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ToxCast™ Program
Predicting Hazard, Characterizing Toxicity Pathways, and Prioritizing the Toxicity Testing of Environmental Chemicals

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Introduction

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.

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.

The second phase of ToxCast™ will screen additional compounds representing broader chemical structure and use classes, in order to evaluate the predictive bioactivity signatures developed in Phase I. Following successful conclusion of Phases I and II, ToxCast™ will provide EPA regulatory programs an efficient tool for rapidly and efficiently screening compounds and prioritizing further toxicity testing.

Data Set Description Download Publication
Landscape Chemicals and Assays Supplemental data , including the set of chemicals and data sources described in the paper “The Toxicity Data Landscape of Environmental Chemicals”. (More Information) Download (15.5 MB, ZIP) Judson et al. (2008) "The Toxicity Data Landscape for Environmental Chemicals" Environmental Health Perspectives
doi:{10.1289/ehp.0800168}

 


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