Internal Relative Potency Factors for the Risk Assessment of Mixtures of Per- and Polyfluoroalkyl Substances (PFAS) in Human Biomonitoring
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BACKGROUND: In human biomonitoring, blood is often used as a matrix to measure exposure to per- and polyfluoroalkyl substances (PFAS). Because the toxicokinetics of a substance (determining the steady-state blood concentration) may affect the toxic potency, the difference in toxicokinetics among PFAS has to be accounted for when blood concentrations are used in mixture risk assessment. OBJECTIVES: This research focuses on deriving relative potency factors (RPFs) at the blood serum level. These RPFs can be applied to PFAS concentrations in human blood, thereby facilitating mixture risk assessment with primary input from human biomonitoring studies. METHODS: Toxicokinetic models are generated for 10 PFAS to estimate the internal exposure in the male rat at the blood serum level over time. By applying dose-response modeling, these internal exposures are used to derive quantitative internal RPFs based on liver effects. RESULTS: Internal RPFs were successfully obtained for nine PFAS. Perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorononanoic acid (PFNA), perfluorododecanoic acid (PFDoDA), perfluorooctane sulfonic acid (PFOS), and hexafluoropropylene oxide-dimer acid (HFPO-DA, or GenX) were found to be more potent than perfluorooctanoic acid (PFOA) at the blood serum level in terms of relative liver weight increase, whereas perfluorobutane sulfonic acid (PFBS) and perfluorohexane sulfonic acid (PFHxS) were found to be less potent. The practical implementation of these internal RPFs is illustrated using the National Health and Nutrition Examination Survey (NHANES) biomonitoring data of 2017-2018. DISCUSSION: It is recommended to assess the health risk resulting from exposure to PFAS as combined, aggregate exposure to the extent feasible. https://doi.org/10.1289/EHP10009.
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Recent studies did not modify the limitation of using rodent parameters to establish TEFs that are intended to be used to estimate human health risks related to PFAS mixtures exposure.
“Recent studies did not modify the limitation of using rodent parameters to establish TEFs that are intended to be used to estimate human health risks related to PFAS mixtures exposure.”
From The EU’s Per- and Polyfluoroalkyl Substances (PFAS) Ban: A Case of Policy over Science (2023) · cites this paper as [49]
The same research group derived RPFs for various PFAS at the blood serum level in male rats; by applying dose-response modeling, these internal exposures are used to derive quantitative internal RPFs based on liver weight effects.
“The same research group derived RPFs for various PFAS at the blood serum level, in male rats. By applying dose–response modeling, these internal exposures are used to derive quantitative internal RPFs based on liver weight effects [49].”
From The EU’s Per- and Polyfluoroalkyl Substances (PFAS) Ban: A Case of Policy over Science (2023) · cites this paper as [49]
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- Authors
- Bil, W., Zeilmaker, M. J., & Bokkers, B. G. H.
- Affiliations
- National Institute for Public Health and the Environment (NL)
- Corresponding author
- Bil, Wieneke
- Venue
- Environmental Health Perspectives
- Publisher
- American Chemical Society (ACS)
- Published
- 2022-07
- Volume
- 130
- Issue
- 7
- Pages
- 77005-77005
- ISSN
- 0091-6765 (ISSN-L)
- 1552-9924
- PMC
- PMC9320915
- OpenAlex
- W4288045194
- Cited by
- 47
- References
- 126
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 8 · 2023: 9 · 2022: 4
- FWCI
- 3.19
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- public-domain
- Locations
- Environmental Health Perspectives (publishedVersion, public-domain)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Rivm Repository (Netherlands National Institute for Public Health and the Environment) (submittedVersion)
- OpenAgrar (submittedVersion)
- Rivm (National Institute for Public Health and the Environment) (submittedVersion, other-oa)
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Fluorine in Organic Chemistry
- Keywords
- per- and polyfluoroalkyl substances, PFAS mixtures, relative potency factors, mixture risk assessment, human biomonitoring, toxicokinetic modeling, internal radiation exposure, liver effects, dose-response modeling, perfluorooctanoic acid, PFOS, GenX, NHANES
- MeSH terms
- Biological Monitoring, Animals, Environmental Pollutants, Fluorocarbons, Humans, Male, Nutrition Surveys, Sulfonic Acids, Alkanesulfonic Acids, Risk Assessment, Rats
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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