Evidence map›Paper›PMID 39218963›Full record

ArticleHuman genomics2024

Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy.

Lucie C Ford, Hsing-Chieh Lin, Yi-Hui Zhou, Fred A Wright, Vijay K Gombar, Alexander Sedykh, Ruchir R Shah, Weihsueh A Chiu, Ivan Rusyn

Abstract read
In one paragraph

Article in Human genomics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. 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
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.

Lucie C FordDepartment of Veterinary Physiology and Pharmacology, TAMU 4466, Texas A&M University, College Station, TX, 77843-4466, USA.
Hsing-Chieh LinDepartment of Veterinary Physiology and Pharmacology, TAMU 4466, Texas A&M University, College Station, TX, 77843-4466, USA.
Yi-Hui ZhouDepartment of Biological Sciences and Statistics, North Carolina State University, Raleigh, NC, 27695, USA.
Fred A WrightDepartment of Biological Sciences and Statistics, North Carolina State University, Raleigh, NC, 27695, USA.
Vijay K GombarSciome LLC, Durham, NC, 27713, USA.
Alexander SedykhSciome LLC, Durham, NC, 27713, USA.
Ruchir R ShahSciome LLC, Durham, NC, 27713, USA.
Weihsueh A ChiuDepartment of Veterinary Physiology and Pharmacology, TAMU 4466, Texas A&M University, College Station, TX, 77843-4466, USA.
Ivan RusynDepartment of Veterinary Physiology and Pharmacology, TAMU 4466, Texas A&M University, College Station, TX, 77843-4466, USA. irusyn@tamu.edu.

Funding

Single cell, multi-parametric high throughput platform to classify endocrine disruptor potential of mixturesP42ES027704 · NIEHS · TEXAS A&M UNIVERSITY · PI Efstratios Pistikopoulos · 2017 to 2026
$21.2M
Regulatory Science in Environmental Health and ToxicologyT32ES026568 · NIEHS · TEXAS A&M UNIVERSITY · PI Weihsueh A Chiu, Natalie M Johnson · 2016 to 2026
$3.8M
NIEHS NIH HHS P42 ES027704NIEHS NIH HHS T32 ES026568U.S. Environmental Protection Agency STAR RD83580201
6 · The paper itself

Abstract

Per- and poly-fluoroalkyl substances (PFAS) are emerging contaminants of concern because of their wide use, persistence, and potential to be hazardous to both humans and the environment. Several PFAS have been designated as substances of concern; however, most PFAS in commerce lack toxicology and exposure data to evaluate their potential hazards and risks. Cardiotoxicity has been identified as a likely human health concern, and cell-based assays are the most sensible approach for screening and prioritization of PFAS. Human-induced pluripotent stem cell (iPSC)-derived cardiomyocytes are a widely used method to test for cardiotoxicity, and recent studies showed that many PFAS affect these cells. Because iPSC-derived cardiomyocytes are available from different donors, they also can be used to quantify human variability in responses to PFAS. The primary objective of this study was to characterize potential human cardiotoxic hazard, risk, and inter-individual variability in responses to PFAS. A total of 56 PFAS from different subclasses were tested in concentration-response using human iPSC-derived cardiomyocytes from 16 donors without known heart disease. Kinetic calcium flux and high-content imaging were used to evaluate biologically-relevant phenotypes such as beat frequency, repolarization, and cytotoxicity. Of the tested PFAS, 46 showed concentration-response effects in at least one phenotype and donor; however, a wide range of sensitivities were observed across donors. Inter-individual variability in the effects could be quantified for 19 PFAS, and risk characterization could be performed for 20 PFAS based on available exposure information. For most tested PFAS, toxicodynamic variability was within a factor of 10 and the margins of exposure were above 100. This study identified PFAS that may pose cardiotoxicity risk and have high inter-individual variability. It also demonstrated the feasibility of using a population-based human in vitro method to quantify population variability and identify cardiotoxicity risks of emerging contaminants.

Indexed as

CardiotoxicityFluorocarbonsInduced Pluripotent Stem CellsMyocytes, CardiacAdultEnvironmental ExposureEnvironmental PollutantsFemaleHumansMaleRisk AssessmentEnvironmental PollutantsFluorocarbons

Identifiers

PMID39218963
PMCPMC11368000

What Socratic 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 Socratic graph.