Due to their unique chemical properties, per- and polyfluoroalkyl substances (PFAS) have been used extensively as industrial surfactants and processing aids. While several types of PFAS have been voluntarily phased out by their manufacturers, these chemicals continue to be of ecological and public health concern due to their persistence in the environment and their presence in living organisms. Moreover, while the compounds referred to as “legacy” PFAS remain in the environment, alternative compounds have emerged as replacements for their legacy predecessors and are now detected in numerous matrices. In this review, we discuss the historical uses of PFAS, recent advances in analytical techniques for analysis of these compounds, and the fate of PFAS in the environment. In addition, we evaluate current biomonitoring studies of human exposure to legacy and emerging PFAS and examine the associations of PFAS exposure with human health impacts, including cancer- and non-cancer-related outcomes. Special focus is given to short-chain perfluoroalkyl acids (PFAAs) and ether-substituted, polyfluoroalkyl alternatives including hexafluoropropylene oxide dimer acid (HFPO-DA; tradename GenX), 4,8-dioxa-3H-perfluorononanoic acid (DONA), and 6:2 chlorinated polyfluoroethersulfonic acid (6:2 Cl-PFESA; tradename F-53B).

Exposure to trace elements and per- and polyfluoroalkyl substances (PFAS) during pregnancy is linked to adverse reproductive and developmental outcomes. High smoking rates in western Pennsylvania may influence exposure to these chemicals. We characterized PFAS, trace element, and smoking exposure in the second trimester of pregnancy among women in western Pennsylvania. We measured 38 urine trace elements and 11 serum PFAS in 46 pregnant women in 2017–2021 as part of a nested pilot study from the Magee Obstetric Maternal and Infant (MOMI) biobank and database. We statistically compared environmental chemical concentrations between smoking and non-smoking participants in the MOMI pilot study. Additionally, we descriptively compared MOMI concentrations to a nationally representative sample of US women of reproductive age from the National Health and Nutrition Examination Survey (NHANES) and to published studies characterizing exposures among international populations. Two PFAS (PFOA and PFOS) and 16 trace elements were highly detected in the MOMI pilot study sample. Smoking participants had distributions of 10 trace element concentrations that tended to be significantly higher compared to non-smoking participants, but no significant differences in the distributions of serum PFAS concentrations. All participants had summed PFAS concentrations > 2 μg/L—the National Academies of Sciences Engineering and Medicine threshold for recommending additional health screening. MOMI non-smoking participants had higher concentrations of seven trace elements and lower concentrations of both PFAS compared with NHANES non-smoking participants, while MOMI smoking participants had higher concentrations of 12 trace elements and lower concentrations of both PFAS compared with NHANES smoking participants. Further research is necessary to identify the sources of exposure, potential health effects, and effective strategies to reduce exposure to these environmental chemicals.