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Updated: Jun 20, 2026
Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation
Published on: June 17, 2015
Profiling bioactivity of the ToxCast chemical library using BioMAP primary human cell systems
Keith A Houck1, David J Dix, Richard S Judson
1National Center for Computational Toxicology, Office of Research and Development, United States Environmental Protection Agency, Research Triangle Park, North Carolina, USA. houck.keith@epa.gov
Abstract:
The complexity of human biology has made prediction of health effects as a consequence of exposure to environmental chemicals especially challenging. Complex cell systems, such as the Biologically Multiplexed Activity Profiling (BioMAP) primary, human, cell-based disease models, leverage cellular regulatory networks to detect and distinguish chemicals with a broad range of target mechanisms and biological processes relevant to human toxicity. Here the authors use the BioMAP human cell systems to characterize effects relevant to human tissue and inflammatory disease biology following exposure to the 320 environmental chemicals in the Environmental Protection Agency's (EPA's) ToxCast phase I library. The ToxCast chemicals were assayed at 4 concentrations in 8 BioMAP cell systems, with a total of 87 assay endpoints resulting in more than 100,000 data points. Within the context of the BioMAP database, ToxCast compounds could be classified based on their ability to cause overt cytotoxicity in primary human cell types or according to toxicity mechanism class derived from comparisons to activity profiles of BioMAP reference compounds. ToxCast chemicals with similarity to inducers of mitochondrial dysfunction, cAMP elevators, inhibitors of tubulin function, inducers of endoplasmic reticulum stress, or NFkappaB pathway inhibitors were identified based on this BioMAP analysis. This data set is being combined with additional ToxCast data sets for development of predictive toxicity models at the EPA.
Insights
Researchers used Biologically Multiplexed Activity Profiling (BioMAP) human cell systems to analyze 320 environmental chemicals from the EPA's ToxCast library. This study identified chemical mechanisms relevant to human toxicity and inflammatory diseases.
Area of Science:
- Toxicology
- Environmental Health
- Cell Biology
Background:
- Predicting environmental chemical health effects is challenging due to human biology complexity.
- Biologically Multiplexed Activity Profiling (BioMAP) uses human cell-based models to identify chemical toxicity mechanisms.
- The Environmental Protection Agency (EPA) ToxCast library contains diverse environmental chemicals for toxicity screening.
Purpose of the Study:
- To characterize the biological effects of 320 EPA ToxCast phase I chemicals using BioMAP human cell systems.
- To identify toxicity mechanisms and biological processes relevant to human inflammatory diseases.
- To classify chemical activities within the BioMAP database for toxicity prediction.
Main Methods:
- Exposure of 8 BioMAP cell systems to 320 ToxCast chemicals at 4 concentrations.
- Measurement of 87 assay endpoints, generating over 100,000 data points.
- Classification of chemical activities based on cytotoxicity and comparison to BioMAP reference compound profiles.
Main Results:
- Identified ToxCast chemicals causing cytotoxicity in human cell types.
- Classified chemicals based on toxicity mechanisms including mitochondrial dysfunction, cAMP elevation, tubulin inhibition, endoplasmic reticulum stress, and NFkappaB pathway inhibition.
- Generated a comprehensive dataset for developing predictive toxicity models.
Conclusions:
- BioMAP systems effectively characterize environmental chemical effects relevant to human disease.
- The study identified specific toxicity pathways for ToxCast chemicals.
- This data contributes to the EPA's development of predictive models for chemical safety assessment.
