ArticleRegulatory toxicology and pharmacology : RTP2019
Development of a prioritization method for chemical-mediated effects on steroidogenesis using an integrated statistical analysis of high-throughput H295R data.
Article in Regulatory toxicology and pharmacology : RTP, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Community-Engaged Research and the Use of Open Access ToxVal/ToxRef In Vivo Databases and New Approach Methodologies (NAM) to Address Human Health Risks From Environmental Contaminants.Birth defects research · 2024Article
- Evaluation of a high-throughput H295R homogenous time resolved fluorescence assay for androgen and estrogen steroidogenesis screening.Toxicology in vitro : an international journal published in association with BIBRA · 2023Article
- Cheminformatics analysis of chemicals that increase estrogen and progesterone synthesis for a breast cancer hazard assessment.Scientific reports · 2022Article
- Evaluating structure-based activity in a high-throughput assay for steroid biosynthesis.Computational toxicology (Amsterdam, Netherlands) · 2022Article
- Advances in computational methods along the exposure to toxicological response paradigm.Toxicology and applied pharmacology · 2022Article
- Comment on "Application of anEnvironmental health perspectives · 2022Article
- Response to "Comment on 'Application of anEnvironmental health perspectives · 2022Article
- Application of anEnvironmental health perspectives · 2021Article
- Comparison of Approaches for Determining Bioactivity Hits from High-Dimensional Profiling Data.SLAS discovery : advancing life sciences R & D · 2021Article
- US EPA's regulatory pesticide evaluations need clearer guidelines for considering mammary gland tumors and other mammary gland effects.Molecular and cellular endocrinology · 2020Review
- The Alginate Immobilization of Metabolic Enzymes Platform Retrofits an Estrogen Receptor Transactivation Assay With Metabolic Competence.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
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4 authors.
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Abstract
Synthesis of 11 steroid hormones in human adrenocortical carcinoma cells (H295R) was measured in a high-throughput steroidogenesis assay (HT-H295R) for 656 chemicals in concentration-response as part of the US Environmental Protection Agency's ToxCast program. This work extends previous analysis of the HT-H295R dataset and model by examining the utility of a novel prioritization metric based on the Mahalanobis distance that reduced these 11-dimensional data to 1-dimension via calculation of a mean Mahalanobis distance (mMd) at each chemical concentration screened for all hormone measures available. Herein, we evaluated the robustness of mMd values, and demonstrate that covariance and variance of the hormones measured appear independent of the chemicals screened and are inherent to the assay; the Type I error rate of the mMd method is less than 1%; and, absolute fold changes (up or down) of 1.5 to 2-fold have sufficient power for statistical significance. As a case study, we examined hormone responses for aromatase inhibitors in the HT-H295R assay and found high concordance with other ToxCast assays for known aromatase inhibitors. Finally, we used mMd and other ToxCast cytotoxicity data to demonstrate prioritization of the most selective and active chemicals as candidates for further in vitro or in silico screening.
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