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).

Per- and polyfluoroalkyl substances (PFAS) constitute a broad class of anthropogenic chemicals that have been used in numerous industrial and consumer-product applications since the late 1940s. The environmental persistence of these compounds in combination with their widespread commercial use have led PFAS to be recognized as contaminants of concern on the global scale. Despite regulatory efforts calling for the decreased use of certain perfluorocarboxylic and -sulfonic acids referred to as “legacy” PFAS, these compounds continue to be detected in both environmental and biological matrices. Moreover, manufacturers have begun to replace the legacy PFAS with emerging alternatives for which the regulations are not established or are less strict, and the potential health effects are far less clear. For these reasons, studies of the disposition of legacy and emerging PFAS remain crucial for assessing their environmental contamination and potential impacts on public health.The goal of this dissertation was to address several knowledge gaps regarding the analytical measurement, environmental occurrence, and bioconcentration of PFAS, with a special emphasis on emerging compounds. First, a large-volume injection (LVI) sample preparation method for the determination of PFAS in drinking water was developed and validated. Evaluation of method performance indicated that, for some applications, LVI was a viable alternative to the standard methods employing solid-phase extraction (SPE). A second study was conducted to improve the analytical sensitivity for a class of emerging replacement PFAS, perfluoroethercarboxylic acids (PFECAs), using liquid chromatography–tandem mass spectrometry (LC–MS/MS). It was demonstrated that by making facile modifications to instrumental parameters, quantitative results can be obtained for these compounds which showed inadequate detection limits when using other methods. A third study was conducted to assess the use of freshwater aquatic insects/benthic macroinvertebrates (BMIs) for monitoring PFAS in the aquatic environment. To accomplish this, PFAS were measured in BMIs collected from two freshwater streams along with sediment and surface water simultaneously collected from the same sites. The results indicated that, although PFAS concentrations in sediment and water were not excessively high, elevated levels were measured in most of the BMI taxa examined. This observation suggests that PFAS contamination in the aquatic environment may be underestimated if only abiotic matrices are used for environmental monitoring. A final study was conducted to compare the uptake of legacy and emerging PFAS into edible plants. Three types of leafy vegetables were grown in hydroponic solutions containing different PFAS mixtures. Root and shoot concentration factors showed similar degrees of uptake