Evidence map›Paper›PMID 35445829›Full record

ArticleArchives of toxicology2022

Comprehensive interpretation of in vitro micronucleus test results for 292 chemicals: from hazard identification to risk assessment application.

Byron Kuo, Marc A Beal, John W Wills, Paul A White, Francesco Marchetti, Andy Nong, Tara S Barton-Maclaren, Keith Houck, Carole L Yauk

Open access · hybridAbstract read
In one paragraph

Article in Archives of toxicology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
3.3field-weighted citation impact, top 6% 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

17 citing papers in PubMed, 38 citations in OpenAlex.

  1. New Approach Methods in Genetic Toxicology.Environmental and molecular mutagenesis · 2026
    Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Critical Evaluation of Methods for the Identification of Aneugens.Environmental and molecular mutagenesis · 2025
    Review
  8. Article
  9. Re-evaluation of neotame (E 961) as food additive.EFSA journal. European Food Safety Authority · 2025
    Article
  10. Review
  11. Benchmark Response (BMR) Values for In Vivo Mutagenicity Endpoints.Environmental and molecular mutagenesis · 2025
    Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. 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

9 authors at 2 institutions in 3 countries.

Byron Kuo *Environmental Health Science and Research Bureau, Environmental and Radiation Health Sciences Directorate, Healthy Environment and Consumer Safety Branch, Health Canada, Ottawa, ON, Canada.
Marc A Beal *Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, ON, Canada.
John W WillsEnvironmental Health Science and Research Bureau, Environmental and Radiation Health Sciences Directorate, Healthy Environment and Consumer Safety Branch, Health Canada, Ottawa, ON, Canada.
Paul A WhiteEnvironmental Health Science and Research Bureau, Environmental and Radiation Health Sciences Directorate, Healthy Environment and Consumer Safety Branch, Health Canada, Ottawa, ON, Canada.
Francesco MarchettiEnvironmental Health Science and Research Bureau, Environmental and Radiation Health Sciences Directorate, Healthy Environment and Consumer Safety Branch, Health Canada, Ottawa, ON, Canada.
Andy NongEnvironmental Health Science and Research Bureau, Environmental and Radiation Health Sciences Directorate, Healthy Environment and Consumer Safety Branch, Health Canada, Ottawa, ON, Canada.
Tara S Barton-MaclarenExisting Substances Risk Assessment Bureau, Safe Environments Directorate, Healthy Environment and Consumer Safety Branch, Health Canada, Ottawa, ON, Canada.
Keith HouckNational Center for Computational Toxicology, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC, 27711, USA.
Carole L YaukEnvironmental Health Science and Research Bureau, Environmental and Radiation Health Sciences Directorate, Healthy Environment and Consumer Safety Branch, Health Canada, Ottawa, ON, Canada. carole.yauk@uottawa.ca.ORCID http://orcid.org/0000-0002-6725-3454
Health Canada · CAEnvironmental Protection Agency · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Risk assessments are increasingly reliant on information from in vitro assays. The in vitro micronucleus test (MNvit) is a genotoxicity test that detects chromosomal abnormalities, including chromosome breakage (clastogenicity) and/or whole chromosome loss (aneugenicity). In this study, MNvit datasets for 292 chemicals, generated by the US EPA's ToxCast program, were evaluated using a decision tree-based pipeline for hazard identification. Chemicals were tested with 19 concentrations (n = 1) up to 200 µM, in the presence and absence of Aroclor 1254-induced rat liver S9. To identify clastogenic chemicals, %MN values at each concentration were compared to a distribution of batch-specific solvent controls; this was followed by cytotoxicity assessment and benchmark concentration (BMC) analyses. The approach classified 157 substances as positives, 25 as negatives, and 110 as inconclusive. Using the approach described in Bryce et al. (Environ Mol Mutagen 52:280-286, 2011), we identified 15 (5%) aneugens. IVIVE (in vitro to in vivo extrapolation) was employed to convert BMCs into administered equivalent doses (AEDs). Where possible, AEDs were compared to points of departure (PODs) for traditional genotoxicity endpoints; AEDs were generally lower than PODs based on in vivo endpoints. To facilitate interpretation of in vitro MN assay concentration-response data for risk assessment, exposure estimates were utilized to calculate bioactivity exposure ratio (BER) values. BERs for 50 clastogens and two aneugens had AEDs that approached exposure estimates (i.e., BER < 100); these chemicals might be considered priorities for additional testing. This work provides a framework for the use of high-throughput in vitro genotoxicity testing for priority setting and chemical risk assessment.

Indexed as

AneugensMutagensAnimalsMicronucleus TestsMutagenicity TestsRatsRisk AssessmentAneugensMutagensBenchmark doseGenotoxicityIVIVEMicronucleusPoint of departureToxicokinetics

Identifiers

PMID35445829
PMCPMC9151546
OpenAlexW4224225277

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.