Evidence map›Paper›PMID 34453843›Full record

ArticleToxicological sciences : an official journal of the Society of Toxicology2021

Potency Ranking of Per- and Polyfluoroalkyl Substances Using High-Throughput Transcriptomic Analysis of Human Liver Spheroids.

Anthony J F Reardon, Andrea Rowan-Carroll, Stephen S Ferguson, Karen Leingartner, Remi Gagne, Byron Kuo, Andrew Williams, Luigi Lorusso, Julie A Bourdon-Lacombe, Richard Carrier and 3 more

Abstract 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 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
–field-weighted citation impact
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

39 citing papers in PubMed.

  1. Article
  2. Article
  3. Analytical choices drive toxicogenomic potency estimates: a systematic evaluation of transcriptomic points of departure.Toxicological sciences : an official journal of the Society of Toxicology · 2026
    Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. ARACRA: Automated RNA-seq Analysis for Chemical Risk Assessment.Computational and structural biotechnology journal · 2026
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Incorporating new approach methods (NAMs) data in dose-response assessments: The future is now!Journal of toxicology and environmental health. Part B, Critical reviews · 2025
    Review
  17. Article
  18. Article
  19. Article
  20. 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

13 authors.

Anthony J F ReardonEnvironmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada.ORCID 0000-0002-7124-1229
Andrea Rowan-CarrollEnvironmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada.
Stephen S FergusonBiomolecular Screening Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.ORCID 0000-0003-3172-8347
Karen LeingartnerEnvironmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada.
Remi GagneEnvironmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada.
Byron KuoEnvironmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada.
Andrew WilliamsEnvironmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada.
Luigi LorussoChemicals and Environmental Health Management Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada.
Julie A Bourdon-LacombeWater and Air Quality Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada.
Richard CarrierWater and Air Quality Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada.
Ivy MoffatWater and Air Quality Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada.
Carole L YaukEnvironmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada.
Ella AtlasEnvironmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada.ORCID 0000-0003-4410-4402

Funding

Safe and Sustainable Alternatives Research ProgramZIAES103381 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI FERGUSON, STEPHEN · 2022 to 2025
$7.0M
Intramural NIH HHS ZIA ES103381
6 · The paper itself

Abstract

Per- and polyfluoroalkyl substances (PFAS) are some of the most prominent organic contaminants in human blood. Although the toxicological implications of human exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are well established, data on lesser-understood PFAS are limited. New approach methodologies (NAMs) that apply bioinformatic tools to high-throughput data are being increasingly considered to inform risk assessment for data-poor chemicals. The aim of this study was to compare the potencies (ie, benchmark concentrations: BMCs) of PFAS in primary human liver microtissues (3D spheroids) using high-throughput transcriptional profiling. Gene expression changes were measured using TempO-seq, a templated, multiplexed RNA-sequencing platform. Spheroids were exposed for 1 or 10 days to increasing concentrations of 23 PFAS in 3 subgroups: carboxylates (PFCAs), sulfonates (PFSAs), and fluorotelomers and sulfonamides. PFCAs and PFSAs exhibited trends toward increased transcriptional potency with carbon chain-length. Specifically, longer-chain compounds (7-10 carbons) were more likely to induce changes in gene expression and have lower transcriptional BMCs. The combined high-throughput transcriptomic and bioinformatic analyses support the capability of NAMs to efficiently assess the effects of PFAS in liver microtissues. The data enable potency ranking of PFAS for human liver cell spheroid cytotoxicity and transcriptional changes, and assessment of in vitro transcriptomic points of departure. These data improve our understanding of the possible health effects of PFAS and will be used to inform read-across for human health risk assessment.

Indexed as

Alkanesulfonic AcidsFluorocarbonsCarboxylic AcidsHumansLiverTranscriptomeAlkanesulfonic AcidsCarboxylic AcidsFluorocarbonsbenchmark concentrationbenchmark dosebiological potencygene expressionhigh-throughput transcriptomicsnew approach methodologiesperfluoroalkyl substancespolyfluoroalkyl substances

Identifiers

PMID34453843
PMCPMC13587228

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.