The effects of the insecticide 2,2,2-trichloro-1-(3,4-dichlorophenyl)ethyl acetate on drug metabolism in the rat

Abstract

The effects of 2,2,2-tricholoro-1-(3,4-dichlorophenyl)ethyl acetate (Penfenate) on hepatic, renal and small intestinal drug-metabolizing enzyme activities, hepatic reduced glutathione content and urinary excretion of thioethers were studied in the rat. A single i.p. dose of Penfenate (500 mg/kg) decreased the body weight of the animals in 1–3 days, increased hepatic protein content at 2 days and increased urinary thioether excretion 12–24 g after the treatment. In liver a single i.p. dose (500 mg/kg) enhanced cytochrome P-450 content 1.7-fold, ethoxycoumarin O-deethylase activity 2.5-fold, 2,5-diphenyloxazole hydroxylase activity 1.6-fold, epoxide hydrolase activity 2.5-fold, glutathione S-transferase activity 1.4-fold and UDPglucuronosyltranferase (4-methylumbelliferone) activity 2.3-fold in 3 days. No effects could be seen 2 weeks after the treatment. Five consecutive daily doses (500 mg/kg) enhanced the drug metabolizing enzyme activities and caused a 50% mortality. A dose of 100 mg/kg had only minor effects on hepatic drug metabolizing enzyme activities. Renal and intestinal enzyme activities were only slightly affected by the administration of Penfenate. These data indicate that quite large doses of Penfenate are needed to bring about any significant effects and the effects are restricted mainly to the liver. However, the ability of Penfenate to change drug metabolizing enzyme activities must be considered when evaluating the advantages and disadvantages of this insecticide as a substitute for DDT.