Comparative toxicity, anticholinesterase action and metabolism of methyl parathion and parathion in sunfish and mice

Abstract

The in vitro metabolism of methyl parathion ( O,O-dimethyl O-p-nitrophenyl phosphorothioate) and parathion ( O,O-diethyl O,p-nitrophenyl phosphorothioate) and the sensitivities of the target cholinesterases to inhibition by their oxygen analogs were studied in sunfish ( Lepomis gibbosus) and mice to determine the basis for the low toxicity of methyl parathion in sunfish (LD50 > 2500 mg/kg). The LD50 values of parathion and methyl parathion in mice were 13.5 and 11 mg/kg, respectively, and the times to death were much shorter for both compounds in mice than in fish. Low sensitivity of fish cholinesterases to paraoxon as compared to mice accounted for the 10-fold lower toxicity of parathion in fish (LD50, 110 mg/kg). By contrast, sunfish had similar cholinesterase sensitivities to methyl paraoxon and paraoxon. Differences in rates of oxidative formation of the oxygen analog or oxidative cleavage to p-nitrophenol and the corresponding dialkyl thiophosphate could not account for the selective resistance of sunfish to methyl parathion toxicity. Fish and mouse liver homogenates catalyzed a glutathione (GSH)-dependent metabolism of methyl parathion and methyl paraoxon but not of parathion or paraoxon. Additionally, hydrolysis of methyl paraoxon by fish liver homogenates exceeded that for parathion by 5-fold, while methyl paraoxon hydrolysis in mice was 1 2 of that of paraoxon. Apparently, a longer time to death in fish provided the opportunity for GSH-dependent and hydrolytic detoxification, which favored methyl parathion and methyl paraoxon relative to parathion and paraoxon. Although in mice the GSH-dependent enzymes also favored detoxification of methyl parathion and methyl paraoxon, this is apparently of less importance because of their high cholinesterase sensitivity and because cleavage and hydrolysis favored parathion and paraoxon.