Exploring Indirect Sources of Human Exposure to Perfluoroalkyl Carboxylates (PFCAs): Evaluating Uptake, Elimination, and Biotransformation of Polyfluoroalkyl Phosphate Esters (PAPs) in the Rat
Open accessAbstract
BACKGROUND: Perfluorinated carboxylic acids (PFCAs) are ubiquitous in human sera worldwide. Biotransformation of the polyfluoroalkyl phosphate esters (PAPs) is a possible source of PFCA exposure, because PAPs are used in food-contact paper packaging and have been observed in human sera. OBJECTIVES: We determined pharmacokinetic parameters for the PAP monoesters (monoPAPs) and PAP diesters (diPAPs), as well as biotransformation yields to the PFCAs, using a rat model. METHODS: The animals were dosed intravenously or by oral gavage with a mixture of 4:2, 6:2, 8:2, and 10:2 monoPAP or diPAP chain lengths. Concentrations of the PAPs and PFCAs, as well as metabolic intermediates and phase II metabolites, were monitored over time in blood, urine, and feces. RESULTS: The diPAPs were bioavailable, with bioavailability decreasing as the chain length increased from 4 to 10 perfluorinated carbons. The monoPAPs were not absorbed from the gut; however, we found evidence to suggest phosphate-ester cleavage within the gut contents. We observed biotransformation to the PFCAs for both monoPAP and diPAP congeners. CONCLUSIONS: Using experimentally derived biotransformation yields, perfluorooctanoic acid (PFOA) sera concentrations were predicted from the biotransformation of 8:2 diPAP at concentrations observed in human serum. Because of the long human serum half-life of PFOA, biotransformation of diPAP even with low-level exposure could over time result in significant exposure to PFOA. Although humans are exposed directly to PFCAs in food and dust, the pharmacokinetic parameters determined here suggest that PAP exposure should be considered a significant indirect source of human PFCA contamination.
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Polyfluoroalkyl phosphate esters belong to a class of precursors of perfluoroalkyl carboxylic acids.
“and are a class of PFCA precursors, 73”
From Non-Target and Suspect Screening of Per- and Polyfluoroalkyl Substances in Airborne Particulate Matter in China (2018) · cites this paper as [73]
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Olsen, G. W., Burris, J. M., Ehresman, D. J., Froehlich, J. W., Seacat, A. M., Butenhoff, J. L., & Zobel, L. R. (2007) · Environmental Health Perspectives · doi:10.1289/ehp.10009 · Cited by 2,049 · see citing works
Calafat, A. M., Wong, L.-Y., Kuklenyik, Z., Reidy, J. A., & Needham, L. L. (2007) · Environmental Health Perspectives · doi:10.1289/ehp.10598 · Cited by 1,247 · see citing works
Perfluorinated compounds – Exposure assessment for the general population in western countries
Fromme, H., Tittlemier, S. A., Völkel, W., Wilhelm, M., & Twardella, D. (2008) · International Journal of Hygiene and Environmental Health · doi:10.1016/j.ijheh.2008.04.007 · Cited by 963 · see citing works
A global survey of perfluorinated acids in oceans
Yamashita, N., Kannan, K., Taniyasu, S., Horii, Y., Petrick, G., & Gamo, T. (2005) · Marine Pollution Bulletin · doi:10.1016/j.marpolbul.2005.04.026 · Cited by 639 · see citing works
Estimating Consumer Exposure to PFOS and PFOA
Trudel, D., Horowitz, L., Wormuth, M., Scheringer, M., Cousins, I. T., & Hungerbühler, K. (2008) · Risk Analysis · doi:10.1111/j.1539-6924.2008.01017.x · Cited by 514 · see citing works
Tracking the Pathways of Human Exposure to Perfluorocarboxylates
Vestergren, R., & Cousins, I. T. (2009) · Environmental Science & Technology · doi:10.1021/es900228k · Cited by 419 · see citing works
Shoeib, M., Harner, T., Wilford, B. H., Jones, K. C., & Zhu, J. (2005) · Environmental Science & Technology · doi:10.1021/es048340y · Cited by 328 · see citing works
Perfluoroalkyl Acids and Related Chemistries—Toxicokinetics and Modes of Action
Andersen, M. E., Butenhoff, J. L., Chang, S., Farrar, D. G., Kennedy, G. L., Lau, C. S., Olsen, G. W., Seed, J. G., & Wallace, K. B. (2007) · Toxicological Sciences · doi:10.1093/toxsci/kfm270 · Cited by 322 · see citing works
Olsen, G. W., Huang, H.-Y., Helzlsouer, K. J., Hansen, K. J., Butenhoff, J. L., & Mandel, J. H. (2005) · Environmental Health Perspectives · doi:10.1289/ehp.7544 · Cited by 318 · see citing works
Haug, L. S., Thomsen, C., & Becher, G. (2009) · Environmental Science & Technology · doi:10.1021/es802827u · Cited by 301 · see citing works
Biodegradation of Polyfluoroalkyl Phosphates as a Source of Perfluorinated Acids to the Environment
Lee, H., D’eon, J., & Mabury, S. A. (2010) · Environmental Science & Technology · doi:10.1021/es9028183 · Cited by 288 · see citing works
Self-citationD’eon, J. C., & Mabury, S. A. (2007) · Environmental Science & Technology · doi:10.1021/es070126x · Cited by 259 · see citing works
Self-citationOhmori, K., Kudo, N., Katayama, K., & Kawashima, Y. (2002) · Toxicology · doi:10.1016/s0300-483x(02)00573-5 · Cited by 251 · see citing works
Polyfluorinated Telomer Alcohols and Sulfonamides in the North American Troposphere
Stock, N. L., Lau, F. K., Ellis, D. A., Martin, J. W., Muir, D. C. G., & Mabury, S. A. (2004) · Environmental Science & Technology · doi:10.1021/es034644t · Cited by 247 · see citing works
Self-citationOlsen, G. W., Mair, D. C., Church, T. R., Ellefson, M. E., Reagen, W. K., Boyd, T. M., Herron, R. M., Medhdizadehkashi, Z., Nobiletti, J. B., Rios, J. A., et al. (2008) · Environmental Science & Technology · doi:10.1021/es800071x · Cited by 244 · see citing works
Migration of fluorochemical paper additives from food-contact paper into foods and food simulants
Begley, T. H., Hsu, W., Noonan, G., & Diachenko, G. (2008) · Food Additives & Contaminants: Part A · doi:10.1080/02652030701513784 · Cited by 235 · see citing works
D’eon, J. C., Crozier, P. W., Furdui, V. I., Reiner, E. J., Libelo, E. L., & Mabury, S. A. (2009) · Environmental Science & Technology · doi:10.1021/es900100d · Cited by 214 · see citing works
Self-citationFromme, H., Schlummer, M., Möller, A., Gruber, L., Wolz, G., Ungewiß, J., Boehmer, S., Dekant, W., Mayer, R. L., Liebl, B., et al. (2007) · Environmental Science & Technology · doi:10.1021/es071244n · Cited by 210 · see citing works
Xu, L. S., Krenitsky, D. M., Seacat, A. M., Butenhoff, J. L., & Anders, M. W. (2004) · Chemical Research in Toxicology · doi:10.1021/tx034222x · Cited by 206 · see citing works
Estimating the contribution of precursor compounds in consumer exposure to PFOS and PFOA
Vestergren, R., Cousins, I. T., Trudel, D., Wormuth, M., & Scheringer, M. (2008) · Chemosphere · doi:10.1016/j.chemosphere.2008.08.011 · Cited by 194 · see citing works
Kärrman, A., Mueller, J. F., van Bavel, B., Harden, F. A., Toms, L.-M. L., & Lindström, G. (2006) · Environmental Science & Technology · doi:10.1021/es060301u · Cited by 188 · see citing works
Disposition of perfluorinated acid isomers in sprague-dawley rats; Part 1: Single dose
Benskin, J. P., Silva, A. O. D., Martin, L. J., Arsenault, G. J., McCrindle, R. I., Riddell, N., Mabury, S. A., & Martin, J. W. (2008) · Environmental Toxicology and Chemistry · doi:10.1897/08-239.1 · Cited by 178 · see citing works
Self-citationChang, S., Das, K. P., Ehresman, D. J., Ellefson, M. E., Gorman, G. S., Hart, J. A., Noker, P. E., Tan, Y., Lieder, P. H., Lau, C. S., et al. (2008) · Toxicological Sciences · doi:10.1093/toxsci/kfn057 · Cited by 147 · see citing works
Hagen, D. F., Belisle, J., Johnson, J. D., & Venkateswarlu, P. (1981) · Analytical Biochemistry · doi:10.1016/0003-2697(81)90591-1 · Cited by 145 · see citing works
Absorption, Distribution, Metabolism, and Elimination of 8-2 Fluorotelomer Alcohol in the Rat
Fasano, W. J., Carpenter, S. C., Gannon, S. A., Snow, T. A., Stadler, J. C., Kennedy, G. L., Buck, R. C., Korzeniowski, S. H., Hinderliter, P. M., & Kemper, R. A. (2006) · Toxicological Sciences · doi:10.1093/toxsci/kfj160 · Cited by 137 · see citing works
Isomer Distribution of Perfluorocarboxylates in Human Blood: Potential Correlation to Source
Silva, A. O. D., & Mabury, S. A. (2006) · Environmental Science & Technology · doi:10.1021/es0600330 · Cited by 134 · see citing works
Self-citationRelationship between dietary exposure and serum perfluorochemical (PFC) levels—A case study
Kärrman, A., Harada, K. H., Inoue, K., Takasuga, T., Ohi, E., & Koizumi, A. (2009) · Environment International · doi:10.1016/j.envint.2009.01.010 · Cited by 128 · see citing works
Disposition of perfluorinated acid isomers in sprague-dawley rats; Part 2: Subchronic dose
Silva, A. O. D., Benskin, J. P., Martin, L. J., Arsenault, G. J., McCrindle, R. I., Riddell, N., Martin, J. W., & Mabury, S. A. (2008) · Environmental Toxicology and Chemistry · doi:10.1897/08-254.1 · Cited by 125 · see citing works
Self-citationOstertag, S., Chan, H. M., Moisey, J., Dabeka, R. W., & Tittlemier, S. A. (2009) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf9014125 · Cited by 59 · see citing works
Biotransformation of the 8:2 fluorotelomer acrylate in rainbow trout. 1. In vivo dietary exposure
Butt, C. M., Muir, D. C. G., & Mabury, S. A. (2010) · Environmental Toxicology and Chemistry · doi:10.1002/etc.349 · Cited by 54 · see citing works
Self-citationUptake and elimination of perfluorinated phosphonic acids in the rat
D'eon, J. C., & Mabury, S. A. (2010) · Environmental Toxicology and Chemistry · doi:10.1002/etc.167 · Cited by 52 · see citing works
Self-citationUptake of perfluorooctanoate in freshly isolated hepatocytes from male and female rats
HAN, X., YANG, C., Snajdr, S. I., Nabb, D. L., & Mingoia, R. T. (2008) · Toxicology Letters · doi:10.1016/j.toxlet.2008.07.002 · Cited by 43 · see citing works
Ward, K. W., Hardy, L. B., Kehler, J. R., et al. (2004) · Xenobiotica · doi:10.1080/0049825042000205540a · Cited by 28 · see citing works
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Buck, R. C., Franklin, J., Berger, U., Conder, J. M., Cousins, I. T., de Voogt, P., Jensen, A. A., Kannan, K., Mabury, S. A., & van Leeuwen, S. P. (2011) · Integrated Environmental Assessment and Management · doi:10.1002/ieam.258 · Cited by 4,641 · see citing works
Self-citationSunderland, E. M., Hu, X. C., Dassuncao, C., Tokranov, A. K., Wagner, C. C., & Allen, J. G. (2019) · Journal of Exposure Science & Environmental Epidemiology · doi:10.1038/s41370-018-0094-1 · Cited by 2,786 · see citing works
Risk to human health related to the presence of perfluoroalkyl substances in food
Panel), E. P. O. C. I. T. F. C. (. C., Schrenk, D., Bignami, M., Bodin, L., Chipman, J. K., del Mazo, J., Grasl‐Kraupp, B., Hogstrand, C., Hoogenboom, L. (., Leblanc, J., et al. (2020) · EFSA Journal · doi:10.2903/j.efsa.2020.6223 · Cited by 989 · see citing works
Post, G. B., Cohn, P. D., & Cooper, K. R. (2012) · Environmental Research · doi:10.1016/j.envres.2012.03.007 · Cited by 639 · see citing works
Xiao, X., Ulrich, B. A., Chen, B., & Higgins, C. P. (2017) · Environmental Science & Technology · doi:10.1021/acs.est.7b00970 · Cited by 391 · see citing works
Brase, R. A., Mullin, E. J., & Spink, D. C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22030995 · Cited by 374 · see citing works
Poothong, S., Papadopoulou, E., Padilla-Sánchez, J. A., Thomsen, C., & Haug, L. S. (2020) · Environment International · doi:10.1016/j.envint.2019.105244 · Cited by 357 · see citing works
Per- and polyfluorinated substances (PFASs): Environmental challenges
Krafft, M. P., & Riess, J. G. (2015) · Current Opinion in Colloid & Interface Science · doi:10.1016/j.cocis.2015.07.004 · Cited by 294 · see citing works
What are the effects of PFAS exposure at environmentally relevant concentrations?
Sinclair, G. M., Long, S. M., & Jones, O. A. H. (2020) · Chemosphere · doi:10.1016/j.chemosphere.2020.127340 · Cited by 285 · see citing works
Zhang, W., Pang, S., Lin, Z., Mishra, S., Bhatt, P., & Chen, S. (2021) · Environmental Pollution · doi:10.1016/j.envpol.2020.115908 · Cited by 280 · see citing works
Observation of emerging per- and polyfluoroalkyl substances (PFASs) in Greenland marine mammals
Gebbink, W. A., Bossi, R., Rigét, F. F., Rosing-Asvid, A., Sonne, C., & Dietz, R. (2016) · Chemosphere · doi:10.1016/j.chemosphere.2015.10.116 · Cited by 266 · see citing works
Yu, N., Guo, H., Yang, J., Jin, L., Wang, X., Shi, W., Zhang, X., Yu, H., & Wei, S. (2018) · Environmental Science & Technology · doi:10.1021/acs.est.8b02492 · Cited by 200 · see citing works
Yao, Y., Zhao, Y., Sun, H., Chang, S., Zhu, L., Alder, A. C., & Kannan, K. (2018) · Environmental Science & Technology · doi:10.1021/acs.est.7b04971 · Cited by 177 · see citing works
Fujii, Y., Harada, K. H., & Koizumi, A. (2013) · Chemosphere · doi:10.1016/j.chemosphere.2013.06.049 · Cited by 162 · see citing works
Aerobic biotransformation of polyfluoroalkyl phosphate esters (PAPs) in soil
Liu, C., & Liu, J. (2016) · Environmental Pollution · doi:10.1016/j.envpol.2016.01.069 · Cited by 121 · see citing works
Indoor exposure to per- and polyfluoroalkyl substances (PFAS) in the childcare environment
Zheng, G., Boor, B. E., Schreder, E., & Salamova, A. (2020) · Environmental Pollution · doi:10.1016/j.envpol.2019.113714 · Cited by 112 · see citing works
Rand, A. A., & Mabury, S. A. (2017) · Toxicology · doi:10.1016/j.tox.2016.11.011 · Cited by 92 · see citing works
Self-citationAllendorf, F., Berger, U., Goss, K.-U., & Ulrich, N. (2019) · Environmental Science: Processes & Impacts · doi:10.1039/c9em00290a · Cited by 74 · see citing works
Benskin, J. P., Ikonomou, M. G., Gobas, F. A. P. C., Woudneh, M. B., & Cosgrove, J. R. (2012) · Environmental Science & Technology · doi:10.1021/es300823m · Cited by 72 · see citing works
Airborne precursors predict maternal serum perfluoroalkyl acid concentrations
Makey, C. M., Webster, T. F., Martin, J. W., Shoeib, M., Harner, T., Dix-Cooper, L., & Webster, G. M. (2017) · Environmental Science & Technology · doi:10.1021/acs.est.7b00615 · Cited by 54 · see citing works
Gao, K., Fu, J., Xue, Q., Li, Y., Liang, Y., Pan, Y., Zhang, A., & Jiang, G. (2018) · Analytica Chimica Acta · doi:10.1016/j.aca.2017.10.038 · Cited by 53 · see citing works
Methodology for studying biotransformation of polyfluoroalkyl precursors in the environment
Ruan, T., Lin, Y., Wang, T., Jiang, G., & Wang, N. (2015) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2014.11.017 · Cited by 37 · see citing works
Biotransformation of 8:2 polyfluoroalkyl phosphate diester in gilthead bream (Sparus aurata)
Zabaleta, I., Bizkarguenaga, E., Izagirre, U., Negreira, N., Covaci, A., Benskin, J. P., Prieto, A., & Zuloaga, O. (2017) · Science of The Total Environment · doi:10.1016/j.scitotenv.2017.07.241 · Cited by 34 · see citing works
Jackson, D. A., & Mabury, S. A. (2013) · Environmental Science & Technology · doi:10.1021/es303152m · Cited by 34 · see citing works
Self-citationRand, A. A., & Mabury, S. A. (2012) · Environmental Science & Technology · doi:10.1021/es3008485 · Cited by 30 · see citing works
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Rand, A. A., & Mabury, S. A. (2011) · Environmental Science & Technology · doi:10.1021/es1043968 · Cited by 30 · see citing works
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Gkika, I. S., Xie, G., van Gestel, C. A. M., Ter Laak, T. L., Vonk, J. A., van Wezel, A. P., & Kraak, M. H. S. (2023) · Environmental Toxicology and Chemistry · doi:10.1002/etc.5729 · Cited by 28 · see citing works
- Authors
- D’eon, J. C., & Mabury, S. A.
- Affiliations
- University of Toronto (CA)
- Corresponding author
- Mabury, Scott A.
- Venue
- Environmental Health Perspectives
- Publisher
- American Chemical Society (ACS)
- Published
- 2010-11-08
- Volume
- 119
- Issue
- 3
- Pages
- 344-350
- ISSN
- 0091-6765 (ISSN-L)
- 1552-9924
- PMC
- PMC3059997
- OpenAlex
- W2092000382
- Cited by
- 193
- References
- 33
- Citations by year
- 2026: 14 · 2025: 6 · 2024: 9 · 2023: 15 · 2022: 17 · 2021: 17 · 2020: 9 · 2019: 9 · 2018: 13 · 2017: 12 · 2016: 14 · 2015: 13 · 2014: 5 · 2013: 16 · 2012: 14
- FWCI
- 10.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- public-domain
- creativecommons.org/licenses/by/4.0/ (vor, 2608 d)
- Locations
- Environmental Health Perspectives (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- Natural Sciences and Engineering Research Council of Canada
- 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
- perfluoroalkyl carboxylates, perfluorooctanoic acid, biotransformation, pharmacokinetics, bioavailability, intestinal metabolism, indirect exposure, rat model
- MeSH terms
- Animals, Biotransformation, Environmental Exposure, Environmental Pollutants, Esters, Feces, Fluorocarbons, Humans, Male, Phosphates, Rats, Sprague-Dawley, Rats
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