Evidence map›Paper›PMID 33049310›Full record

ArticleToxicology in vitro : an international journal published in association with BIBRA2021

Evaluation of a multiplexed, multispecies nuclear receptor assay for chemical hazard assessment.

Keith A Houck, Anita Simha, Audrey Bone, Jon A Doering, Sara M F Vliet, Carlie LaLone, Alex Medvedev, Sergei Makarov

Open access · greenAbstract read
In one paragraph

Article in Toxicology in vitro : an international journal published in association with BIBRA, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 15% 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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.

  1. Weight of evidence for cross-species conservation of androgen receptor-based biological activity.Toxicological sciences : an official journal of the Society of Toxicology · 2023
    Pooled it
  2. Article
  3. Article
  4. Article
  5. Burnt Plastic (Pyroplastic) from the M/VEnvironment & health (Washington, D.C.) · 2025
    Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Keith A HouckCenter for Computational Toxicology and Exposure, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. Electronic address: houck.keith@epa.gov.
Anita SimhaORAU, Contractor to U.S. Environmental Protection Agency through the National Student Services Contract, United States.
Audrey BoneCenter for Computational Toxicology and Exposure, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Jon A DoeringNational Research Council, 6201 Congdon Blvd., Duluth, MN 55804, USA.
Sara M F VlietOffice of Research and Development, Center for Computational Toxicology and Ecology, Great Lakes Toxicology and Ecology Division, Oak Ridge Institute for Science and Education, U.S. Environmental Protection Agency, Duluth, MN 55804, USA.
Carlie LaLoneGreat Lakes Toxicology and Ecology Division, Office of Research and Development, U.S. Environmental Protection Agency, Duluth, MN, United States of America.
Alex MedvedevAttagene, Inc., 7030 Kit Creek Rd, Morrisville, NC 27560, United States of America.
Sergei MakarovAttagene, Inc., 7030 Kit Creek Rd, Morrisville, NC 27560, United States of America.
Environmental Protection Agency · USAttagene · USNational Academies of Sciences, Engineering, and Medicine · US

Funding

Predicting DILI liability by transcription factor profilingR44GM125469 · NIGMS · ATTAGENE, INC. · PI MAKAROV, SERGEI S · 2017 to 2019
$3.0M
Intramural EPA EPA999999NIGMS NIH HHS R44 GM125469
6 · The paper itself

Abstract

Sensitivity to potential endocrine disrupting chemicals in the environment varies across species and is influenced by sequence conservation of their nuclear receptor targets. Here, we evaluated a multiplexed, in vitro assay testing receptors relevant to endocrine and metabolic disruption from five species. The TRANS-FACTORIAL™ system of human nuclear receptors was modified to include additional species: mouse (Mus musculus), frog (Xenopus laevis), zebrafish (Danio rerio), chicken (Gallus gallus), and turtle (Chrysemys picta). Receptors regulating endocrine function and xenobiotic recognition were included, specifically: ERα, ERβ, AR, TRα, TRβ, PPARγ and PXR. The assay, ECOTOX-FACTORIAL™, was evaluated with 191 chemicals enriched with known receptor ligands. Hierarchical clustering of potency values demonstrated strong coherence of receptor families. Interspecies comparisons of responses within a receptor family showed moderate to high concordance for potencies under 50 μM. PPARγ showed high concordance between mammalian species, 89%, but only 63% between mammalian and zebrafish. For chemicals with potencies below 1 μM, concordances were 89-100% for all receptors except PXR. Concordance showed a strong positive relationship to ligand-binding domain sequence similarity and critical amino acid residues obtained by the Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool. In combination with SeqAPASS, ECOTOX-FACTORIAL may provide efficient screening of important receptors to identify species of high priority for effects monitoring.

Indexed as

AnimalsBiological AssayChickensHazardous SubstancesHep G2 CellsHumansMiceReceptors, Cytoplasmic and NuclearTurtlesXenopus laevisZebrafishHazardous SubstancesReceptors, Cytoplasmic and NuclearEcotoxicologyEndocrine disruptorsMultiplexed assayNuclear receptorReporter geneZebrafish

Identifiers

PMID33049310
PMCPMC11267479
OpenAlexW3092150875

What OpenQuestion holds

Textmetadata
LicenceTDM
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.