Evidence map›Paper›PMID 34718810›Full record

ArticleToxicological sciences : an official journal of the Society of Toxicology2021

Ozone Responsive Gene Expression as a Model for Describing Repeat Exposure Response Trajectories and Interindividual Toxicodynamic Variability In Vitro.

Emma C Bowers, Elizabeth M Martin, Annie M Jarabek, David S Morgan, Hannah J Smith, Lisa A Dailey, Emily R Aungst, David Diaz-Sanchez, Shaun D McCullough

Open access · greenAbstract read
In one paragraph

Article in Toxicological sciences : an official journal of the Society of Toxicology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 23% 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

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Evaluating the role of alveolar macrophages in tolerance to ozone.Toxicological sciences : an official journal of the Society of Toxicology · 2025
    Article
  4. Article
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  6. Review
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  8. Review
  9. Technical evaluation and standardization of the human thyroid microtissue assay.Toxicological sciences : an official journal of the Society of Toxicology · 2024
    Article
  10. Article
  11. New approach methodologies (NAMs) for theFrontiers in toxicology · 2024
    Review
  12. Article
  13. Review
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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 3 institutions in 1 country.

Emma C BowersCurriculum in Toxicology and Environmental Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Elizabeth M MartinDepartment of Health and Human Services, Epigenetics & Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, North Carolina 27709, USA.
Annie M JarabekHealth and Environmental Effects Assessment Division, Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27709, USA.
David S MorganPublic Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency, Chapel Hill, North Carolina 27599, USA.
Hannah J SmithDepartment of Environmental Sciences and Engineering, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Lisa A DaileyPublic Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency, Chapel Hill, North Carolina 27599, USA.
Emily R AungstPublic Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency, Chapel Hill, North Carolina 27599, USA.
David Diaz-SanchezPublic Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency, Chapel Hill, North Carolina 27599, USA.
Shaun D McCulloughPublic Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency, Chapel Hill, North Carolina 27599, USA.ORCID 0000-0001-6660-346X
Environmental Protection Agency · USUniversity of North Carolina at Chapel Hill · USNational Institutes of Health · US

Funding

TOXICOLOGYT32ES007126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ILONA JASPERS, Bernard E. Weissman · 1985 to 2026
$13.0M
Eukaryotic Transcriptional RegulationZ01ES101965 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI WADE, PAUL A · 2005 to 2008
$3.5M
Pregnancy-induced epigenetic changes in breast duct epithelia as biological mechanism influencing breast cancer riskFI2GM133546 · NIGMS · U.S. NATIONAL INST OF ENVIRON HLTH SCIS · PI MARTIN, ELIZABETH MARIE · 2019 to 2019
–
Intramural NIH HHS Z01 ES101965NIEHS NIH HHS T32 ES007126
6 · The paper itself

Abstract

Inhaled chemical/material exposures are a ubiquitous part of daily life around the world. There is a need to evaluate potential adverse effects of both single and repeat exposures for thousands of chemicals and an exponentially larger number of exposure scenarios (eg, repeated exposures). Meeting this challenge will require the development and use of in vitro new approach methodologies (NAMs); however, 2 major challenges face the deployment of NAMs in risk assessment are (1) characterizing what apical outcome(s) acute assays inform regarding the trajectory to long-term events, especially under repeated exposure conditions, and (2) capturing interindividual variability as it informs considerations of potentially susceptible and/or vulnerable populations. To address these questions, we used a primary human bronchial epithelial cell air-liquid interface model exposed to ozone (O3), a model oxidant and ubiquitous environmental chemical. Here we report that O3-induced proinflammatory gene induction is attenuated in repeated exposures thus demonstrating that single acute exposure outcomes do not reliably represent the trajectory of responses after repeated or chronic exposures. Further, we observed 10.1-, 10.3-, 14.2-, and 7-fold ranges of induction of interleukin (IL)-8, IL-6, heme oxygenase 1, and cyclooxygenase 2 transcripts, respectively, within in our population of 25 unique donors. Calculation of sample size estimates that indicated that 27, 24, 299, and 13 donors would be required to significantly power similar in vitro studies to identify a 2-fold change in IL-8, IL-6, HMOX1, and cyclooxygenase 2 transcript induction, respectively, to inform considerations of the uncertainty factors to reflect variability within the human population for in vitro studies.

Indexed as

OzoneEpithelial CellsGene ExpressionHumansRisk AssessmentOzoneair-liquid interface (ALI)inhalation risk assessmentinterindividual variabilityin vitro to in vivo extrapolationnew approach methods (NAMs)ozone

Identifiers

PMID34718810
PMCPMC8714356
OpenAlexW3209105829

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.