Metabolism of O, O-Dimethyl O-[4-(Methylthio)-m-Tolyl] Phosphorothioate by White Rats1

Abstract

O, O-dimethyl O-[4-(methylthio)-m-tolyl] phosphorothioate or Bayer 29493 was oxidized by rats at the phosphoryl sulfur and the thiophenyl group; the sulfoxide and sulfone derivatives of the parent material and its oxygen analog were isolated and identified. Oxidation rather than isomerization was the predominant activation process. The urine and feces contained different percentages of each metabolite. Hydrolysis occurred primarily at the P-O-phenyl bond; cleavage of the P-O-methyl bond was not demonstrated. The percentage of hydrolytic products in the urine decreased as the number of doses increased (10 mg./kg./ day for 10 days). The cholinesterase of the blood and brain of rats was inhibited rapidly and recovered slowly. The acetonitrile-soluble residues in the liver, kidney, muscle, skin, and heart were negligible at 3 days following oral (100 mg./kg.) or intraperitoneal treatment of rats. About 80% of the administered Bayer 29493 equivalents was eliminated in the excreta regardless of the route of administration.