Sury Vulimiri and Babasaheb Sonawane
U.S. EPA, USA
Posters-Accepted Abstracts: J Drug Metab Toxicol
Exposure to environmental chemicals may cause toxicity through multiple mechanisms including perturbations to endogenous metabolic pathways, most of which are conserved across species. Such perturbations can alter the levels of several endogenous metabolites depending on the nature, dose, and duration of the exposure of the chemical. Metabolomics approach which can identity, quantify, and characterize these low molecular weight metabolites with a medium-to-high-throughput platform, appears to be promising technique for evaluating chemical exposure and biological response. We explored whether hazard identification, one of the four steps in the human health risk assessment (HHRA), can be characterized by metabolomics approach using the hepatocarcinogen carbon tetrachloride (CCl4) as the case study. We show that the metabolomics approach can be utilized for analyzing different �key events� (e.g., lipid peroxidation, cytotoxicity) that may contribute to different mode(s) of action (MOAs) leading to the hazard identification of CCl4. Since the metabolomics approach can detect early changes in endogenous metabolite levels, such metabolites can be used as biomarkers of exposure and effect for investigating MOA of xenobiotics. Further, we observed that the metabolomics data can also be combined with data from other �omics� approaches, such as genomics and proteomics, to inform MOA of xenobiotics. Future studies need to focus on the dose-response determination of chemicals with metabolomics approach.
