Effects of pesticides on drug and steroid metabolism

Abstract

Treatment of experimental animals with small amounts of halogenated hydrocarbon insecticides stimulates the activity of oxidative enzymes in liver microsomes that metabolize drugs and steroid hormones. The enhancing effect of these pesticides on drug metabolism alters the duration and intensity of drug action in animals and also markedly influences drug toxicity. The minimum exposure to DDT required to decrease the hypnotic action of pentobarbital in rats gives rise to 10 to 15 μg of DDT per gram of fat, a concentration approaching that reported to occur in the human population. The physiological significance of pesticide‐induced increases in steroid hydroxylases in liver microsomes is not known, and further studies are necessary to elucidate the importance of this effect. In contrast to the stimulatory effect of halogenated hydrocarbon insecticides on hepatic steroid hydroxylases, treatment of rats with organophosphate insecticides, such as chlorthion, inhibits the liver microsomal metabolism of several steroid hormones. Chlorthion has a greater inhibitory effect on the 16α‐hydroxylation of testosterone than on the 6β‐ or 7 α‐hydroxylation of this steroid, suggesting that separate enzyme systems are required for the various hydroxylation reactions. Since the stimulatory effects of several drugs on drug and steroid metabolism in animals is paralleled by enhanced drug and steroid hydroxylation in man, further studies should be carried out to determine whether the chronic environmental exposure of humans to pesticides is sufficient to alter their metabolism of drugs and steroids.