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 formulaBIOLOGICAL 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)