PESTICIDE RESIDUES IN FOOD - 1979 Sponsored jointly by FAO and WHO EVALUATIONS 1979 Joint meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Expert Group on Pesticide Residues Geneva, 3-12 December 1979 OMETHOATE Explanation Omethoate was evaluated in 1971 and reviewed in 1975 and 1978. The ADI established in 1971 was a temporary basis because no long-term studies were available. Data on subacute dermal toxicity, acute and subacute inhalation toxicity and on pharmacokinetics were received and are reviewed, and summarized in this monograph addendum. EVALUATION FOR ACCEPTABLE DAILY INTAKE Absorption, Distribution and Elimination The distribution and elimination of 14C-omethoate was investigated in the rat. After oral administration of 0, 3, 5 or 10 mg/kg omethoate, 96-97% of the radioactivity was eliminated within 48 hours in urine and 1-2% in faeces. Over this period, about 1% of the radioactive dose was exhaled as 14CO2. Intravenous injection of 0.3 mg/kg resulted in a similar rapid elimination pattern. Maximal tissue residues were reached one hour after administration. After the first eight hours, about 18% of the residual radioactivity was observed in the body. After 2 days, less than 0.55% of the administered dose was observed. From quantitative data and whole body autoradiography, a relatively homogeneous distribution of 14C-activity was observed, with the exception of the thyroid, in which a 10-20 fold higher concentration was found (Weber, et al., 1978). TOXICOLOGICAL STUDIES Acute Inhalation Toxicity Groups of 10 Wistar rats of each sex were exposed by inhalation to aerosols of omethoate and observed for 14 days. Estimates of the LC50 are summarized in Table 1. Table 1. Exposure by inhalation of rats to aerosols of omethoate Exposure time LC50 (mg/m3) Lowest concentration causing clinical signs of poisoning 1 hour 1000 338 4 hours 300 (male) <60 220 (female) 60 5 × 4 hours <49 13 Clinical signs of poisoning were observed for up to 10 days after exposure. Acetylcholinesterase depression in plasma and erythrocytes, measures in the multiple-exposure experiment, was found to be dose-related. Cholinesterase activity was depressed at all dose levels tested. Three days after the last exposure, no enzyme inhibition was noted in plasma. This recovery was not noted with erythrocyte cholinesterase. No treatment-related pathological effects were observed in the lungs (Thyssen, 1978). Subacute Dermal Toxicity Groups of rabbits (3 male and 3 female rabbits per group) were dermally administered 0, 2.5 or 20 mg/kg body weight omethoate in aqueous solutions for three weeks (7 hours/day, 5 days/week) to the intact or abraded skin. No dose-related effects were observed on body weight or a variety of clinical chemistry, hematological, or urological parameters. The gross weight of tissues and organs (heart, lungs, liver, spleen, kidneys, adrenals, thyroid, testes and ovaries) did not deviate from control values. Pathological examination of these organs, as well as of the uterus, epididymis, and skin showed no changes attributable to dermal omethoate treatment. Inhibition of acetylcholinesterase activity in plasma, erythrocytes, and brain was observed in those rabbits receiving 20 mg/kg. After 1-3 days of treatment, the enzyme depression was accompanied by clinical signs of poisoning in animals with abraded skin. In the lower dose group, only females with abraded skins showed an inhibition of brain cholinesterase activity (Flucke and Luckhaus, 1979). COMMENTS Additional information was reviewed confirming that omethoate-induced inhibition of cholinesterase is the most predominant toxicological parameter as was previously noted in acute and subacute experiments. Omethoate is rapidly absorbed following oral administration, and elimination is complete within a few days. The residual concentrations found in specific organs of the body decreased very rapidly after administration, with the exception of the thyroid gland, in which elimination was relatively slow. The meeting was informed that the previously required long-term study was complete, and the report was to be made available shortly. The existing temporary ADI was therefore extended. TOXICOLOGICAL EVALUATION Level Causing No Toxicological Effect Rat: 1.0 ppm in the diet, equivalent to 0.05 mg/kg body weight Dog: 1.6 ppm in the diet, equivalent to 0.12 mg/kg body weight ESTIMATE OF TEMPORARY ACCEPTABLE DAILY INTAKE FOR MAN 0-0.0005 mg/kg body weight FURTHER WORK OR INFORMATION Required by June 30, 1980: Report of the long-term study. Desirable: Information on the possible accumulation of omethoate in the thyroid. REFERENCES Flucke, W. and Luckhaus, G. Folimat-Wirkstoff (S 6876, Omethoat). Subkuter kutaner Toxizitätsversuch an Kanichen. (1979) Unpublished report submitted by Bayer AG. Thyssen, J. S 6876 (Folimat-Wirkstoff). Akute Inhalationstoxizität. (1978) Unpublished report submitted by Bayer AG. Weber H., Patzschke, K., and Wegner, L.A. Omethoat-14C (Folimat(R)-Wirkstoff). Biokinetische Untersuchungen an Ratten. (1978) Unpublished report submitted by Bayer AG.
See Also: Toxicological Abbreviations Omethoate (WHO Pesticide Residues Series 1) Omethoate (WHO Pesticide Residues Series 5) Omethoate (Pesticide residues in food: 1978 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)