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    PESTICIDE RESIDUES IN FOOD - 1982


    Sponsored jointly by FAO and WHO






    EVALUATIONS 1982





    Data and recommendations of the joint meeting
    of the FAO Panel of Experts on Pesticide Residues
    in Food and the Environment and the
    WHO Expert Group on Pesticide Residues
    Rome, 23 November - 2 December 1982

    Food and Agriculture Organization of the United Nations
    Rome 1983


    ETRIMFOS

    CHEMICAL STRUCTURE 1

    Explanation

         Etrimfos was evaluated by the 1980 JMPR (FAO 1981).1 A temporary
    ADI for man was recommended, based on no-effect levels observed in
    2-year studies in the rat and dog.

         The 1980 JMPR Report required disposition and kinetic data on the
    whole molecule of etrimfos and its triester metabolites in animals and
    considered observations in man as being desirable.

         Daily sheet reports on field applicators and comments on the
    required information have been provided and are summarized in this
    monograph addendum.

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    BIOCHEMICAL ASPECTS

    Metabolism

         Metabolism studies in the rat have shown that the P-O-pyrimidine
    ester bond in etrimfos is rapidly cleaved. This is the major
    detoxification process. Studies with rat and mouse liver homogenates
    (Ioannou and Dauterman 1978) have shown that the P-O-CH3 and the
    P-O-pyrimidine ester bonds are rapidly cleaved. These studies clearly
    show that the triester molecule has only a transient existence in the
    animal system and that the phosphoric acid moiety exists either as
    the mono-methyl ester, or possibly as free phosphoric acid.
    Re-esterification of the phosphoric acid moiety in the animal system,
    if it occurs, would not be something specific to etrimfos, but would
    be common to organophosphorus insecticides in general (Karapally
    1982).

              

    1  See Annex 2 for WHO and FAO documentation.

    TOXICOLOGICAL STUDIES

    Observations in Humans

         During the developing phase of etrimfos, 167 daily sheet reports
    on field trials personnel were completed. The reports cover more than
    220 hours of work in the field with different etrimfos-containing
    formulations. Applicators worked in different locations under varying
    weather conditions for periods of 0.5 to 3 hours/day, wearing in most
    cases only boots and protective overcoats.

         No noteworthy symptoms or complaints during or at the end of the
    working period were recorded.

         No clinical investigations were carried out (Sandoz 1976).

    COMMENTS

         Etrimfos was evaluated for an acceptable daily intake for man by
    the 1980 JMPR. The Meeting examined the submitted comments regarding
    the metabolism of etrimfos and reports on people engaged in field
    applications of etrimfos formulations that were made available.

         Studies of the metabolism and distribution of etrimfos in rats
    undertaken with 14C in the pyrimidine moiety have provided useful
    information and, following clarification by the manufacturers, further
    disposition and kinetic data were not considered necessary.

         Although the Meeting agreed that the submitted observations in
    humans were of little value, primarily because no clinical
    investigations were carried out, an ADI was allocated.

    TOXICOLOGICAL EVALUATION

    Level Causing no Toxicological Effect

    Rat : 6 ppm in the diet, equivalent to 0.3 mg/kg bw.

    Dog : 10 ppm in the diet, equivalent to 0.25 mg/kg bw.

    Estimate of Acceptable Daily Intake for Man

    0 - 0.003 mg/kg bw

    FURTHER WORK OR INFORMATION

    Desirable

    Further observations in humans.

    REFERENCES

    Ioannou, Y.M. Dauterman, W.C. In vitro metabolism of etrimfos by rat
    1978      and mouse liver. Pest.Biochem. Physiol. 9:190-195.

    Karapally, J.C. Personal communication to WHO. Sandroz, Switzerland
    1982

    Sandoz, Daily sheet reports of field applicators. Agrochemical
    1976      Division, Basle, Switzerland. Report from Sandoz submitted
              to the WHO by Sandoz. (Unpublished)


    See Also:
       Toxicological Abbreviations
       Etrimfos (Pesticide residues in food: 1980 evaluations)