Cited by 16Per- and polyfluoroalkyl substances researchFluorine in Organic ChemistryMetabolomics and Mass Spectrometry Studies

Novel and Legacy Per- and Polyfluoroalkyl Substances in Humans: Long-Term Temporal Variability and Metabolic Perturbations

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Chang, Che-Jung, Young, Anna S., Keil, Alexander, Mullins, Catherine E., Liang, Donghai, Zhao, Shanshan, Jones, Dean P., Hu, Xin +2 more·2025·Environment International

Abstract

As legacy per- and polyfluoroalkyl substances (PFAS) are phased out, numerous substitutes have emerged, raising concerns about their potential health impacts. Using targeted and untargeted approaches, we evaluated plasma PFAS on an -omic scale, examining temporal variability and associated metabolomic disruptions. A total of 400 blood samples from 200 Sister Study participants (collected in 2007-2008 and 2013-2014) were analyzed using liquid chromatography with high-resolution mass spectrometry. Temporal variability was assessed using Spearman correlations and intraclass correlation coefficients. Network analysis, metabolome-wide association studies, and pathway analysis were used to evaluate the impacts of PFAS mixtures on the human metabolome. We detected 24 legacy PFAS via the targeted approach and 1,802 features annotated as potential PFAS via the untargeted approach (21 confirmed by reference standards). While legacy PFAS demonstrated low temporal variability, novel PFAS, especially those that have increased in abundance over time, demonstrated greater temporal variability. The legacy PFAS mixture was associated with lipid and amino acid metabolism, while other PFAS mixtures consisting of novel PFAS affected a wider range of metabolic pathways in addition to amino and lipid metabolism, such as carbohydrate, cofactor and vitamin, and endocrine metabolism. These findings underscore the need for further research on these novel PFAS and their health effects.

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  • Newer PFAS compounds exert broader effects across metabolic pathways, including carbohydrate processing, vitamin/cofactor utilization, and endocrine regulation.

    “Legacy PFAS mixtures have been shown to primarily disrupt amino acid and lipid metabolism, while newer PFAS compounds exert broader effects across metabolic pathways, including those involved in carbohydrate processing, vitamin/cofactor utilization, and endocrine regulation [79].”
  • Legacy PFAS mixtures primarily disrupt amino acid and lipid metabolism.

    “Legacy PFAS mixtures have been shown to primarily disrupt amino acid and lipid metabolism, while newer PFAS compounds exert broader effects across metabolic pathways, including those involved in carbohydrate processing, vitamin/cofactor utilization, and endocrine regulation [79].”

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Authors
Chang, C.-J., Young, A. S., Keil, A., Mullins, C. E., Liang, D., Zhao, S., Jones, D. P., Hu, X., Walker, D. I., & White, A. J.
Affiliations
  • National Institutes of Health (US)
  • Emory University (US)
  • National Institute of Environmental Health Sciences (US)
Corresponding author
White, Alexandra J.
Venue
Environment International
Publisher
Elsevier BV
Published
2025-07
Volume
201
Pages
109590
ISSN
0160-4120 (ISSN-L)
OpenAlex
W4411081266
Cited by
16
References
67
Citations by year
2026: 11 · 2025: 5
FWCI
4.45
Type
journal article
Language
en
Open access
Locations
  • Environment International (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institute of Environmental Health Sciences (Z01-ES044005, R01ES032831, Z1AES103332)
Topics
  • Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Fluorine in Organic Chemistry
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
Keywords
per- and polyfluoroalkyl substances, legacy PFAS, temporal variation, human metabolome, lipid metabolism, amino acid metabolism, carbohydrate metabolism, endocrine metabolism, cofactor and vitamin metabolism, Sister Study, PFAS mixtures
MeSH terms
Adult, Environmental Exposure, Environmental Pollutants, Female, Fluorocarbons, Humans, Middle Aged, Metabolome

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