A KINETIC-ANALYSIS OF HEPATIC-MICROSOMAL ACTIVATION OF PARATHION AND CHLORPYRIFOS IN CONTROL AND PHENOBARBITAL-TREATED RATS

A kinetic analysis of cytochrome P450-mediated desulfuration (activati on) or dearylation (detoxication) showed that rat hepatic microsomes h ave a greater capacity to detoxify and a lower capacity to activate ch lorpyrifos compared to parathion. Kinetic curves for the desulfuration of both parathion and chlorpyrifos were biphasic; K(mapp)s of 0.23 an d 71.3 mu M were calculated for parathion, and 1.64 and 50.4 mu M for chlorpyrifos. While phenobarbital (PB) exposure seemed to generally lo wer the K(mapp)s for desulfuration except for the low K-m activity on chlorpyrifos, the results were not statistically significant. While th e low K-m activity contributed 44 and 60% of the control V-max for par athion and chlorpyrifos, respectively, it contributed 50 and 17% in PB -treated rats. These studies have indicated the presence of a low K-m activity capable of functioning at very low substrate concentrations. A single dearylation K-mapp was calculated 56.0 and 9.8 mu M for parat hion and chlorpyrifos, respectively. Phenobarbital exposure seemed to raise the K(mapp)s of dearylation; however, again, the results were no t statistically significant. While numerous biochemical factors contri bute to the overall toxicity levels of phosphorothionate insecticides, the in vitro efficiencies of hepatic microsomal desulfuration and dea rylation of parathion and chlorpyrifos correspond to the acute toxicit y levels.