Alterations in drug metabolism in workers exposed to polychlorinated biphenyls

Abstract

Administration of the polychlorinated biphenyls (PCRs) mixture, Aroclor 1016, to rats elicited a barbiturate type of inducing effeet on the hepatic microsomal oxidative enzyme system. Aroclor 1016 eaused significant increases in liver eytoehrome P-450 eontent, microsomal protein, and ethylmorphine N-demethylase activity; its effeet on benzoiaipyrene hydroxylase activity was minimal. Unlike the widely studied PCRs mixture, Aroclor 1254, Aroclor 1016 did not induce eytoehrome 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-PCRs--exposed normal subjeets. These differenees in half-life were aeeompanied by increased metabolie clearanee rates in workers exposed to the PCRs, whieh strongly suggests that PCRs accelerate the rate of drug metabolism in man. Dur studies show that Aroclor 10/6 elicits the barbiturate type of inducing effeets on drug metabolism in man as weil as animals.