg/kg/day
    given for 21 days. Recovery in the 0 10 mg/kg group on withdrawal of
    chlorpyrifos was complete within four weeks. No changes in
    erythrocyte cholinesterase were seen for any dose level given. Other
    blood tests and results of urinalysis were normal. Neither
    chlorpyrifos nor its oxygen analogue nor the metabolite
    3,5,6-trichloro-2-pyridinol were detectable in the urine.

    An adult male human volunteer exposed by inhalation to chlorpyrifos
    1.1 mg/m3 for 8 min, showed no reduction of plasma or erythrocyte
    cholinesterase levels at 4, 22 and 70 h after treatment. Human
    volunteers of both sexes similarly exposed to lower concentrations
    of chlorpyrifos for shorter periods showed no cholinesterase

    Adult human volunteers exposed dermally to chlorpyrifos at doses of
    1.0, 1.5, 3.0, 5.0 and 7.5 mg/kg body weight for 12 h displayed no
    evidence of reduction in plasma or erythrocyte cholinesterase

    2.2.5  Reported mishaps

    No information.


    The entries in these sections are intended to draw attention to
    special risks and to give warnings of any needs for special

    2.3.1  Fish

    Toxic to fish.

    2.3.2  Birds

    Toxicity to birds varies between and within species: it is generally
    fairly high, with LD50 below 50 mg/kg for several species. Shows
    some degree of cumulative toxicity.

    2.3.3  Other species

    Toxic to shrimps, crabs and other aquatic invertebrates.

    Part 3 - For regulatory authorities


    of categories, see introduction)

    Liquid formulations over 50%, category 3 and over 5%, category 4.
    Solid formulations over 20%, category 4, all other formulations,
    category 5.


    All formulations in categories 3 and 4

    Should be transported or stored in clearly labelled rigid and
    leakproof containers under lock and key safe from access by
    unauthorized persons and children. No food or drink should be stored
    in the same compartment.

    Formulations in category 5

    Should be stored in clearly labelled leakproof containers, out of
    reach of children and away from food and drink.

    3.3  HANDLING

    All formulations in categories 3 and 4

    Protective clothing (see 4.1.3 - Part 4) should be used by those
    handling the compound. Adequate washing facilities should be
    available 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 handling of any chemical
    need to be required.


    All formulations

    Container may be decontaminated (for method, see para. 4.3 - 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.


    All formulations, categories 3 and 4

    Pre-employment medical examination for workers desirable. Workers
    suffering from active hepatic or renal disease should be excluded
    from contact. Pre-employment and periodic cholinesterase test for
    workers desirable. Special account should be taken of the workers'
    mental ability to comprehend and follow instructions. Training of
    workers in techniques to avoid contact essential.

    Formulations, category 5

    No special cholinesterase test for workers necessary. Warning of
    workers to minimize contact essential.


    All  formulations

    Pilot and loaders should have special training in application
    methods and early symptoms of poisoning, and must wear a suitable
    respirator. Flagmen, if used, should wear overalls and be located
    well away from the dropping zone.

    3.7  LABELLING

    All  formulations, categories 3 and 4

    "Chlorpyrifos is an organophosohorus compound which inhibits
    cholinesterase. It is poisonous if swallowed. 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 reach of children and well away from foodstuffs, animal feed
    and their containers."

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

    All formulations, category 5

    "This formulation contains chlorpyrifos which is a toxic substance.
    Keep the material out of reach of children and well away from
    foodstuffs, animal feed and their containers."


    3.8.1  Maximum residue levels

    "The Joint FAO/WHO Meeting on Pesticide Residues (1972) has
    recommended the following limits:

         Fat of meat of cattle                          2.0  ppm
         Apples, chinese cabbage, grapes, kale          1.0  ppm
         Pears, carrots, tomatoes                       0.5  ppm
         Beans, aubergines, peppers, raspberries        0.2  ppm
         Fat of meat of sheep and of poultry            0.2  ppm.
         Lettuce, sugarbeet, rice (in husk)             0.1  ppm
         Celery, cottonseed, cottonseed oil (crude),
           mushrooms, onions                            0.05  ppm
         Cauliflower, red cabbage, potatoes             0.01  ppm
         Milk (fat basis)                               0.01  ppm

    Part 4 - Prevention of poisoning in man and emergency aid


    4.1.1  General

    Chlorpyrifos is an organophosphorus pesticide of moderate toxicity.
    It is readily absorbed by the gastrointestinal tract and may also be
    absorbed through the intact skin and by inhalation.

    4.1.2  Manufacture and formulation

    A TLV value of 0.2 mg/m3 has been proposed (A.C.G.I.H.).

    Closed systems of forced ventilation may be required to reduce as
    much as possible the exposure of workers to the chemical.

    4.1.3  Mixers and applicators

    When opening the container and when mixing, protective impermeable
    boots, clean overalls, gloves and respirator should be worn. Mixing,
    if not mechanical, should always be carried out with a paddle of
    appropriate length. When spraying tall crops or during aerial
    application, a face mask should be worn as well as an impermeable
    hood, clothing, boots, and gloves. The applicator should avoid
    working in spray mist and avoid contact with the mouth. Particular
    care is needed when equipment is being washed after use. All
    protective clothing should be washed immediately after use,
    including the insides of the gloves. Splashes must 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

    Persons exposed to chlorpyrifos and associated with its application
    should wear protective clothing and observe the precautions
    described above in 4.1.3 under "Mixers and applicators".

    4.1.5  Other populations likely to be affected

    With correct use in agriculture and public health, other persons
    should not be exposed to hazardous amounts of chlorpyrifos.


    Unprotected persons should be kept out of treated areas for 12 h.


    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 and its formulations should be removed by
    washing with 5% sodium hydroxide solution and then rinsing with
    large quantities of water.


    4.4.1  Early symptoms of poisoning

    Early symptoms of poisoning may include excessive sweating,
    headache, weakness, giddiness, nausea, vomiting, stomach pains,
    blurred vision, slurred speech, and muscle twitching. Later there
    may be convulsions, coma, loss of reflexes and loss of sphincter

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

    The person should stop work immediately, remove contaminated
    clothing and wash the affected skin with water and soap, if
    available, and flush the area with large quantities of water. If
    swallowed, vomiting should be induced if the person is conscious. In
    the event of collapse, artificial respiration should be given,
    bearing in mind that if mouth-to-mouth respiration is used, vomit
    may contain toxic amounts of chlorpyrifos.

    Part 5 - For medical and laboratory personnel


    5.1.1  General information

    Chlorpyrifos is an organophosphorus pesticide of moderate toxicity
    which is active against a variety of agricultural and public health
    arthropod pests. It is readily absorbed by the gastrointestinal
    tract and may also be absorbed through the intact skin and by
    inhalation. Although rapidly excreted, largely in the urine, there
    is some persistence of the unchanged compound in fatty tissues.

    5.1.2  Symptoms and signs

    Initial symptoms of poisoning may include excessive sweating,
    headache, weakness, giddiness, nausea, vomiting, stomach pains,
    blurred vision, slurred speech and muscle twitching. More advanced
    symptoms of poisoning may be convulsions, coma, loss of reflexes and
    loss of sphincter control.

    5.1.3  Laboratory

    The most important laboratory finding is reduction in activity of
    blood cholinesterases. Urinary levels of ether-extractable
    phosphorus containing compounds may also be used as an index of
    exposure. Neither of these methods is specific for chlorpyrifos.

    Urinary levels of 3,5,6-trichloro-2-pyridinol should also be able to
    be used as an index of exposure to chlorpyrifos and related

    5.1.4  Treatment

    If the pesticide has been ingested, unless the patient is vomiting,
    rapid gastric lavage should be performed using 5% sodium
    bicarbonate, if available. For skin contact, the skin should be
    washed with soap and water. If the compound has entered the eyes,
    they should be washed with isotonic saline or water.

    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 5-1.0 min intervals. The patients'
    condition, including respiration, convulsions, 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 first, then
    atropine sulfate.

    The airways should be kept free and artificial respiration should be
    applied, if required, preferably by mechanical means. If necessary,
    intubation should be performed.

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

    5.1.5  Prognosis

    Although there have been reports of reduced cholinesterase activity,
    there have been no reports of overt symptoms resulting from
    poisoning of man by chlorpyrifos. For this reason, the prognosis is
    not known. However, by analogy with other 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, it is possible that without adequate artificial respiration,
    prolonged anoxia could give rise to permanent brain damage.

    5.1.6  References of previously reported cases



       Test             Normal level   Hazard level*  Symptomatic level*

       cholinesterase      100%*            50%             variable

       cholinesterase      100%             70%            usually <40%

           *Expressed as percentage of pre-exposure activity.

    Urinary levels of ether-extractable organic phosphorus should also
    be able to be used to determine degrees of exposure.


    References are given only.

    5.3.1  Detection and assay of compound

    Methods for determining chlorpyrifos in plant and animal tissues and
    milk have been extensively reviewed by FAO/WHO (1973). The review
    includes suitable clean-up procedures and recommends
    gas-chromatographic methods as being suitable for regulatory
    purposes. The multi-residue method of Abbott et al. (1970) would
    also probably be satisfactory, but has not yet been fully
    established for chlorpyrifos.

    5.3.2  Other tests in cases of poisoning

    Levels of cholinesterase in the blood, particularly plasma, provide
    the most useful diagnosis of poisoning:

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

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

    Levels of diethyl phosphate and phosphorothioate in urine may also
    be determined in order to give an indication of the extent of
    exposure (see Shafik & Enos, 1969; Shafik et al., 1970). Unchanged
    chlorpyrifos might be detectable in the blood in cases of poisoning:
    the gas-chromatographic method of Machin et al. (1973) should be
    adaptable to chlorpyrifos.


    Abbott, D. C., Crisp, S., Tarrant, K. R. & Tatton, J. O'G.
    Pesticide Residues in the Total Diet in England and Wales,
    1966-1967. III. Organophosphorus Pesticide Residues in the Total
    Diet. Pestic. Sci., 1970, 1, 10

    1972 Evaluations of some pesticide residues in food. FAO/AGP:
    1972/M/9/1; WHO/1973, p. 190

    Shafik, M. T. & Enos, H. F.
    Determination of Metabolic and Hydrolytic Products of
    Organophosphorus Pesticide Chemicals in Human Blood and Urine.
    J. Agric. Fd Chem., 1969, 17, 1186

    Shafik, M. T., Bradway, D., Biros, F. J. & Enos, H. F.
    Characterization of Alkylation Products of Diethyl Phosphorothioate.
    J. Agric. Fd Chem., 1970, 18, 1174

    Machin, A. F., Quick, M. P. & Waddell, D. F.
    The Rapid Determination of the Organophosphorus Pesticides Diazinon
    and Dichlorvos in Blood by Gas Chromatography. Analyst, 1973,
    98, 176

See Also:
        Chlorpyrifos (PIM 752)