ArticleNature biotechnology2014
Phenotypic screening of the ToxCast chemical library to classify toxic and therapeutic mechanisms.
Article in Nature biotechnology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
97 citing papers in PubMed, 208 citations in OpenAlex.
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- Synergistic toxicity in alcohol-associated liver disease and PFAS exposure.Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
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- Engineering a computable epiblast for in silico modeling of developmental toxicity.Reproductive toxicology (Elmsford, N.Y.) · 2024Article
- Pervasive environmental chemicals impair oligodendrocyte development.Nature neuroscience · 2024Article
- A Comparison of In Vitro Points of Departure with Human Blood Levels for Per- and Polyfluoroalkyl Substances (PFAS).Toxics · 2024Article
- Editorial: Five grand challenges in toxicology.Frontiers in toxicology · 2024Article
- Guidelines on Developmental Toxicity Tests: Brief Insights.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Structure-Guided Design of a Domain-Selective Bromodomain and Extra Terminal N-Terminal Bromodomain Chemical Probe.Journal of medicinal chemistry · 2023Article
- Pharmaceutical agent cetylpyridinium chloride inhibits immune mast cell function by interfering with calcium mobilization.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2023Article
- Computational Construction of Toxicant Signaling Networks.Chemical research in toxicology · 2023Article
- Knowledge graph aids comprehensive explanation of drug and chemical toxicity.CPT: pharmacometrics & systems pharmacology · 2023Article
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- Pervasive environmental chemicals impair oligodendrocyte development.bioRxiv : the preprint server for biology · 2023Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Addressing the safety aspects of drugs and environmental chemicals has historically been undertaken through animal testing. However, the quantity of chemicals in need of assessment and the challenges of species extrapolation require the development of alternative approaches. Our approach, the US Environmental Protection Agency's ToxCast program, utilizes a large suite of in vitro and model organism assays to interrogate important chemical libraries and computationally analyze bioactivity profiles. Here we evaluated one component of the ToxCast program, the use of primary human cell systems, by screening for chemicals that disrupt physiologically important pathways. Chemical-response signatures for 87 endpoints covering molecular functions relevant to toxic and therapeutic pathways were generated in eight cell systems for 641 environmental chemicals and 135 reference pharmaceuticals and failed drugs. Computational clustering of the profiling data provided insights into the polypharmacology and potential off-target effects for many chemicals that have limited or no toxicity information. The endpoints measured can be closely linked to in vivo outcomes, such as the upregulation of tissue factor in endothelial cell systems by compounds linked to the risk of thrombosis in vivo. Our results demonstrate that assaying complex biological pathways in primary human cells can identify potential chemical targets, toxicological liabilities and mechanisms useful for elucidating adverse outcome pathways.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.