Hydrolysis of the Alkyl-Phosphate Bond in Certain Dialkyl Aryl Phosphorothioate Insecticides by Rats, Cockroaches, and Alkali1

Abstract

The nature of the products formed by in vitro and in vivo hydrolysis of parathion, methyl parathion, Diazinon, Dow ET-57, Chlorthion, and dicapthon was studied. All these dialkyl aryl phosphorothioates were hydrolyzed at both the alkylphosphate and the aryl-phosphate bonds. Alkyl-phosphate hydrolysis was proportionately greater with the dimethyl than with the diethyl phosphorothioates in rats and under the alkaline conditions employed. In rats it was found that the per cent of hydrolytic metabolites formed by cleavage of the alkyl-phosphate bond varied with the amount of insecticide administered, being greater at higher dosages. Alkl-phosphate hydrolysis appeared to be an alternate mechanism for detoxication in mammals when the dosage was too great to be metabolized through hydrolysis at the aryl-phosphate bond. It did not seem to be a major factor in the large toxicity differences among dialkyl aryl phosphorothioates with mammals. Very little alkyl-phosphate hydrolysis occurred with cockroaches with five of the six compounds studied. The lower alkylphosphate hydrolysis with cockroaches as compared to rats may contribute to the lower relative toxicity of the dimethyl aryl phosphorothioates to mammals. Differences were also noted in the rate of oxidation of the various hydrolytic metabolites between rats and cockroaches.