Paper Report for: Dalvi_2004_Vet.Hum.Toxicol_46_297

This study compared CYP-mediated activation and toxicity of chlorpyrifos (CPF) in male and female rats, since gender difference in CPF toxicity in rats has been reported. A dose of 50 mg/kg of CPF in corn oil was administered ip to 2 groups of male and female rats while the respective control groups received the vehicle alone. Measurement of cholinesterase activity in brain showed no difference in cholinesterase inhibition between male and female rats 3 h following CPF administration. In contrast, inhibition of plasma cholinesterase was significantly greater in females than males. The activities of microsomal CYP 1A1, 2B1, 2E1 and 3AV 2 determined whether CPF, a suicide substrate of cytochrome P450 enzymes, was metabolized by the liver CYP enzymes. The CYP 1A1 and 2B1 activities were significantly decreased in both male and female rats, with the CYP 1A1 decrease in females markedly greater than that in males. CPF produced a significant inhibition of only CYP 3A1/2 activity, but not CYP 2E1 activity, irrespective of gender effect. These results demonstrated that CYP 1A1, 2B1 and 3A1/2 were differentially involved in the metabolism of CPF to CPF-oxon in both genders and the extent of plasma cholinesterase inhibition was significantly greater in female than male rats.