Carcinogenicity of perfluorooctanoic acid and perfluorooctanesulfonic acid
By Shelia Zahm, Jens Peter Bonde, Weihsueh A Chiu, Jane Hoppin, Jun Kanno, Mohamed Abdallah, Chad R Blystone, Miriam M Calkins, Guang, Hui Dong, David C Dorman, Rebecca Fry, Huan Guo, Line S Haug, Jonathan N Hofmann, Motoki Iwasaki, Miroslav Machala, Francesca R Mancini, Silvya S Maria-Engler, Peter Møller, Jack C Ng, Marc Pallardy, Gloria B Post, Samira Salihovic, Jennifer Schlezinger, Anatoly Soshilov, Kyle Steenland, Inger-Lise Steffensen, Volodymyr Tryndyak, Alexandra White, Susan Woskie, Tony Fletcher, Ayat Ahmadi, Nahid Ahmadi, Lamia, Benbrahim-Tallaa, Wendy Bijoux, Shirisha Chittiboyina, Aline de Conti, Caterina Facchin, Federica Madia, Heidi Mattock, Mira Merdas, Elisa Pasqual, Eero Suonio, Susana Viegas, Ljubica Zupunski, Roland Wedekind, Mary K Schubauer-Berigan
Lancet Onc.
November 30, 2023
DOI: 10.1016/S1470-2045(23)00622-8
PFOA was classified as “carcinogenic to humans” (Group 1) based on “sufficient” evidence for cancer in experimental animals and “strong” mechanistic evidence in exposed humans. The evidence for cancer in experimental animals was “sufficient” because an increased incidence of an appropriate combination of benign and malignant neoplasms was observed in both sexes of a single species in a Good Laboratory Practice (GLP) study. The mechanistic evidence was “strong” in exposed humans because PFOA was found to induce epigenetic alterations and to be immunosuppressive. Additionally, there was “limited” evidence for cancer in humans for renal cell carcinoma and testicular cancer. PFOS was classified as “possibly carcinogenic to humans” (Group 2B) based on “strong” mechanistic evidence. The evidence for cancer in experimental animals was “limited” for PFOS, and the evidence regarding cancer in humans was “inadequate”. These assessments will be published in Volume 135 of the IARC Monographs.
PFOA and PFOS are perfluoroalkyl and polyfluoroalkyl substances (PFAS) that have had widespread use in industrial applications and consumer products due to their hydrophobicity and lipophobicity, surface-active properties, and chemical stability. PFOA has been used extensively in the manufacture of fluoropolymers. Applications for fluoropolymers and PFOA include surface coatings for stain, oil, and water resistance on household products, carpets, textiles, and food packaging; personal care products; seals; coatings for cables and wires; and construction materials. PFOS has some overlapping applications with PFOA—such as in waxes, carpets, and food packaging— and has also been used to make imaging devices, semiconductors, dyes, and ink, and in photolithography and electroplating processes. PFOS has been used extensively in class B firefighting foams known as aqueous film-forming foams. PFOA and PFOS are extremely resistant to degradation and are found globally, but environmental levels vary greatly in various regions due to different pollution sources.
Occupationally exposed populations have some of the highest exposures to PFOA and PFOS, with inhalation as the main exposure route, as well as potentially dermal absorption and dust ingestion. The highest exposure occurs in fluorochemical manufacturing. The general population is mainly exposed to PFOA and PFOS via diet and drinking water, and potentially via consumer products. In communities near polluted sites, the general population is mainly exposed via drinking water. PFOA and PFOS are detected in blood samples in studied populations worldwide, and median levels are up to a hundred times higher in communities near polluted sites. Some of the body burden might also originate from precursors, which are PFAS that transform into PFOA or PFOS in the body. There is no evidence that PFOA or PFOS are biotransformed. They accumulate in various tissues, including blood, liver, and lung. They are found in the placenta, cord blood, and embryonic tissues, and can be transferred to infants via breast milk. Both agents undergo enterohepatic recirculation and kidney reabsorption. They are excreted in urine and faeces with half-lives on the order of several years in humans, or in the range of hours to months in experimental animals.
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