Perfluoroalkyl Substances (PFASs) Are Substrates of the Renal Human Organic Anion Transporter 4 (OAT4)
Open accessAbstract
Poly- and perfluoroalkyl substances (PFASs) are omnipresent in the environment and have been shown to accumulate in humans. Most PFASs are not biotransformed in animals and humans, so that elimination is largely dependent on non-metabolic clearance via bile and urine. Accumulation of certain PFASs in humans may relate to their reabsorption from the pre-urine by transporter proteins in the proximal tubules of the kidney, such as URAT1 and OAT4. The present study assessed the in vitro transport of 7 PFASs (PFHpA, PFOA, PFNA, PFDA, PFBS, PFHxS and PFOS) applying URAT1- or OAT4-transfected human embryonic kidney (HEK) cells. Virtually no transport of PFASs could be measured in URAT1-transfected HEK cells. All PFASs, except PFBS, showed clear uptake in OAT4-transfected HEK cells. In addition, these in vitro results were further supported by in silico docking and molecular dynamic simulation studies assessing transporter-ligand interactions. Information on OAT4-mediated transport may provide insight into the accumulation potential of PFASs in humans, but other kinetic aspects may play a role and should also be taken into account. Quantitative information on all relevant kinetic processes should be integrated in physiologically based kinetic (PBK) models, to predict congener-specific accumulation of PFASs in humans in a more accurate manner.
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In HEK cells transfected with URAT1, there was no significant PFAS transport; however, all PFAS except PFBS were taken up in HEK cells transfected with OAT4.
“The results indicated that there was no significant PFAS transport in HEK cells transfected with URAT1. However, all PFAS, except PFBS, were taken up in HEK cells transfected with OAT4 [44].”
From The EU’s Per- and Polyfluoroalkyl Substances (PFAS) Ban: A Case of Policy over Science (2023) · cites this paper as [44]
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References 39 · Cited by 84
Research works printed but not linked: 1
- UNEP (2009) Recommendations of the Persistent Organic Pollutants Review Committee of the Stockholm Convention to amend Annexes A, B or C of the Convention. UNEP/POPS/COP.4/17
- Authors
- Louisse, J., Dellafiora, L., van den Heuvel, J. J. M. W., Rijkers, D., Leenders, L., Dorne, J.-L. C. M., Punt, A., Russel, F. G. M., & Koenderink, J. B.
- Affiliations
- Wageningen University & Research (NL)
- University of Parma (IT)
- European Food Safety Authority (IT)
- Radboud University Medical Center (NL)
- Corresponding author
- Louisse, Jochem
- Venue
- Archives of Toxicology
- Published
- 2022-11-27
- Volume
- 97
- Issue
- 3
- Pages
- 685-696
- ISSN
- 0340-5761 (ISSN-L)
- 1432-0738
- PMC
- PMC9968691
- OpenAlex
- W4310027142
- Cited by
- 84
- References
- 39
- Citations by year
- 2026: 35 · 2025: 24 · 2024: 19 · 2023: 5 · 2022: 1
- FWCI
- 4.34
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Archives of Toxicology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Socio-Environmental Systems Modeling (submittedVersion, cc-by)
- Radboud Repository (Radboud University) (submittedVersion, cc-by)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Ministerie van Landbouw, Natuur en Voedselkwaliteit (KB-37-002-010, KB-37-002-031)
- EFSA (OC/EFSA/SCER/2020/03)
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Keywords
- perfluorinated compounds, PFAS, OAT4, URAT1, tubular reabsorption, urinary excretion, PFOS, perfluorooctanoic acid, PFBS, PFHxS, PFNA, perfluorodecanoic acid, PFHpA, molecular docking, molecular dynamics simulation, physiologically based kinetic modeling
- MeSH terms
- Animals, Carrier Proteins, Fluorocarbons, Humans, Kidney, Kidney Tubules, Proximal, Alkanesulfonic Acids, Organic Anion Transporters
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