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High Content Screening Analysis to Evaluate the Toxicological Effects of Harmful and Potentially Harmful Constituents HPHC
Published on: May 10, 2016
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Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy.
Lucie C Ford1, Hsing-Chieh Lin1, Yi-Hui Zhou2,3
1Department of Veterinary Physiology and Pharmacology, TAMU 4466, Texas A&M University, College Station, TX, 77843-4466, USA.
Human Genomics
|September 1, 2024
Summary
This study assessed cardiotoxicity of 56 per- and poly-fluoroalkyl substances (PFAS) using human stem cell-derived heart cells. Many PFAS showed effects, revealing significant human variability in cardiotoxicity risk.
Area of Science:
- Environmental Toxicology
- Cardiovascular Toxicology
- Stem Cell Biology
Background:
- Per- and poly-fluoroalkyl substances (PFAS) are widespread environmental contaminants with limited toxicological data.
- Cardiotoxicity is a significant human health concern, necessitating robust screening methods.
- Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes offer a viable model for assessing cardiotoxicity and inter-individual variability.
Purpose of the Study:
- To characterize the cardiotoxic hazard, risk, and inter-individual variability of 56 PFAS using human iPSC-derived cardiomyocytes.
- To identify specific PFAS that pose a cardiotoxicity risk and exhibit high variability in human responses.
- To demonstrate the utility of population-based in vitro methods for evaluating emerging contaminants.
Main Methods:
- Tested 56 PFAS across different subclasses using concentration-response assays.
- Utilized human iPSC-derived cardiomyocytes from 16 healthy donors.
- Employed kinetic calcium flux and high-content imaging to assess phenotypes like beat frequency, repolarization, and cytotoxicity.
Main Results:
- 46 out of 56 PFAS exhibited concentration-response effects in at least one phenotype and donor.
- Significant inter-individual variability in sensitivity to PFAS effects was observed across donors.
- Risk characterization was performed for 20 PFAS, with most showing margins of exposure above 100.
Conclusions:
- This study identified several PFAS that may pose cardiotoxicity risks and exhibit high inter-individual variability.
- Human iPSC-derived cardiomyocytes are effective for quantifying population variability in response to PFAS.
- The findings support the use of in vitro human cell-based assays for prioritizing and assessing risks of emerging contaminants.
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