227B16A3-AEE1-4724-A91B-D4119F5A2C1B en-us utf8 nonGeographicDataset Richard Judson U.S. EPA Office of Research & Development (ORD) - National Center for Computational Toxicology (NCCT) judson.richard@epa.gov author 2014 ISO 19115 Geographic information - Metadata ISO 19115:2003(E) ToxCast Phase I 2014 publication 2014 revision Richard Judson U.S. EPA Office of Research & Development (ORD) - National Center for Computational Toxicology (NCCT) judson.richard@epa.gov originator 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. Richard Judson U.S. EPA Office of Research & Development (ORD) - National Center for Computational Toxicology (NCCT) judson.richard@epa.gov owner asNeeded chemical safetychemical safety researchchemicalschemical testinginnovative chemical testingcomputational toxicologychemical screeningToxCastTox21EPA researchchemical sciencechemical health effects Environment theme User Environment theme EPA GIS Keyword Thesaurus United States place None Please check sources, scale, accuracy, currentness and other available information. Please confirm that you are using the most recent copy of both data and metadata. Acknowledgement of the EPA would be appreciated. otherRestrictions otherRestrictions https://edg.epa.gov/EPA_Data_License.html public unclassified FIPS Pub 199 Standard Technical Controls en-us environment USA -180 -66 18 72 Richard Judson U.S. EPA Office of Research & Development (ORD) - National Center for Computational Toxicology (NCCT) judson.richard@epa.gov distributor 1 http://epa.gov/ncct/toxcast/data.html http web browser Download URL providing direct access to the downloadable distribution of the data. download 1 Lineage provided in documentation.