Abstract
Per- and polyfluoroalkyl substances (PFAS) constitute a large class of environmentally persistent chemicals used in industrial and consumer products. Human exposure to PFAS is extensive, and PFAS contamination has been reported in drinking water and food supplies as well as in the serum of nearly all people. The most well-studied member of the PFAS class, perfluorooctanoic acid (PFOA), induces tumors in animal bioassays and has been associated with elevated risk of cancer in human populations. GenX, one of the PFOA replacement chemicals, induces tumors in animal bioassays as well. Using the Key Characteristics of Carcinogens framework for cancer hazard identification, we considered the existing epidemiological, toxicological and mechanistic data for 26 different PFAS. We found strong evidence that multiple PFAS induce oxidative stress, are immunosuppressive, and modulate receptor-mediated effects. We also found suggestive evidence indicating that some PFAS can induce epigenetic alterations and influence cell proliferation. Experimental data indicate that PFAS are not genotoxic and generally do not undergo metabolic activation. Data are currently insufficient to assess whether any PFAS promote chronic inflammation, cellular immortalization or alter DNA repair. While more research is needed to address data gaps, evidence exists that several PFAS exhibit one or more of the key characteristics of carcinogens.
Highlights
Per- and polyfluoroalkyl substances (PFAS) are human-made fluorinated chemicals that have become pervasive contaminants in people and the environment
Data were not identified from in vitro studies. b The following long-chain PFAS are not presented in the table since no data were avaible to assess this key characteristic: PFTrDA, PFTeDA, 8: monoPAP, 8:2 TriPAP. * PFAS listed as having an “Association” with this key characteristic undergo metabolic activation but are not electrophilic. c The following short-chain PFAS are not presented in the table since no data were avaible to assess this key characteristic: PFPeA, PMPP/ADONA, 4:2 fluorotelomer alcohols (FTOHs)
The following long-chain PFAS are not presented in the table since no data were avaible to assess this key characteristic: PFDA, PFDoA, PFTrDA, PFTeDA, perfluorooctane sulfonamide (PFOSA), 8:2 FTOH, 8:2 monoPAP, 8:2 diPAP, 8:2 triPAP, 10:2 diPAP; b The following short-chain PFAS are not presented in the table since no data were avaible to assess this key characteristic: PFBS, PFHxA, PFBA, PFPeA, PFHpA, GenX (HFPO-DA); PMOH, PMPP/ADONA, 4:2 FTOH, 6:2
Summary
Per- and polyfluoroalkyl substances (PFAS) are human-made fluorinated chemicals that have become pervasive contaminants in people and the environment. Since the 1950s, thousands of different PFAS have been produced for use in industrial and consumer products. The use of PFAS in firefighting foams and presence in industrial discharges has resulted in extensive contamination worldwide. PFAS are detectable in most humans, with exposures beginning during fetal development. As detailed in this article, a growing body of research suggests that exposure to PFAS at contaminated sites and in the general population can adversely impact human health. One well-studied PFAS, perfluorooctanoic acid (PFOA) was reviewed by the International Agency for Research on Cancer (IARC) in 2016 and classified as group 2B, a possible human carcinogen [1]
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