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The U.S. EPA ToxCast Program: Moving from Data Generation to Application (SOT Tox21 update symposium presentation)
Citation:
Thomas, R. The U.S. EPA ToxCast Program: Moving from Data Generation to Application (SOT Tox21 update symposium presentation). Presented at SOT annual meeting, San Diego, CA, March 22 - 26, 2015. https://doi.org/10.23645/epacomptox.5083654
Impact/Purpose:
SOT presentation
Description:
The U.S. EPA ToxCast program is entering its tenth year. Significant learning and progress have occurred towards collection, analysis, and interpretation of the data. The library of ~1,800 chemicals has been subject to ongoing characterization (e.g., identity, purity, stability) and is unique in its scope, structural diversity, and use scenarios making it ideally suited to investigate the underlying molecular mechanisms of toxicity. The ~700 high-throughput in vitro assay endpoints cover 327 genes and 293 pathways as well as other integrated cellular processes and responses. The integrated analysis of high-throughput screening data has shown that most environmental and industrial chemicals are very non-selective in the biological targets they perturb, while a small subset of chemicals are relatively selective for specific biological targets. The selectivity of a chemical informs interpretation of the screening results while also guiding future mode-of-action or adverse outcome pathway approaches. Coupling the high-throughput in vitro assays with medium-throughput pharmacokinetic assays and reverse dosimetry allows conversion of the potency estimates to an administered dose. Comparison of the administered dose to human exposure provides a risk-based context. The lessons learned from this effort will be presented and discussed towards application to chemical safety decision making and the future of the computational toxicology program at the U.S. EPA.
URLs/Downloads:
DOI: The U.S. EPA ToxCast Program: Moving from Data Generation to Application (SOT Tox21 update symposium presentation)
THOMAS_SOT_2015_ABSTRACT_TOX21REVISED_08112014.PDF (PDF, NA pp, 60.413 KB, about PDF)
TOXCAST GENERAL_SOT_MARCH_2015_V3.PDF (PDF, NA pp, 3112.633 KB, about PDF)