Pesticides and Hepatotoxicity

Pesticides are ubiquitous contaminants of the human environment and, as such, not only interact with hepatic enzymes as substrates, inhibitors, activators, and inducers but are also involved as the causative agents of numerous toxic end points. While the exposure of the general public to pesticides and their metabolites is usually low, exposures are of concern in occupational and other settings. Furthermore, interactions between pesticides and other xenobiotics are known to occur, frequently through the generation of reactive intermediates. Such reactive intermediates may exert their effects in the liver itself or may bring about toxicity in other tissues. The bioprocessing of pesticides by liver enzymes is first considered, including interactions with other xenobiotics or between pesticides and endogenous metabolites brought about by inhibition, induction, and/or activation of xenobiotic-metabolizing enzymes. The role of pesticides as hepatotoxicants, including both noncarcinogenic and carcinogenic end points and the effect of pesticides in modifying the toxicity of other nonpesticidal toxicants, is also considered.