Health-related toxicity of emerging per- and polyfluoroalkyl substances: Comparison to legacy PFOS and PFOA

Per- and polyfluoroalkyl substances (PFAS) are highly persistent, manufactured chemicals used in various manufacturing processes and found in numerous commercial products. With over 9000 compounds belonging to this chemical class, there is increasing concern regarding human exposure to these compounds due to their persistent, bioaccumulative, and toxic nature. Human exposure to PFAS may occur from a variety of exposure sources, including, air, food, indoor dust, soil, water, from the transfer of PFAS from non-stick wrappers to food, use of cosmetics, and other personal care products. This critical review presents recent research on the health-related impacts of PFAS exposure, highlighting compounds other than Perfluorooctanoic acid (PFOA) and Perfluoroctane sulfonate (PFOS) that cause adverse health effects, updates the current state of knowledge on PFAS toxicity, and, where possible, elucidates cause-and-effect relationships. Recent reviews identified that exposure to PFAS was associated with adverse health impacts on female and male fertility, metabolism in pregnancy, endocrine function including pancreatic dysfunction and risk of developing Type 2 diabetes, lipid metabolism and risk of childhood adiposity, hepatic and renal function, immune function, cardiovascular health (atherosclerosis), bone health including risk for dental cavities, osteoporosis, and vitamin D deficiency, neurological function, and risk of developing breast cancer. However, while cause-and-effect relationships for many of these outcomes were not able to be clearly elucidated, it was identified that 1) the evidence derived from both animal models and humans suggested that PFAS may exert harmful impacts on both animals and humans, however extrapolating data from animal to human studies was complicated due to differences in exposure/elimination kinetics, 2) PFAS precursor kinetics and toxicity mechanism data are still limited despite ongoing exposures, and 3) studies in humans, which provide contrasting results require further investigation of the long-term-exposed population to better evaluate the biological toxicity of chronic exposure to PFAS. •PFAS toxicity data for humans remains highly variable.•The toxic kinetics and tissue distribution of PFAS are species-specific.•Extrapolating data from animal to human studies is complex and inconclusive.•Emerging PFAS can induce toxicity like legacy PFOS and PFOA.•Adverse response pathways to PFAS differ among species, sexes, and life stage