The effect of hepatic microsomal monooxygenase induction on the metabolism and toxicity of the organophosphorus insecticide chlorfenvinphos.

The induction of rat liver microsomal monooxygenase by pretreatment of rats with dieldrin affords a 10-fold protection against the acute toxic effects of the organophosphorus insecticide, chlorfenvinphos. Metabolism studies were carried out to confirm that the protection was due to an enhanced rate of detoxification (via oxidative deethylation). At low doses of chlorfenvinphos (2.5 mg . kg-1), dieldrin pretreatment caused minimal changes in the metabolic profiles. However, at a higher dose (13.2 mg . kg-1), giving clinical signs of intoxication in the control animals, the dieldrin pretreated rats produced 5 times more deethylchlorofenvinphos than did the control animals. The results support the conclusion that the effect of enzyme induction on the metabolism of substrates of that enzyme are dose-dependent. Alterations in metabolism, therefore, are not an automatic consequence of enzyme induction.