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ToxCast Phase I

Dataset Summary

Agency	Environmental Protection Agency
Sub-Agency
Category	Science and Technology
Date Released	12/21/2009
Date Updated	12/21/2009
Time Period	NA
Frequency	NA
Description	Background: Chemical toxicity testing is being transformed by advances in biology and computer modeling, concerns over animal use and the thousands of environmental chemicals lacking toxicity data. EPA's ToxCast program aims to address these concerns by screening and prioritizing chemicals for potential human toxicity using in vitro assays and in silico approaches. Objectives: This project aims to evaluate the use of in vitro assays for understanding the types of molecular and pathway perturbations caused by environmental chemicals and to build initial prioritization models of in vivo toxicity. Methods: We tested 309 mostly pesticide active chemicals in 467 assays across 9 technologies, including high-throughput cell-free assays and cell-based assays in multiple human primary cells and cell lines, plus rat primary hepatocytes. Both individual and composite scores for effects on genes and pathways were analyzed. Results: Chemicals display a broad spectrum of activity at the molecular and pathway levels. Many expected interactions are seen, including endocrine and xenobiotic metabolism enzyme activity. Chemicals range in promiscuity across pathways, from no activity to affecting dozens of pathways. We find a statistically significant inverse association between the number of pathways perturbed by a chemical at low in vitro concentrations and the lowest in vivo dose at which a chemical causes toxicity. We also find associations between a small set in vitro assays and rodent liver lesion formation. Conclusions: This approach promises to provide meaningful data on the thousands of untested environmental chemicals, and to guide targeted testing of environmental contaminants. (more)

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Dataset Metrics

Number of Downloads

504

Dataset Information

Data.gov Data Category Type	Raw Data Catalog
Specialized Data Category Designation	Research
Keywords	Toxicology, In vitro screening, prioritization, cancer, ToxCast, Tox21, toxic, toxicity, chemical, compound, pesticide, pollution, pollutant, environment, contaminant, test
Unique ID	1336

Contributing Agency Information

Citation	Judson RS, Houck KA, Kavlock RJ, Knudsen TB, Martin MT, Mortensen HM, et al. 2009. In Vitro Screening of Environmental Chemicals for Targeted Testing Prioritization - The ToxCast Project. Environ Health Perspect :-. doi:10.1289/ehp.0901392
Agency Program Page	http://www.epa.gov/ncct/
Agency Data Series Page	http://www.epa.gov/ncct/toxcast/

Dataset Coverage

Unit of Analysis	309 Environmental chemicals (mostly pesticides) 500 in vitro assays
Granularity	NA
Geographic Coverage	NA

Data Description

Collection Mode	NA
Data Collection Instrument	NA
Data Dictionary/Variable List	See data files

Additional Dataset Documentation

Technical Documentation	http://www.epa.gov/ncct/toxcast/
Additional Metadata	NA

OMB Control No. 3090-0284