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Chlorpyrifos [O,O'-diethyl-O-(3,5,6-trichloro-2-pyridyl) phosphorothionate, CPF] undergoes oxidative desulfuration or dearylation by hepatic microsomal cytochrome P450 (CYP)-mediated monooxygenase reaction to CPF oxon or desethyl CPF, which are further metabolized to 3,5,6-trichloropyridinol (TCP). The present study showed that CPF exposure caused induction of hepatic CYP levels in rats. Phenobarbitone (PB) treatment elevated CYP activity by about 2.2-folds in controls, while CPF exposure to PB-treated rats did not cause further elevation in CYP levels. The levels of CPF in liver tissue and serum of rats given 50 and 100 mg CPF/kg body wt for 3 weeks were 17.15 ng and 29.39 ng/g and 33.71 ng and 56.34 ng/ml, respectively. The levels of TCP in these rats were 123.58 ng and 215.26 ng/g in liver tissue and 391.73 ng and 599.32 ng/ml in serum respectively. On PB-treatment, CPF levels were decreased by 46% and 38% in liver and 23% and 20% in serum of rats receiving 50 mg and 100 mg CPF/kg body wt for 3 days, while TCP levels were increased by 6% and 22% in liver and 22% and 44% serum, respectively. Results of this study clearly show that CYP2B, the PB-inducible form can biotransform CPF faster into TCP.

The effect of chlorpyrifos (O, O'-diethyl-3, 5, 6-trichloro-2-pyridyl phosphorothionate, CPF) exposure on acetylcholinesterase (AChE) activity, lipid peroxidation and different ATPases activities was studied in rats. CPF caused significant inhibition of synaptosomal AChE activity in different regions of brain (fore, mid and hind) and inhibition ranged from 36 to 82% in rats receiving 20-100 mg CPF/kg body wt for 3 days. It also produced oxidative stress, resulting in marked increase in peroxidative damage of membrane lipids in a dose-dependent manner. The levels of malondialdehyde (MDA) and 4-hydroxy-2-nonanal (4-HNE), two major end products of lipid peroxidation were significantly increased in all the regions of brain. Increase in MDA levels was 66%, 117% and 172% in fore brain, 70%, 108% and 170% in mid brain and 40%, 110% and 169% in hind brain of rats given 20, 50 and 100 mg CPF/kg body wt for 3 days. The maximum increase in 4-HNE levels in all the three regions of brain was observed in the animals receiving CPF 100 mg/kg body wt. Na+/K+, Mg2+ and Ca(2+)-ATPases were inhibited to different extents in fore-, mid- and hind brain regions of rats given 20, 50 and 100 mg/kg body wt CPF for 3 days. Highest inhibition in the activity of Na+/K(+)-ATPase observed more than 90% in mid and hind-brain. Mg(2+)-ATPase in hind brain showed inhibition up to 97%. Inhibition in Ca(2+)-ATPase activity was also ranged from 22-94% in synaptosomes at different doses of CPF.