There are 9,000+ per- and polyfluoroalkyl substances (PFAS) in existence, which makes studying and regulating PFAS individually, or even as small mixtures, infeasible. Multiple PFAS definitions based on structure have been proposed, yet these definitions do not consider the implications for the full suite of organofluorine chemicals. For example, organofluorine pharmaceuticals, whose use may be essential and are found in human serum and wastewater, are not uniformly identified across all definitions. Using nine definitions prepared by various stakeholders, we screened the 360 organofluorine pharmaceuticals approved and used globally between 1954 and 2021. Definitions ranged in their inclusion of organofluorine pharmaceuticals (1%–100%). The most inclusive definitions include several top prescribed pharmaceuticals, e.g., Prozac and Lipitor. This analysis provides a framework against which organizations can make decisions about how best to proceed when defining PFAS.

Wastewater receives per- and polyfluoroalkyl substances (PFAS) from diverse consumer and industrial sources, and discharges are known to be a concern for drinking water quality. The PFAS family includes thousands of potential chemical structures containing organofluorine moieties. Exposures to a few well-studied PFAS, mainly perfluoroalkyl acids (PFAA), have been associated with increased risk of many adverse health outcomes, prompting federal drinking water regulations for six compounds in 2024. Here, we find that the six regulated PFAS (mean = 7 to 8%) and 18 measured PFAA (mean = 11 to 21%) make up only a small fraction of the extractable organofluorine (EOF) in influent and effluent from eight large municipal wastewater treatment facilities. Most of the EOF in influent (75%) and effluent (62%) consists of mono- and polyfluorinated pharmaceuticals. The treatment technology and sizes of the treatment facilities in this study are similar to those serving 70% of the US population. Despite advanced treatment technologies, the maximum EOF removal efficiency among facilities in this work was <25%. Extrapolating our measurements to other large facilities across the United States results in a nationwide EOF discharge estimate of 1.0 to 2.8 million moles F y ⁻¹ . Using a national model that simulates connections between wastewater discharges and downstream drinking water intakes, we estimate that the sources of drinking water for up to 23 million Americans could be contaminated above regulatory thresholds by wastewater-derived PFAS alone. These results emphasize the importance of further curbing ongoing PFAS sources and additional evaluations of the fate and toxicity of fluorinated pharmaceuticals.

Extensive use of per- and polyfluoroalkyl substances (PFAS) has resulted in their ubiquitous presence in human blood. PFAS exposures have been associated with multiple adverse human health effects. Biomonitoring studies have focused on long-chain PFASs, but these are being replaced by short-chain PFASs or with alternate PFAS chemistries (or replacement chemistries such as GenX), resulting in changes in human exposures with time. Here, we take advantage of serum samples collected as part of a clinical trial testing the efficacy of a dietary fiber intervention to reduce serum cholesterol to investigate exposure to PFASs in Canadian participants. Serum samples were collected from 72 participants (adult males with elevated cholesterol) in 2019–2020 at baseline and after 4 weeks of the intervention and were analyzed for 17 PFASs. The highest geometric mean serum concentrations of PFAS measured at baseline corresponded to PFOSA (7.1 ng/ml), PFOS (4.2, ng/ml), PFOA (1.8 ng/ml) and PFHxS (1.3 ng/ml). Four long-chain PFASs (PFOA, PFOS, PFOSA and PFHxS) and two short-chain PFASs (PFBA, PFHxA) were detected in 100% of participants. GenX was detected in 71% of participants. Analyses of associations between serum-PFAS concentrations and biomarkers of adverse health outcomes showed the PFBA, PFHxA, PFDA and PFOSA were associated with higher serum gamma-glutamyl transferase concentrations but not with measures of serum-total or low-density lipoprotein cholesterol. Comparison of PFAS concentrations at baseline and after a 4-week follow-up showed that the total PFAS detected decreased in both the control and cholesterol intervention groups. However, the suite of long-chain PFASs of concern identified by the United States National Academies of Sciences, Engineering, and Medicine, significantly decreased only in the cholesterol intervention group. This observation suggests that a sustained dietary fiber intervention may reduce long-chain PFAS body burden, but future intervention studies need to control for PFAS exposure sources and extend the dietary supplement intake beyond 4 weeks. Overall, the results show that exposures to short-chain and replacement chemistry PFASs are common in this Canadian population.

People are exposed to per- and polyfluoroalkyl substances (PFAS) through multiple sources, with diet historically considered a major source in general populations. This study characterized legacy PFAS in serum from 700 California adults and examined contributions from diet and drinking water. We applied robust regression to estimate associations between nontransformed serum PFAS concentrations, self-reported food consumption, and drinking water PFAS concentrations measured under the USEPA's third Unregulated Contaminant Monitoring Rule (2013-2015). Detectable drinking water concentrations were associated with increased serum perfluorooctanoic acid (PFOA) (0.26 ng/mL; 95% CI: 0.077, 0.43), perfluorohexanesulfonic acid (PFHxS) (0.64 ng/mL; 95% CI: 0.058, 1.23), and perfluorooctanesulfonic acid (PFOS) (0.39 ng/mL; 95% CI: -0.76, 0.86). Seafood consumption was associated with increased perfluorononanoic acid (PFNA) (0.013 ng/mL; 95% CI: 0.0058, 0.021), perfluorodecanoic acid (PFDeA) (0.0059 ng/mL; 95% CI: 0.0026, 0.0092), and perfluoroundecanoic acid (PFUnDA) (0.010 ng/mL; 95% CI: 0.0054, 0.015), while eggs were associated with increased PFDeA (0.0035 ng/mL; 95% CI: 0.00010, 0.0069) and PFNA (0.0073 ng/mL; 95% CI: 0.00017, 0.014). Findings could indicate that dietary contributions may be less than those in earlier studies conducted in other populations, possibly due to shifts in PFAS production over the past 20 years, and that drinking water remains an important source of exposure to PFOA and PFHxS in this population.

Organofluorines occur in human serum as complex mixtures of known and unidentified compounds. Human biomonitoring traditionally uses targeted analysis to measure the presence of known and quantifiable per- and polyfluoroalkyl substances (PFAS) in serum, yet characterization of exposure to and quantification of PFAS are limited by the availability of methods and analytical standards. Studies comparing extractable organofluorine (EOF) in serum to measured PFAS using organofluorine mass balance show that measurable PFAS only explain a fraction of EOF in human serum and that other sources of organofluorine may exist. The gap in fluorine mass balance has important implications for human biomonitoring because the total body burden of PFAS cannot be characterized and the chemical species that make up unidentified EOF are unknown. Many highly prescribed pharmaceuticals contain organofluorine (e.g., Lipitor, Prozac) and are prescribed with dosing regimens designed to maintain a therapeutic range of concentrations in serum. Therefore, we hypothesize organofluorine pharmaceuticals contribute to EOF in serum. We use combustion ion chromatography to measure EOF in commercial serum from U.S. blood donors. Using fluorine mass balance, we assess differences in unexplained organofluorine (UOF) associated with pharmaceutical use and compare them with concentrations of organofluorine predicted based on the pharmacokinetic properties of each drug. Pharmacokinetic estimates of organofluorine attributable to pharmaceuticals ranged from 0.1 to 55.6 ng F/mL. Analysis of 44 target PFAS and EOF in samples of commercial serum (n = 20) shows the fraction of EOF not explained by Σ₄₄ PFAS ranged from 15% to 86%. Self-reported use of organofluorine pharmaceuticals is associated with a 0.36 ng F/mL (95% CL: −1.26 to 1.97) increase in UOF, on average, compared to those who report not taking organofluorine pharmaceuticals. Our study is the first to assess sources of UOF in U.S. serum and examine whether organofluorine pharmaceuticals contribute to EOF. Discrepancies between pharmacokinetic estimates and EOF may be partly explained by differences in analytical measurements. Future analyses using EOF should consider multiple extraction methods to include cations and zwitterions. Whether organofluorine pharmaceuticals are classified as PFAS depends on the definition of PFAS.

Extensive use of per- and polyfluoroalkyl substances (PFAS) has resulted in their ubiquitous presence in human blood. PFAS exposures have been associated with multiple adverse human health effects including increased risk of liver damage, elevated serum lipids, impaired vaccine response, adverse birth outcomes and cancer. Biomonitoring studies have focused on measuring long-chain PFAS, but these are being replaced by shorter chain PFAS and PFAS with alternative structures, resulting in incomplete understanding of human exposures. Here, we take advantage of serum samples collected as part of a clinical trial testing the efficacy of a dietary fiber intervention to reduce serum cholesterol to investigate exposure to legacy and replacement PFAS chemicals in Canadian participants. Serum samples were collected from 72 participants in 2019-2020 at baseline and after 4 weeks of the intervention and were analyzed for 17 PFAS species. The highest geometric mean concentrations of PFAS measured at baseline corresponded to PFOSA (7.1 ng/ml), PFOS (4.2, ng/ml), PFOA (1.8 ng/ml) and PFHxS (1.3 ng/ml). Short chain PFAS including PFBuA, PFHxS and/or PFHpA were detected in 100% of participants and GenX was detected in 70% of participants. Analyses of associations between PFAS serum concentrations and biomarkers of adverse health outcomes showed the PFBuA, PFHxA, PFDA and PFOSA were associated with higher serum gamma-glutamyl transferase concentrations but not with measures of serum total or low-density lipoprotein cholesterol. Comparison of PFAS concentrations at baseline and after a 4-week follow-up showed that total PFAS concentrations decreased in both the control and cholesterol intervention groups. However, the suite of PFAS of concern identified by the United States National Academies of Sciences, Engineering, and Medicine, significantly decreased only in the cholesterol intervention group. This observation suggests that a dietary fiber intervention may reduce PFAS body burden, but future intervention studies need to control for PFAS exposure sources and extend beyond 4 weeks. Overall, the results show that exposures to short-chain and alternative PFAS are common in this Canadian population.