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    FAO Meeting Report No. PL/1965/10/1
    WHO/Food Add./27.65

    EVALUATION OF THE TOXICITY OF PESTICIDE RESIDUES IN FOOD

    The content of this document is the result of the deliberations of the
    Joint Meeting of the FAO Committee on Pesticides in Agriculture and
    the WHO Expert Committee on Pesticide Residues, which met in Rome,
    15-22 March 19651

    Food and Agriculture Organization of the United Nations
    World Health Organization
    1965

                
    1 Report of the second joint meeting of the FAO Committee on
    Pesticides in Agriculture and the WHO Expert Committee on Pesticide
    Residues, FAO Meeting Report No. PL/1965/10; WHO/Food Add./26.65

    METHYL PARATHION

    Chemical name

           Dimethyl-4-nitrophenyl phosphorothionate;
    O,O-dimethyl-O-(-4-nitrophenyl) phosphorothioate.

    Synonyms

           Methaphos; Wolfatox; Dimethylparathion; Metacide.

    Empirical formula

           C8H10O5NSP

    Structural formula

    CHEMICAL STRUCTURE 

    BIOLOGICAL DATA

    Biochemical aspects

           Methyl parathion has biological properties similar to those of
    parathion. Methyl parathion is oxidized to methyl paraoxon, mainly in
    the liver, and this has a weaker inhibitory effect on cholinesterase
    than paraoxon (Davison, 1955a; Hazleton, 1955). The molar I50 of
    methyl paraoxon (rat brain 30 min. at 37) was 4.0  10-8 (Davison,
    1955b).

           In guinea-pigs given orally 32P-labelled methyl parathion, the
    compound began to enter the organs at once and the maximum tissue
    levels were reached in 1-2 hours. A high concentration of the compound
    was found in the liver (Gar et al., 1958).

    Acute toxicity

                                                                    
    Animal        Route         LD50 mg/kg     References
                                body-weight
                                                                    

    Rat           Oral           9.0-42.0*     Deichmann et al., 1952
                                               Gaines, 1960
                                               Metcalf, 1955

    (continued)
                                                                    
    Animal        Route         LD50 mg/kg     References
                                body-weight
                                                                    
    Rat           Oral           9.7-14.8      Deichmann et al., 1952
                              (pure product)   Gaines, 1960
                                               Metcalf, 1955

    Rat      Intraperitoneal        3.5        DuBois & Coon, 1952

    Mouse         Oral             32.1        Ikeda, 1962
                                                                    

    * Dependent on the sex of the animal, the vehicle used and the purity
      of the sample.


    Short-term studies

           Dog. Groups of 2 dogs, one male and one female, were maintained
    on diets containing 5, 20 and 50 ppm of methyl parathion for 12 weeks.
    The two highest dosage levels produced significant depression in
    erythrocyte cholinesterase activity. Plasm cholinesterase activity was
    significantly depressed at 50 ppm but only a doubtful change was seen
    at 20 ppm. The 5 ppm level produced no significant inhibition of
    cholinesterase activity (Williams et al., 1959).

           Man. A group of 5 subjects was given 3 mg of methyl parathion
    orally per day for 28 days, 3.5 mg per day for 28 days, and 4.0 mg per
    day for 43 days. No depression of erythrocyte or plasm cholinesterase
    activity occurred and no side-effects were seen (Moeller & Rider,
    1961).

           A group of 5 subjects was given daily 4.5 mg during 30 days
    followed by 5 mg for 29 days. Another group received 5.5 mg for 20
    days followed by 6 mg for 29 days and the last group received 6.5 mg
    for 35 days, followed by 7 mg for 24 days. The maximum depression of
    whole-blood cholinesterase activity was 15% (Moeller & Rider, 1962).

           Groups of 5 subjects were given methyl parathion for 30 days in
    the following amounts: 7 mg per day, 7.5 mg per day, 8 and 9 mg per
    day. The plasma and erythrocyte cholinesterase activities remained
    within 20% of the control values (Moeller & Rider, 1963).

    Long-term studies

           No information available.

    Comments on experimental studies reported

           The biochemical and toxicological studies on this compound are
    not as extensive as in the case of parathion but it would seem to have

    been adequately investigated in man from the point of view of its
    effect on cholinesterase activity.

    EVALUATION

    Level causing no significant toxicological effect

           The highest dietary dose having no effect on cholinesterase
    activity was 7-9 mg per day in man, equivalent to approximately 0.1
    mg/kg body-weight per day.

    Estimate of acceptable daily intake for man

           0-0.01 mg/kg body-weight per day.

    Further work desirable

           Reproduction studies in the rat.

    REFERENCES

    Davison, A. N. (1955a) Biochem., J., 61, 203

    Davison, A. N. (1955b) Biochem. J., 60, 399

    Deichmann, W. B., Pugliese, W. & Cassidy, J. (1952) A.M.A. Arch.
    industr. Hyg., 5, 523

    DuBois, K. P. & Coon, J. M. (1952) A.M.A. Arch. industr. Hyg., 6,
    9

    Gaines, T. B. (1960) Toxicol. appl. Pharmacol., 2, 88

    Gar, K. Sazonova, N. A., Fadeer, Y. N. Vladimirova, I. L. & Golubeva,
    N. A. (1958) Org. Insektofungitsidy i Gerbitsidy, 93 (From Chem.
    Abstr., 54, 15688)

    Hazleton, L. W. (1955) Agr. Food Chem., 3, 312

    Ikeda, Y. (1962) Report to the Japan Academy of Sciences

    Metcalf, R. L. (1955) Organic insecticides, Interscience, New York

    Moeller, H. C. & Rider, J. A. (1961) Fed. Proc., 20, 434

    Moeller, H. C. & Rider, J. A. (1962) Fed. Proc., 21, 451

    Moeller, H. C. & Rider, J. A. (1963) Fed. Proc., 22, 189

    Williams, M. W., Fuyat, H. N. & Fitzhugh, O. G. (1959) Toxicol.
    appl. Pharmacol., 1, 1
    


    See Also:
       Toxicological Abbreviations
       Methyl parathion (EHC 145, 1992)
       Methyl parathion (HSG 75, 1992)
       Methyl parathion (ICSC)
       Methyl Parathion  (IARC Summary & Evaluation, Supplement7, 1987)
       Methyl Parathion (IARC Summary & Evaluation, Volume 30, 1983)