Alterations in drug metabolism in workers exposed to polychlorinated biphenyls

Abstract

Administration of the polychlorinated biphenyls (PCBs) mixture, Aroclor 1016, to rats elicited a barbiturate type of inducing effect on the hepatic microsomal oxidative enzyme system. Aroclor 1016 caused significant increases in liver cytochrome P-450 content, microsomal protein, and ethylmorphine N-demethylase activity; its effect on benzo(a)pyrene hydroxylase activity was minimal. Unlike the widely studied PCBs mixture, Aroclor 1254, Aroclor 1016 did not induce cytochrome P-448 in liver microsomes. Five workers occupationally exposed to Aroclor 1016 in a capacitor-manufacturing plant showed a significantly lower mean antipyrine half-life (10.8 hr) than the mean half-life of 15.6 hr in non-PCBs-exposed normal subjects. These differences in half-life were accompanied by increased metabolic clearance rates in workers exposed to the PCBs, which strongly suggests that PCBs accelerate the rate of drug metabolism in man. Our studies show that Aroclor 1016 elicits the barbiturate type of inducing effects on drug metabolism in man as well as animals.