Structure-related differences in plasma protein binding of per- and polyfluoroalkyl substances in mice and humans
Abstract
Understanding interspecies and structure-based differences in the toxicokinetics of perfluoroalkyl substances (PFAS) is important to explain their persistence and improve health risk assessment. Since renal clearance is the main elimination pathway, this study measured the free (protein-unbound) fraction (f u ) of PFAS in human and mouse plasma using the Dianorm R system, selected for its robustness and rapid equilibrium. Sixteen PFAS were tested, including perfluoroalkyl carboxylic acids (PFCA), sulfonic acids (PFSA), and ether derivatives (PFECA). Mean f u values ranged from 0.21% (PFOS) to 50% (PFPeA) in mice and from 0.02% (PFHpS) to 8.5% (PFPeA) in humans. Interspecies differences were most pronounced for short-chain PFAS and PFECA, but not observed for longer chains. A U-shaped relationship between f u and molecular weight (MW) was found, with the lowest values near 400–500 g/mol. These results highlight plasma protein binding as a key determinant of PFAS persistence and provide predictive models linking f u to MW. • Importance of equilibrium efficiency in the comparison of three dialysis systems for studying PFAS protein binding. • Plasma protein binding of PFAS in mice and humans, including two emerging compounds. • Predictive models of the free fraction of PFAS as a function of their molecular weight.
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BibTeX
@article{argoul2026structurerelated,
title = {{Structure-related differences in plasma protein binding of per- and polyfluoroalkyl substances in mice and humans}},
author = {Chloé Ml. Argoul and Pierre-Louis Toutain and Sarah Berard and Nicole Picard-Hagen and Véronique Gayrard and Marlène Lacroix},
journal = {Environmental Toxicology and Pharmacology},
year = {2026},
month = oct,
doi = {10.1016/j.etap.2025.104879},
url = {https://hal.science/hal-05791816v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Structure-related differences in plasma protein binding of per- and polyfluoroalkyl substances in mice and humans
AU - Chloé Ml. Argoul
AU - Pierre-Louis Toutain
AU - Sarah Berard
AU - Nicole Picard-Hagen
AU - Véronique Gayrard
AU - Marlène Lacroix
PY - 2026
DA - 2026/10/11
JO - Environmental Toxicology and Pharmacology
DO - 10.1016/j.etap.2025.104879
UR - https://hal.science/hal-05791816v1
AB - Understanding interspecies and structure-based differences in the toxicokinetics of perfluoroalkyl substances (PFAS) is important to explain their persistence and improve health risk assessment. Since renal clearance is the main elimination pathway, this study measured the free (protein-unbound) fraction (f u ) of PFAS in human and mouse plasma using the Dianorm R system, selected for its robustness and rapid equilibrium. Sixteen PFAS were tested, including perfluoroalkyl carboxylic acids (PFCA), sulfonic acids (PFSA), and ether derivatives (PFECA). Mean f u values ranged from 0.21% (PFOS) to 50% (PFPeA) in mice and from 0.02% (PFHpS) to 8.5% (PFPeA) in humans. Interspecies differences were most pronounced for short-chain PFAS and PFECA, but not observed for longer chains. A U-shaped relationship between f u and molecular weight (MW) was found, with the lowest values near 400–500 g/mol. These results highlight plasma protein binding as a key determinant of PFAS persistence and provide predictive models linking f u to MW. • Importance of equilibrium efficiency in the comparison of three dialysis systems for studying PFAS protein binding. • Plasma protein binding of PFAS in mice and humans, including two emerging compounds. • Predictive models of the free fraction of PFAS as a function of their molecular weight.
SN - 1382-6689
ER -