Application of the Key Characteristics of Carcinogens to Per and Polyfluoroalkyl Substances

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.

Per and polyfluoroalkyl substances scientific literature review: water exposure, impact on human health, and implications for regulatory reform

“…Although Cl-PFESA is a widely used PFOS alternative in China, there is no human data available to assess the reproductive toxicity of this PFAS [8]. As Temkin, et al noted, for the majority of 600 PFAS in wide use for the past decade, there is no toxicological data [64].…”

“…Temkin et al examined PFASs, including short PFASs, from a toxicological standpoint using the Key Carcinogens framework. They also noted the lack of studies on PFOS and PFOA alternatives, such as short-chain PFASs [64].…”

“…Their evaluation found adequate proof that PFAS exposure increased blood cholesterol by a low but significant amount. They found additional but limited proof of PFAS links to kidney disease, kidney cancer, testicular cancer, high uric acid concentration in the blood, and immunity for rubella and diphtheria following vaccination [64].…”

“…In 2020, because PFAS has been identified as a probable human carcinogen, a novel, state-of-science review by Temkin et al applied key characteristics analysis into risk assessments. This approach is being increasingly used in the USA and international government agencies, to data for several PFAS (26 chemicals) for each characteristic to evaluate the strength of evidence as a carcinogen [64]. Temkin et al applied the Key Characteristics of Carcinogens framework.…”

“…Well-studied PFAS such as PFOA and PFOS were found to have up to five key characteristics of carcinogens. Temkin et al noted that although over 600 different PFAS are known to be inactive use over the last decade, for most of those compounds, no toxicological information is available [64].…”