Short Communication Human Hepatic Cytochrome P450-Specific Metabolism of

Organophosphorus pesticides (OPs) remain a potential concern to human health because of their continuing worldwide use. Thio-phosphorus OPs, once bioactivated by cytochromes P450 (P450s), form oxon metabolites, which are potent acetylcholinesterase in-hibitors. This study investigated the rate of desulfation (activation) and dearylation (detoxification) of parathion and chlorpyrifos in human liver microsomes. In addition, recombinant human P450s were used to quantify, for the first time, the P450-specific kinetic variables (Km and Vmax) for each compound for future use in refin-ing human physiologically based pharmacokinetic/pharmacody-namic (PBPK/PD) models of OP exposure. CYP1A2, 2B6, 2C9, 2C19, 3A4, 3A5, and 3A7 were found to be active to a widely varying degree in parathion metabolism, whereas all, with the exception of CYP2C9, were also found to be active in chlorpyrifos metabolism. CYP2B6 and CYP2C19 demonstrated low Km and high Vmax value