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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/88.68

                                                      ORIGINAL: ENGLISH

                                                      Distr.: LIMITED




    DATA SHEETS ON PESTICIDES No. 68

    1988

    DISULFOTON






         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, acaricide, miticide

                            Secondary use: None

                            Chemical group: Organophosphorus compound

                            Date issued: March 1988


    1.0  GENERAL INFORMATION

    1.1  COMMON NAME

         disulfoton (BSI, E-ISO, F-ISO, ESA), ethylthiodemeton (JMAF),
    M-74 (USSR)

    1.1.1  Identity

         IUPAC: O,O-diethyl S-2-ethylthioethyl phosphorodithioate

         CAS: O,O-diethyl S-[2-(ethylthio)ethyl] phosphorodithioate

         CAS Reg. No.: 298-04-4

         Molecular formula: C8H19O2PS3

         Relative molecular mass: 274.4

         Structural formula:

    CHEMICAL STRUCTURE

         Synonyms: Bay S276, Bay 19639, Bayer 19639, Dimaz, Disipton,
    Disulfaton, Di-syston G, DisystonR, Di-syston, Disystox,
    dithiosystox, ENT-23347, ethyl thiometon, ethylthiometon, Frumin,
    Frumin ALR, Frumin G, Glebofos, M 74, Solvigran, SolvirexR,
    thiodemeton, TwinSpan, Vuagt 1-4, Vuagt 1964.

    1.2  SYNOPSIS

         Disulfoton is a systemic insecticide and acaricide used as a
    seed coating and for soil application to protect from insect attack.
    Control for up to seven weeks may be obtained. Disulfoton is
    metabolized to potent inhibitors of cholinesterases, and has an
    extremely high acute toxicity in mammals.

    1.3  SELECTED PROPERTIES

    1.3.1  Physical characteristics

         The pure product is a colourless oil with a sulfurous odour,
    m.p. > -25 °C, b.p. 128 °C at 1.33 hPa, density d20 1.14. The
                                                      4
    technical product is a yellowish oil.

    1.3.2  Solubility

         In water 15 mg/L at 20 °C. Soluble in most organic solvents.

    1.3.3  Stability

         It is relatively stable under normal storage conditions.
    Hydrolysis occurs in alkaline media.

    1.3.4  Vapour pressure

         24 mPa at 20 °C.

    1.4  AGRICULTURE, HORTICULTURE AND FORESTRY

    1.4.1  Common formulations

         Granules (20-150 g/kg), emulsifiable concentrates (850 g/kg).
    Also in combination with DasanitR, Ethimeton and Ekanon in spray
    concentrates, granular (20-100 g/kg) and emulsifiable concentrates.

    1.4.2  Susceptible pests

         Used against aphids and mites on corn, sorghum, cotton,
    vegetables, fruits, nuts, ornamentals, small grains and other field
    crops; also used against leafhoppers, fleabeetles, lacebugs,
    leafrollers, whiteflies, mealybugs, leafminers and Mexican bean
    beetles.

    1.4.3  Use pattern

         Applied at 560 to 3 400 g per hectare on crops. Applied to soil
    by drilling, side dressing or broadcasting; applied prior to
    planting, prior to emergence or post-emergence. Work into the soi

    and water thoroughly. May be used as a seed dressing and on fruit
    trees by spreading from drip line to trunk of tree.

    1.4.4  Unintended effects

         High dosages may injure seeds. Some leafburn in alfalfa has
    occurred, garden lily bulbs have been injured. Plant injury may be
    enhanced when used with some pre-emergence herbicides. Disulfoton
    may be toxic to insect pest predators and bees.

    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

         Disulfoton may be absorbed from the gastrointestinal tract,
    through the intact skin or by inhalation of fine dusts.

    2.1.2  Mode of action

         Acetylcholinesterase inhibition by some of the metabolites of
    disulfoton.

    2.1.3  Excretion products

         Excretion is rapid, half of an oral dose of O-ethyl-14C-
    labelled disulfoton was recovered in the excreta within six hours in
    male rats, 32 hours in female rats. For either sex urinary excretion
    accounted for 80% of the dose, expired air 9%. For both sexes the
    major urinary metabolites diethylphosphate and diethylthiophosphate
    accounted for >90% of the urinary excretion. These metabolites were
    probably formed by hydrolysis of the products of oxidative
    metabolism, namely: the sulfone and sulfoxide of disulfoton, and the
    sulfone and sulfoxide of the oxygen analogue of disulfoton. Minor
    proportions of the latter three metabolites were identified in rat
    urine.

    2.1.4  Toxicity, single dose

         As for many other pesticides, the nature of the solvent or
    carrier used to aid administration of the compound may affect the
    magnitude of the observed LD50 values.

         Oral LD50:

                         Rat         (M)  6.2 - 12.5 mg/kg b.w.
                         Rat         (F)  1.9 -  4.2 mg/kg b.w.
                         Mouse       (M)  5.8 - 27.0 mg/kg b.w.
                         Mouse       (F)  2.7 - 27.0 mg/kg b.w.
                         Guinea pig  (M)         8.9 mg/kg b.w.
                         Guinea pig  (F)        12.7 mg/kg b.w.

         Dermal LD50:

    24 hour exposure     Rat        (M)    15.9 - 25 mg/kg b.w.
    24 hour exposure     Rat        (F)     3.6 -  6 mg/kg b.w.
    4 hour exposure      Rat                      41 mg/kg b.w

         Intraperitoneal LD50:

                         Rat        (M)          7.5 mg/kg b.w.
                         Rat        (F)    2.1 - 3.1 mg/kg b.w.
                         Mouse      (M)          6.7 mg/kg b.w.
                         Mouse      (M,F)       14.0 mg/kg b.w.

         Inhalation LC50:

         1 hour          Rat        (M)          290 mg/m3
         1 hour          Rat        (F)           63 mg/m3
         4 hour          Rat        (M,F)   15 - 60 mg/m3

         Most susceptible species: Among the mammals tested, the rat
    and mouse appear equally to be the most susceptible to disulfoton
    poisoning, and in both species the female is more susceptible than
    the male.

    2.1.5  Toxicity, repeated doses

         Tolerance to continued exposure of sub-lethal amounts of
    disulfoton has been demonstrated following gavage, dietary exposure
    or intraperitoneal injection. Although the cholinergic symptoms
    (tremors, fasciculations, excessive salivation) may disappear as the
    duration of exposure increases, the acetylcholinesterase activity
    remains depressed. (See 2.1.7 for biochemical interpretation.) The
    rate and extent of adaptation are dependent on the route of
    administration, the magnitude of the dose and the animal species, or
    even the strain.

         Female rats receiving disulfoton during 30 days 1.0 mg/kg/day
    intraperitoneally fully recovered from symptoms of cholinergic
    poisoning and weight loss which had been evident for the first seven
    days of administration. Although symptomless, the brain and serum
    cholinesterase activities in these rats, and in rats receiving 0.25
    mg/kg/day (intraperitoneally), remained low throughout the 30 day
    period.

         Histopathological changes in the optic nerve and retina were
    observed in all dogs receiving a gelatin capsule dose of 0.5, 1.0 or
    1.5 mg/kg/day, five days/week for two years. Retinal lesions
    observed were mild.

    2.1.6  Dietary Studies

         Short term: No mortality or effect on body weight gain,
    haematology, urinalysis, clinical chemistry or gross and microscopic
    tissue and organ analyses were observed in studies on rats fed on a
    diet of > 5 ppm disulfoton for 90 days, in mice fed on a diet
    containing 10 ppm for 16 weeks, nor in mongrel dogs on a diet
    containing 10 ppm for 12 weeks. Cholinesterase activity wa

    depressed in brain tissue, measured in rats and mice only, generally
    more severely in females than males and in erythrocytes and in
    plasma of all three species. In dogs plasma cholinesterase activity
    rapidly returned to normal after cessation of dosing, but
    erythrocyte cholinesterase remained inhibited for more than four
    weeks. The no observed effect level (NOEL) for cholinesterase
    inhibition was determined as 1 ppm for all three species.

         Dietary administration of disulfoton at a dose of 7.5 ppm to
    male albino rats for 30 days resulted in 4/71 deaths, decreased
    weight gain and inhibition of cholinesterase activity in the brain,
    stomach and diaphragm. Cholinesterase activity of the stomach and
    diaphragm regain pre-treatment values after 19 days but the brain
    cholinesterase activity remained depressed. Dietary administration
    of disulfoton at a dose of 7.5 ppm to female Holtzman rats for 62
    days produced no overt signs of toxicity. At a dose of 20 ppm,
    diarrhoea, excessive urination and tremors were seen initially. The
    severity of the symptoms decreased with duration of exposure but
    some tremors, fasciculations and reduced weight gain were apparent
    at 62 days.

         Long term: In a two year dietary study in rats at 1, 4 and 16
    ppm the no observed adverse effect level (NOAEL) for cholinesterase
    depression in both sexes was observed to be 1.0 ppm while body
    weight decrease was reported at 16 ppm in both sexes. No other
    significant adverse effects were observed at any dose level.

         Beagle dogs received a diet of 0.5 or 1.0 ppm for two years. An
    additional dose group was fed on a diet of 2.0 ppm, for 69 weeks,
    increased to 5.0 ppm from week 70-72, and increased again to 8.0 ppm
    from week 73-104. No adverse effect on mortality, behaviour, growth,
    ophthalmological, clinical chemistry or haematology parameters, or
    urinalysis were recorded. Plasma and erythrocyte cholinesterase
    activity were depressed in a group fed on a diet of 2.0 ppm. The
    effect was accentuated by increased magnitude and duration of
    dosing. Brain cholinesterase activity was inhibited by 8.0 ppm diet
    at week 104. NOAEL for beagle dogs is 1.0 ppm.

    2.1.7  Supplementary studies of toxicity

         Carcinogenicity: No evidence of carcinogenicity was observed
    in a two year rat dietary study up to and including 16 ppm, the
    highest dose tested.

         Teratogenicity: No teratogenic effects were observed in rats
    treated by gavage with 0.1, 0.3 or 1.0 mg/kg/day, embryotoxicity was
    observed at the highest dose and the NOAEL for cholinesterase
    activity in the dams was 0.1 mg/kg/day.

         In rabbits, doses of 1.5 mg/kg/day and above were found to be
    maternally toxic, causing clinical signs of poisoning and death i

    some animals. No teratogenic, fetotoxic nor embryotoxic effects were
    observed at any dose level, up to aud including 1.5 mg/kg/day.

         Reproduction: In a rat dietary study at 1, 3 and 9 ppm the
    NOAEL was reported to be 1 ppm for reproductive effects including
    reduced litter size, pup weight and pup viability at 3 ppm and
    above. Maternal toxicity, weight loss and clinical signs of
    cholinesterase depression, were observed in the high dose group.

         In another study dietary administration of disulfoton at doses
    of 2, 5 and 10 ppm had no adverse effect on rat reproduction
    parameters. At 10 ppm an increased mortality at weaning was observed
    in the first generation, and some fatty changes in the liver, (males
    especially) of the third generation. Erythrocyte cholinesterase
    activity was decreased in all treatment groups.

         Inhalation: In a three week study with rats the NOAEL was
    reported to be 0.02 mg/m3 (6 hours/day) for both sexes for signs
    of toxicity due to cholinesterase depression at higher doses.

         Mutagenicity: Disulfoton was not mutagenic in metabolically
    activated or unactivated systems with  Saccharomyces cerevisiae D3
    and D7, nor in metabolically activated systems with several
     Salmonella typhimurium strains,  Escherichia coli strains or
     Bacillus subtilus strains. However, other workers report that
    disulfoton was mutagenic without metabolic activation in several  S.
     typhimurium and  E. coli strains. Disulfoton did not induce
    sister chromatid exchange  in vitro with three mammalian cell
    lines. In a mouse micronucleus test, and also in a dominant lethal
    test in mice, mutagenic potential was not demonstrated.

         Neurotoxicity: No clinical nor histopathologic evidence of
    delayed neurotoxicity was observed in a study with hens.

         Following oral administration of 0.5-1.5 mg/kg/day to dogs for
    two years (Section 2.1.5) no degeneration of the optic nerves was
    observed.

         Miscellaneous effects: Induction of microsomal multisubstrate
    oxygenases and particularly cytochrome P-450 have been demonstrated
    in the liver of mice. Barbiturate sleeping times were reduced in
    mice receiving 1/2 LD50 doses for 10 days. Phenobarbital pre-
    treatment protected rats or mice against the lethal effects of oral
    or intraperitoneal administration of LD50 doses of disulfoton.

    2.2  TOXICOLOGY - MAN

    2.2.1  Absorption

         Disulfoton may be absorbed from the gastrointestinal tract,
    through the intact skin and by inhalation of fine dusts or mist

    2.2.2  Dangerous doses

         No published information available.

    2.2.3  Observations in occupationally exposed workers

         Between 1966 and June 1978, incidents of human exposure to
    disulfoton alone were reported in the United States of America: 48
    involved agricultural, industrial or transportation accidents. The
    majority of the incidents arose from container damage, failure to
    decontaminate skin and clothing after exposure and failure to wear
    adequate protective equipment. Hospitalization was necessary in some
    cases, but there were no fatalities from exposure to disulfoton
    alone. The majority of urine samples collected daily for 25 weeks
    from 10 male formulators of disulfoton contained significant
    concentrations of the metabolites diethylphosphate,
    diethylthiophosphate and diethylphosphorothiolate. Plasma and
    erythrocyte cholinesterase activities were not, however,
    significantly reduced.

    2.2.4  Observations on exposure of the general public

         Several instances of contamination of people during aerial
    application were reported in the United States of America between
    1966 and 1978, none requiring hospitalization.

    2.2.5  Observations on volunteers

         Five volunteers received an oral dose of 0.75 mg/day for 30
    days without an adverse effect on plasma or erythrocyte
    cholinesterase.

    2.2.6  Reported mishaps

         In two separate incidents in the United States of America,
    drums or pesticide bags contaminated with disulfoton residues
    resulted in symptoms of severe poisoning and coma in three children
    playing with the containers. Hospitalization and atropine therapy
    gave slow but continuing recovery, the children were fully recovered
    after two or five days treatment. Alleged incidents of disulfoton
    ingestion were generally asymptomatic.

    2.3  TOXICITY TO NON-MAMMALIAN SPECIES

    2.3.1  Fish

         Disulfoton is highly toxic to fish and crustaceans, however,
    there are no reported environmental killings of fish or other
    aquatic organisms. Disulfoton has no effect upon the hatchability of
    brine shrimp at 10 mg/L

    2.3.2  Birds

         Oral LD50:

         Starlings                        133.O mg/kg b.w.
         Mallards                           6.54 mg/kg b.w.
         Bobwhite quail (M)                31.0 mg/kg b.w.
         Bobwhite quail (F)                28.0 mg/kg b.w.

         Oral LC50 (five days):

         Bobwhite                         715 ppm
         Japanese quail                   333 ppm
         Ring-necked pheasant             634 ppm
         Mallard                          510 ppm

         Dermal LD50:

         Mallard (M)                      192 mg/kg b.w.

    2.3.3  Other species

         Disulfoton is toxic to bees and terrestrial wildlife.

    3.0  FOR REGULATORY AUTHORITIES: RECOMMENDATIONS ON REGULATION OF
         COMPOUND

    3.1  RECOMMENDED RESTRICTIONS ON AVAILABILITY

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

         Liquid formulations greater than 130 g/L and solid formulations
    greater than 500 g/kg, Category 1.

         All other formulations, Category 2.

    3.2  TRANSPORTATION AND STORAGE

         All formulations

         Should be transported or stored in clearly labelled rigid and
    leakproof containers, and away from containers of food and drink.
    Storage should be under lock and key and secure from access by
    children and other unauthorized persons.

    3.3  HANDLING

         All formulations: Full protective clothing (see part 4)
    should be used by those handling the compound. Adequate washing
    facilities should be available close at hand. Eating, drinking and
    smoking should be prohibited during handling and before washing
    after handling.

    3.4  DISPOSAL AND/OR DECONTAMINATION OF CONTAINER

         Empty containers should not be re-used. After decontamination
    the container must be either burned or 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

         All formulations: Pre-employment medical examination for
    workers is necessary. Workers suffering from active hepatic or renal
    diseases should be excluded from contact with disulfoton. 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 fol!ow instructions. Training of workers
    in techniques to avoid contact is essential.

    3.6  ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT

         All formulations: Pilots and loaders should have special
    training in application methods and early symptoms of poisoning, an

    they must wear protective clothing. It is not advisable to employ
    flagmen, but if essential they must wear protective gloves,
    overalls, boots, a respirator and an impermeable hat and be located
    well away from the dropping zone.

    3.7  LABELLING

         All formulations

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

         Disulfoton is an organophosphorus compound which inhibits
    cholinesterases. It has an extremely high mammalian toxicity.
    Contact with the skin, inhalation of dust or spray, or swallowing
    may be fatal. Wear protective gloves, clean protective clothing, and
    a respirator of the organic-vapour type when handling this material.
    Bathe immediately after work. Ensure that containers are stored
    under lock and key. Empty containers must be decontaminated and
    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. Do not tank mix with phosalone. 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
    an effective drug if applied in time, repeated doses may be
    necessary. Artificial respiration also may be needed.

    3.8  RESIDUES IN FOOD

    Maximum residue levels

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

    4.0  PREVENTION OF POISONING IN MAN AND EMERGENCY AID

    4.1  PRECAUTIONS IN USE

    4.1.1  General

         Disulfoton, an organophosphorus pesticide, is extremely toxic
    by the oral route. It is also readily absorbed through the intact
    skin, and by inhalation of dust or spray mist. Repeated exposure may
    have a cumulative effect on cholinesterase activity.

    4.1.2  Manufacture and formulation - T.L.V.

         0.1 mg/m3. Closed systems and forced ventilation are 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 hoots, clean overalls, gloves and a 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 respirator should be worn, as well as an
    impermeable hat, overalls, 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 or smoking, hands and any other exposed skin should
    be washed.

    4.1.4  Other associated workers (including flagmen in aerial
           operations)

         Persons exposed to disulfoton 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 good agricultural practice, other persons should not be
    exposed to hazardous amounts of disulfoton.

    4.2  ENTRY OF PERSONS INTO TREATED AREA

         Unprotected persons should be kept out of treated areas for at
    least one day

    4.3  DECONTAMINATION OF SPILLAGE AND CONTAINERS

         Re-use of containers should not be permitted. Residues in
    containers should be emptied in a diluted form into a deep pit,
    taking care to avoid contamination of ground waters. The empty
    container should be rinsed with 5% sodium hydroxide, which should be
    left in the container overnight. The rinse should be emptied into a
    deep pit, and the container crushed and buried, avoiding
    contamination of ground waters. Impermeable groves should be worn
    during this work. Spillage of disulfoton 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 signs and symptoms of poisoning may include excessive
    sweating, headache, weakness, giddiness, nausea, vomiting,
    hypersalivation, stomach pains, blurred vision, slurred speech, and
    muscle twitching. Later there may be convulsions and coma in cases
    of severe poisoning.

    4.4.2  Treatment before person is seen by a physician if these signs
           and 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
    respiratory difficulty ventilatory support should be given, bearing
    in mind that if mouth-to-mouth resuscitation is used, vomit may
    contain dangerous amounts of disulfoton.

    5.0  FOR MEDICAL AND LABORATORY PERSONNEL

    5.1  MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING

    5.1.1  General information

         Disulfoton, an organophosphorus pesticide, is extremely toxic
    to mammals. It is readily absorbed from the gastrointestinal tract
    through the intact skin and from the lungs following inhalation of
    dust or spray mist. It is metabolized to the oxygen analogues of
    disulfoton which are potent inhibitors of cholinesterases. It does
    not accumulate in body tissues.

    5.1.2  Symptoms and signs

         Initial symptoms and signs of poisoning may include excessive
    sweating, headache, weakness, giddiness, nausea, hypersalivation,
    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 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 disulfoton.

    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. Care should be taken to avoid pulmonary complications
    from solvents which may be present in emulsifiable concentrate
    formulations. For 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. Care must
    be taken by the victims attendants to avoid their own intoxication
    from contaminated clothing, skin or vomit.

         Persons without signs of respiratory insufficiency but with
    manifest peripheral symptoms, should be treated with 2-4 mg of
    atropine sulfate by intravenous injection followed by 1 000 mg
    pralidoxime chloride in split doses or 250 mg of toxogonin (adult
    dose) by slow intravenous injection. the additional therapy with
    pralidoxime or toxogonin is most effective if given within 24 hours
    of the onset of intoxication. However, treatment should continue for
    as long as benefits are observed. More atropine may be given as
    needed. Persons with severe intoxication, with respiratory
    difficulties, cyanosis, convulsions, or who are unconscious should
    immediately be given oxygen followed by atropine sulfate and the

    pralidoxime chloride. 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 until atropinization. Symptoms will
    reappear if tissue concentrations of disulfoton remain high when the
    effect of atropine wears off. Rales in the lung bases, myosis,
    nausea, or bradycardia may indicate inadequate atropinization;
    overdosage with atropine (pulse rate over 140, dry mouth, flushed
    face) is rarely serious, but under-dosage may be fatal. Diazepam may
    be given to control convulsions. The patient's condition including
    respiration, blood pressure, pulse rate, salivation and convulsions
    should be carefully observed as a guide to further administration of
    atropine.

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

         Application of morphine, aminophylline, phenothiazines,
    reserpine and central nervous system stimulants is contraindicated.
    Return to work should be delayed until blood cholinesterase activity
    reaches at least 80% of the pre-exposure value.

    5.1.5  Prognosis

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

    5.1.6  References of previously reported cases

         US EPA (1978) "Summary for Reported Incidents Involving
              Disulfoton". Report No. 105, Office of Pesticide Programs,
              Environmental Protection Agency, United States of America.

    5.2  SURVEILLANCE TESTS

    Test                       Normal    Action    Symptomatic
                               level*    level*    level*

    Plasma                       100%       50%      variable
      cholinesterase

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

                   

    * Expressed as percentage of pre-exposure activity

    5.3  LABORATORY METHODS

    5.3.1  Detection and assay of compound

         Analysis of metabolites in urine may be performed by several
    methods:

         Abbot, D.C., Crisp, S.S., Tarrant, V.R., Tatton, J.O'G. (1970),
           Pestic. Sci., 1, 10-13.

         Bowman, M.C., Beroza, M. (1969,) J. Assoc. Offic. Anal.
           Chem., 52, 1231-1237.

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

         Jensen, T.L. (1980), J. Assoc. Offic. Anal. Chem., 64,
           869-872.

    5.3.2  Other tests in case of poisoning

         Acetylcholinesterase activity in blood, provide the most useful
    diagnosis of poisoning.

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

         Fleischer, J., Woodson, S., Simet, L. (1956), Arch. Indust.
           Hyg., 14, (6), 510-520.

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

         Wilhelm, D., Reiner, E. (1973), Bull. Wld. Health Org., 48,
           235-238.

    REFERENCES

    1.   ACGIH (1984), Supplementary documentation. American Conference
           Governmental Industrial Hygienists, Cincinnati, Ohio 45211,
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    2.   Dreisbach, R.H., (1983), Handbook of Poisoning: Prevention,
           Diagnosis and Treatment. Eleventh Edition, Lange Medical
           Publications, California 94022, United States of America.

    3.   FAO/WHO (1974) - 1973 Evaluations of some Pesticide Residues in
           Food. AGP 1973/M/9/1: WHO, Pesticide Residue Series, No. 3,
           Rome, Italy.

    4.   FAO/W-HO (1976) - 1975 Evaluations of some Pesticide Residues
           in Food. AGP 1975/M/13: WHO, Pesticide Residue Series No. 5,
           Rome, Italy.

    5.   Hayes, W.J. (1982), Pesticides Studied in Man. Williams and
           Williams, Baltimore, United States of America.

    6.   Farm Chemicals Handbook (1984), Meister Publishing Co.,
           Willoughby, Ohio 44040, United States of America.

    7.   Hartley D., Kidd, H. (1983), The Agrochemicals Handbook, Royal
           Society of Chemistry, Unwin Bros. Ltd., Surrey, United
           Kingdom.

    8.   Thomson, W.T. (1982), Agricultural Chemicals. Book I
           Insecticides, 1982-1983 Revision. Thomson Publications,
           California 93791, United States of America.

    9.   USEPA (1982), Recognition and Management of Pesticide
           Poisonings, Third edition, EPA 540/9-80-005.

    10.  WHO (1986), Environmental Health Criteria 63, Organophosphorus
           Insecticides: A General Introduction. UNEP/ILO/WHO, Geneva,
           Switzerland.

    11.  Worthing, C.R. (1987), The Pesticide Manual. A World
           Compendium, Eighth Edition, British Crop Protection Council,
           United Kingdom.

See Also:
        Disulfoton (ICSC)
        Disulfoton (PIM 770)