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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/88.70

                                                      ORIGINAL: ENGLISH

                                                      Distr.: LIMITED




    DATA SHEETS ON PESTICIDES No. 70

    1988

    ETHOPROPHOS






         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: Nematicide

                                       Secondary use: Insecticide

                                       Chemical group: Organophosphorus
                                                       compound

                                       Date issued: July 1988

    1.0  GENERAL INFORMATION

    1.1  COMMON NAME

         ethoprophos (E-ISO, F-ISO, BSI) ethoprop (ANSI, ES)

    1.1.1  Identity

         IUPAC and CAS No. 1:  O-ethyl  S,S-dipropyl phosphorodithioate

         CAS Reg. No.: 13194-48-4

         Molecular formula: C8H19O2PS2

         Relative molecular mass: 242.3

         Structural formula:

    CHEMICAL STRUCTURE

    1.1.2 Synonyms: ENT 27 318, Ethoprop, JoltR, MocapR, ProphosR,
    VC9-104.

    1.2  SYNOPSIS

         Ethrophos is a broad spectrum, non-cumulative and non-systemic
    organophosphorus pesticide that is extremely toxic to mammals. It is
    a direct cholinesterase inhibitor, with excellent contact action. It
    has moderate residual activity and is not phytotoxic.

    1.3  SELECTED PROPERTIES

    1.3.1  Physical characteristics

         Ethoprophos is a clear, pale yellow liquid having a boiling
    point of 86-91 °C (27.7 Pa) density (d 20) of 1.094.
                                           4

    1.3.2  Solubility

         In water, 750 mg/L (at 25 °C) very soluble in organic solvents.

    1.3.3  Stability

         Ethoprophos is very stable in acid aqueous medium up to 100 °C,
    but is rapidly hydrolysed in alkaline media at 25 °C and above.

    1.3.4  Vapour pressure

         46.7 Pa at 26 °C.

    1.4  AGRICULTURE, HORTICULTURE AND FORESTRY

    1.4.1  Common formulations

         Ethoprophos is available in an emulsifiable concentrate, 700 g
    a.i./L and in granular preparations, 60-150 g/kg.

    1.4.2  Susceptible pests

         These include wire worms, nematodes and corn rootworms and soil
    inhabiting arthropods.

    1.4.3 Use pattern

         It is almost exclusively recommended as a pre-plant, soil
    application for tobacco, sweet potatoes, bananas, plantains,
    cabbage, corn, pineapple, sugar cane, soybeans, peanuts, cucumber,
    snap and lima beans, potatoes and commercial turf.

    1.4.4  Unintended effects

         It is not phytotoxic when used as directed.

    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

         Ethoprophos may be absorbed from the gastrointestinal tract,
    through the intact skin, and by inhalation of spray mist and dusts.

    2.1.2  Mode of action

         Ethoprophos is a direct inhibitor of cholinesterases through
    phosphorylation of the esteratic site of the enzyme. Accumulation of
    acetylcholine at the nerve synapses and myoneural junctions causes
    toxic effects.

    2.1.3  Excretion products

         Following oral administration of 14C-labelled ethoprophos to
    rats,  O-ethyl- S-propyl phosphorothioic acid,  O-ethyl-
    phosphoric acid and desethyl ethoprophos were the major urinary
    metabolites. The urine also contained traces of methyl propyl
    sulfide, methyl propyl sulfoxide and methyl propyl sulfone.  In
     vitro hepatic microsome and supernatant preparations produced
    similar degradation products, ethoprophos was de-ethylated in the
    presence of glutathione.

    2.1.4  Toxicity, single dose:

         Oral LD50:

         Rat (M)         62 mg/kg b.w.; technical material in corn oil
         Rat (F)         33 mg/kg b.w.; technical material in corn oil
         Mouse (M,F)     31 mg/kg b.w.; technical material in water
         Rabbit (F)      33 mg/kg b.w.; technical material, vehicle
                                        unknown

         Dermal LD50:

         Rat (M,F)      226 mg/kg b.w.; technical material in water
         Rabbit          26 mg/kg b.w.; technical material, vehicle
                                        unknown
         Mouse           18 mg/kg b.w.; technical material in acetone
         Pig            327 mg/kg b.w.; technical material, no vehicle

         Inhalation LC50: (4 hour)

         Rat            250 mg/L air

         Most susceptible species: Probably mice

    2.1.5  Toxicity, repeated doses

         No information available.

    2.1.6  Dietary studies

         Short-term: In a 90 day study in rats, using dose levels of
    0.3, 1.0 or 100 ppm in diet a no-effect level could not be
    demonstrated since brain cholinesterase activity depression was
    recorded at the low-dose level. Growth depression was also observed
    at the high-dose level.

         In a similar dog study cholinesterase depression was observed
    at the lowest dose level, 1.0 ppm in a diet. The incidence of
    myocardial lesions was increased at the high-dose level, 100 ppm,
    relative to control values, however, the lower dose group was not
    examined for this effect.

         Long-term: In a rat study test animals (60/sex/group) were
    selected from among pups of first generation control and treatment
    group litters of a reproduction study (see reproduction section
    below). The treatment group pups were first placed on a diet
    containing ethoprophos 4.5, 9.0 and 18.0 ppm for 12 weeks, then 49,
    98 and 196 ppm for the remainder of the 109 week study. The only
    adverse effects observed were plasma and brain cholinesterase
    activity depression at all dose levels. However, erythrocyte
    cholinesterase activity was not changed at: any dose level.

    2.1.7  Supplementary studies of toxicity

         Carcinogenicity: After 109 weeks of dietary exposure the
    incidence of thyroid C-cell adenoma was significantly increased
    among male rats in the high dose group (see 2.1.6).

         Teratogenicity: In rats, dose levels of 0.16, 1.6 and 16.0
    mg/kg b.w. of ethoprophos administered daily by gavage caused an
    increased incidence of incomplete vertebral ossification in 43, 39
    and 58 percent of the treatment group litters respectively. An
    increased incidence in rudimentary and extra ribs was also observed
    at 1.6 mg/kg b.w./day.

         In a gavage study in rabbits, an increased total incidence of
    skeletal variants, per foetus, was observed at all ethoprophos dose
    levels (0.125, 0.5 and 2 mg/kg b.w./day). However, since no single
    variant change was observed to be increased, a teratogenic no-effect
    level was estimated to be 2.0 mg/kg b.w./day for ethoprophos in
    rabbits.

         Reproduction: In a three generation study, rats were fed
    ethoprophos at dose levels of 60.5, 131 or 262 ppm. The no-adverse
    effect level was observed to be 60.5 ppm for parental growt

    depression at higher doses in all generations. There were no other
    compound related adverse effects which were consistently observed in
    all generations.

         Mutagenicity: Ethoprophos was not observed to have any
    mutagenic potential in two  in vitro studies, an unscheduled DNA
    synthesis test in primary rat hepatocytes at (25 µl/ml) and in a
    mouse lymphoma specific-locus mutation assay at 0.237 nl/ml, nor in
    an  in vitro male rat cytogenetic study at 20 mg/kg b.w./day for
    five days.

         Neurotoxicity: In two studies ethoprophos could not be
    evaluated for delayed neurotoxic effects due to study inadequacies.

         Primary irritation: Skin and eye irritation effects could not
    be adequately evaluated due to high mortality of test animals
    following administration of recommended dose levels.

    2.1.8  Modification of toxicity

         No published information available.

    2.2  TOXICOLOGY - MAN

         No published information available.

    2.3  TOXICITY, NON MAMMALIAN SPECIES

    2.3.1  Fish, LC50:

         Goldfish                 13.6 ppm (96 hours)
         Bluegill                 2.07 ppm (96 hours)
         Rainbow trout            13.8 ppm (96 hours)

    2.3.2  Birds

         Oral LD50:

         Mallard                  12.6 mg/kg b.w.; technical material
         Pheasant                  4.2 mg/kg b.w.; technical material
         Chicken                   6.1 mg/kg b.w.; technical material

         Dermal LD50:

         Mallard                  10 mg/kg b.w.; technical material

    2.3.3  Other species

         Not toxic to bees.

    3.0  FOR REGULATORY AUTHORITIES - RECOMMENDATIONS OF COMPOUND

    3.1  RECOMMENDED RESTRICTIONS ON AVAILABILITY

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

         Liquid formulations of 70% and over category 2

         Other liquid formulations, Category 3

         Solid formulations (granules) of 101 and over, Category 3

    3.2  TRANSPORTATION AND STORAGE

         All formulations: Should be transported and stored in clearly
    labelled impermeable containers under lock and key, secure from
    access by unauthorized persons and children. 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 site of handling. Eating, drinking and smoking should be
    prohibited during handling and before washing after handling.

    3.4  DISPOSAL AND/OR DECONTAMINATION OF CONTAINERS

         Container must 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
    diseases should be excluded from contact with ethoprophos. Pre-
    employment and periodic blood cholinesterase tests for workers are
    desirable. Special account should be taken of the workers' 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: No recommended aerial applications

    3.7  LABELLING

         All formulations

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

         Ethoprophos is an organophosphorus compound which inhibits
    cholinesterase. It is of very high toxicity. Contact with the skin,
    inhalation of dust or spray, or swallowing may be fatal.

         Wear protective gloves, clean protective clothing, and a
    respirator when handling this material. Bathe 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
    food containers.

         In case of contact, immediately remove contaminated clothing
    and wash the skin thoroughly with soap and water; for eye contact,
    flush with water for 15 minutes. If poisoning occurs, call a
    physician. Atropine sulfate is a recommended antidote, repeated
    doses may be necessary. Artificial resuscitation may also be needed.

    3.8  RESIDUES IN FOOD

         Maximum residue limits - The Joint FAO/WHO Meeting on
    Pesticides Residues has been unable, in the absence of an acceptable
    daily intake, to recommend maximum residue limits, but has proposed
    guidelines for residues in a limited number of foods.

    4.0  PREVENTION OF POISONING IN MAN AND EMERGENCY AID

    4.1  PRECAUTIONS IN USE

    4.1.1  General

         Ethoprophos is an organophosphorus pesticide of very high
    toxicity. It is absorbed through the intact skin by inhalation of
    dust and fine spray mist and from the gastrointestinal tract. Most
    formulations should be handled by trained personnel wearing
    protective clothing.

    4.1.2  Manufacture and formulations - T.L.V.

         No information available. 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 a respirator should be
    worn. Mixing, if not mechanical, should always be carried out with a
    paddle of appropriate length. The applicator should wear an
    impermeable hat, protective clothing, boots and gloves. The
    applicator should avoid working in spray mist and avoid contact by
    the mouth. Particular care is needed when equipment is being washed
    after use. All protective clothing should be washed separately from
    other laundry 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 other exposed skin should be washed.

    4.1.4  Other associated workers (including flagmen in aerial
    operations)

         Persons exposed to ethoprophos 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 application practice, subject to 4.2 below, other
    persons are not likely to be exposed to hazardous amounts of
    ethoprophos.

    4.2  ENTRY OF PERSONS INTO TREATED AREA

         Unprotected persons should be kept out of application sites for
    at least one day

    4.3  DECONTAMINATION OF SPILLAGE AND CONTAINERS

         Residues in containers should be emptied in a diluted form into
    a pit, taking care to avoid contamination of ground waters. A
    soakage pit should be provided for the rinsings. Decontaminated
    containers should not be used for any purpose. Spillage of
    ethoprophos and its formulations should be removed by washing with
    5% sodium hydroxide solution and then rinsing with large quantities
    of water. Impermeable gauntlets should be worn during this work.

    4.4  EMERGENCY AID

    4.4.1  Early symptoms of poisoning

         Early 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.

    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, 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 resuscitation should be given, bearing in mind that if
    mouth-to-mouth resuscitation is used, vomit may contain hazardous
    amounts of ethoprophos.

    5.0  FOR MEDICAL AND LABORATORY PERSONNEL

    5.1  MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING

    5.1.1  General information

         Ethoprophos is an organophosphorus pesticide of very high
    mammalian toxicity. It is readily absorbed from the gastrointestinal
    tract, through intact skin, and by inhalation of dust or fine spray
    mist.

    5.1.2  Symptoms and signs

         Initial symptoms 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 include 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 ethoprophos.

    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. 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.

         Persons without signs of respiratory insufficiency but with
    manifest peripheral symptoms should be treated with 2-4 mg of
    atropine sulfate by intravenous injection and 1 000 mg 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 provided with ventilatory
    support and 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. Diazepam may be
    given to control convulsions. 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, oxygen
    should be given at the same time as atropine sulfate. The airways
    should be kept free and artificial resuscitation should be applied
    if required, preferably by mechanical means

         Contraindications are morphine, barbituates, phenothiazine and
    central stimulants of all kinds. Pralidoxime and toxogonin alone are
    not regarded as effective antidotes in ethoprophos poisoning.

    5.1.5  Prognosis

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

    5.1.6  References of previously reported cases

         No published information.

    5.2  SURVEILLANCE TESTS

         Test                     Normal    Action    Symptomatic
                                  level*    level*    level*

         Plasma cholinesterase     100%       50%     variable

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

    5.3  LABORATORY METHODS

    5.3.1  Detection and assay of compound

         Thin layer chromatography and gas-liquid chromatography methods
    have been used to analyse ethoprophos in technical products and its
    formulations. Analysis of residues in plant and animal tissues may
    be performed by gas chromatography and flame photometry methods.

         Foster R. L., (1974), Proc. Annu. Ind. Air Pllut. Conf., 4,
           66.

         Hunt T. W., (1979), Diss. Abst. Int. B., 40, 1 437.

         Hunt T. W., Leidy R. B., Sheets T. J., and Duncan H. E. (1981),
           Bull. Environ. Contam. Toxicol., 27, 84.

                   

    * Expressed as percentage of pre-exposure activity.

         Leidy R. B. and Sheets T. J. (1980), Beitr. Tabakforsch.
           Int., 10, 127.

         Sagredos A. N. N. and Echert, W. R. (1976), Beitr.
           Tabakforsch., 8, 447.

    5.3.2  Other tests in case of poisoning

         Blood cholinesterase activity, particularly erythrocyte provide
    the most useful diagnosis of poisoning. Urine metabolites may also
    be determined in order to give an indication of exposure. For
    methods, see section 5.3.1.

    REFERENCES

    1.   Hartley, D., Kidd, H. (1983) "The Agrochemicals Handbook".
           Royal Society of Chemistry. Unwin Bors. Surrey, United
           Kingdom

    2.   Hudson, R. M. "Handbook of Toxicity of Pesticides to Wildlife",
           2nd Edition (1985): p. 41

    3.   FAO/WHO (1985) - 1985 Evaluations of Some Pesticide Residues in
           Food. FAO Plant Production and Protection Paper 61.

    4.   Worthing, C. R. (1987) "The Pesticide Manual. A World
           Compendium". British Crop Protection Council, United Kingdom,
           Eighth Edition.
See Also:
        Ethoprophos (PIM 774)