Limited toxicokinetic and toxicologic information is available about a diverse set of per- and polyfluoroalkyl substances (PFAS), but methods based on gas chromatography–tandem mass spectrometry (GC–MS/MS) can help unravel some of the mystery.
A study published in a recent issue of the journal Toxics proposed targeted methods, developed using gas chromatography coupled to tandem mass spectrometry (GC–MS/MS), to measure human plasma protein binding and hepatocyte clearance in a group of 73 per- and polyfluoroalkyl substances, commonly known as PFAS or “forever chemicals” (1). The in vitro toxicokinetic (TK) information sought by the seven researchers who contributed to the piece, most of whom are affiliated with the U.S. Environmental Protection Agency (EPA), may close gaps in TK or toxicologic knowledge that could signal the environmental fates of some of these PFAS regarding their metabolism, volatility, or other modes of transport.
According to the Centers for Disease Control and Prevention (CDC), PFAS are used to make fluoropolymer coatings that can be found in products ranging from clothing to adhesives to food packaging to electrical wire insulation (2). These chemicals bioaccumulate in fish, wildlife, and water and therefore, in the humans who consume these contaminated sources. Biologically, the Paris-based Organisation for Economic Co-Operation and Development (OECD) classifies PFAS as having at least one fully fluorinated methyl or methylene carbon atom; the OECD has established a list of 4730 known such substances, though countless PFAS are thought to exist and specific information is available for all but a relative few—chief among them perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) (1,2).
The methods devised by the researchers in this study were borne out of the EPA’s PFAS Strategic Roadmap, released in 2021, which provides an outline for how to use in vitro toxicity testing and TK studies to broaden knowledge of PFAS bioactivity (1). Of the 73 PFAS this team identified as amenable to GC–MS/MS across multiple functional groups, targeted methods of analysis were successfully developed for 61 of them (also encompassing the use of traditional gas chromatography–mass spectrometry, GC–MS) with either positive or negative chemical ionization (PCI or NCI respectively). The authors said that abiotic stability, also measured in vitro, gave clues about the potential of PFAS for hydrolysis in aqueous environments.
Addressing the testing of human plasma protein binding, the study confirmed that PFAS are high binders in general terms, though values varied (1). However, no trends were observed specific to any one of 21 functional categories which were evaluated. The authors found it likely that some PFAS would metabolize to other, more stable PFAS, with PFAS sulfonamides just one such instance of “precursor products” (1).
Although many questions remain, the researchers concluded that their study enriched the known information about PFAS, in the interest of grouping these chemicals together for identification and prioritization in future biomonitoring efforts.
(1) Kreutz, A.; Clifton, M. S.; Henderson, W. M.; Smeltz, M. G.; Phillips, M.; Wambaugh, J. F.; Wetmore, B. A. Category-Based Toxicokinetic Evaluations of Data-Poor Per- and Polyfluoroalkyl Substances (PFAS) using Gas Chromatography Coupled with Mass Spectrometry. Toxics 2023, 11 (5), 463. DOI: 10.3390/toxics11050463
(2) Per- and Polyfluorinated Substances (PFAS) Factsheet. Centers for Disease Control and Prevention – National Biomonitoring Program. U.S. Department of Health & Human Services, 2022. https://www.cdc.gov/biomonitoring/PFAS_FactSheet.html#:~:text=Print-,Per%2D%20and%20Polyfluorinated%20Substances%20(PFAS),stains%2C%20grease%2C%20and%20water. (accessed 2024-03-25).
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