Differences in the in vivo and in vitro effects of the carbamate insecticide, carbaryl on rat hepatic monooxygenases.

The effects of one of the most widely used insecticides, carbaryl, on the hepatic cytochrome P-450-dependent monooxygenases were determined. Addition of carbaryl to liver microsomes from untreated or phenobarbital (PB)-pretreated rats resulted in a weak Type I binding spectrum. A much stronger spectral Type I interaction was observed when microsomes from 3-methylcholanthrene(3-MC)-treated rats were used. In vitro, carbaryl caused marked inhibition of ethylmorphine and benzphetamine N-demethylases, benzo(a)pyrene hydroxylase, 7-ethoxycoumarin and 7-ethoxyresorufin O-deethylase in liver microsomes. Kinetic studies demonstrated that carbaryl was a competitive inhibitor of ethylmorphine N-demethylase activity. Daily administration of carbaryl for 4 days by gavage or intraperitoneally resulted in no significant alterations in hepatic cytochrome P-450 levels, ethylmorphine N-demethylase or benzo(a)-pyrene hydroxylase activities. The lack of effect of carbaryl in vivo may be due to the rapid metabolism of the insecticide, such that the insecticide may not be present in the liver endoplasmic reticulum to cause the inhibitory effects observed in vitro.