Evidence map›Paper›PMID 39893674›Full record

ArticleEnvironmental science & technology2025

Unraveling Human Hepatocellular Responses to PFAS and Aqueous Film-Forming Foams (AFFFs) for Molecular Hazard Prioritization and In Vivo Translation.

Kevin A Mauge-Lewis, Sreenivasa C Ramaiahgari, Scott S Auerbach, Georgia K Roberts, Suramya Waidyanatha, Suzanne E Fenton, Dhiral P Phadke, Michele R Balik-Meisner, Arpit Tandon, Deepak Mav and 5 more

Abstract read
In one paragraph

Article in Environmental science & technology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
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

15 authors.

Kevin A Mauge-LewisDivision of Translational Toxicology, National Institute for Environmental Sciences, 111 TW Alexander Drive, Durham, North Carolina 27709, United States.
Sreenivasa C RamaiahgariDivision of Translational Toxicology, National Institute for Environmental Sciences, 111 TW Alexander Drive, Durham, North Carolina 27709, United States.
Scott S AuerbachDivision of Translational Toxicology, National Institute for Environmental Sciences, 111 TW Alexander Drive, Durham, North Carolina 27709, United States.
Georgia K RobertsDivision of Translational Toxicology, National Institute for Environmental Sciences, 111 TW Alexander Drive, Durham, North Carolina 27709, United States.
Suramya WaidyanathaDivision of Translational Toxicology, National Institute for Environmental Sciences, 111 TW Alexander Drive, Durham, North Carolina 27709, United States.
Suzanne E FentonDivision of Translational Toxicology, National Institute for Environmental Sciences, 111 TW Alexander Drive, Durham, North Carolina 27709, United States.
Dhiral P PhadkeSciome, 1920 NC-54 Suite 510 & 520, Durham, North Carolina 27713, United States.
Michele R Balik-MeisnerSciome, 1920 NC-54 Suite 510 & 520, Durham, North Carolina 27713, United States.
Arpit TandonSciome, 1920 NC-54 Suite 510 & 520, Durham, North Carolina 27713, United States.
Deepak MavSciome, 1920 NC-54 Suite 510 & 520, Durham, North Carolina 27713, United States.
Brian HowardSciome, 1920 NC-54 Suite 510 & 520, Durham, North Carolina 27713, United States.
Ruchir ShahSciome, 1920 NC-54 Suite 510 & 520, Durham, North Carolina 27713, United States.
Barney SparrowBattelle, 505 King Avenue, Columbus, Ohio 43201, United States.
Jenni GorospeBattelle, 505 King Avenue, Columbus, Ohio 43201, United States.
Stephen S FergusonDivision of Translational Toxicology, National Institute for Environmental Sciences, 111 TW Alexander Drive, Durham, North Carolina 27709, United States.ORCID 0000-0003-3172-8347

Funding

TOXICOLOGYT32ES007126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ILONA JASPERS, Bernard E. Weissman · 1985 to 2026
$13.0M
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 ES103381NIEHS NIH HHS HHSN273201500006CNIEHS NIH HHS HHSN273201700005CNIEHS NIH HHS T32 ES007126
6 · The paper itself

Abstract

Aqueous film-forming foams (AFFFs) are complex product mixtures that often contain per- and polyfluorinated alkyl substances (PFAS) to enhance fire suppression and protect firefighters. However, PFAS have been associated with a range of adverse health effects (e.g., liver and thyroid disease and cancer), and innovative approach methods to better understand their toxicity potential and identify safer alternatives are needed. In this study, we investigated a set of 30 substances (e.g., AFFF, PFAS, and clinical drugs) using differentiated cultures of human hepatocytes (HepaRG, 2D), high-throughput transcriptomics, deep learning of cell morphology images, and liver enzyme leakage assays with benchmark dose analysis to (1) predict the potency ranges for human liver injury, (2) delineate gene- and pathway-level transcriptomic points-of-departure for molecular hazard characterization and prioritization, (3) characterize human hepatocellular response similarities to inform regulatory read-across efforts, and (4) introduce an innovative approach to translate mechanistic hepatocellular response data to predict the potency ranges for PFAS-induced hepatomegaly in vivo. Collectively, these data fill important mechanistic knowledge gaps with PFAS/AFFF and represent a scalable platform to address the thousands of PFAS in commerce for greener chemistries and next-generation risk assessments.

Indexed as

FluorocarbonsHepatocytesHumansLiverFluorocarbonsAFFFbiological-response similarityCARenvironmental healthhepatomegalyhuman liver injuryPFASPPARαprioritizationtranscriptomic response pathwaystranslationVDR

Identifiers

PMID39893674
PMCPMC11823446

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.