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Cited by 742Per- and polyfluoroalkyl substances researchPeroxisome Proliferator-Activated ReceptorsCarcinogens and Genotoxicity Assessment

The DOI matches its Crossref record; 136 of the 136 references it cites were found in a registry or an index.

The Toxicology of Perfluorooctanoate

Kennedy, Gerald L., Butenhoff, John L., Olsen, Geary W., O'Connor, John C., Seacat, Andrew M., Perkins, Roger G., Biegel, Lisa B., Murphy, Sandra R., Farrar, David G.·2004·Critical Reviews in Toxicology
DOI 10.1080/10408440490464705
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Abstract

PFOA is a peroxisome proliferator (PPAR agonist) and exerts morphological and biochemical effects characteristic of PPAR agonists. These effects include increased beta-oxidation of fatty acids, increases in several cytochrome P-450 (CYP450)-mediated reactions, and inhibition of the secretion of very low-density lipoproteins and cholesterol from the liver. These effects on lipid metabolism and transport result in a reduction of cholesterol and triglycerides in serum and an accumulation of lipids in the liver. The triad of tumors observed (liver, Leydig cell, and pancreatic acinar-cell) is typical of many PPAR agonists and is believed to involve nongenotoxic mechanisms. The hepatocellular tumors observed in rats are likely to have been the result of the activation of the peroxisome proliferator activated receptor alpha (PPARalpha). The tumors observed in the testis (Leydig-cell) have been hypothesized to be associated with an increased level of serum estradiol in concert with testicular growth factors. The mechanism responsible for the acinar-cell tumors of the pancreas in rats remains the subject of active investigation. The mechanism resulting in the hepatocellular tumors in rats (PPARalpha activation) is not likely to be relevant to humans. Similarly, the proposed mechanism for Leydig-cell tumor formation is of questionable relevance to humans. Acinar tumors of the pancreas are rare in humans, and the relevance of the these tumors, as found in rats, to humans is uncertain. Epidemiological investigations and medical surveillance of occupationally exposed workers have not found consistent associations between PFOA exposure and adverse health effects.

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Metadata

Authors
Kennedy, G. L., Butenhoff, J. L., Olsen, G. W., O'Connor, J. C., Seacat, A. M., Perkins, R. G., Biegel, L. B., Murphy, S. R., & Farrar, D. G.
Affiliations
  • DuPont (United States) (US)
  • 3M (United States) (US)
  • DuPont, Newark, Delaware, USA
  • Covance, Madison, Wisconsin, USA
  • Atofina, Philadelphia, Pennsylvania, USA
  • Ineos (United Kingdom) (GB)
Corresponding author
Kennedy, Gerald L.
ORCID
Venue
Critical Reviews in Toxicology
Publisher
Informa UK Limited
Published
2004-01
Volume
34
Issue
4
Pages
351-384
ISSN
  • 0045-6446 (ISSN-L)
  • 1040-8444
  • 1547-6898
DOI
10.1080/10408440490464705
OpenAlex
W2111493612
Cited by
742
References
135
Citations by year
2026: 8 · 2025: 26 · 2024: 15 · 2023: 25 · 2022: 15 · 2021: 32 · 2020: 30 · 2019: 27 · 2018: 34 · 2017: 32 · 2016: 34 · 2015: 29 · 2014: 42 · 2013: 45 · 2012: 36
FWCI
4.28
Type
journal article
Language
en
Open access
closed
Locations
  • Critical Reviews in Toxicology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
Keywords
perfluorooctanoic acid, PPAR agonists, PPARα, hepatocellular tumors, Leydig cell tumor, lipid metabolism, cytochrome P450, very low density lipoprotein secretion, non-genotoxic carcinogenesis, occupational exposure, toxicokinetics
MeSH terms
Animals, Caprylates, Female, Fluorocarbons, Humans, Leydig Cell Tumor, Liver Neoplasms, Male, Mutagenicity Tests, Pancreatic Neoplasms, Skin, Testicular Neoplasms, Tissue Distribution, Peroxisome Proliferators, Rats

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