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 (activation) or dearylation (detoxication) showed that rat hepatic microsomes have a greater capacity to detoxify and a lower capacity to activate chlorpyrifos compared to parathion. Kinetic curves for the desulfuration of both parathion and chlorpyrifos were biphasic; Kmapps of 0.23 and 71.3 microM were calculated for parathion, and 1.64 and 50.4 microM for chlorpyrifos. While phenobarbital (PB) exposure seemed to generally lower the Kmapps for desulfuration except for the low Km activity on chlorpyrifos, the results were not statistically significant. While the low Km activity contributed 44 and 60% of the control Vmax for parathion and chlorpyrifos, respectively, it contributed 50 and 17% in PB-treated rats. These studies have indicated the presence of a low Km activity capable of functioning at very low substrate concentrations. A single dearylation Kmapp was calculated, 56.0 and 9.8 microM for parathion and chlorpyrifos, respectively. Phenobarbital exposure seemed to raise the Kmapps of dearylation; however, again, the results were not statistically significant. While numerous biochemical factors contribute to the overall toxicity levels of phosphorothionate insecticides, the in vitro efficiencies of hepatic microsomal desulfuration and dearylation of parathion and chlorpyrifos correspond to the acute toxicity levels.