In vitro covalent binding of cismethrin, bioresmethrin, and their common alcohol to hepatic proteins.

H Hoellinger, M Sonnier, A J Gray, T A Connors, J Pichon, H N Nguyen

Index: Toxicol. Appl. Pharmacol. 77(1) , 11-8, (1985)

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Abstract

When [14C]Alcohol-labeled cismethrin, bioresmethrin, and 5-benzyl-3-furylmethyl alcohol (BFA) were incubated with rat liver S 9 homogenates or microsomes, a proportion of the radioactive compounds was covalently bound to proteins. The covalent binding was greater with phenobarbital-pretreated rats, and dependent on a NADPH-generating system. When a S 9 homogenate was used, the bound compounds were twofold higher for cismethrin than for bioresmethrin and BFA. Inversely, when microsomes were used more covalent binding occurred with bioresmethrin and BFA than with cismethrin. The inhibition of esterases by tetraethyl pyrophosphate (TEPP) in a S 9 homogenate did not alter the amount of covalent binding to the three compounds whereas malathion inhibited this binding. Treatment of a S 9 homogenate with piperonyl butoxide, however, greatly reduced covalent binding. Covalent binding was inhibited when the microsomes were incubated with carbon monoxide or modified by thermal denaturation. It is suggested that oxidative metabolism was responsible for the covalent binding.