Implications of PFAS definitions using fluorinated pharmaceuticals

Abstract

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.

Keywords: Chemistry; Organic chemistry; Per- and polyfluoroalkyl substances; Pharmaceutical science; Toxicology.

Graphical abstract

Figure 1

Substructures identified among organofluorine pharmaceuticals

Figure 2

Examples of organofluorine pharmaceuticals that meet the nine PFAS definitions (A) Buck et al. includes the contrast agent, perflubron (CAS No. 423-55-2). (B) 2018 OECD and TURA 2021a both include the general anesthetic enflurane (CAS No. 13838-16-9). (C) The 2021 OECD definition includes the antineoplastic alpelisib (CAS No.: 1217486-61-7). (D) Glüge et al. includes the antidiabetic medication gemigliptin (CAS No. 911637-19-9). (E) The TURA 2021b definition includes the cardiac ultrasound imaging agent perflexane (CAS No. 355-42-0). (F) U.S. EPA OPPT includes the ultrasound contrast agent Perflutren (CAS No. 76-19-7). (G) The ≥1 fully fluorinated carbon definition includes the antidepressant fluoxetine (Prozac) (CAS No. 54910-89-3). (H) The “all-organofluorine” and ≥1 fully fluorinated carbon definitions include the cholesterol lowering medication atorvastatin (Lipitor) (CAS No. 134523-00-5).