Perfluoroalkyl substance excretion: Effects of organic anion-inhibiting and resin-binding drugs in a community setting

Alan Ducatman; Michael Luster; Tony Fletcher

doi:10.1016/j.etap.2021.103650

Perfluoroalkyl substance excretion: Effects of organic anion-inhibiting and resin-binding drugs in a community setting

Alan Ducatman^*, Michael Luster, Tony Fletcher

^*Corresponding author for this work

Chemicals & Environmental Effects

Research output: Contribution to journal › Article › peer-review

30 Citations (Scopus)

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Abstract

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.

Original language	English
Article number	103650
Journal	Environmental Toxicology and Pharmacology
Volume	85
Early online date	2 Apr 2021
DOIs	https://doi.org/10.1016/j.etap.2021.103650
Publication status	Published - Jul 2021

Bibliographical note

Funding 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.

DOI: https://doi.org/10.1016/j.etap.2021.103650

Keywords

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)

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Ducatman2021PerfluoroalkylSubstanceExcretionEnvironToxicolPharmacolFinal published version, 427 KBLicence: CC BY-NC-ND

Cite this

@article{514fcf550f0b4a199bba5fafbc514ce5,

title = "Perfluoroalkyl substance excretion: Effects of organic anion-inhibiting and resin-binding drugs in a community setting",

abstract = "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.",

keywords = "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)",

author = "Alan Ducatman and Michael Luster and Tony Fletcher",

note = "Funding 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{\textquoteright}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:{\textcopyright} 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. DOI: https://doi.org/10.1016/j.etap.2021.103650",

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doi = "10.1016/j.etap.2021.103650",

language = "English",

volume = "85",

journal = "Environmental Toxicology and Pharmacology",

issn = "1382-6689",

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T1 - Perfluoroalkyl substance excretion

T2 - Effects of organic anion-inhibiting and resin-binding drugs in a community setting

AU - Ducatman, Alan

AU - Luster, Michael

AU - Fletcher, Tony

N1 - Funding 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. DOI: https://doi.org/10.1016/j.etap.2021.103650

PY - 2021/7

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N2 - 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.

AB - 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.

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KW - Perfluorohexane sulfonic acid

KW - Perfluorononanoic acid

KW - Perfluorooctane sulfonic acid

KW - Perfluorooctanoic acid

KW - Probenecid (MeSH)

KW - Uricosuric agents (MeSH, pharmacologic action)

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VL - 85

JO - Environmental Toxicology and Pharmacology

JF - Environmental Toxicology and Pharmacology

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Perfluoroalkyl substance excretion: Effects of organic anion-inhibiting and resin-binding drugs in a community setting

Abstract

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Keywords

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