Background: Longer serum half-lives of perfluoroalkyl substances (PFAS) in humans compared to other species has been attributed to differences in the activity of organic anion transporters (OAT).
Methods: Among 56,175 adult participants in the community-based C8 Health Project, 23 subjects were taking the uricosuric OAT-inhibitor probenecid, and 36 subjects were taking the bile acid sequestrant cholestyramine. In regression models of log transformed serum PFAS, medication effects were estimated in terms of mean ratios, adjusting for age, gender, BMI, estimated glomerular filtration rate (eGFR) and water-district of residence.
Results: Probenecid was associated with modest, but not statistically significant increases in serum PFAS concentrations. In contrast, cholestyramine significantly lowered serum PFAS concentrations, notably for perfluorooctane sulfonic acid (PFOS).
Conclusions: The effectiveness of cholestyramine in a community setting supports the importance of gastrointestinal physiology for PFAS excretion kinetics, especially for PFOS. We did not find clear evidence that probenecid, an inhibitor of OAT, affects PFAS clearance.
Bibliographical noteFunding Information: Dr Tony Fletcher was a member of the C8 Science Panel established under the C8 Class Action Settlement Agreement (Circuit Court of Wood County, WV, USA) between DuPont and plaintiffs, which resulted from releases of perfluorooctanoate (PFOA, or C8) into drinking water. Dr Fletcher is a consortium partner of the European Union’s Horizon 2020 research and innovation program under grant agreement 733032 HBM4EU ( www.HBM4EU.eu ); and part-funded from the National Institute for Health Research (NIHR) Health Protection Research Unit in Environmental Exposures and Health, a partnership between Public Health England, the Health and Safety Executive and the University of Leicester. Alan Ducatman was the principal investigator for the Health Communications for health communications related to the C8 Health Project. The views expressed are those of the author(s) and not necessarily those of the NIHR, Public Health England, the Health and Safety Executive or the Department of Health and Social Care.
Open Access: This is an open access article under the CC BY-NC-ND license
Publisher Copyright:© 2021 The Authors. Published by Elsevier B.V.
Citation: Ducatman, Alan M., Michael Luster, and Tony Fletcher. "Perfluoroalkyl substance excretion: Effects of organic anion-inhibiting and resin-binding drugs in a community setting." Environmental Toxicology and Pharmacology (2021): 103650.
- Cholestyramine resin (MeSH) organic anion transporters (MeSH) antagonists and inhibitors (subheading)
- Perfluoroalkyl substances (MeSH)
- Perfluorohexane sulfonic acid
- Perfluorononanoic acid
- Perfluorooctane sulfonic acid
- Perfluorooctanoic acid
- Probenecid (MeSH)
- Uricosuric agents (MeSH, pharmacologic action)