ArticleChemical research in toxicology2013
Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays.
Article in Chemical research in toxicology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed.
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- A 2024 inventory of test methods relevant to thyroid hormone system disruption for human health and environmental regulatory hazard assessment.Open research Europe · 2024Review
- Computational Construction of Toxicant Signaling Networks.Chemical research in toxicology · 2023Article
- Advancing the science of a read-across framework for evaluation of data-poor chemicals incorporating systematic and new approach methods.Regulatory toxicology and pharmacology : RTP · 2023Article
- Principles and Procedures for Assessment of Acute Toxicity IncorporatingComputational toxicology (Amsterdam, Netherlands) · 2022Article
- Protocol for inducing inflammation and acute myelin degeneration in larval zebrafish.STAR protocols · 2022Article
- RAID: Regression Analysis-Based Inductive DNA Microarray for Precise Read-Across.Frontiers in pharmacology · 2022Article
- Acetylcholinesterase Inhibition Assays for High-Throughput Screening.Methods in molecular biology (Clifton, N.J.) · 2022Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding potential health risks is a significant challenge due to the large numbers of diverse chemicals with poorly characterized exposures and mechanisms of toxicities. The present study analyzes 976 chemicals (including failed pharmaceuticals, alternative plasticizers, food additives, and pesticides) in Phases I and II of the U.S. EPA's ToxCast project across 331 cell-free enzymatic and ligand-binding high-throughput screening (HTS) assays. Half-maximal activity concentrations (AC50) were identified for 729 chemicals in 256 assays (7,135 chemical-assay pairs). Some of the most commonly affected assays were CYPs (CYP2C9 and CYP2C19), transporters (mitochondrial TSPO, norepinephrine, and dopaminergic), and GPCRs (aminergic). Heavy metals, surfactants, and dithiocarbamate fungicides showed promiscuous but distinctly different patterns of activity, whereas many of the pharmaceutical compounds showed promiscuous activity across GPCRs. Literature analysis confirmed >50% of the activities for the most potent chemical-assay pairs (54) but also revealed 10 missed interactions. Twenty-two chemicals with known estrogenic activity were correctly identified for the majority (77%), missing only the weaker interactions. In many cases, novel findings for previously unreported chemical-target combinations clustered with known chemical-target interactions. Results from this large inventory of chemical-biological interactions can inform read-across methods as well as link potential targets to molecular initiating events in adverse outcome pathways for diverse toxicities.
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