Study of the possible mode of action of O-ethyl S-methyl ethylphosphonothioate via the formation of S-oxide in chemical and metabolic oxidation systems

O-ethyl S-methyl ethylphosphonothioate [ (rat, oral) 4.6mg/kg ; (bovine erythrocyte acetylcholinesterase) 303 ] was selected as a model compound to study the mode of action of O, S-dialkyl alkylphosphonothioates which have been hypothesized to be toxic via a bioactivation process. Two chemical oxidants, meta-chloroperoxybenzoic acid and monoperoxyphthalic acid, and rat liver microsomal oxidases were used to mimic the action of mixed function oxidases on the model compound. The formation of S-oxide, a very unstable active intermediate, was proposed based on the identification of metabolic products.Furthermore, a trapping experiment with ethanol showed that the unstable intermediate S-oxide had the ability to phosphorylate acetylcholinesterase which is an important enzyme in nerve systems. The S-oxide intermediates are presumed to be responsible for the toxicity of O,S-dialkyl alkylphosphonothioates.