Metabolism and Hepatotoxicity of Pesticides

Pesticides are ubiquitous contaminants of the human environment and, as such, interact with hepatic enzymes as substrates, inhibitors, and inducers. Exposure of the general public to pesticides is usually low but not necessarily without toxicity. However, there is more concern about exposure in occupational settings. Furthermore, interactions between pesticides and other xenobiotics occur, frequently through the generation of reactive intermediates. In this article bioprocessing of pesticides by liver enzymes is first considered, including interactions with other xenobiotics and endogenous metabolites through induction and/or inhibition of xenobiotic-metabolizing enzymes. The role of pesticides as hepatotoxicants, including both noncarcinogenic and carcinogenic end points, cytotoxicity, oxidative stress and the effect of pesticides in modifying toxicity of other nonpesticidal toxicants, is also considered. Human studies, including human variation, are stressed particularly because of their importance in new approaches to risk assessment.