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Overview of ToxCast™
Citation:
KAVLOCK, R. J. Overview of ToxCast™ . Presented at CarcinoGENOMICS Workshop, Brussels, BELGIUM, June 08 - 11, 2008.
Impact/Purpose:
In its first phase, ToxCast™ is profiling over 300 well-characterized chemicals (primarily pesticides) in over 400 HTS endpoints. These endpoints include biochemical assays of protein function, cell-based transcriptional reporter assays, multi-cell interaction assays, transcriptomics on primary cell cultures, and developmental assays in zebrafish embryos. Almost all of the compounds being examined in Phase 1 of ToxCast™ have been tested in traditional toxicology tests, including developmental toxicity, multi-generation studies, and sub-chronic and chronic rodent bioassays. ToxRefDB, a relational database being created to house this information, will contain nearly $1B worth of toxicity studies in animals when completed. ToxRefDB is integrated into a more comprehensive data management system developed by NCCT called ACToR (Aggregated Computational Toxicology Resource), that manages the large-scale datasets of ToxCast™. ACToR is comprised of several independent data repositories linked to a common database of chemical structures and properties, and to tools for development of predictive HTS and genomic bioactivity signatures that strongly correlate with specific toxicity endpoints from ToxRefDB. These ToxCast™ signatures will be defined and evaluated by their ability to predict outcomes from existing mammalian toxicity testing, and identify toxicity pathways that are relevant to human health effects.
Description:
In 2007, EPA launched ToxCast™ in order to develop a cost-effective approach for prioritizing the toxicity testing of large numbers of chemicals in a short period of time. Using data from state-of-the-art high throughput screening (HTS) bioassays developed in the pharmaceutical industry, ToxCast™ is building computational models to forecast the potential human toxicity of chemicals. These hazard predictions will provide EPA regulatory programs with science-based information helpful in prioritizing chemicals for more detailed toxicological evaluations, and lead to more efficient use of animal testing.