Profiling of Environmental Chemicals for Mitochondrial Dysfunction

The Tox21 program, a collaboration of the National Institutes of Health, Environmental Protection Agency, and Food and Drug Administration, has utilized a quantitative high throughput screening (qHTS) approach to profile thousands and thousands of environmental chemicals against a battery of biologically relevant cell- or biochemical-based assays. The data generated from Tox21 screening can be used to identify mechanisms of compound action, prioritize chemicals for more extensive toxicological evaluation, and develop the predictive models of in vivo biological responses. As the part of Tox21 program, we have screened the Tox21 10K compounds against mitochondrial membrane potential (MMP) assay using a qHTS approach. From the primary screening (1), a group of known and novel chemicals (e.g. parabens) that decreased the MMP have been identified. The identified compounds have been tested in the human and rat hepatocytes to measure MMP changes, mitochondria related cellular pathways including p53 and Nrf2/ARE, and mitochondrial respiration. These results will be useful for prioritizing chemicals for further in-depth mechanism-based toxicity testing.