Insecticides: Effect on drug metabolism

Abstract

The effects of chlorinated organic insecticides on the half‐life and rate of elimination of a variety of drugs were studied in laboratory animals; observations were made in humans occupationally exposed and in birds environmentally exposed to pesticides. Species differences are reported depending on the insecticide tested: DDT decreased hexobarbital sleep time of rats but had no effect in mice, which did respond similarly when treated with chlordane. All isomers of DDT as well as their metabolites were potent inducers of hepatic microsomal drug‐metabolizing enzymes in rats. In treated dogs, plasma elimination half‐life of hexobarbital was shortened, but the half‐life of pentobarbital was lengthened. Exterminators exposed to a mixture of chlorinated organic pesticides, showed significantly shorter antipyrine plasma elimination half‐lives as contrasted to office personnel from the same company. Similar observations were made on workers in a DDT factory, with decreasing plasma half‐lives of phenylbutazone as compared with findings in a control group. Induction of mixed Junction oxidase (MFO) activity by chlorinated insecticides was associated with frequency of eggshell breakage and decreased eggshell weight in breeding birds, e.g., falcon, sparrow hawks, and others with a declining population. It was postulated that the eggshell defects resulted from altered metabolism due to excess steroid inactivation secondary to induction of MFO activity.