STUDIES ON THE MECHANISM OF DETOXIFICATION OF CHOLINERGIC PHOSPHOROTHIOATES

¹ Department of Pharmacology, University of Chicago, Chicago, Illinois

The enzymatic degradation of O-ethyl O-(4-nitrophenyl) phenylphosphonothioate (EPN), parathion, methyl parathion and Chlorthion was studied to elucidate the mechanism responsible for their detoxification. It was found that the detoxification of these organophosphates involves the action of an oxidative enzyme in the microsome fraction of the liver followed by hydrolysis to yield phenols. A quantitative method was developed for measuring the degradation of EPN and related compounds. Application of the procedure to the livers of rats, mice and guinea pigs showed that the rate of detoxification of EPN and related compounds is correlated with the in vivo susceptibility of animals to the acute toxicity of these compounds. Thus the rate of degradation of these organophosphates was more rapid in adult male rats than in females and weanling males, and species differences in the rate of degradation of the compounds were also consistent with known differences in the acute toxicity of these cholinergic phosphorothioates.