Category-Based Toxicokinetic Evaluations of Data-Poor Per- and Polyfluoroalkyl Substances (PFAS) using Gas Chromatography Coupled with Mass Spectrometry
Concern over per- and polyfluoroalkyl substances (PFAS) has increased as more is learned about their environmental presence, persistence, and bioaccumulative potential. The limited monitoring, toxicokinetic (TK), and toxicologic data available are inadequate to inform risk across this diverse domain...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Toxics |
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| Online Access: | https://www.mdpi.com/2305-6304/11/5/463 |
| _version_ | 1797598168264736768 |
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| author | Anna Kreutz Matthew S. Clifton W. Matthew Henderson Marci G. Smeltz Matthew Phillips John F. Wambaugh Barbara A. Wetmore |
| author_facet | Anna Kreutz Matthew S. Clifton W. Matthew Henderson Marci G. Smeltz Matthew Phillips John F. Wambaugh Barbara A. Wetmore |
| author_sort | Anna Kreutz |
| collection | DOAJ |
| description | Concern over per- and polyfluoroalkyl substances (PFAS) has increased as more is learned about their environmental presence, persistence, and bioaccumulative potential. The limited monitoring, toxicokinetic (TK), and toxicologic data available are inadequate to inform risk across this diverse domain. Here, 73 PFAS were selected for in vitro TK evaluation to expand knowledge across lesser-studied PFAS alcohols, amides, and acrylates. Targeted methods developed using gas chromatography–tandem mass spectrometry (GC-MS/MS) were used to measure human plasma protein binding and hepatocyte clearance. Forty-three PFAS were successfully evaluated in plasma, with fraction unbound (f<sub>up</sub>) values ranging from 0.004 to 1. With a median f<sub>up</sub> of 0.09 (i.e., 91% bound), these PFAS are highly bound but exhibit 10-fold lower binding than legacy perfluoroalkyl acids recently evaluated. Thirty PFAS evaluated in the hepatocyte clearance assay showed abiotic loss, with many exceeding 60% loss within 60 min. Metabolic clearance was noted for 11 of the 13 that were successfully evaluated, with rates up to 49.9 μL/(min × million cells). The chemical transformation simulator revealed potential (bio)transformation products to consider. This effort provides critical information to evaluate PFAS for which volatility, metabolism, and other routes of transformation are likely to modulate their environmental fates. |
| first_indexed | 2024-03-11T03:15:33Z |
| format | Article |
| id | doaj.art-8fc4fde069ed42aab4652e0a1ed3ded5 |
| institution | Directory Open Access Journal |
| issn | 2305-6304 |
| language | English |
| last_indexed | 2024-03-11T03:15:33Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxics |
| spelling | doaj.art-8fc4fde069ed42aab4652e0a1ed3ded52023-11-18T03:33:00ZengMDPI AGToxics2305-63042023-05-0111546310.3390/toxics11050463Category-Based Toxicokinetic Evaluations of Data-Poor Per- and Polyfluoroalkyl Substances (PFAS) using Gas Chromatography Coupled with Mass SpectrometryAnna Kreutz0Matthew S. Clifton1W. Matthew Henderson2Marci G. Smeltz3Matthew Phillips4John F. Wambaugh5Barbara A. Wetmore6Oak Ridge Institute for Science and Education, 1299 Bethel Valley Road, Oak Ridge, TN 37830, USAUS Environmental Protection Agency, Office of Research and Development, Center for Environmental Measurement and Modeling, Research Triangle Park, NC 27711, USAUS Environmental Protection Agency, Office of Research and Development, Center for Environmental Measurement and Modeling, Athens, GA 30605, USAUS Environmental Protection Agency, Office of Research and Development, Center for Environmental Measurement and Modeling, Research Triangle Park, NC 27711, USAOak Ridge Associated Universities, 100 ORAU Way, Oak Ridge, TN 37830, USAUS Environmental Protection Agency, Office of Research and Development, Center for Computational Toxicology and Exposure, Research Triangle Park, NC 27711, USAUS Environmental Protection Agency, Office of Research and Development, Center for Computational Toxicology and Exposure, Research Triangle Park, NC 27711, USAConcern over per- and polyfluoroalkyl substances (PFAS) has increased as more is learned about their environmental presence, persistence, and bioaccumulative potential. The limited monitoring, toxicokinetic (TK), and toxicologic data available are inadequate to inform risk across this diverse domain. Here, 73 PFAS were selected for in vitro TK evaluation to expand knowledge across lesser-studied PFAS alcohols, amides, and acrylates. Targeted methods developed using gas chromatography–tandem mass spectrometry (GC-MS/MS) were used to measure human plasma protein binding and hepatocyte clearance. Forty-three PFAS were successfully evaluated in plasma, with fraction unbound (f<sub>up</sub>) values ranging from 0.004 to 1. With a median f<sub>up</sub> of 0.09 (i.e., 91% bound), these PFAS are highly bound but exhibit 10-fold lower binding than legacy perfluoroalkyl acids recently evaluated. Thirty PFAS evaluated in the hepatocyte clearance assay showed abiotic loss, with many exceeding 60% loss within 60 min. Metabolic clearance was noted for 11 of the 13 that were successfully evaluated, with rates up to 49.9 μL/(min × million cells). The chemical transformation simulator revealed potential (bio)transformation products to consider. This effort provides critical information to evaluate PFAS for which volatility, metabolism, and other routes of transformation are likely to modulate their environmental fates.https://www.mdpi.com/2305-6304/11/5/463PFAStoxicokineticsin vitro–in vivo extrapolationplasma protein bindinghepatic clearancenew approach methods |
| spellingShingle | Anna Kreutz Matthew S. Clifton W. Matthew Henderson Marci G. Smeltz Matthew Phillips John F. Wambaugh Barbara A. Wetmore Category-Based Toxicokinetic Evaluations of Data-Poor Per- and Polyfluoroalkyl Substances (PFAS) using Gas Chromatography Coupled with Mass Spectrometry Toxics PFAS toxicokinetics in vitro–in vivo extrapolation plasma protein binding hepatic clearance new approach methods |
| title | Category-Based Toxicokinetic Evaluations of Data-Poor Per- and Polyfluoroalkyl Substances (PFAS) using Gas Chromatography Coupled with Mass Spectrometry |
| title_full | Category-Based Toxicokinetic Evaluations of Data-Poor Per- and Polyfluoroalkyl Substances (PFAS) using Gas Chromatography Coupled with Mass Spectrometry |
| title_fullStr | Category-Based Toxicokinetic Evaluations of Data-Poor Per- and Polyfluoroalkyl Substances (PFAS) using Gas Chromatography Coupled with Mass Spectrometry |
| title_full_unstemmed | Category-Based Toxicokinetic Evaluations of Data-Poor Per- and Polyfluoroalkyl Substances (PFAS) using Gas Chromatography Coupled with Mass Spectrometry |
| title_short | Category-Based Toxicokinetic Evaluations of Data-Poor Per- and Polyfluoroalkyl Substances (PFAS) using Gas Chromatography Coupled with Mass Spectrometry |
| title_sort | category based toxicokinetic evaluations of data poor per and polyfluoroalkyl substances pfas using gas chromatography coupled with mass spectrometry |
| topic | PFAS toxicokinetics in vitro–in vivo extrapolation plasma protein binding hepatic clearance new approach methods |
| url | https://www.mdpi.com/2305-6304/11/5/463 |
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