TOXICITY AND TOXICOKINETICS OF PERFLUOROOCTANOIC ACID IN HUMANS AND ANIMALS
Open accessAbstract
Perfluorooctanoic acid (PFOA) is an octanoic acid derivative to which all aliphatic hydrocarbons are substituted by fluorine. PFOA and its salts are commercially used in various industrial processes. The chemical is persistent in the environment and does not undergo biotransformation. It was reported that PFOA is found not only in the serum of occupationally exposed workers but also general populations. Recent studies have suggested that the biological half-life of PFOA in humans is 4.37 years based on study of occupationally exposed workers. It is increasingly suspect that PFOA accumulates and affects human health, although the toxicokinetics of PFOA in humans remain unclear. In experimental animals, PFOA seems low in toxicity. PFOA is well-absorbed following oral and inhalation exposure, and to a lesser extent following dermal exposure. Once absorbed in the body, it distributes predominantly to the liver and plasma, and to a lesser extent the kidney and lungs. PFOA is excreted in both urine and feces. Biological half-life of PFOA is quite different between species and sexes and the difference is due mainly to the difference in renal clearance. In rats, renal clearance of PFOA is regulated by sex hormones, especially testosterone. PFOA is excreted into urine by active tubular secretion, and certain organic anion transporters are though to be responsible for the secretion. Fecal excretion is also important in the elimination of PFOA. There is evidence that PFOA undergoes enterohepatic circulation resulting in reduced amounts of fecal excretion. Elucidation of the mechanisms of transport in biological systems leads to elimination and detoxification of this chemical in the human body.
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Urinary excretion, facilitated by renal tubular organic anion transporters (OATs), is considered the predominant elimination route for most PFAS in both animal models and human studies.
“Urinary excretion, facilitated by renal tubular organic anion transporters (OATs), is considered the predominant elimination route for most PFAS in both animal models and human studies (Kudo and Kawashima, 2003).”
From Estimation of per- and polyfluoroalkyl substances (PFAS) half-lives in human studies: a systematic review and meta-analysis (2024) · cites this paper as Kudo and Kawashima, 2003
The Elimination section reports urinary excretion of PFOA in rats and identifies organic anion transporters 2 and 3 as candidate renal transporters. It does not establish that urine is the predominant elimination route for most PFAS in animals and humans: the paper concerns PFOA, reports substantial fecal excretion, and says human PFOA toxicokinetics remain unclear. No page number is available in our copy. (LLM, conf=0.89)
Experimental — accuracy not yet measuredAn increase in xenobiotic metabolism is not likely to be relevant for PFOS concentrations in the body, as PFAAs are resistant to enzymatic metabolism.
“While potentially important for BDE-47, an increase in xenobiotic metabolism is not likely to be relevant for PFOS concentrations in the body, as PFAAs are resistant to enzymatic metabolism (Kudo and Kawashima, 2003; Lau et al., 2007).”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Kudo and Kawashima, 2003
The Metabolism and Elimination sections report that PFOA was found as the parent compound and is excreted without biotransformation. That supports the rationale for PFOA, but the paper does not establish that increased xenobiotic metabolism is irrelevant to PFOS concentrations or that all PFAAs resist enzymatic metabolism. Page numbers are not available in our copy. (LLM, conf=0.88)
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Cites
Walum, E. (1998) · Environmental Health Perspectives · doi:10.1289/ehp.98106497 · Cited by 372 · see citing works
Sex hormone-regulated renal transport of perfluorooctanoic acid
Kudo, N., Katakura, M., Sato, Y., & Kawashima, Y. (2002) · Chemico-Biological Interactions · doi:10.1016/s0009-2797(02)00006-6 · Cited by 293 · see citing works
Self-citationTissue distribution, metabolism, and elimination of perfluorooctanoic acid in male and female rats
Heuvel, J. P. V., Kuslikis, B. I., Rafelghem, M. J. V., & Peterson, R. E. (1991) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.2570060202 · Cited by 289 · see citing works
Evidence that there are Two Forms of Fluoride in Human Serum
Taves, D. R. (1968) · Nature · doi:10.1038/2171050b0 · Cited by 253 · see citing works
Ohmori, K., Kudo, N., Katayama, K., & Kawashima, Y. (2002) · Toxicology · doi:10.1016/s0300-483x(02)00573-5 · Cited by 251 · see citing works
Self-citationMortality Among Employees of a Perfluorooctanoic Acid Production Plant
Gilliland, F. D., & Mandel, J. S. (1993) · Journal of Occupational and Environmental Medicine · doi:10.1097/00043764-199309000-00020 · Cited by 183 · see citing works
Olson, C. T., & Andersen, M. E. (1983) · Toxicology and Applied Pharmacology · doi:10.1016/0041-008x(83)90154-0 · Cited by 172 · see citing works
Olsen, G. W., Gilliland, F. D., Burlew, M., Burris, J. M., Mandel, J. S., & Mandel, J. H. (1998) · Journal of Occupational and Environmental Medicine · doi:10.1097/00043764-199807000-00006 · Cited by 169 · see citing works
JOHNSON, J. (1984) · Fundamental and Applied Toxicology · doi:10.1016/0272-0590(84)90235-5 · Cited by 161 · see citing works
Effects of peroxisome proliferators on the thymus and spleen of mice
Yang, Q., Xie, Y., & DePierre, J. W. (2000) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.2000.01367.x · Cited by 143 · see citing works
Health status of plant workers exposed to fluorochemicals - a preliminary report
UBEL, F. A., SORENSON, S. D., & Roach, D. E. (1980) · American Industrial Hygiene Association Journal · doi:10.1080/15298668091425310 · Cited by 135 · see citing works
Yang, Q., Xie, Y., Alexson, S. E. H., Dean Nelson, B., & DePierre, J. W. (2002) · Biochemical Pharmacology · doi:10.1016/s0006-2952(02)00923-1 · Cited by 131 · see citing works
Yang, Q., Xie, Y., Eriksson, A. M., Nelson, B. D., & DePierre, J. W. (2001) · Biochemical Pharmacology · doi:10.1016/s0006-2952(01)00752-3 · Cited by 115 · see citing works
The Sex-Related Difference in Perfluorooctanoate Excretion in the Rat
Hanhijärvi, H., Ophaug, R. H., & Singer, L. (1982) · Experimental Biology and Medicine · doi:10.3181/00379727-171-41476 · Cited by 102 · see citing works
The modulation of rat liver carcinogenesis by perfluorooctanoic acid, a peroxisome proliferator
ABDELLATIF, A. (1991) · Toxicology and Applied Pharmacology · doi:10.1016/0041-008x(91)90257-f · Cited by 76 · see citing works
Metabolic Handling of Perfluorooctanoic Acid in Rats
Ophaug, R. H., & Singer, L. (1980) · Experimental Biology and Medicine · doi:10.3181/00379727-163-40715 · Cited by 72 · see citing works
Disposition of perfluorooctanoic acid in the rat after single and subchronic administration
Ylinen, M., Kojo, A., Hanhijärvi, H., & Peura, P. (1990) · Bulletin of Environmental Contamination and Toxicology · doi:10.1007/bf01702360 · Cited by 68 · see citing works
Renal excretion of perfluorooctanoic acid in male rats: Inhibitory effect of testosterone
Heuvel, J. P. V., Davis, J. W., Sommers, R., & Peterson, R. E. (1992) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.2570070107 · Cited by 65 · see citing works
Dermal toxicity of ammonium perfluorooctanoate
Kennedy, G. L. (1985) · Toxicology and Applied Pharmacology · doi:10.1016/0041-008x(85)90172-3 · Cited by 54 · see citing works
Inhalation toxicity of ammonium perfluorooctanoate
Kennedy, G. L., Hall, G. T., Brittelli, M. R., Barnes, J. R., & Chen, H. C. (1986) · Food and Chemical Toxicology · doi:10.1016/0278-6915(86)90066-9 · Cited by 53 · see citing works
Stimulation by Oestradiol of the Urinary Excretion of Perfluorooctanoic Acid in the Male rat
Ylinen, M., Hanhijärvi, H., Jaakonaho, J., & Peura, P. (1989) · Pharmacology & Toxicology · doi:10.1111/j.1600-0773.1989.tb01172.x · Cited by 51 · see citing works
On the mechanism of the hepatocarcinogenicity of peroxisome proliferators
Nilsson, R., Beije, B., Véronique Préat, A., Erixon, K., & Ramel, C. (1991) · Chemico-Biological Interactions · doi:10.1016/0009-2797(91)90017-2 · Cited by 48 · see citing works
Hanhijärvi, H., Ylinen, M., Haaranen, T., & Nevalainen, T. (1988) · Springer eBooks · doi:10.1007/978-94-009-3281-4_66 · Cited by 41 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Olsen, G.W., Burris, J.M., Lundberg, J.K., Hansen, K.J., Mandel, J.H. and Zobel, L.R. (2002b): Identification of fluorochemicals in human sera. II. Elderly participants of adult changes in thought study. Final Report, 3M Medical Vol. 28 No. 2
Cited by
Sorted by citations
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
The Developmental Toxicity of Perfluoroalkyl Acids and Their Derivatives
Lau, C., Butenhoff, J. L., & Rogers, J. M. (2004) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2003.11.031 · Cited by 867 · see citing works
Accumulation of perfluorinated alkyl substances (PFAS) in agricultural plants: A review
Ghisi, R., Vamerali, T., & Manzetti, S. (2019) · Environmental Research · doi:10.1016/j.envres.2018.10.023 · Cited by 705 · 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
Perfluoroalkyl Contaminants in a Food Web from Lake Ontario
Martin, J. W., Whittle, D. M., Muir, D. C. G., & Mabury, S. A. (2004) · Environmental Science & Technology · doi:10.1021/es049331s · Cited by 514 · see citing works
Rayne, S., & Forest, K. (2009) · Journal of Environmental Science and Health, Part A · doi:10.1080/10934520903139811 · Cited by 475 · see citing works
Johansson, N., Fredriksson, A., & Eriksson, P. (2008) · NeuroToxicology · doi:10.1016/j.neuro.2007.10.008 · Cited by 463 · see citing works
Johnson, P. I., Sutton, P., Atchley, D. S., Koustas, E., Lam, J., Sen, S., Robinson, K. A., Axelrad, D. A., & Woodruff, T. J. (2014) · Environmental Health Perspectives · doi:10.1289/ehp.1307893 · Cited by 449 · see citing works
“Environmental Health Perspectives • volume 122 | number 10 | October 2014 1029 there have been inconsistent conclusions about the evidence of an association between PFOA and fetal growth (DeWitt et al. 2009; Hekster et al. 2003; Jensen and Leffers 2008; Kennedy et al. 2004; Kudo and Kawashima 2003; Lau et al. 2004, 20…”
BackgroundWoodruff, T. J., & Sutton, P. (2014) · Environmental Health Perspectives · doi:10.1289/ehp.1307175 · Cited by 427 · see citing works
Toxicology of perfluorinated compounds
Stahl, T., Mattern, D., & Brunn, H. (2011) · Environmental Sciences Europe · doi:10.1186/2190-4715-23-38 · Cited by 432 · see citing works
Koustas, E., Lam, J., Sutton, P., Johnson, P. I., Atchley, D. S., Sen, S., Robinson, K. A., Axelrad, D. A., & Woodruff, T. J. (2014) · Environmental Health Perspectives · doi:10.1289/ehp.1307177 · Cited by 349 · see citing works
Hines, E. P., White, S. S., Stanko, J. P., Gibbs-Flournoy, E. A., Lau, C., & Fenton, S. E. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.02.021 · Cited by 282 · see citing works
Frisbee, S. J., Shankar, A., Knox, S. S., Steenland, K., Savitz, D. A., Fletcher, T., & Ducatman, A. M. (2010) · Archives of Pediatrics & Adolescent Medicine · doi:10.1001/archpediatrics.2010.163 · Cited by 274 · see citing works
Rosato, I., Bonato, T., Fletcher, T., Batzella, E., & Canova, C. (2024) · Environmental Research · doi:10.1016/j.envres.2023.117743 · Cited by 273 · see citing works
Renal elimination of perfluorocarboxylates (PFCAs)
Han, X., Nabb, D. L., Russell, M. H., Kennedy, G. L., & Rickard, R. W. (2012) · Chemical Research in Toxicology · doi:10.1021/tx200363w · Cited by 250 · see citing works
Thirty years of medical surveillance in perfluooctanoic acid production workers
Costa, G., Sartori, S., & Consonni, D. (2009) · Journal of Occupational & Environmental Medicine · doi:10.1097/jom.0b013e3181965d80 · Cited by 238 · see citing works
PFAS Environmental Pollution and Antioxidant Responses: An Overview of the Impact on Human Field
Bonato, M., Corrà, F., Bellio, M., Guidolin, L., Tallandini, L., Irato, P., & Santovito, G. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17218020 · Cited by 243 · see citing works
Lam, J., Koustas, E., Sutton, P., Johnson, P. I., Atchley, D. S., Sen, S., Robinson, K. A., Axelrad, D. A., & Woodruff, T. J. (2014) · Environmental Health Perspectives · doi:10.1289/ehp.1307923 · Cited by 214 · see citing works
Yang, C.-H., Glover, K. P., & Han, X. (2010) · Toxicological Sciences · doi:10.1093/toxsci/kfq219 · Cited by 197 · see citing works
Starnes, H. M., Rock, K. D., Jackson, T. W., & Belcher, S. M. (2022) · Frontiers in Toxicology · doi:10.3389/ftox.2022.881584 · Cited by 166 · see citing works
Bjork, J. A., & Wallace, K. B. (2009) · Toxicological Sciences · doi:10.1093/toxsci/kfp093 · Cited by 137 · see citing works
Chang, S.-C., Ehresman, D. J., Bjork, J. A., Wallace, K. B., Parker, G. A., Stump, D. G., & Butenhoff, J. L. (2009) · Reproductive Toxicology · doi:10.1016/j.reprotox.2009.01.005 · Cited by 118 · see citing works
Woodcroft, M. W., Ellis, D. A., Rafferty, S. P., Burns, D. C., March, R. E., Stock, N. L., Trumpour, K. S., Yee, J., & Munro, K. (2010) · Environmental Toxicology and Chemistry · doi:10.1002/etc.199 · Cited by 65 · see citing works
Nakamura, T., Ito, Y., Yanagiba, Y., Ramdhan, D. H., Kono, Y., Naito, H., Hayashi, Y., Li, Y., Aoyama, T., Gonzalez, F. J., et al. (2009) · Toxicology · doi:10.1016/j.tox.2009.09.004 · Cited by 57 · see citing works
Why Toxic Equivalency Factors Are Not Suitable for Perfluoroalkyl Chemicals
Peters, J. M., & Gonzalez, F. J. (2011) · Chemical Research in Toxicology · doi:10.1021/tx200316x · Cited by 48 · see citing works
Cheng, W., Doering, J. A., LaLone, C., & Ng, C. (2021) · Toxicological Sciences · doi:10.1093/toxsci/kfab004 · Cited by 49 · see citing works
Ducatman, A., Luster, M., & Fletcher, T. (2021) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2021.103650 · Cited by 42 · see citing works
Perfluorododecanoic Acid Induces Cognitive Deficit in Adult Rats
Kawabata, K., Matsuzaki, H., Nukui, S., Okazaki, M., Sakai, A., Kawashima, Y., & Kudo, N. (2017) · Toxicological Sciences · doi:10.1093/toxsci/kfx058 · Cited by 37 · see citing works
Self-citationHsu, J.-Y., Hsu, J.-F., Ho, H.-H., Chiang, C.-F., & Liao, P.-C. (2013) · Chemosphere · doi:10.1016/j.chemosphere.2013.06.047 · Cited by 32 · see citing works
- Authors
- KUDO, N., & KAWASHIMA, Y.
- Affiliations
- Department of Toxicology and Applied Pharmacology, Faculty of Pharmaceutical Sciences
- ORCID
- KUDO, Naomi
- Venue
- The Journal of Toxicological Sciences
- Publisher
- Japanese Society of Toxicology
- Published
- 2003
- Volume
- 28
- Issue
- 2
- Pages
- 49-57
- ISSN
- 0388-1350 (ISSN-L)
- 1880-3989
- OpenAlex
- W2053849036
- Cited by
- 392
- References
- 23
- Citations by year
- 2026: 7 · 2025: 16 · 2024: 19 · 2023: 17 · 2022: 21 · 2021: 23 · 2020: 21 · 2019: 19 · 2018: 14 · 2017: 12 · 2016: 14 · 2015: 13 · 2014: 23 · 2013: 25 · 2012: 25
- FWCI
- 1.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Toxicological Sciences (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (publishedVersion)
- Josai University Repository of Academia (Josai University) (submittedVersion)
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Physical Sciences › Environmental Science › Water Science and Technology › Fluoride Effects and Removal
- Keywords
- perfluorooctanoic acid, toxicokinetics, biological half-life, renal clearance, sex differences, testosterone, organic anion transporters, renal tubular secretion, enterohepatic circulation, occupational exposure, environmental persistence
- MeSH terms
- Animals, Caprylates, Carcinogens, Fluorocarbons, Humans, Teratogens, Tissue Distribution
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