Evidence map›Paper›PMID 29216406›Full record

ArticleToxicological sciences : an official journal of the Society of Toxicology2018

High-Throughput H295R Steroidogenesis Assay: Utility as an Alternative and a Statistical Approach to Characterize Effects on Steroidogenesis.

Derik E Haggard, Agnes L Karmaus, Matthew T Martin, Richard S Judson, R Woodrow Setzer, Katie Paul Friedman

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

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. An erratum has been issued. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
2.9field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

35 citing papers in PubMed, 57 citations in OpenAlex.

  1. Review of in vitro approaches for assessing the toxicity of chemical stressors across diverse physiological systems.Toxicological sciences : an official journal of the Society of Toxicology · 2026
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  9. NAM journal · 2025
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  14. 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 · 2023
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Derik E HaggardOak Ridge Institute for Science and Education Postdoctoral Fellow, Oak Ridge, TN. 37831.
Agnes L KarmausOak Ridge Institute for Science and Education Postdoctoral Fellow, Oak Ridge, TN. 37831.
Matthew T MartinNational Center for Computational Toxicology, Office of Research and Development, US Environmental Protection Agency, Durham, NC 27711.
Richard S JudsonNational Center for Computational Toxicology, Office of Research and Development, US Environmental Protection Agency, Durham, NC 27711.
R Woodrow SetzerNational Center for Computational Toxicology, Office of Research and Development, US Environmental Protection Agency, Durham, NC 27711.
Katie Paul FriedmanNational Center for Computational Toxicology, Office of Research and Development, US Environmental Protection Agency, Durham, NC 27711.
Environmental Protection Agency · USOak Ridge Associated Universities · US

Funding

Intramural EPA EPA999999
6 · The paper itself

Abstract

The U.S. Environmental Protection Agency Endocrine Disruptor Screening Program and the Organization for Economic Co-operation and Development (OECD) have used the human adrenocarcinoma (H295R) cell-based assay to predict chemical perturbation of androgen and estrogen production. Recently, a high-throughput H295R (HT-H295R) assay was developed as part of the ToxCast program that includes measurement of 11 hormones, including progestagens, corticosteroids, androgens, and estrogens. To date, 2012 chemicals have been screened at 1 concentration; of these, 656 chemicals have been screened in concentration-response. The objectives of this work were to: (1) develop an integrated analysis of chemical-mediated effects on steroidogenesis in the HT-H295R assay and (2) evaluate whether the HT-H295R assay predicts estrogen and androgen production specifically via comparison with the OECD-validated H295R assay. To support application of HT-H295R assay data to weight-of-evidence and prioritization tasks, a single numeric value based on Mahalanobis distances was computed for 654 chemicals to indicate the magnitude of effects on the synthesis of 11 hormones. The maximum mean Mahalanobis distance (maxmMd) values were high for strong modulators (prochloraz, mifepristone) and lower for moderate modulators (atrazine, molinate). Twenty-five of 28 reference chemicals used for OECD validation were screened in the HT-H295R assay, and produced qualitatively similar results, with accuracies of 0.90/0.75 and 0.81/0.91 for increased/decreased testosterone and estradiol production, respectively. The HT-H295R assay provides robust information regarding estrogen and androgen production, as well as additional hormones. The maxmMd from this integrated analysis may provide a data-driven approach to prioritizing lists of chemicals for putative effects on steroidogenesis.

Indexed as

High-Throughput Screening AssaysCell Line, TumorData Interpretation, StatisticalDose-Response Relationship, DrugEndocrine DisruptorsEstrogensHumansOrganisation for Economic Co-Operation and DevelopmentPredictive Value of TestsReproducibility of ResultsTestosteroneUnited StatesUnited States Environmental Protection AgencyEndocrine DisruptorsEstrogensTestosterone

Identifiers

PMID29216406
PMCPMC10716795
OpenAlexW2772752440

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.