{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:12:17Z","timestamp":1788437537362,"version":"build-2803163510"},"reference-count":45,"publisher":"American Chemical Society (ACS)","issue":"34","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Per- and polyfluoroalkyl substances (PFAS) accumulate in breast milk and pose a distinct hazard to breastfed infants, whose immature renal clearance substantially prolongs internal PFAS half-lives. We developed a two-compartment physiologically based pharmacokinetic (PBPK) model incorporating a postnatal glomerular filtration rate (GFR) maturation function to estimate individual-level infant blood PFAS concentrations from breast milk ingestion, and applied it to two prospective Korean birth cohorts (Cohort A: n = 221, 2018; Cohort B: n = 204, 2023). Five PFAS\u2500perfluorodecanoic acid (PFDeA), perfluorohexanesulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), and perfluorooctanesulfonate (PFOS)\u2500were quantified by LC\u2013MS\/MS. Age-adjusted ANCOVA revealed compound-specific temporal shifts: PFHxS declined 66.7% (adjusted ratio: 0.33; p &amp;lt; 0.001), while PFNA and PFDeA increased 161.5% and 135.1% (both p &amp;lt; 0.001), evidencing regrettable substitution. PFOA and PFOS remained unchanged (both p &amp;gt; 0.69). Global sensitivity analysis confirmed that breast milk concentration and daily intake volume dominated model output uncertainty (|PRCC| = 0.82\u20130.91), whereas pharmacokinetic clearance parameters (elimination half-life and GFR maturation) had negligible influence on peak concentration (|PRCC| \u2264 0.05), reflecting accumulation-dominated kinetics over the first six months. External benchmarking against Fromme et al. (2010) yielded predicted-to-observed ratios of 0.67 and 0.61, respectively, within the prespecified acceptable range of 0.5\u20132.0. PBPK-estimated four-compound daily intake exceeded the EFSA (2020) TWI daily equivalent of 0.63 ng\/kg\/day (median multiples: 61\u00d7 and 77\u00d7). These findings demonstrate that compound-specific regulatory action has not reduced aggregate infant fluorinated burden and highlight the urgent need for infant-specific PFAS reference values accounting for GFR immaturity.<\/jats:p>","DOI":"10.1021\/acs.est.6c05230","type":"journal-article","created":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:18:14Z","timestamp":1787444294000},"page":"23826-23839","source":"Crossref","is-referenced-by-count":0,"title":["Two-Compartment\nPhysiologically Based Pharmacokinetic\nModeling with Postnatal Glomerular Filtration Rate Maturation to Estimate\nIndividual-Level Infant Blood Polyfluoroalkyl Substances Concentrations\nfrom Breast Milk: Persistent Burden amid Shifting Compound Profiles\nin Korean Cohorts (2018\u20132023)"],"prefix":"10.1021","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6586-7244","authenticated-orcid":true,"given":"Ju Hee","family":"Kim","sequence":"first","affiliation":[{"name":"Kyung Hee University , , ,","place":["Seoul, Republic of Korea, 02447"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jisu","family":"Jung","sequence":"additional","affiliation":[{"name":"Kyung Hee University , , ,","place":["Seoul, Republic of Korea, 02447"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jungmin","family":"Kwak","sequence":"additional","affiliation":[{"name":"Kyung Hee University , , ,","place":["Seoul, Republic of Korea, 02447"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"issue":"16","key":"2026090307124808000_cit1","doi-asserted-by":"publisher","first-page":"11172","DOI":"10.1021\/acs.est.2c02765","article-title":"Outside the\nSafe Operating Space of a New Planetary Boundary for Per- and Polyfluoroalkyl\nSubstances (PFAS)","volume":"56","author":"Cousins","year":"2022","journal-title":"Environ. Sci. Technol."},{"issue":"2","key":"2026090307124808000_cit2","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/s41370-018-0094-1","article-title":"A review of the\npathways of human exposure to poly-\nand perfluoroalkyl substances (PFASs) and present understanding of\nhealth effects","volume":"29","author":"Sunderland","year":"2019","journal-title":"J. Expo Sci. Environ. Epidemiol"},{"key":"2026090307124808000_cit3","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.chemosphere.2014.05.044","article-title":"Helsingor\nstatement on poly- and\nperfluorinated alkyl substances (PFASs)","volume":"114","author":"Scheringer","year":"2014","journal-title":"Chemosphere"},{"issue":"Pt 1","key":"2026090307124808000_cit4","doi-asserted-by":"publisher","first-page":"119777","DOI":"10.1016\/j.envres.2024.119777","article-title":"Temporal trends\nof per- and polyfluoroalkyl\nsubstances concentrations: Insights from Australian human biomonitoring\n2002\u20132021 and the U.S. NHANES programs 2003\u20132018","volume":"262","author":"Taucare","year":"2024","journal-title":"Environ. Res."},{"issue":"1","key":"2026090307124808000_cit5","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1136\/oemed-2017-104651","article-title":"Half-lives of PFOS, PFHxS and PFOA\nafter end of exposure to contaminated drinking water","volume":"75","author":"Li","year":"2018","journal-title":"Occup. Environ. Med."},{"issue":"9","key":"2026090307124808000_cit6","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.1289\/ehp.10009","article-title":"Half-life of serum\nelimination of perfluorooctanesulfonate,perfluorohexanesulfonate,\nand perfluorooctanoate in retired fluorochemical production workers","volume":"115","author":"Olsen","year":"2007","journal-title":"Environ. Health Perspect."},{"issue":"9","key":"2026090307124808000_cit7","doi-asserted-by":"publisher","DOI":"10.2903\/j.efsa.2020.6223","article-title":"Risk to human health related to the\npresence of perfluoroalkyl substances in food","volume":"18","author":"Schrenk","year":"2020","journal-title":"EFSA J."},{"issue":"3","key":"2026090307124808000_cit8","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":"2020","journal-title":"Environ. Toxicol.\nChem."},{"issue":"1","key":"2026090307124808000_cit9","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1080\/1547691X.2017.1360968","article-title":"Estimated exposures to perfluorinated\ncompounds in infancy predict attenuated vaccine antibody concentrations\nat age 5-years","volume":"14","author":"Grandjean","year":"2017","journal-title":"J. Immunotoxicol."},{"issue":"7","key":"2026090307124808000_cit10","doi-asserted-by":"publisher","first-page":"691","DOI":"10.3390\/ijerph14070691","article-title":"Exposure\nto Perfluorinated Alkyl\nSubstances and Health Outcomes in Children: A Systematic Review of\nthe Epidemiologic Literature","volume":"14","author":"Rappazzo","year":"2017","journal-title":"Int. J. Environ.\nRes. 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Nephrol."},{"issue":"S10","key":"2026090307124808000_cit14","doi-asserted-by":"publisher","first-page":"S10","DOI":"10.1002\/jcph.1284","article-title":"Developmental Changes in Pharmacokinetics and Pharmacodynamics","volume":"58","author":"van den Anker","year":"2018","journal-title":"J. Clin. Pharmacol."},{"issue":"12","key":"2026090307124808000_cit15","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1007\/s40262-015-0298-7","article-title":"Effect of Kidney Function\non Drug Kinetics and Dosing in Neonates, Infants, and Children","volume":"54","author":"Rodieux","year":"2015","journal-title":"Clin. Pharmacokinet."},{"issue":"1","key":"2026090307124808000_cit16","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.yrtph.2007.10.012","article-title":"Development and specification of\nphysiologically based\npharmacokinetic models for use in risk assessment","volume":"50","author":"Clewell","year":"2008","journal-title":"Regul. Toxicol. Pharmacol."},{"issue":"4","key":"2026090307124808000_cit17","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1016\/j.reprotox.2011.04.006","article-title":"3rd. Comparison and evaluation of\npharmacokinetics of PFOA and PFOS in the adult rat using a physiologically\nbased pharmacokinetic model","volume":"33","author":"Loccisano","year":"2012","journal-title":"Reprod. Toxicol."},{"issue":"7","key":"2026090307124808000_cit18","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1124\/dmd.115.068031","article-title":"Physiologically\nBased Pharmacokinetic Modeling in Pediatric\nOncology Drug Development","volume":"44","author":"Rioux","year":"2016","journal-title":"Drug Metab. Dispos."},{"key":"2026090307124808000_cit19","unstructured":"UNEP.\n          . Listing of perfluorooctanoic acid\n(PFOA), its salts\nand PFOA-related compounds (UNEP\/POPS\/COP. 9\/SC-9\/12). In  Proceedings of the Ninth Meeting of the Conference of\nthe Parties to the Stockholm Convention on Persistent Organic Pollutants; UNEP: Geneva, Switzerland, 2019."},{"key":"2026090307124808000_cit20","volume-title":"Act on Registration and Evaluation\nof Chemical Substances","author":"Ministry of Environment, R. o. K.","year":"2019"},{"issue":"5","key":"2026090307124808000_cit21","doi-asserted-by":"publisher","first-page":"2508","DOI":"10.1021\/acs.est.6b04806","article-title":"A Never-Ending Story\nof Per- and Polyfluoroalkyl Substances (PFASs)?","volume":"51","author":"Wang","year":"2017","journal-title":"Environ. Sci. Technol."},{"issue":"12","key":"2026090307124808000_cit22","doi-asserted-by":"publisher","first-page":"2345","DOI":"10.1039\/D0EM00291G","article-title":"An overview of the uses of per- and polyfluoroalkyl substances (PFAS)","volume":"22","author":"Gluge","year":"2020","journal-title":"Environ. Sci.: Processes Impacts"},{"key":"2026090307124808000_cit23","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.scitotenv.2017.08.094","article-title":"Perfluoroalkyl\nsubstances (PFASs) in breast milk from Korea: Time-course trends,\ninfluencing factors, and infant exposure","volume":"612","author":"Lee","year":"2018","journal-title":"Sci.\nTotal Environ."},{"issue":"1","key":"2026090307124808000_cit24","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.yrtph.2010.12.004","article-title":"3rd. Evaluation\nand prediction of pharmacokinetics of PFOA and PFOS in the monkey\nand human using a PBPK model","volume":"59","author":"Loccisano","year":"2011","journal-title":"Regul. Toxicol.\nPharmacol."},{"issue":"2","key":"2026090307124808000_cit25","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1093\/toxsci\/kft204","article-title":"Dosimetric anchoring\nof in vivo and in vitro studies for perfluorooctanoate\nand perfluorooctanesulfonate","volume":"136","author":"Wambaugh","year":"2013","journal-title":"Toxicol. Sci."},{"key":"2026090307124808000_cit26","article-title":"WHO child\ngrowth standards: length\/height-for-age,\nweight-for-age, weight-for-length, weight-for-height and body mass\nindex-for-age","volume-title":"Methods and Development","author":"World Health Organization.","year":"2006"},{"issue":"2","key":"2026090307124808000_cit27","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1289\/ehp.0901252","article-title":"Rate of decline\nin serum PFOA concentrations after\ngranular activated carbon filtration at two public water systems in\nOhio and West Virginia","volume":"118","author":"Bartell","year":"2010","journal-title":"Environ. Health Perspect."},{"issue":"18","key":"2026090307124808000_cit28","doi-asserted-by":"publisher","first-page":"10619","DOI":"10.1021\/es401905e","article-title":"Biomonitoring of\nperfluoroalkyl acids in human urine and estimates of biological half-life","volume":"47","author":"Zhang","year":"2013","journal-title":"Environ. Sci. Technol."},{"key":"2026090307124808000_cit29","doi-asserted-by":"publisher","first-page":"117743","DOI":"10.1016\/j.envres.2023.117743","article-title":"Estimation\nof per- and polyfluoroalkyl substances (PFAS) half-lives in human\nstudies: a systematic review and meta-analysis","volume":"242","author":"Rosato","year":"2024","journal-title":"Environ. Res."},{"issue":"2","key":"2026090307124808000_cit30","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1093\/toxsci\/kfq219","article-title":"Characterization\nof cellular uptake\nof perfluorooctanoate via organic anion-transporting polypeptide 1A2,\norganic anion transporter 4, and urate transporter 1 for their potential\nroles in mediating human renal reabsorption of perfluorocarboxylates","volume":"117","author":"Yang","year":"2010","journal-title":"Toxicol. Sci."},{"issue":"5","key":"2026090307124808000_cit31","doi-asserted-by":"publisher","first-page":"3214","DOI":"10.1021\/acs.est.1c07176","article-title":"Effect of Enterohepatic Circulation\non the Accumulation of Per- and Polyfluoroalkyl Substances: Evidence\nfrom Experimental and Computational Studies","volume":"56","author":"Cao","year":"2022","journal-title":"Environ. Sci. Technol."},{"issue":"2","key":"2026090307124808000_cit32","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1542\/peds.58.2.259","article-title":"A simple estimate\nof glomerular filtration rate in children derived from body length\nand plasma creatinine","volume":"58","author":"Schwartz","year":"1976","journal-title":"Pediatrics"},{"issue":"1","key":"2026090307124808000_cit33","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1208\/ps020103","article-title":"Maturation\nand growth of renal function: dosing renally cleared drugs in children","volume":"2","author":"Hayton","year":"2000","journal-title":"AAPS PharmSci"},{"issue":"18","key":"2026090307124808000_cit34","doi-asserted-by":"publisher","first-page":"7123","DOI":"10.1021\/es101184f","article-title":"Pre-and\npostnatal exposure to perfluorinated compounds (PFCs)","volume":"44","author":"Fromme","year":"2010","journal-title":"Environ. Sci. Technol."},{"issue":"7","key":"2026090307124808000_cit35","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1016\/j.envint.2011.05.001","article-title":"Comparison on gestation and lactation exposure of perfluorinated\ncompounds for newborns","volume":"37","author":"Liu","year":"2011","journal-title":"Environ. Int."},{"issue":"1","key":"2026090307124808000_cit36","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/S0951-8320(03)00058-9","article-title":"Latin hypercube\nsampling and the propagation of uncertainty\nin analyses of complex systems","volume":"81","author":"Helton","year":"2003","journal-title":"Reliab. Eng.\nSyst. Saf."},{"issue":"6","key":"2026090307124808000_cit37","doi-asserted-by":"publisher","first-page":"2131","DOI":"10.1007\/s00204-020-02715-4","article-title":"Internal exposure\nto perfluoroalkyl substances (PFASs) and biological markers in 101\nhealthy 1-year-old children: associations between levels of perfluorooctanoic\nacid (PFOA) and vaccine response","volume":"94","author":"Abraham","year":"2020","journal-title":"Arch. Toxicol."},{"issue":"2","key":"2026090307124808000_cit38","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1021\/acs.est.5b04399","article-title":"A Simple\nPharmacokinetic Model of Prenatal and Postnatal Exposure to Perfluoroalkyl\nSubstances (PFASs)","volume":"50","author":"Verner","year":"2016","journal-title":"Environ. Sci. Technol."},{"issue":"2","key":"2026090307124808000_cit39","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1021\/acs.est.3c07415","article-title":"Binding\nof Per- and Polyfluoroalkyl Substances (PFAS) to Serum Proteins: Implications\nfor Toxicokinetics in Humans","volume":"58","author":"Fischer","year":"2024","journal-title":"Environ. Sci.\nTechnol."},{"issue":"3","key":"2026090307124808000_cit40","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1007\/s00467-020-04770-6","article-title":"Estimated glomerular\nfiltration rate in children: adapting existing equations for a specific\npopulation","volume":"36","author":"Holness","year":"2021","journal-title":"Pediatr. Nephrol."},{"key":"2026090307124808000_cit41","volume-title":"Health Consultation: Evaluation of Per-\nand Polyfluoroalkyl Substances (PFAS) Detected in Private Residential\nDrinking Water Wells Located Within 1 Mile of the Pease International\nTradeport: Pease Air Force Base Portsmouth, Newington, and Greenland,\nNew Hampshire","author":"United States. Agency for Toxic Substances and Disease Registry. Division of Community Health Investigations.","year":"2022"},{"key":"2026090307124808000_cit42","unstructured":"Zeilmaker, M. J., Fragki, S., Verbruggen, E. M. J., Bokkers, B. G. H., Lijzen, J. P. A.\n          Mixture\nExposure\nto PFAS: A Relative Potency Factor Approach; National Institute for Public Health and the Environment (RIVM): Bilthoven; 2018."},{"issue":"1","key":"2026090307124808000_cit43","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1080\/15287394.2012.722523","article-title":"Development of PBPK models for PFOA\nand PFOS for human\npregnancy and lactation life stages","volume":"76","author":"Loccisano","year":"2013","journal-title":"J. Toxicol.\nEnviron. Health, Part A"},{"key":"2026090307124808000_cit44","doi-asserted-by":"publisher","first-page":"108621","DOI":"10.1016\/j.envint.2024.108621","article-title":"Estimating the dynamic early life\nexposure to PFOA and PFOS of the HELIX children: Emerging profiles\nvia prenatal exposure, breastfeeding, and diet","volume":"186","author":"Ratier","year":"2024","journal-title":"Environ. Int."},{"issue":"12","key":"2026090307124808000_cit45","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1289\/ehp.1408837","article-title":"Associations\nof Perfluoroalkyl Substances (PFAS) with Lower Birth Weight: An Evaluation\nof Potential Confounding by Glomerular Filtration Rate Using a Physiologically\nBased Pharmacokinetic Model (PBPK)","volume":"123","author":"Verner","year":"2015","journal-title":"Environ.\nHealth Perspect."}],"container-title":["Environmental Science &amp;\nTechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.est.6c05230","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/esthag\/article-pdf\/60\/34\/23826\/67014375\/acs.est.6c05230.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/esthag\/article-pdf\/60\/34\/23826\/67014375\/acs.est.6c05230.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:12:55Z","timestamp":1788433975000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/esthag\/article\/60\/34\/23826\/5288292\/Two-Compartment-Physiologically-Based"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,21]]},"references-count":45,"journal-issue":{"issue":"34","published-online":{"date-parts":[[2026,8,21]]},"published-print":{"date-parts":[[2026,9,1]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.est.6c05230","relation":{},"ISSN":["0013-936X","1520-5851"],"issn-type":[{"value":"0013-936X","type":"print"},{"value":"1520-5851","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,21]]}}}