Metabolism of¹⁴C-leptophos in the rat

Abstract

The metabolic fate of leptophos [O-(4-Bromo-2,5-dichlorophenyl)O-methyl phenyl phosphonothioate] in the rat was investigatedin vivo, using¹⁴C-phenyl and¹⁴C-methyl-labeled insecticide. Following the administration of a single oral dose of¹⁴C-phenyl leptophos (15 mg/kg) 46 to 75% of the¹⁴C-activity was recovered after nine days, in the urine. No radioactivity was eliminated in the expired air.O-methyl phenylphosphonic,O-methyl phenylphosphonothioic and phenylphosphonic acids were identified among the urinary metabolites, together with two metabolites of unknown nature. Demethylation of leptophos and/or its oxygen analog occurredin vivo to a small extent, as confirmed by the elimination of¹⁴CO₂ in the expired air, from¹⁴C-methyl leptophos.

The insecticide seemed to accumulate in omental and subcutaneous fat since traces were still found in fat 12 weeks after administration of the chemical. A study of the kinetics of acetylcholinesterase inhibition revealed that the oxon was the most potent inhibitor. The degradation products were generally weak inhibitors.