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Analysis of Chemical Bioactivity through In Vitro Profiling using ToxCast and Tox21 High-Throughput Screening (China tox. conf. TATT)
Citation:
Houck, K. Analysis of Chemical Bioactivity through In Vitro Profiling using ToxCast and Tox21 High-Throughput Screening (China tox. conf. TATT). Presented at Annual Conference on Toxicological Alternatives and Translational Toxicology, Xi'An, CHINA, July 26 - 29, 2015. https://doi.org/10.23645/epacomptox.5080027
Impact/Purpose:
Presentation of EPA's computational toxicology approach to conference sponsored by the Chinese Society of Toxicology
Description:
Safety assessment of drugs and environmental chemicals relies extensively on animal testing. However, the quantity of chemicals needing assessment and challenges of species extrapolation drive the development of alternative approaches. The EPA’s ToxCast and the multiagency Tox21 programs address this through use of an extensive in vitro screening program to generate data on a large library of important environmental chemicals. These in vitro assays encompass both cell-free, biochemical assays targeting proteins that may be potential molecular initiating events and cellular assays that provide coverage of critical signaling pathways and toxicity phenotypes. Effects on model organisms such as the developing zebrafish, are also part of the testing strategy. A variety of computational approaches are used to analyze the resulting complex data sets to gain insight in to inherent biological activity of chemicals and possible mechanisms of toxicity. Several case studies including identification of modulators of estrogen receptor and aromatic hydrocarbon receptor pathways with effects in primary human cell systems will be described. In addition, existing in vivo data from a subset of the chemicals was used to anchor predictive models using in vitro data for a number of adverse endpoints including reproductive and developmental toxicities. The strengths and weaknesses of this approach will be described. This work does not necessarily reflect official Agency policy.
URLs/Downloads:
DOI: Analysis of Chemical Bioactivity through In Vitro Profiling using ToxCast and Tox21 High-Throughput Screening (China tox. conf. TATT)
Analysis of Chemical Bioactivity through In Vitro Profiling using ToxCast and Tox21 High-Throughput Screening (PDF, NA pp, 4515 KB, about PDF)