Biotransformation of the organophosphorus insecticides parathion and methyl parathion in male and female rat livers perfused in situ

Although numerous previous reports have characterized the mammalian biotransformation of the organophosphorus insecticides parathion and methyl parathion, questions still remain regarding the toxicological significance of certain metabolic pathways in vivo. The present study utilized rat liver perfusions in order to better characterize the hepatic biotransformation of parathion and methyl parathion in intact liver. Single-pass liver perfusions with parathion and methyl parathion over a range of perfusate concentrations of 10-80 μM resulted in the appearance of paraoxon and methyl paraoxon, respectively, in effluent. Furthermore, rat blood did not have the capacity to prevent transport of paraoxon and methyl paraoxon to extrahepatic tissues, suggesting that oxon produced hepatically can distribute to extrahepatic tissues. In addition, striking sex differences were noted in the metabolite profile of parathion and methyl parathion in perfused livers. However, these differences could not account for the observation that females are more susceptible to parathion, but less susceptible to methyl parathion, compared to males. And finally, S-methyl glutathione or S-p-nitrophenyl glutathione could not be detected in effluent or bile of livers from either sex perfused with methyl parathion, suggesting that glutathione-dependent detoxification of this insecticide does not occur to any significant degree in intact rat liver.