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

                                                      WHO/VBC/DS/88.75

                                                      ORIGINAL: ENGLISH

                                                      Distr.: Limited




    DATA SHEETS ON PESTICIDES No. 75

    1988

    PHORATE






         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     rsum 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 Sant.

                                      CLASSIFICATION:

                                      Primary use: Insecticide

                                      Secondary use: Acaricide, nematocide

                                      Chemical group: Organophosphorus
                                                      compound

                                      Date Issued: July 1988

    1.0  GENERAL INFORMATION

    1.1  COMMON NAME

            phorate (E-ISO, F-ISO, BSI ANSI, ESA), timet (U.S.S.R.)

    1.1.1  Identity

            IUPAC:  O,O-diethyl  S-ethylthiomethyl phosphorodithioate

            CAS:  O,O-diethyl  S-[(ethylthio)methyl] phosphorodithioate

            CAS Reg. No.: 298-02-2

            Molecular formula: C7H17O2PS3

            Relative molecular mass: 260.4

            Structural formula:

    CHEMICAL STRUCTURE

    1.1.2  Synonyms

            AC 3911, AgrimetR, CL 35024, EI 3911, ENT 24 042, foraat,
    GeometR, GranutoxR, L 11/6, phorat, RampartR, ThimenoxR,
    ThimetR, timet, Vergfru ForatoxR.

    1.2  SYNOPSIS

            Phorate is a broad spectrum, non-biocumulative organophosphorus
    insecticide and acaricide, an indirect inhibitor of cholinesterase
    with good contact, stomach and fumigant action against target
    organisms. It is extremely toxic to mammals and other non-target
    organisms. It is a plant systemic with no residual action. Granular
    formulations are most commonly used. The sulphone metabolite may
    persist in soil, and relatively long pre-harvest intervals are
    recommended

    1.3  SELECTED PROPERTIES

    1.3.1  Physical characteristics

            Phorate is a clear, pale yellow mobile liquid. It has a boiling
    point of 118-120 C (107 Pa), and a freezing point of -42.9 C; a
    density (d25) of 1.167. The technical material is over 90% pure.

    1.3.2  Solubility

            Water, 50 mg/L at 25 C; miscible with carbon tetrachloride,
    dioxane, vegetable oils, xylene, alcohols, ethers and esters.

    1.3.3  Stability

            Phorate is stable for at least two years at room temperature in
    media between pH 5 and 7. In very acidic (pH <2) or very alkaline
    (pH >9) media, hydrolysis occurs at rates dependent upon pH and
    temperature.

    1.3.4  Vapour pressure

            85 mPa (25 C)

    1.4  AGRICULTURE, HORTICULTURE AND FORESTRY

    1.4.1  Common formulations

            Emulsifiable concentrates of various concentrations including
    960 g tech./L and 250 g a.i./L are still available, however,
    granular formulations containing 50, 100, 150, 200 g a.i./kg are
    almost universally used.

    1.4.2  Susceptible pests

            Mites, aphids, greenbugs, thrips, leafhoppers, sorghum
    shootfly, leafminers, corn rootworms, psyllids, cutworms, Hessian
    fly, foliar nematodes, wireworms, flea beetles, whiteflies, pine tip
    moth, and others.

    1.4.3  Use pattern

            Phorate may be used in foliar or soil treatments on alfalfa,
    barley, beans, brassicas, coffee, corn, cotton, grapes, hops,
    lettuce, oats, peanuts, potatoes, rice, sorghum, soybeans, sugar
    cane, sugar beets, tomatoes, watermelon, wheat and on ornamentals
    and pine nursery stock.

            Soil applications may be applied as a band treatment on each
    side of the seed row or incorporated into the soil as a side dress,
    irrigation should follow as soon as possible. Care should be taken
    to avoid contact with seed in the furrow. In foliar treatments apply
    under dry conditions into plant crowns as insects appear.

    1.4.4  Unintended effects

            Phorate is toxic to many seeds and to many non-target
    organisms, including bees and fish. Contamination of standing water
    and waterways must be avoided. Good agricultural practices and the
    use of granular formulations diminish these adverse effects.

    1.5  PUBLIC HEALTH USE

            No recommended use.

    1.6  HOUSEHOLD USE

            No recommended use.

    2.0  TOXICOLOGY AND RISKS

    2.1  TOXICOLOGY - MAMMALS

    2.1.1  Absorption route

            Phorate may be absorbed from the gastrointestinal tract,
    through the intact skin and by inhalation of spray mists or fine
    dust.

    2.1.2  Mode of action

            Several metabolites of phorate inhibit the activity of both
    acetylcholinesterase and pseudocholinesterase.

    2.1.3  Metabolism and excretion products

            Phorate is metabolized in animals to yield phorate sulphoxide
    and phorate sulphone and the oxygentated analogues (phoratoxon,
    phoratoxone sulphoxide and phoratoxone sulphone) which are excreted
    as diethyl phosphoric acid,  O-O-diethyl phosphorothioic and  O-O-
    diethylphosphorodithioic acid.

            Oral administration of a single dose of 2 mg/kg of labelled
    phorate to rats resulted in 35% of material being excreted in urine
    and 3.5% in the faeces, within six days.

            Six daily doses of 1 mg/kg/day of phorate to rats resulted in
    12% and 6% being excreted in the urine and faeces respectively
    within seven days. At necropsy brain, liver and kidney tissue
    contained unidentified and largely unextractable residues.

    2.1.4  Toxicity, single dose (technical material)

            Oral LD50:

            Rat (M)                       2.3-3.2 mg/kg b.w.
            Rat (F)                       1.1-1.6 mg/kg b.w.
            Mouse (M,F)                   3.5-6.5 mg/kg b.w.

            Dermal LD50:

            Rat (M)                       5.7-9.3 mg/kg b.w.
            Rat (F)                       2.5-3.9 mg/kg b.w.
            Rabbit                            5.2 mg/kg b.w.

            Inhalation LC50:

            Rat (M)                            60 mg/m3 (1 hour)
            Rat (F)                            11 mg/m3 (1 hour

            I.V. LD50:

            Rat (M)                           2.2 mg/kg b.w.
            Rat (F)                           1.2 mg/kg b.w.

            I.P. LD50:

            Rat                              1.98 mg/kg b.w.
            Mouse                            3.0  mg/kg b.w.

    2.1.5  Toxicity, repeated doses

            Oral: Mongrel dogs given 0.05 mg/kg/day for 15 weeks had
    significantly depressed plasma and erythrocyte cholinesterase
    activity. At 2.5 mg/kg two dogs died following a single dose.

    2.1.6  Dietary studies

            Short term: The plasma, erythrocyte and brain cholinesterase
    activity of rats fed on a diet containing phorate at levels greater
    than 0.66 ppm was depressed. In rats fed on a diet containing up to
    6 ppm of phorate no effect on growth, food consumption, or
    histopathology was noticed.

            Long term: In a two year rat dietary study at dose levels of
    1, 3 or 6 ppm, growth was depressed at the highest dose level, among
    females only, and only 36% of animals in this group survived
    terminally. Erythrocyte cholinesterase activity was not affected at
    any dose level whereas plasma cholinesterase activity was depressed
    at 6 ppm in males and at 3 and 6 ppm in females.

            In an 18 month study in mice fed on a diet containing phorate
    1, 3 or 6 ppm, growth was retarded in females at 6 ppm. However, in
    all dose groups food aversion was observed for both sexes. There
    were no observed compound related adverse effects other than
    clinical signs of cholinesterase inhibition.

    2.1.7  Supplementary studies of toxicity

            Carcinogenicity: Results of rat and mouse chronic toxicity
    studies have not demonstrated any carcinogenic potential for
    phorate.

            Mutagenicity: Phorate was not mutagenic in a dominant lethal
    test in mice and in several microbial systems including  Salmonella
     typhimurium (reverse mutation),  Saccharomyces cerevisiae
    (mitotic recombination) and in several Ames tests with  E. coli and
     B. subtilis.

            Teratogenicity: In a rat study phorate was not observed to be
    teratogenic at oral doses up to 0.25 mg/kg/day. At 0.5 mg/kg/da

    (high dose level), an increased incidence of hypertrophy of the
    heart was observed. In another rat study, exposure to phorate by
    inhalation at the dose of 1.94 mg/m3/day, during the seventh
    through fourteenth day of gestation, caused increased foetal
    mortality and decreased foetal weight gain but teratogenic effects
    were not observed.

            Reproduction: In a three generation study in mice, with
    phorate levels in diet up to 3 ppm, no compound related effects on
    the fertility, gestation, viability or lactation indices were
    observed.

            Neurotoxicity: Phorate produced no adverse effects on nerve
    fibres or the myelin sheath in hens fed dietary levels of 40 ppm for
    four weeks. In a separate study no delayed neurotoxicity was noted
    in hens given phorate as a single dose of 14.2 mg/kg.

    2.1.8  Modification of toxicity

            No potentiation of toxicity was observed in male rats treated
    with equitoxic portions of phorate and each of 10 other pesticides.

    2.2  TOXICOLOGY - MAN

    2.2.1  Absorption route

            Phorate may be absorbed from the gastrointestinal tract,
    through the intact skin, or by inhalation of dust.

            Single: 5 mg/kg b.w.

            Repeated: Not known

    2.2.3  Observations in occupationally exposed workers

            There have been no reports of fatalities associated with the
    use of phorate. A 16 year old youth became ill after working with
    phorate treated cotton seed. Symptoms included coma, undetectable
    blood pressure, pinpoint pupils, blood tinged frothy sputum and
    occasional convulsions. One day after onset, erythrocyte and plasma
    cholinesterase activities were 21% and 49% of normal respectively.
    Two illnesses occurred in the same formulating plant where phorate
    concentrations in the air were measured at 0.07-14.60 mg/m3. In
    another incident, a formulator experienced neurological symptoms
    following exposure to phorate while cleaning a mixing tank. This was
    accompanied by a 50% reduction in plasma and erythrocyte
    cholinesterase and increased urinary levels of diethyl phosphate, a
    metabolite of phorate

    2.2.4  Observations on exposures of the general population

            No published information available. However, when recommended
    agricultural practices are followed no adverse effects are expected.

    2.2.5  Observations on volunteers

            No published information available.

    2.2.6  Reported mishaps

            No published information available.

    2.3  TOXICOLOGY TO NON MAMMALIAN SPECIES

    2.3.1  Birds

            Oral LD50 (technical material):

                  Mallard (F)                   0.62-2.55 mg/kg b.w.
                  Pheasant (F)                       7.12 mg/kg b.w.
                  Chukar (F)                        12.8  mg/kg b.w.
                  Red-winged blackbird               1.00 mg/kg b.w.
                  Starlings                          7.5  mg/kg b.w.
                  Grackles                           1.30 mg/kg b.w.

            Dermal LD50 (technical material):

                  Mallard (F)                         203 mg/kg b.w.

            Dietary LD50 (5 day):

                  Bobwhile quail                      373 ppm
                  Japanese quail                      200 ppm
                  Ring-necked pheasant                441 ppm
                  Mallard                             248 ppm

    2.3.2  Fish

            Highly toxic to fish

            Bluegill TLM               5.5 g/L (48 hour) technical material
            Rainbow trout LC50        13.0 g/L (96 hour) technical material
            Channel catfish LC50     280.0 g/L (96 hour) technical material

    2.3.3  Other species

            Highly toxic to bees

            Oral LD50:

                  Bullfrog (F)              85.2 mg/kg b.w. (technical material)

    3.0  FOR REGULATORY AUTHORITIES - RECOMMENDATIONS ON REGULATION OF
         COMPOUND

    3.1  RECOMMENDED RESTRICTIONS ON AVAILABILITY

            (For definition of categories see the Introduction to Data Sheets.)

            Liquid formulation of 10% and over, Category 1.

            Other liquid formulations, Category 2.

            Solid formulations of 40% and over, Category 1.

            Other solid formulations, 4-40%, Category 2, less than 4%,
            Category 3.

    3.2  TRANSPORTATION AND STORAGE

            All formulations: Phorate should be transported and stored in
    clearly labelled impermeable containers under lock and key, secure
    from access by children and other unauthorized persons. No food or
    drink should be stored in the same compartment.

    3.3  HANDLING

            All formulations: Full protective clothing (see 4.3) should
    be used by those handling the compound. Adequate washing facilities
    should be available at all times during the handling and should be
    close to the site of handling. Eating, drinking and smoking should
    be prohibited during handling and prior to washing after handling.

    3.4  DISPOSAL AND/OR DECONTAMINATION OF CONTAINERS

            All formulations: Container must first be decontaminated and
    then crushed and buried below topsoil. Care must be taken to avoid
    subsequent contamination of water sources. Decontamination of
    containers in order to use them for other purposes should not be
    permitted.

    3.5  SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS

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

    3.6  ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT

            All formulations: Not recommended for aerial application.

    3.7  LABELLING

            All formulations

                                    "DANGER - POISON"
                           (skull and cross-bones insignia

            Phorate is an organophosphorus compound which inhibits
    cholinesterase. It is extremely toxic. Contact with the skin,
    inhalation of dust or spray, or swallowing may he fatal. Wear
    protective gloves, clean protective clothing, and a respirator of
    the organic-vapour type when handling this material. Wash
    immediately after work. Ensure that containers are stored under lock
    and key. Empty containers must be disposed of in such a way as to
    prevent all possibility of accidental contact with them. Keep the
    material out of reach of children and well away from foodstuffs,
    animal feed and their containers.

            In case of contact, immediately remove contaminated clothing
    and wash the skin thoroughly with soap and water; for eyes, flush
    with water for 15 minutes.

            If poisoning occurs, call a physician. Atropine sulfate is the
    principal antidote, repeated doses may be necessary. Pralidoxime
    chloride (2-PAM or protopam chloride) may be effective as an adjunct
    to atropine treatment. Artificial respiration also may be needed.

    3.8  RESIDUES IN FOOD

         Maximum residue levels: Maximum residue levels were estimated
    by the Joint FAO/WHO Meeting on Pesticide Residues in 1984 for
    several commodities as temporary.

    4.0  PREVENTION OF POISONING IN MAN AND EMERGENCY AID

    4.1  PRECAUTIONS IN USE

         General: Phorate is an extremely toxic organophosphorus
    pesticide. It penetrates the intact skin and is also absorbed by
    inhalation and from the gastrointestinal tract. Repeated exposure
    may have a cumulative effect on the cholinesterase activity. Most
    formulations should be handled by trained personnel wearing
    protective clothing.

    4.1.2  Manufacture and formulation - T.L.V.

         0.05 mg/m3 (TWA); 0.2 mg/m3 (STEL) for skin absorption.
    Closed systems and 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 all crops a face mask
    should be worn, as well as an impermeable hat, 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 gloves. Splashes
    must be washed immediately from the skin, or eyes, with large
    quantities of water. Before eating, drinking, smoking, hands and
    other exposed skin should be washed.

    4.1.4  Other associated workers

         Persons exposed to the compound 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

         Respecting good agricultural practice, subject to 4.2 below,
    other persons should not be exposed to hazardous amounts of the
    compound.

    4.2  ENTRY OF PERSONS INTO TREATED AREA

         Unprotected persons should be kept out of tall crops for four
    days and out of other crops for 24 hours

    4.3  DECONTAMINATION OF SPILLAGE AND CONTAINERS

         Residues in containers should be emptied in a diluted form into
    a shallow pit, taking care to avoid contamination of ground waters.
    The empty container may be decontaminated prior to disposal by
    rinsing two or three times with water and scrubbing the sides.
    Impermeable gauntlets should be worn during this work, and a soakage
    pit should be provided for the rinsings. Decontamination of
    containers in order to use them for other purposes including storage
    of food and drink should not be permitted. Spillage of the compound
    and its formulations should be removed by washing with 5% sodium
    hydroxide solution and theft rinsing with large quantities of water

    4.4  EMERGENCY AID

    4.4.1  Early symptoms of poisoning

         Early symptoms of poisoning may include tightness of chest,
    non-reactive pinpoint pupils, excessive sweating, headache,
    weakness, giddiness, nausea, vomiting, hypersalivation, diarrhoea,
    abdominal pains, blurred vision, slurred speech and muscle
    twitching. Advanced symptoms are: convulsions, coma, loss of
    reflexes and loss of sphincter control.

    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 soap and water and flush
    the area with large quantities of water. If swallowed and if the
    person is conscious, vomiting should be induced. In the event of
    collapse, artificial respiration should be given, bearing in mind
    that if mouth-to-mouth respiration is used, vomit may contain
    hazardous amounts of the pesticide. Call a physician immediately and
    transport the patient to the nearest medical facility if necessary.

    5.0  FOR MEDICAL AND LABORATORY PERSONNEL

    5.1  MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING

    5.1.1  General information

         Phorate, an organophosphorus pesticide, is extremely toxic to
    mammals. It is readily absorbed from the gastrointestinal tract,
    through the intact skin and by inhalation. It is converted in vivo
    to the oxygen analogue which inhibits cholinesterase. It does not
    accumulate in body tissues.

    5.1.2  Symptoms and signs

         Initial symptoms of poisoning may include tightness of chest,
    non-reactive pinpoint pupils, excessive sweating, headache,
    weakness, giddiness, nausea, hypersalivation, vomiting, diarrhoea,
    abdominal 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 finding is reduction of activity of blood
    cholinesterases. Urinary levels of organic phosphorus containing
    metabolites may also be used as a measure of exposure. Neither
    method is specific for the compound.

    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. In case of skin contact, the skin should
    be washed with soap and water. If the compound has entered the eyes,
    they should be washed with large quantities of isotonic saline or
    water.

         Persons without signs of respiratory impairment but with
    manifest peripheral symptoms should be treated with 2-4 mg of
    atropine sulfate by intravenous or intramuscular injection and 1 000
    mg of pralidoxime chloride or 250 mg of toxogonin (adult dose) by
    slow intravenous infusion. More atropine may be given as needed.
    Persons with severe intoxication, with respiratory difficulties,
    convulsions and unconsciousness should immediately be given
    ventilatory support followed by 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.
    Diazepam may be given to control convulsions which are unresponsive
    to atropine and pralidoxime. The patient's condition including
    respiration, blood pressure, pulse frequency, salivation and
    convulsions should be carefully observed as a guide to furthe

    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 should be
    applied if required, preferably by mechanical means. If necessary,
    intubation should be performed.

         Contraindications are morphine, aminophylline, phenothiazines,
    reserpine, furosemide or ethacrynic acid.

         Pralidoxime and toxogonin alone are not regarded as effective
    antidotes organophosphorus poisoning, but may be effective as an
    adjunct to atropine.

    5.1.5  Prognosis

         If the acute poisoning episode is survived and if needed
    adequate artificial respiration has been given the chances of
    complete recovery are good. However, in very severe cases,
    particularly if artificial respiration has been inadequate,
    prolonged anoxia may give rise to permanent brain damage.

    5.1.6  References of previously reported cases

         Phorate has been implicated in a number of cases of pesticide
    poisoning.

         Brokopp, C.D., Wyatt, J. L and Gabica, J., Dialkyl Phosphates
           in Urine Samples from Pesticide Formulators to Disulfoton and
           Phorate. (1981), Bull. Environ. Contam. Toxicol., 26,
           524-529.

         Hayes, W. J. (1982), "Pesticides Studied in Man" p. 360,
           Williams and Wilkins, Baltimore, USA

         Young, R. J., Jung, F. P. and Ayer H. E., Phorate Intoxication
           at an Insecticide Formulating Plant. (1979), Amer. Indust.
           Hyg. Assoc. 40, 1 013-1 016.

    5.2  SURVEILLANCE TESTS

         Test                          Normal    Action    Symptomatic
                                       level*    level*    level*

         Plasma cholinesterase          100%      50%      variable

         Whole blood or                 100%      70%      usually 40%
           erythrocyte
           cholinesteras

                   
    * Expressed as a percentage of pre-exposure activity.

    5.3  LABORATORY METHODS

    5.3.1  Detection and assay of compound

         Product analysis is by I.R. spectroscopy. Residues of phorate
    and its oxidation products may be determined by GLC.

         Boshoff, P.R. and Pretorius, V., (1979), J. Agric. Food Chem.
           27, 626-630.

         Boyd, J.G. (1972), Anal. Methods Pestic. Plant Growth Regul.
           Food Addit., 6, 493-510.

         Brokopp, C.D., Wyatt, J. L and Gabica, J., (1981), Bull.
           Environ. Contam. Toxicol., 26, 524-529.

         Carson, L.J. (1981), J. Assoc. Off. Anal. Chem., 64, 714-719.

         Mount, M.E. and Oehme F. W. (1981), Vet. Hum. Toxicol., 23,
           34-42.

         Sans, W.W. (1978), Assoc. Off. Anal. Chem., 61, 837-840.

         Stan, A.J., Abraham, B., June, J., Kellert, M., Steinland, K.
           (1977), Fresenius Z. Anal. Chem., 287, 271-285.



    See Also:
       Toxicological Abbreviations
       Phorate (ICSC)
       Phorate (Pesticide residues in food: 1977 evaluations)
       Phorate (Pesticide residues in food: 1982 evaluations)
       Phorate (Pesticide residues in food: 1984 evaluations)
       Phorate (Pesticide residues in food: 1985 evaluations Part II Toxicology)
       Phorate (Pesticide residues in food: 1994 evaluations Part II Toxicology)
       Phorate (Pesticide residues in food: 1996 evaluations Part II Toxicological)