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    OMETHOATE       JMPR 1978

    Explanation

         Omethoate was evaluated by the Meetings in 1971 and 1975
    (FAO/WHO, 1972b, 1976b). A temporary ADI was established and
    further toxicological information required (1978); also information
    on residues occurring in food in commerce was listed as desirable.
    The Tenth Session of the Codex Committee on Pesticide Residues
    (1978) raised some questions regarding this compound. Information
    received is reviewed in this monograph addendum.

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    BIOCHEMICAL ASPECTS

         Omethoate is a direct inhibitor of cholinesterase activity. In
    a study evaluating the reversibility of cholinesterase depression
    following oral acute intoxication, cholinesterase activity of
    plasma, RBC and brain was evaluated at various times up to 14 days
    after treatment. Groups of female rats were administered omethoate
    at dose levels ranging from 0 to 17.8 mg/kg. Plasma cholinesterase
    was rapidly depressed (within 2 hours) and was more sensitive than
    RBC cholinesterase.

         Recovery of plasma activity was essentially complete within 7
    days. RBC cholinesterase was not substantially depressed at any
    dose level tested. In contrast, brain cholinesterase was
    substantially depressed at 1.3 mg/kg. Brain cholinesterase was
    recovered completely at this level within 24 hours while at the
    highest dose level recovery occurred some time between 3 and 7 days
    (Flucke and Kimmerle, 1978).

    Acute toxicity
                                                                              
    Species  Sex    Route         LD50              Reference
                                  mg/kg
                                                                              
    Rat      M      Oral          27.3 (25.5-29.6)    Flucke & Kimmerle, 1978
             F      Oral          25.6 (23.8-27.6)    Flucke & Kimmerle, 1978
             M      Dermal        1018 (937-1118)     Flucke & Kimmerle, 1978
             F      Dermal        865 (774-943)       Flucke & Kimmerle, 1978
                                                                              

    COMMENTS

         Acute toxicity and cholinesterase depression and recovery data
    were received and reviewed in this monograph addendum. The data on
    brain cholinesterase depression suggest this enzyme to be the most
    sensitive parameter for evaluating the anticholinesterase effects
    of omethoate. The recovery of cholinesterase activity was
    essentially complete in 7 days after poisoning attesting to the
    rapid reversibility of enzyme depression. Assurances were presented

    to the Meeting that the data required for the long-term studies which 
    were in progress since 1975, would be available in the near future. 
    The temporary ADI was maintained until the next meeting.

    TOXICOLOGICAL EVALUATION

    Level causing no toxicological effect

         Rat: 1.0 ppm in the diet equivalent to 0.05 mg/kg bw.

         Dog: 1.6 ppm in the diet equivalent to 0.12 mg/kg bw.

    Estimation of temporary ADI for man

         0 - 0.0005 mg/kg body weight.

    RESIDUES IN FOOD AND THEIR EVALUATION

    RESIDUES RESULTING FROM SUPERVISED TRIALS

         In written comments to the 10th Session of CCPR (1978) the
    delegation of the Netherlands had questioned the usefulness of
    limits for omethoate in sugar beet in the absence of MRLs for milk
    and meat. No information on this subject was received by the
    Meeting, but review of the data from animal feeding trials reported
    by the 1971 Meeting (FAO/WHO, 1972b) showed that it could be
    possible for omethoate to occur in the milk of cows fed on
    material, such as sugar beet leaves, containing omethoate at the
    recommended MRL of 1 mg/kg. Data would be required to clarify this
    matter and to provide information on any occurrence in meat.

    RESIDUES IN FOOD IN COMMERCE

         Data received from New Zealand (1978) showed that of 16 random
    retail samples of apples examined in 1975, 10 contained residues of
    omethoate in the range 0-0.2 mg/kg with a mean of 0.14 mg/kg. One
    sample of 16 of canned fruit (unspecified) contained 0.02 mg/kg of
    omethoate. Apples known to have been treated with omethoate were
    also examined. In 1975, levels in 8 samples ranged up to 0.4 mg/kg
    with a mean of 0.13 mg/kg in 1977, levels in 10 samples reached 1.9
    mg/kg with a mean value of 0.66 mg/kg. These are all within the MRL
    of 2 mg/kg recommended in 1971 (FAO/WHO, 1972a, b).

         Samples of raw produce examined continuously in routine
    national surveys (Australia, 1978) had led to no reports of
    omethoate residues in meat, grain, dairy products, fruit or
    vegetables. This report indicated that omethoate was used in
    Australia on pome fruits, citrus, potatoes, onions and cotton.

    APPRAISAL

         Some information was made available concerning residues of
    omethoate occurring in food in commerce, this confirmed the
    applicability of the previously recommended MRLs.

         Data on omethoate residues occurring in milk and meat from
    feeding animals with treated crops such as sugar beet leaves was
    not available. The limited evidence showed that such data were
    desirable.

    RECOMMENDATIONS

         No change in suggested in the MRLs previously recommended.

    FURTHER WORK OR INFORMATION

    Required (by 1979)

         Submission of the long-term studies on rats currently in
    progress.

    Desirable

         Data on omethoate residues in meat and milk following feeding
    of animals with treated forage such as sugar beet leaves.

    REFERENCES

    Australia  Data on use patterns and residues of omethoate in food
    (1978)         in Australia.  Unpublished report.

    CCPR  Report of the 1977 Meeting of the Codex Committee on
    (1978)         Pesticide Residues. ALINORM 78/24, Para. 115.

    Flucke W. and G. Kimmerle Folimat-Wirkstoff (S-6876) Untersuchungen
    (1978)         zur akuten toxiaitat bei ratten mit bestimmung der
                   activitat der cholinesterasen in blutplasma,
                   erythrozyten und gehirn. Unpublished report from
                   the Institute for Toxicologie, Bayer AG submitted
                   by Bayer AG to the WHO.

    New Zealand  Data on residues of omethoate in food. Unpublished
    (1978)         report.
    


    See Also:
       Toxicological Abbreviations
       Omethoate (WHO Pesticide Residues Series 1)
       Omethoate (WHO Pesticide Residues Series 5)
       Omethoate (Pesticide residues in food: 1979 evaluations)
       Omethoate (Pesticide residues in food: 1980 evaluations)
       Omethoate (Pesticide residues in food: 1981 evaluations)
       Omethoate (Pesticide residues in food: 1984 evaluations)
       Omethoate (Pesticide residues in food: 1985 evaluations Part II Toxicology)