PESTICIDE RESIDUES IN FOOD - 1984 Sponsored jointly by FAO and WHO EVALUATIONS 1984 The monographs 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, 24 September - 3 October 1984 Food and Agriculture Organization of the United Nations Rome 1985 PARATHION METHYL Explanation Parathion Methyl was evaluated by the Joint Meeting in 1968, 1972, 1975, 1979 and 1980 (FAO/WHO 1969, 1973, 1976, 1980, 1981). A temporary ADI of 0-0.001 mg/kg bw was allocated in 1980. New data were presented to the JMPR in 1982, including mutagenicity data, a 3-generation reproduction study and data from a two-year rat feeding study. However, since the available oncogenicity data did not permit a complete evaluation of the carcinogenic potential of parathion methyl the meeting extended the temporary ADI and requested additional data on the two-year feeding study in rats by 1984. Additional information is reviewed in this monograph addendum. EVALUATION FOR ACCEPTABLE DAILY INTAKE TOXICOLOGICAL STUDIES Special Studies on Carcinogenicity Rat Additional data on a 2-year feeding study in rats as requested by the Joint Meeting in 1982 (FAO/WHO 1983) were available. Historical data on the incidence of follicular and parafollicular thyroid adenomas as well as uterine adenocarcinomas in SPF Wistar TNO/W74 rats used in previous report (Bomhard et al., 1981) have been provided. Tumours of the same type in both thyroid lobes were counted as being one tumour. The incidence of thyroid carcinomas were also included. The historical control data were collected from 15 experiments. The thyroid and uterine tumour incidence of the high dose group (50 ppm) is within the range of the historical controls. Only fifty percent of the control animals from Bomhard et al., 1981, study were examined histologically. Histological examination of the 2 and 10 ppm dose groups were performed and these data were presented as well. In both groups there were no pathomorphological indications of compound related effects on the organ systems evaluated. Type and location of benign and malignant tumours did not demonstrate an oncogenic effect from parathion methyl as they were randomly distributed and within the normal range for this strain of rat (Schilde and Bomhard, 1984). Acute Toxicity The acute toxicity of parathion methyl via oral and dermal routes is summarized in Table 1. TABLE 1: Acute Toxicity of Parathion Methyl Species Sex Route LD50 Reference Rat (fasted) M Oral 2.9 mg/kg Heiman, 1982 F Oral 3.2 mg/kg Heiman, 1982 Rat M Oral 10.8 mg/kg Heiman, 1982 (non-fasted) F Oral 9.3 mg/kg Heiman, 1982 Rabbit M Oral 10.0 mg/kg Heiman, 1982 (fasted) F Oral 19.4 mg/kg Heiman, 1982 Rat M Dermal 46.0 mg/kg Heiman, 1982 F Dermal 41.0 mg/kg Heiman, 1982 Special Study on Eye and Skin Irritation Instillation of 0.1 g of parathion methyl into the conjunctival sac of albino rabbits did not produce irritation. Application of 0.5g of parathion methyl (as a wet paste) to the skin of albino rabbits did not produce primary skin irritation (Pauluhn, 1983). Short-term Studies Rabbit - Dermal Groups of New Zealand white rabbits (6 males and 6 females per group) were administered parathion methyl (purity 96.3%) dermally at dose levels of 0, 50 and 250 mg/kg bw formulated in Cremophor E.I., applied daily for 3 weeks (15 consecutive workdays). Material was left uncovered for 6 hours. The skin was then cleaned with soap and water. There was a dose-related inhibition of erythrocyle and brain cholinesterases in both dose groups. Plasma cholinesterase was also significantly depressed in the high dose group. These animals presented symptoms of cholinergic poisoning and 5 animals in this group died. The results of the remaining clinical chemistry, hematological evaluations and organ weight data did not demonstrate significant differences from controls. Microscopic examination revealed epithelial proliferation with hyperkeratosis of the treated skin. Since a no effect level was not established a separate three-week dermal study was initiated using 0 and 10 mg/kg bw. No signs of dermal involvement or proliferative changes were noted and cholinesterase levels were comparable to controls (Mihail and Vogel, 1984). Rat - Inhalation Groups of Wister albino rats (10 males and 10 females per group) were exposed to parathion methyl aerosol concentrations of 0 (solvent only), 0.9, 2.6 and 9.7 mg per 120 m air. Animals were exposed for 6 hours/day, 5 days/ week for 3 consecutive weeks. No mortality occurred. Plasma and brain cholinesterase levels were significantly depressed in high dose groups animals. They presented signs of cholinergic poisoning, reduced body weight gain and decreased organ weights. The mid dose group presented slight inhibition of plasma cholinesterase levels. Histopathological examinations were unremarkable between treated and control groups (Thyssen and Mohr, 1982). COMMENTS Parathion methyl was allocated a temporary ADI of 0-0.001 mg/kg by the 1980 JMPR. New data were presented at the 1982 JMPR including a two-year rat study but as this did not allow full evaluation of the carcinogenic potential of parathion methyl, or permit a no-effect level to be established, the temporary ADI was extended and additional data were requested from the two-year rat study by 1984. Re-evaluation of these data, the additional data requested and now provided, and carcinogenicity studies of parathion methyl in mouse and rat of the National Cancer Institute (1979) have indicated no evidence of carcinogenicity and have allowed the calculation of a no-effect dose in the two-year rat feeding study of 2 ppm in respect to terminal brain cholinesterase, plasma and erythrocyte cholinesterasis. This allowed the allocation of a full ADI, based partly on data in man (see 1975 JMPR). Level causing no toxicological effect Rat: 2 ppm in the diet equivalent to 0.1 mg/kg bw Man: 0.3 mg/kg bw/day Estimate of acceptable daily intake for man 0 - 0.02 mg/kg bw FURTHER WORK OR INFORMATION Desirable: Further observations in man. REFERENCES Bomhard, E., Loser, E., and Schilde, B. (1981) E605-Methyl (parathion-methyl) chronic toxicological study on rats (feeding experiment of two years). Report submitted to the World Health Organization by Bayer AG. (Unpublished) Bomhard, E. (1984). Ref: Parathion Methyl/report no. 9889: WHO requirements. Report submitted to the World Health Organization by Bayer AG. (Unpublished) Heinmann, K.G. (1982). E 120 (Parathion-Methyl)/Tests for acute oral and acute dermal toxicity. Report submitted to the World Health Organization by Bayer AG. (Unpublished) Mihail, F. and Vogel, O. (1984). E 120 (Parathion-Methyl)/Subacute dermal toxicity studies with rabbits. Report submitted to the World Health Organization by Bayer AG.(Unpublished) NCI, (1979). Bioassay of Methyl Parathion for possible carcinogenicity study. D.H.E.W. publication NCI-CG-TR-157. National Institutes of Health Bethesda M.D. Pauluhn, J. (1983). Parathion Methyl (E 120)/Study for irritant/corrosive effect on skin and eye (Rabbits). Report submitted to the World Health Organization by Bayer AG. (Unpublished) Schilde, N. and Bomhard, E. (1984). E 605-methyl (Parathion Methyl) /Supplementary histopathological examination for the two year feeding study with rats (addendum to Rep. No. 9889). Report submitted to the World Health Organization by Bayer AG. (Unpublished) Thyssen, J. and Mohr. U. (1982). E 120 (Parathion Methyl) /Subacute inhalation study with rats. Report submitted to the World Health Organization by Bayer AG. (Unpublished)
See Also: Toxicological Abbreviations Parathion Methyl (Pesticide residues in food: 1982 evaluations)