ArticleToxicological sciences : an official journal of the Society of Toxicology2018
Differentiating Pathway-Specific From Nonspecific Effects in High-Throughput Toxicity Data: A Foundation for Prioritizing Adverse Outcome Pathway Development.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed.
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- Beyond Estrogenicity: A Comparative Assessment of Bisphenol A and Its Alternatives in In Vitro Assays Questions Safety of Replacements.Environmental science & technology · 2025Article
- Following the Mixtures of Organic Micropollutants withACS environmental Au · 2025Article
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- Linking Mechanistic Effects of Pharmaceuticals and Personal Care Products to Ecologically Relevant Outcomes: A Decade of Progress.Environmental toxicology and chemistry · 2024Article
- Comparison between endocrine activity assessed using ToxCast/Tox21 database and human plasma concentration of sunscreen active ingredients/UV filters.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Assessing utility of thyroid in vitro screening assays through comparisons to observed impacts in vivo.Regulatory toxicology and pharmacology : RTP · 2023Review
- Reactivity of Acrylamides Causes Cytotoxicity and Activates Oxidative Stress Response.Chemical research in toxicology · 2023Article
- Prioritizing Pesticides of Potential Concern and Identifying Potential Mixture Effects in Great Lakes Tributaries Using Passive Samplers.Environmental toxicology and chemistry · 2023Article
- A geospatial modeling approach to quantifying the risk of exposure to environmental chemical mixtures via a common molecular target.The Science of the total environment · 2023Article
- The ToxCast pipeline: updates to curve-fitting approaches and database structure.Frontiers in toxicology · 2023Article
- Leveraging ToxCast data and protein sequence conservation to complement aquatic life criteria derivation.Integrated environmental assessment and management · 2023Article
- Advances in computational methods along the exposure to toxicological response paradigm.Toxicology and applied pharmacology · 2022Article
- Prioritizing Pharmaceutical Contaminants in Great Lakes Tributaries Using Risk-Based Screening Techniques.Environmental toxicology and chemistry · 2022Article
- IVIVE: Facilitating the Use ofToxics · 2022Review
- Risk-Based Prioritization of Organic Chemicals and Locations of Ecological Concern in Sediment From Great Lakes Tributaries.Environmental toxicology and chemistry · 2022Article
- Identifying the link between chemical exposures and breast cancer in African American women via integrated in vitro and exposure biomarker data.Toxicology · 2021Article
- Identifying Chemicals and Mixtures of Potential Biological Concern Detected in Passive Samplers from Great Lakes Tributaries Using High-Throughput Data and Biological Pathways.Environmental toxicology and chemistry · 2021Article
- Assessing the Ecological Risks of Per- and Polyfluoroalkyl Substances: Current State-of-the Science and a Proposed Path Forward.Environmental toxicology and chemistry · 2021Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
The U.S. Environmental Protection Agency's ToxCast program has screened thousands of chemicals for biological activity, primarily using high-throughput in vitro bioassays. Adverse outcome pathways (AOPs) offer a means to link pathway-specific biological activities with potential apical effects relevant to risk assessors. Thus, efforts are underway to develop AOPs relevant to pathway-specific perturbations detected in ToxCast assays. Previous work identified a "cytotoxic burst" (CTB) phenomenon wherein large numbers of the ToxCast assays begin to respond at or near test chemical concentrations that elicit cytotoxicity, and a statistical approach to defining the bounds of the CTB was developed. To focus AOP development on the molecular targets corresponding to ToxCast assays indicating pathway-specific effects, we conducted a meta-analysis to identify which assays most frequently respond at concentrations below the CTB. A preliminary list of potentially important, target-specific assays was determined by ranking assays by the fraction of chemical hits below the CTB compared with the number of chemicals tested. Additional priority assays were identified using a diagnostic-odds-ratio approach which gives greater ranking to assays with high specificity but low responsivity. Combined, the two prioritization methods identified several novel targets (e.g., peripheral benzodiazepine and progesterone receptors) to prioritize for AOP development, and affirmed the importance of a number of existing AOPs aligned with ToxCast targets (e.g., thyroperoxidase, estrogen receptor, aromatase). The prioritization approaches did not appear to be influenced by inter-assay differences in chemical bioavailability. Furthermore, the outcomes were robust based on a variety of different parameters used to define the CTB.
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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.