{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:14:11Z","timestamp":1792120451371,"version":"4.4.0"},"reference-count":39,"publisher":"American Chemical Society (ACS)","issue":"1","license":[{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/100004322","name":"Agilent Technologies","doi-asserted-by":"publisher","award":["ACT-UR 4522"],"award-info":[{"award-number":["ACT-UR 4522"]}],"id":[{"id":"10.13039\/100004322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Per- and polyfluoroalkyl substances (PFAS) are widely used persistent synthetic chemicals that have been linked to adverse health effects. While the behavior of PFAS has been evaluated in the environment, our understanding of reaction products in mammalian systems is limited. This study identified biological PFAS transformation products and generated mass spectral libraries to facilitate an automated search and identification. The biological transformation products of 27 PFAS, spanning 5 chemical subclasses (alcohols, sulfonamides, carboxylic acids, ethers, and esters), were evaluated following enzymatic reaction with mouse liver S9 fractions. Four major pathways were identified by liquid chromatography-high-resolution mass spectrometry: glucuronidation, sulfation, dealkylation, and oxidation. Class-based fragmentation rules and associated PFAS transformation product libraries were generated and integrated into an automated nontargeted PFAS data analysis software (FluoroMatch). Fragmentation was additionally predicted for the potential transformation products of more than 2,500 PFAS in the EPA CompTox Chemicals Dashboard PFASSTRUCTv4. Generated mass spectral libraries were validated by applying FluoroMatch to a data set of urine from aqueous film-forming foam (AFFF)-dosed mice. Toxicity predictions showed identified PFAS transformation products to be potential developmental and mutagenic toxicants. This research enables more comprehensive PFAS characterization in biological systems, which will improve the assessment of exposures and evaluation of the associated health impacts.<\/jats:p>","DOI":"10.1021\/acs.est.4c07750","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T06:03:04Z","timestamp":1734674584000},"page":"119-131","source":"Crossref","is-referenced-by-count":19,"title":["Expanding PFAS Identification\nwith Transformation\nProduct Libraries: Nontargeted Analysis Reveals Biotransformation\nProducts in Mice"],"prefix":"10.1021","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0653-0427","authenticated-orcid":true,"given":"Sheng","family":"Liu","sequence":"first","affiliation":[{"name":"Yale School of Public Health , , , ,","place":["New Haven, Connecticut, United States, 06511"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Dukes","sequence":"additional","affiliation":[{"name":"Stony Brook University , , , ,","place":["Stony Brook, New York, United States, 11794"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9985-8901","authenticated-orcid":true,"given":"Jeremy P.","family":"Koelmel","sequence":"additional","affiliation":[{"name":"Yale School of Public Health , , , ,","place":["New Haven, Connecticut, United States, 06511"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Stelben","sequence":"additional","affiliation":[{"name":"Yale School of Public Health , , , ,","place":["New Haven, Connecticut, United States, 06511"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasen","family":"Finch","sequence":"additional","affiliation":[{"name":"Aberystwyth University , , , ,","place":["Aberystwyth, Ceredigion, U.K., SY23 3EB"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7604-0736","authenticated-orcid":true,"given":"Joseph","family":"Okeme","sequence":"additional","affiliation":[{"name":"Yale School of Public Health , , , ,","place":["New Haven, Connecticut, United States, 06511"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9151-6157","authenticated-orcid":true,"given":"Charles","family":"Lowe","sequence":"additional","affiliation":[{"name":"U.S. Environmental Protection Agency , , , ,","place":["Research Triangle Park, North Carolina, United States, 27711"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2668-4821","authenticated-orcid":true,"given":"Antony","family":"Williams","sequence":"additional","affiliation":[{"name":"U.S. Environmental Protection Agency , , , ,","place":["Research Triangle Park, North Carolina, United States, 27711"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Godri","sequence":"additional","affiliation":[{"name":"Third Floor Solutions , , ,","place":["Toronto, ON, Canada, M5V 3L9"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma E.","family":"Rennie","sequence":"additional","affiliation":[{"name":"Agilent Technologies , , ,","place":["Santa\nClara, California, United States, 95051"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Parry","sequence":"additional","affiliation":[{"name":"Agilent Technologies , , ,","place":["Santa\nClara, California, United States, 95051"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5152-8495","authenticated-orcid":true,"given":"Carrie A.","family":"McDonough","sequence":"additional","affiliation":[{"name":"Carnegie Mellon University , , , ,","place":["Pittsburgh, Pennsylvania, United States, 15213"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7332-2228","authenticated-orcid":true,"given":"Krystal J","family":"Godri Pollitt","sequence":"additional","affiliation":[{"name":"Yale School of Public Health , , , ,","place":["New Haven, Connecticut, United States, 06511"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2024,12,20]]},"reference":[{"issue":"4","key":"2026081212021961100_cit1","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1038\/jes.2012.7","article-title":"Urinary phthalate metabolites and\ntheir biotransformation products: Predictors and temporal variability\namong men and women","volume":"22","author":"Meeker","year":"2012","journal-title":"J. Expo. Sci. Environ.\nEpidemiol."},{"key":"2026081212021961100_cit2","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1016\/j.jhazmat.2018.11.021","article-title":"Nationwide reconnaissance\nof five parabens, triclosan, triclocarban and its transformation products\nin sewage sludge from China","volume":"365","author":"Chen","year":"2019","journal-title":"J. Hazard. Mater."},{"key":"2026081212021961100_cit3","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s12940-016-0131-2","article-title":"Direct measurement of Bisphenol A\n(BPA), BPA glucuronide and BPA sulfate in a diverse and low-income\npopulation of pregnant women reveals high exposure, with potential\nimplications for previous exposure estimates: A cross-sectional study","volume":"15","author":"Gerona","year":"2016","journal-title":"Environ. Health"},{"issue":"2","key":"2026081212021961100_cit4","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1016\/j.taap.2012.08.009","article-title":"Kinetics\nof di\u00ad(2-ethylhexyl) phthalate (DEHP) and mono\u00ad(2-ethylhexyl) phthalate\nin blood and of DEHP metabolites in urine of male volunteers after\nsingle ingestion of ring-deuterated DEHP","volume":"264","author":"Kessler","year":"2012","journal-title":"Toxicol.\nAppl. Pharmacol."},{"key":"2026081212021961100_cit5","doi-asserted-by":"publisher","first-page":"1750368","DOI":"10.1155\/2018\/1750368","article-title":"Toxic Effects of Di-2-ethylhexyl\nPhthalate: An Overview","volume":"2018","author":"Rowdhwal","year":"2018","journal-title":"BioMed. Res. Int."},{"issue":"2","key":"2026081212021961100_cit6","doi-asserted-by":"publisher","first-page":"21","DOI":"10.3390\/toxics7020021","article-title":"A Review of Biomonitoring of Phthalate Exposures","volume":"7","author":"Wang","year":"2019","journal-title":"Toxics"},{"issue":"1","key":"2026081212021961100_cit7","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.tox.2004.11.013","article-title":"Evaluation of anti-androgenic activity of di-(2-ethylhexyl)\u00adphthalate","volume":"208","author":"Stroheker","year":"2005","journal-title":"Toxicology"},{"issue":"4","key":"2026081212021961100_cit8","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1002\/ieam.258","article-title":"Perfluoroalkyl and polyfluoroalkyl\nsubstances in the\nenvironment: Terminology, classification, and origins","volume":"7","author":"Buck","year":"2011","journal-title":"Integr. Environ. Assess. Manage."},{"issue":"3","key":"2026081212021961100_cit9","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1002\/etc.4890","article-title":"Per- and Polyfluoroalkyl Substance\nToxicity and Human Health Review: Current State of Knowledge and Strategies\nfor Informing Future Research","volume":"40","author":"Fenton","year":"2021","journal-title":"Environ. Toxicol.\nChem."},{"issue":"7","key":"2026081212021961100_cit10","doi-asserted-by":"publisher","first-page":"77004","DOI":"10.1289\/EHP7169","article-title":"A Roadmap to the Structure-Related\nMetabolism Pathways of Per- and Polyfluoroalkyl Substances in the\nEarly Life Stages of Zebrafish (Danio rerio)","volume":"129","author":"Han","year":"2021","journal-title":"Environ. Health Perspect."},{"issue":"W1","key":"2026081212021961100_cit11","doi-asserted-by":"publisher","first-page":"W115","DOI":"10.1093\/nar\/gkac313","article-title":"BioTransformer 3.0-a web server for\naccurately predicting metabolic transformation products","volume":"50","author":"Wishart","year":"2022","journal-title":"Nucleic Acids Res."},{"issue":"47","key":"2026081212021961100_cit12","doi-asserted-by":"publisher","first-page":"12777","DOI":"10.1039\/D0SC02639E","article-title":"Prediction\nof drug metabolites using neural machine\ntranslation","volume":"11","author":"Litsa","year":"2020","journal-title":"Chem. Sci."},{"key":"2026081212021961100_cit13","doi-asserted-by":"publisher","first-page":"115908","DOI":"10.1016\/j.envpol.2020.115908","article-title":"Biotransformation of\nperfluoroalkyl acid precursors from various\nenvironmental systems: Advances and perspectives","volume":"272","author":"Zhang","year":"2021","journal-title":"Environ. Pollut."},{"issue":"3","key":"2026081212021961100_cit14","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1007\/s00216-021-03392-7","article-title":"FluoroMatch 2.0-making automated and comprehensive\nnon-targeted PFAS annotation a reality","volume":"414","author":"Koelmel","year":"2022","journal-title":"Anal.\nBioanal. Chem."},{"issue":"4","key":"2026081212021961100_cit15","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1021\/jasms.0c00261","article-title":"Software Comparison for Nontargeted\nAnalysis of PFAS in AFFF-Contaminated Soil","volume":"32","author":"Nason","year":"2021","journal-title":"J. Am. Soc. Mass Spectrom."},{"issue":"16","key":"2026081212021961100_cit16","doi-asserted-by":"publisher","first-page":"11186","DOI":"10.1021\/acs.analchem.0c01591","article-title":"Toward Comprehensive\nPer- and Polyfluoroalkyl Substances Annotation Using FluoroMatch Software\nand Intelligent High-Resolution Tandem Mass Spectrometry Acquisition","volume":"92","author":"Koelmel","year":"2020","journal-title":"Anal. Chem."},{"issue":"1","key":"2026081212021961100_cit17","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/s13321-017-0247-6","article-title":"The CompTox\nChemistry Dashboard: A community data resource for environmental chemistry","volume":"9","author":"Williams","year":"2017","journal-title":"J. Cheminf"},{"issue":"30","key":"2026081212021961100_cit18","doi-asserted-by":"publisher","first-page":"7495","DOI":"10.1007\/s00216-021-03713-w","article-title":"Predicting compound\namenability with liquid chromatography-mass\nspectrometry to improve non-targeted analysis","volume":"413","author":"Lowe","year":"2021","journal-title":"Anal. Bioanal. Chem."},{"key":"2026081212021961100_cit19","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1186\/1471-2105-10-227","article-title":"Metabolite\nsignal identification in accurate mass metabolomics\ndata with MZedDB, an interactive m\/z annotation tool utilising predicted\nionisation behaviour\u2019rules\u2019","volume":"10","author":"Draper","year":"2009","journal-title":"BMC\nBioinf."},{"key":"2026081212021961100_cit20","doi-asserted-by":"publisher","first-page":"2274","DOI":"10.1002\/etc.5939","article-title":"N-glucuronidation\nand Excretion of Perfluoroalkyl Sulfonamides\nin Mice Following Ingestion of Aqueous Film-Forming Foam","volume":"43","author":"Dukes","year":"2024","journal-title":"Environ. Toxicol. Chem."},{"issue":"1","key":"2026081212021961100_cit21","doi-asserted-by":"publisher","first-page":"osac006","DOI":"10.1093\/exposome\/osac006","article-title":"Interactive software\nfor visualization of nontargeted mass spectrometry data&#x97;FluoroMatch\nvisualizer","volume":"2","author":"Koelmel","year":"2022","journal-title":"Exposome"},{"issue":"9","key":"2026081212021961100_cit22","doi-asserted-by":"publisher","first-page":"5700","DOI":"10.1021\/acs.est.0c00234","article-title":"Bioaccumulation\nof Novel Per- and Polyfluoroalkyl Substances in Mice Dosed with an\nAqueous Film-Forming Foam","volume":"54","author":"McDonough","year":"2020","journal-title":"Environ. Sci. Technol."},{"key":"2026081212021961100_cit23","doi-asserted-by":"publisher","first-page":"163579","DOI":"10.1016\/j.scitotenv.2023.163579","article-title":"Novel perfluoroalkyl substances (PFAS) discovered in\nwhole blood using automated non-targeted analysis of dried blood spots","volume":"883","author":"Koelmel","year":"2023","journal-title":"Sci. Total Environ."},{"key":"2026081212021961100_cit24","unstructured":"Koelmel, J.; Lin, E.; Stelben, P.; Pollitt, K.\n          Non-Target PFAS Analysis in Dried\nBlood Spots Using the Agilent 6546 LC\/Q-TOF with Profinder and FluoroMatch. 2024. https:\/\/www.agilent.com\/cs\/library\/applications\/an-non-target-pfas-dried-blood-6546-lc-q-tof-5994-7023en-agilent.pdf accessed 30 September 2024."},{"key":"2026081212021961100_cit25","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1016\/j.envpol.2017.12.021","article-title":"Simultaneous\ndetermination of (N-ethyl perfluorooctanesulfonamido ethanol)-based\nphosphate diester and triester and their biotransformation to perfluorooctanesulfonate\nin freshwater sediments","volume":"234","author":"Zhang","year":"2018","journal-title":"Environ. Pollut."},{"issue":"13","key":"2026081212021961100_cit26","doi-asserted-by":"publisher","first-page":"4799","DOI":"10.1021\/es070126x","article-title":"Production\nof Perfluorinated Carboxylic Acids (PFCAs)\nfrom the Biotransformation of Polyfluoroalkyl Phosphate Surfactants\n(PAPS): Exploring Routes of Human Contamination","volume":"41","author":"Mabury","year":"2007","journal-title":"Environ. Sci. Technol."},{"issue":"2","key":"2026081212021961100_cit27","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.cbi.2009.03.015","article-title":"Kinetics of 8\u20132 fluorotelomer\nalcohol and its metabolites, and liver glutathione status following\ndaily oral dosing for 45 days in male and female rats","volume":"180","author":"Fasano","year":"2009","journal-title":"Chem. Biol. Interact."},{"issue":"2","key":"2026081212021961100_cit28","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1002\/etc.2407","article-title":"Biotransformation\npathways of fluorotelomer-based\npolyfluoroalkyl substances: A review","volume":"33","author":"Butt","year":"2014","journal-title":"Environ.\nToxicol. Chem."},{"issue":"10","key":"2026081212021961100_cit29","doi-asserted-by":"publisher","first-page":"1758","DOI":"10.1039\/D2EM00225F","article-title":"The human fecal microbiome contributes to the biotransformation\nof the PFAS surfactant 8: 2 monosubstituted polyfluoroalkyl phosphate\nester","volume":"24","author":"Peskett","year":"2022","journal-title":"Environ. Sci. Process Impacts"},{"issue":"10","key":"2026081212021961100_cit30","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1007\/s00204-009-0450-y","article-title":"Subacute exposure\nto N-ethyl perfluorooctanesulfonamidoethanol results in the formation\nof perfluorooctanesulfonate and alters superoxide dismutase activity\nin female rats","volume":"83","author":"Xie","year":"2009","journal-title":"Arch. Toxicol."},{"issue":"10","key":"2026081212021961100_cit31","doi-asserted-by":"publisher","first-page":"6004","DOI":"10.1021\/acs.est.2c00254","article-title":"Widening the Lens\non PFASs: Direct Human Exposure to Perfluoroalkyl Acid Precursors\n(pre-PFAAs)","volume":"56","author":"McDonough","year":"2022","journal-title":"Environ. Sci. Technol."},{"issue":"18","key":"2026081212021961100_cit32","doi-asserted-by":"publisher","first-page":"10216","DOI":"10.1021\/acs.est.6b01170","article-title":"Identification\nof Biomarkers of Exposure to FTOHs and PAPs in Humans Using a Targeted\nand Nontargeted Analysis Approach","volume":"50","author":"Dagnino","year":"2016","journal-title":"Environ.\nSci. Technol."},{"issue":"6","key":"2026081212021961100_cit33","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1021\/acs.estlett.2c00206","article-title":"Communicating Confidence of Per- and Polyfluoroalkyl\nSubstance Identification via High-Resolution Mass Spectrometry","volume":"9","author":"Charbonnet","year":"2022","journal-title":"Environ. Sci. Technol. Lett."},{"key":"2026081212021961100_cit34","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1016\/j.chemosphere.2016.11.127","article-title":"Multianalyte\nprofiling of per- and polyfluoroalkyl substances (PFASs) in liquid\ncommercial products","volume":"171","author":"Favreau","year":"2017","journal-title":"Chemosphere"},{"issue":"8","key":"2026081212021961100_cit35","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1016\/j.chemosphere.2012.03.035","article-title":"Perfluoroalkyl\nand polyfluoroalkyl\nsubstances (PFASs) in consumer products in Norway - a pilot study","volume":"88","author":"Herzke","year":"2012","journal-title":"Chemosphere"},{"issue":"8","key":"2026081212021961100_cit36","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1124\/dmd.106.009399","article-title":"N-glucuronidation\nof perfluorooctanesulfonamide\nby human, rat, dog, and monkey liver microsomes and by expressed rat\nand human UDP-glucuronosyltransferases","volume":"34","author":"Xu","year":"2006","journal-title":"Drug\nMetab. Dispos."},{"issue":"6","key":"2026081212021961100_cit37","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1021\/tx034222x","article-title":"N-Ethyl-N-(2-hydroxyethyl)\u00adperfluorooctanesulfonamide\nby Rat Liver Microsomes, Cytosol, and Slices and by Expressed Rat\nand Human Cytochromes P450","volume":"17","author":"Xu","year":"2004","journal-title":"Chem. Res. Toxicol."},{"key":"2026081212021961100_cit38","doi-asserted-by":"publisher","first-page":"74","DOI":"10.3390\/toxics11010074","article-title":"PFAS Biotransformation\nPathways: A Species Comparison Study","volume":"11","author":"Kolanczyk","year":"2023","journal-title":"Toxics"},{"key":"2026081212021961100_cit39","doi-asserted-by":"publisher","first-page":"143522","DOI":"10.1016\/j.scitotenv.2020.143522","article-title":"Is a liver comparable to a liver?\nA comparison of different rat-derived S9-fractions with a biotechnological\nanimal-free alternative in the Ames fluctuation assay","volume":"759","author":"Brendt","year":"2021","journal-title":"Sci. Total Environ."}],"container-title":["Environmental Science &amp;\nTechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.est.4c07750","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/esthag\/article-pdf\/59\/1\/119\/66514934\/es4c07750.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/esthag\/article-pdf\/59\/1\/119\/66514934\/es4c07750.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T16:02:24Z","timestamp":1786550544000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/esthag\/article\/59\/1\/119\/3661121\/Expanding-PFAS-Identification-with-Transformation"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,20]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12,20]]},"published-print":{"date-parts":[[2025,1,14]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.est.4c07750","relation":{},"ISSN":["0013-936X","1520-5851"],"issn-type":[{"value":"0013-936X","type":"print"},{"value":"1520-5851","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,20]]}}}