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A review of the pathways of human exposure to poly- and perfluoroalkyl substances (PFASs) and present understanding of health effects
Open accessAbstract
Here, we review present understanding of sources and trends in human exposure to poly- and perfluoroalkyl substances (PFASs) and epidemiologic evidence for impacts on cancer, immune function, metabolic outcomes, and neurodevelopment. More than 4000 PFASs have been manufactured by humans and hundreds have been detected in environmental samples. Direct exposures due to use in products can be quickly phased out by shifts in chemical production but exposures driven by PFAS accumulation in the ocean and marine food chains and contamination of groundwater persist over long timescales. Serum concentrations of legacy PFASs in humans are declining globally but total exposures to newer PFASs and precursor compounds have not been well characterized. Human exposures to legacy PFASs from seafood and drinking water are stable or increasing in many regions, suggesting observed declines reflect phase-outs in legacy PFAS use in consumer products. Many regions globally are continuing to discover PFAS contaminated sites from aqueous film forming foam (AFFF) use, particularly next to airports and military bases. Exposures from food packaging and indoor environments are uncertain due to a rapidly changing chemical landscape where legacy PFASs have been replaced by diverse precursors and custom molecules that are difficult to detect. Multiple studies find significant associations between PFAS exposure and adverse immune outcomes in children. Dyslipidemia is the strongest metabolic outcome associated with PFAS exposure. Evidence for cancer is limited to manufacturing locations with extremely high exposures and insufficient data are available to characterize impacts of PFAS exposures on neurodevelopment. Preliminary evidence suggests significant health effects associated with exposures to emerging PFASs. Lessons learned from legacy PFASs indicate that limited data should not be used as a justification to delay risk mitigation actions for replacement PFASs.
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“PFAS exposures via food chains are more difficult to resolve, and dietary exposure through drinking water and contaminated food sources (e.g., seafood and other animal products) are among the greatest exposure sources for ecosystems and human populations alike (109, 111).”
From Per- and polyfluoroalkyl substances in the environment (2022) · cites this paper as [109]
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“Solubilized (i.e., waterborne) rather than dietary exposure was linked to reduced amphipod survival and reproduction (133) while higher trophic-level organisms are exposed primarily through ingestion (109).”
From Per- and polyfluoroalkyl substances in the environment (2022) · cites this paper as [109]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“Fluoropolymer manufacturing plants, wastewater treatment plants [10,11], landfills, and military bases [89,90] are major sources of PFAS pollution in the environment.”
From Industrial Applications, Environmental Fate, Human Exposure, and Health Effects of PFAS (2025) · cites this paper as [90]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“Mechanistically, PFASs can activate peroxisome proliferatoractivated receptor alpha (PPAR α ), disrupt nuclear receptor signaling, and interfere with genes regulating lipid and cholesterol homeostasis.”
From Industrial Applications, Environmental Fate, Human Exposure, and Health Effects of PFAS (2025) · cites this paper as [90]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“Furthermore, PFAS exposure leads to immune suppression, with multiple studies reporting significant associations between PFAS exposure and reduced immune function, particularly in children.”
From Industrial Applications, Environmental Fate, Human Exposure, and Health Effects of PFAS (2025) · cites this paper as [90]
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“Significant gaps exist in PFAS research, with only a small fraction of the thousands of known PFAS compounds being routinely studied-most human and wildlife exposure assessments focus on just 2-30 legacy PFASs, leaving the uses and risks of the vast majority unknown [90,237,238].”
From Industrial Applications, Environmental Fate, Human Exposure, and Health Effects of PFAS (2025) · cites this paper as [90]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“For example, hundreds to thousands of PFASs are used in global commerce, but analytical methods and available standards lag behind, making it difficult to even identify or quantify many compounds [90,237].”
From Industrial Applications, Environmental Fate, Human Exposure, and Health Effects of PFAS (2025) · cites this paper as [90]
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“Exposure estimates can vary by two orders of magnitude due to uncertainties in source contributions and lack of standardized methods [90].”
From Industrial Applications, Environmental Fate, Human Exposure, and Health Effects of PFAS (2025) · cites this paper as [90]
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“In environmental and biomonitoring studies, up to 48% of total organofluorine in human plasma remains unaccounted for, indicating that a substantial proportion of exposure is from unidentified PFASs [90].”
From Industrial Applications, Environmental Fate, Human Exposure, and Health Effects of PFAS (2025) · cites this paper as [90]
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“Human exposure occurs primarily through contaminated food and water, inhalation of household dust, and dermal or parenteral contact with PFAS-containing products [9].”
From Exposure to Per- and Polyfluoroalkyl Substances (PFASs) in Healthcare: Environmental and Clinical Insights (2025) · cites this paper as [9]
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“Extensive studies have found positive associations between PFAS exposure and immunotoxic, neuro-developmental toxicity, thyroid and kidney disorders, hormonal effects, carcinogenic potency, infertility, and cancers [98,111,119].”
From Investigating the extent of PFAS contamination in the Upper Danube Basin across environmental compartments (2025) · cites this paper as [119]
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“Human-health effects from exposure to PFAS have been studied extensively, identifying possible carcinogenic, reproductive, endocrine, neurotoxic, dyslipidemia, and immunotoxic effects (6, 108, 109).”
From Per- and polyfluoroalkyl substances in the environment (2022) · cites this paper as [109]
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“In the realm of lipid metabolism, PFAS exposure is robustly linked to dyslipidemia and altered lipid metabolism.”
From Industrial Applications, Environmental Fate, Human Exposure, and Health Effects of PFAS (2025) · cites this paper as [90]
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“PFASs are highly persistent in natural environments due to their chemical stability and resistance to degradation.”
From Exposure to Per- and Polyfluoroalkyl Substances (PFASs) in Healthcare: Environmental and Clinical Insights (2025) · cites this paper as [9]
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“exposure to PFAS has been associated with adverse human health consequences (Sunderland et al., 2019).”
From Per and poly-fluoroalkyl substances (PFAS) as a contaminant of emerging concern in surface water: A transboundary review of their occurrences and toxicity effects (2021) · cites this paper as Sunderland et al., 2019
In the citing paper
“some PFAS are known or suspected to be associated with adverse human-health effects.11−13”
From Perfluoroalkyl and Polyfluoroalkyl Substances in Groundwater Used as a Source of Drinking Water in the Eastern United States (2022) · cites this paper as [13]
In the citing paper
“Globally, almost the entire human population has detectable blood serum levels of PFAS8, in major part due to environmental exposure from water or food sources12.”
From The link between ancient microbial fluoride resistance mechanisms and bioengineering organofluorine degradation or synthesis (2024) · cites this paper as [12]
In the citing paper
“Polyfluorinated compounds are found in every corner of earth, and human and ecosystem toxicity are now well documented (Ahrens and Bundschuh, 2014; Sunderland et al., 2019; Sinclair et al., 2020; Brase et al., 2021; Podder et al., 2021; Rice et al., 2021).”
From Nothing lasts forever: understanding microbial biodegradation of polyfluorinated compounds and perfluorinated alkyl substances (2022) · cites this paper as Sunderland et al., 2019
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Metadata
- Authors
- Sunderland, E. M., Hu, X. C., Dassuncao, C., Tokranov, A. K., Wagner, C. C., & Allen, J. G.
- Affiliations
- Harvard University (US)
- Corresponding author
- Sunderland, Elsie M.
- ORCID
- Venue
- Journal of Exposure Science & Environmental Epidemiology
- Published
- 2018-11-23
- Volume
- 29
- Issue
- 2
- Pages
- 131-147
- ISSN
- 1559-0631 (ISSN-L)
- 1559-064X
- PMC
- PMC6380916
- OpenAlex
- W2901377336
- Semantic Scholar
- da9ab49d9dc184966e90b5c960d678e87cb4df51
- Cited by
- 2,786
- References
- 154
- Citations by year
- 2026: 540 · 2025: 586 · 2024: 483 · 2023: 382 · 2022: 328 · 2021: 249 · 2020: 180 · 2019: 34
- FWCI
- 9.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Exposure Science & Environmental Epidemiology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Environmental Protection Agency
- National Institute for Health and Care Research
- National Health Research Institutes
- National Institute of Environmental Research
- National Institutes of Health
- National Institute of Environmental Health Sciences (P30ES000002, P42ES027706)
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Physical Sciences › Materials Science › Polymers and Plastics › Synthesis and properties of polymers
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Keywords
- per- and polyfluoroalkyl substances, human exposure, emerging PFASs, PFAS precursors, seafood contamination, drinking water contamination, groundwater contamination, aqueous film-forming foam, food packaging, indoor air exposure, cancer risk, immune function, dyslipidemia, brain development, serum PFAS concentrations, risk mitigation
- MeSH terms
- Environmental Exposure, Environmental Pollutants, Fluorocarbons, Humans, Water Pollutants, Chemical, Water Pollution, Chemical, Groundwater, Drinking Water
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