{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T18:03:04Z","timestamp":1789840984460,"version":"4.0.1"},"reference-count":105,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:00:00Z","timestamp":1777161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC3703205"],"award-info":[{"award-number":["2022YFC3703205"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Per- and polyfluoroalkyl substances (PFAS) are a class of synthetic chemicals notable for their high persistence and extensive applications. With the advancement of detection technologies in recent years, PFAS have been frequently identified in environmental media and human biological samples, raising significant global concerns about their potential health risks. PFAS exhibit distinctive toxicokinetic behaviors, including efficient absorption, strong protein binding, limited metabolism, and slow excretion, which lead to prolonged biological half-lives and considerable bioaccumulation in humans. These properties contribute to a range of adverse health outcomes, such as endocrine disruption, immune suppression, liver damage, reproductive toxicity, carcinogenic potential, and cardiovascular disease. This review synthesizes evidence on PFAS-associated health risks from a multisystem, multitarget perspective, elucidating the key molecular pathways involved, thereby providing a scientific basis for understanding their complex toxicological effects and for developing targeted prevention and control strategies. Future research should prioritize characterizing the toxicological profiles of individual PFAS compounds, evaluating the health impacts of combined (mixture) exposures, and assessing risks associated with chronic, low-dose exposure to support the development of public health strategies and regulatory decisions.<\/jats:p>","DOI":"10.3390\/toxics14050374","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T09:55:39Z","timestamp":1777370139000},"page":"374","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Toxicological Effects and Health Impacts of Per- and Polyfluoroalkyl Substances (PFAS) in Humans"],"prefix":"10.3390","volume":"14","author":[{"given":"Jie","family":"Ma","sequence":"first","affiliation":[{"name":"Center for Environmental Health Risk Assessment and Research, Chinese Research Academy of Environmental Sciences, Beijing 100012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Gao","sequence":"additional","affiliation":[{"name":"Center for Environmental Health Risk Assessment and Research, Chinese Research Academy of Environmental Sciences, Beijing 100012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5191-4400","authenticated-orcid":false,"given":"Bitan","family":"Meng","sequence":"additional","affiliation":[{"name":"Center for Environmental Health Risk Assessment and Research, Chinese Research Academy of Environmental Sciences, Beijing 100012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinni","family":"Wei","sequence":"additional","affiliation":[{"name":"Center for Environmental Health Risk Assessment and Research, Chinese Research Academy of Environmental Sciences, Beijing 100012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Zhao","sequence":"additional","affiliation":[{"name":"Center for Environmental Health Risk Assessment and Research, Chinese Research Academy of Environmental Sciences, Beijing 100012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaiming","family":"Ge","sequence":"additional","affiliation":[{"name":"Center for Environmental Health Risk Assessment and Research, Chinese Research Academy of Environmental Sciences, Beijing 100012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"eBioMedicine (2023). Forever Chemicals: The Persistent Effects of Perfluoroalkyl and Polyfluoroalkyl Substances on Human Health. eBioMedicine, 95, 104806.","DOI":"10.1016\/j.ebiom.2023.104806"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"142168","DOI":"10.1016\/j.chemosphere.2024.142168","article-title":"Individual and Joint Associations of Per- and Polyfluoroalkyl Substances (PFAS) with Gallstone Disease in Adults: A Cross-Sectional Study","volume":"358","author":"Shi","year":"2024","journal-title":"Chemosphere"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e37003","DOI":"10.1016\/j.heliyon.2024.e37003","article-title":"Exploring the Environmental Contamination Toxicity and Potential Carcinogenic Pathways of Perfluorinated and Polyfluoroalkyl Substances (PFAS): An Integrated Network Toxicology and Molecular Docking Strategy","volume":"10","author":"Lin","year":"2024","journal-title":"Heliyon"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Lindell, A.E., Grie\u00dfhammer, A., Michaelis, L., Papagiannidis, D., Ochner, H., Kamrad, S., Guan, R., Blasche, S., Ventimiglia, L., and Ramachandran, B. (2024). Extensive PFAS Accumulation by Human Gut Bacteria. bioRxiv.","DOI":"10.1101\/2024.09.17.613493"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"eabg9065","DOI":"10.1126\/science.abg9065","article-title":"Per- and Polyfluoroalkyl Substances in the Environment","volume":"375","author":"Evich","year":"2022","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"109117","DOI":"10.1016\/j.envint.2024.109117","article-title":"Per- and Polyfluoroalkyl Substances (PFAS): Trends in Mass Spectrometric Analysis for Human Biomonitoring and Exposure Patterns from Recent Global Cohort Studies","volume":"194","author":"Kee","year":"2024","journal-title":"Environ. Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"100879","DOI":"10.1016\/j.eti.2020.100879","article-title":"Recent Advances in the Analysis of Per- and Polyfluoroalkyl Substances (PFAS)\u2014A Review","volume":"19","author":"Sobhani","year":"2020","journal-title":"Environ. Technol. Innov."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"176158","DOI":"10.1016\/j.scitotenv.2024.176158","article-title":"Per- and Polyfluoroalkyl Substances (PFAS) and Cancer: Detection Methodologies, Epidemiological Insights, Potential Carcinogenic Mechanisms, and Future Perspectives","volume":"953","author":"Zheng","year":"2024","journal-title":"Sci. Total Environ."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.scib.2023.01.003","article-title":"Novel Strategies and Approaches toward Toxicity Assessment: A Key Factor for Safety Assessment and Management of per- and Polyfluoroalkyl Substances","volume":"68","author":"Lu","year":"2023","journal-title":"Sci. Bull."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e535","DOI":"10.1016\/S2542-5196(22)00090-0","article-title":"Pollution and Health: A Progress Update","volume":"6","author":"Fuller","year":"2022","journal-title":"Lancet Planet. Health"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/s41370-018-0094-1","article-title":"A Review of the Pathways of Human Exposure to Poly- and Perfluoroalkyl Substances (PFASs) and Present Understanding of Health Effects","volume":"29","author":"Sunderland","year":"2019","journal-title":"J. Expo. Sci. Environ. Epidemiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"108844","DOI":"10.1016\/j.envint.2024.108844","article-title":"Human Exposure to Per- and Polyfluoroalkyl Substances (PFAS) via the Consumption of Fish Leads to Exceedance of Safety Thresholds","volume":"190","author":"Langberg","year":"2024","journal-title":"Environ. Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1080\/10643389.2023.2223118","article-title":"A Critical Review on the Bioaccumulation, Transportation, and Elimination of per- and Polyfluoroalkyl Substances in Human Beings","volume":"54","author":"Lu","year":"2024","journal-title":"Crit. Rev. Environ. Sci. Technol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Bonato, M., Corr\u00e0, F., Bellio, M., Guidolin, L., Tallandini, L., Irato, P., and Santovito, G. (2020). PFAS Environmental Pollution and Antioxidant Responses: An Overview of the Impact on Human Field. Int. J. Environ. Res. Public Health, 17.","DOI":"10.20944\/preprints202010.0086.v1"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"121181","DOI":"10.1016\/j.envres.2025.121181","article-title":"A Review of the Occurrence and Distribution of Per- and Polyfluoroalkyl Substances (PFAS) in Human Organs and Fetal Tissues","volume":"272","author":"Domingo","year":"2025","journal-title":"Environ. Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"MacMillan, D.K., Wetmore, B.A., Dasgupta, S., and Baldwin, W.S. (2024). Closing the Gaps in Understanding PFAS Toxicology and Metabolism. Toxics, 13.","DOI":"10.3390\/toxics13010019"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"121044","DOI":"10.1016\/j.watres.2023.121044","article-title":"The Untold Story of PFAS Alternatives: Insights into the Occurrence, Ecotoxicological Impacts, and Removal Strategies in the Aquatic Environment","volume":"250","author":"Hamid","year":"2024","journal-title":"Water Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Alvarez, M.E., Antwi-Boasiako, C., and Keating, A.F. (2024). Effects of Per- and Polyfluoroalkylated Substances on Female Reproduction. Toxics, 12.","DOI":"10.3390\/toxics12070455"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Qu, R., Wang, J., Li, X., Zhang, Y., Yin, T., and Yang, P. (2024). Per- and Polyfluoroalkyl Substances (PFAS) Affect Female Reproductive Health: Epidemiological Evidence and Underlying Mechanisms. Toxics, 12.","DOI":"10.3390\/toxics12090678"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Barali\u0107, K., Petkovski, T., Pileti\u0107, N., Mari\u0107, \u0110., Buha Djordjevic, A., Antonijevi\u0107, B., and \u0110uki\u0107-\u0106osi\u0107, D. (2024). Exploring Toxicity of Per- and Polyfluoroalkyl Substances (PFAS) Mixture Through ADMET and Toxicogenomic In Silico Analysis: Molecular Insights. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252212333"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/S1470-2045(23)00622-8","article-title":"Carcinogenicity of Perfluorooctanoic Acid and Perfluorooctanesulfonic Acid","volume":"25","author":"Zahm","year":"2024","journal-title":"Lancet Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1021\/acs.estlett.1c00481","article-title":"The Air That We Breathe: Neutral and Volatile PFAS in Indoor Air","volume":"8","author":"Becanova","year":"2021","journal-title":"Environ. Sci. Technol. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.shaw.2026.01.002","article-title":"Distribution and Concentration of Airborne Per- and Polyfluoroalkyl Substances (PFAS) in Indoor and Outdoor Environments: A Systematic Review","volume":"17","author":"Lee","year":"2026","journal-title":"Saf. Health Work"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"143372","DOI":"10.1016\/j.chemosphere.2024.143372","article-title":"Per- and Polyfluoroalkyl Substances (PFAS) in Floor Dust from Different Indoor Environments in Australia: Levels, Variation, and Human Exposure Risks","volume":"366","author":"Li","year":"2024","journal-title":"Chemosphere"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"127767","DOI":"10.1016\/j.envpol.2026.127767","article-title":"Ionic PFAS in PM2.5 and Dust: Insights on Indoor-Outdoor Profiles and Distribution","volume":"395","author":"Li","year":"2026","journal-title":"Environ. Pollut."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"119478","DOI":"10.1016\/j.envpol.2022.119478","article-title":"Dermal Uptake: An Important Pathway of Human Exposure to Perfluoroalkyl Substances?","volume":"307","author":"Abdallah","year":"2022","journal-title":"Environ. Pollut."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"076002","DOI":"10.1289\/EHP11885","article-title":"A State-of-the-Science Review of Interactions of Per- and Polyfluoroalkyl Substances (PFAS) with Renal Transporters in Health and Disease: Implications for Population Variability in PFAS Toxicokinetics","volume":"131","author":"Niu","year":"2023","journal-title":"Environ. Health Perspect."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Starnes, H.M., Rock, K.D., Jackson, T.W., and Belcher, S.M. (2022). A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior. Front. Toxicol., 4.","DOI":"10.3389\/ftox.2022.881584"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1002\/etc.4935","article-title":"PFAS Exposure Pathways for Humans and Wildlife: A Synthesis of Current Knowledge and Key Gaps in Understanding","volume":"40","author":"Armitage","year":"2020","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"117336","DOI":"10.1016\/j.taap.2025.117336","article-title":"Estimation of Species- and Sex-Specific PFAS Pharmacokinetics in Mice, Rats, and Non-Human Primates Using a Bayesian Hierarchical Methodology","volume":"499","author":"Zurlinden","year":"2025","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"142390","DOI":"10.1016\/j.chemosphere.2024.142390","article-title":"Evaluation of 14 PFAS for Permeability and Organic Anion Transporter Interactions: Implications for Renal Clearance in Humans","volume":"361","author":"Ryu","year":"2024","journal-title":"Chemosphere"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1007\/s00204-022-03428-6","article-title":"Perfluoroalkyl Substances (PFASs) Are Substrates of the Renal Human Organic Anion Transporter 4 (OAT4)","volume":"97","author":"Louisse","year":"2023","journal-title":"Arch. Toxicol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1007\/s00216-019-02263-6","article-title":"Simultaneous Determination of Perfluoroalkyl Substances and Bile Acids in Human Serum Using Ultra-High-Performance Liquid Chromatography\u2013Tandem Mass Spectrometry","volume":"412","author":"Dickens","year":"2020","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"125634","DOI":"10.1016\/j.envpol.2025.125634","article-title":"Insights into Toxicological Mechanisms of Per-\/Polyfluoroalkyl Substances by Using Omics-Centered Approaches","volume":"367","author":"Zhou","year":"2025","journal-title":"Environ. Pollut."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"126764","DOI":"10.1016\/j.chemosphere.2020.126764","article-title":"Perfluoroalkyl Substances Cause Leydig Cell Dysfunction as Endocrine Disruptors","volume":"253","author":"Zhu","year":"2020","journal-title":"Chemosphere"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.tem.2024.07.021","article-title":"Per- and Polyfluoroalkyl Substances as Persistent Pollutants with Metabolic and Endocrine-Disrupting Impacts","volume":"36","author":"Gaillard","year":"2025","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"117962","DOI":"10.1016\/j.ecoenv.2025.117962","article-title":"Emerging Per- and Polyfluoroalkyl Substance Perfluoro-(3,5,7,9-Tetraoxadecanoic) Acid (PFO4DA) Impairs Steroidogenesis and Spermatogenesis by Suppressing StAR and CYP11A1 Expression in Mice","volume":"292","author":"Mutalifu","year":"2025","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"175958","DOI":"10.1016\/j.scitotenv.2024.175958","article-title":"Association between PFAS Exposure and Thyroid Health: A Systematic Review and Meta-Analysis for Adolescents, Pregnant Women, Adults and Toxicological Evidence","volume":"953","author":"Du","year":"2024","journal-title":"Sci. Total Environ."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"7920","DOI":"10.1038\/s41598-025-92678-2","article-title":"Integrated Computational Analysis of Molecular Mechanisms Underlying Perfluorooctane Sulfonic Acid Induced Thyroid Toxicity","volume":"15","author":"Li","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Roy, S., Moran, J., Danasekaran, K., O\u2019Brien, K., and Dakshanamurthy, S. (2024). Large-Scale Screening of Per- and Polyfluoroalkyl Substance Binding Interactions and Their Mixtures with Nuclear Receptors. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25158241"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Coperchini, F., Croce, L., Ricci, G., Magri, F., Rotondi, M., Imbriani, M., and Chiovato, L. (2021). Thyroid Disrupting Effects of Old and New Generation PFAS. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.612320"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.chemosphere.2017.06.024","article-title":"Endocrine-Disrupting Activity of per- and Polyfluoroalkyl Substances: Exploring Combined Approaches of Ligand and Structure Based Modeling","volume":"184","author":"Kar","year":"2017","journal-title":"Chemosphere"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9130","DOI":"10.1021\/acs.est.3c01094","article-title":"Linking Transthyretin-Binding Chemicals and Free Thyroid Hormones: In Vitro to In Vivo Extrapolation Based on a Competitive Binding Model","volume":"57","author":"Huang","year":"2023","journal-title":"Environ. Sci. Technol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1002\/etc.4890","article-title":"Per- and Polyfluoroalkyl Substance Toxicity and Human Health Review: Current State of Knowledge and Strategies for Informing Future Research","volume":"40","author":"Fenton","year":"2020","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_45","first-page":"39554","article-title":"Per- and Polyfluoroalkyl (PFAS) Disruption of Thyroid Hormone Synthesis","volume":"9","author":"Bali","year":"2024","journal-title":"ACS Omega"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"153031","DOI":"10.1016\/j.tox.2021.153031","article-title":"Per- and Poly-Fluoroalkyl Substances (PFAS) and Female Reproductive Outcomes: PFAS Elimination, Endocrine-Mediated Effects, and Disease","volume":"465","author":"Rickard","year":"2022","journal-title":"Toxicology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"128243","DOI":"10.1016\/j.jhazmat.2022.128243","article-title":"In Vitro Characterization of the Endocrine Disrupting Effects of Per- and Poly-Fluoroalkyl Substances (PFASs) on the Human Androgen Receptor","volume":"429","author":"Tachachartvanich","year":"2022","journal-title":"J. Hazard. Mater."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1080\/10408444.2025.2501420","article-title":"Per- and Polyfluoroalkyl Substances (PFAS): Immunotoxicity at the Primary Sites of Exposure","volume":"55","author":"Arnesdotter","year":"2025","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s12940-022-00958-5","article-title":"Consideration of Pathways for Immunotoxicity of Per- and Polyfluoroalkyl Substances (PFAS)","volume":"22","author":"Ehrlich","year":"2023","journal-title":"Environ. Health"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1265\/ehpm.24-00047","article-title":"Is Japan at Low Risk for PFAS Immunotoxicity?: Human Biomonitoring Study in Contaminated Areas in Japan","volume":"29","author":"Lyu","year":"2024","journal-title":"Environ. Health Prev. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1186\/s13643-024-02596-z","article-title":"Childhood PFAS Exposure and Immunotoxicity: A Systematic Review and Meta-Analysis of Human Studies","volume":"13","author":"Antoniou","year":"2024","journal-title":"Syst. Rev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"119221","DOI":"10.1016\/j.envres.2024.119221","article-title":"Immune Cell Profiles Associated with Human Exposure to Perfluorinated Compounds (PFAS) Suggest Changes in Natural Killer, T Helper, and T Cytotoxic Cell Subpopulations","volume":"256","author":"Tursi","year":"2024","journal-title":"Environ. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"139204","DOI":"10.1016\/j.chemosphere.2023.139204","article-title":"Mixtures of Per- and Poly-Fluoroalkyl Substances (PFAS) Reduce the in Vitro Activation of Human T Cells and Basophils","volume":"336","author":"Maddalon","year":"2023","journal-title":"Chemosphere"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"143075","DOI":"10.1016\/j.chemosphere.2024.143075","article-title":"Perfluoroalkyl Substances and Immunotoxicity: An in Vitro Structure-Activity Relationship Study in THP-1-Derived Monocytes and Macrophages","volume":"364","author":"Amstutz","year":"2024","journal-title":"Chemosphere"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"10841","DOI":"10.1021\/acs.est.5c01138","article-title":"Integration of Animal, Population, and Toxicogenomic Evidence on the Hematotoxic and Immunosuppressive Effects of Environmental Exposure to PFAS Mixtures in Adolescents","volume":"59","author":"Du","year":"2025","journal-title":"Environ. Sci. Technol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Martano, P., Mahdi, S., Zhou, T., Barazandegan, Y., Iha, R., Do, H., Burken, J., Nam, P., Yang, Q., and Mu, R. (2025). Visceral, Neural, and Immunotoxicity of Per- and Polyfluoroalkyl Substances: A Mini Review. Toxics, 13.","DOI":"10.3390\/toxics13080658"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1007\/s00204-022-03405-z","article-title":"Perfluoroalkyl Substances (PFASs) Decrease the Expression of Recombination-Activating Genes (RAG1 and RAG2) in Human B Lymphoma Namalwa Cells","volume":"97","author":"Janssen","year":"2023","journal-title":"Arch. Toxicol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"14817","DOI":"10.1021\/acs.est.3c02765","article-title":"Paired Liver:Plasma PFAS Concentration Ratios from Adolescents in the Teen-LABS Study and Derivation of Empirical and Mass Balance Models to Predict and Explain Liver PFAS Accumulation","volume":"57","author":"Baumert","year":"2023","journal-title":"Environ. Sci. Technol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"100485","DOI":"10.1016\/j.jlr.2023.100485","article-title":"From NAFLD to MASLD: Updated Naming and Diagnosis Criteria for Fatty Liver Disease","volume":"65","author":"Rinella","year":"2024","journal-title":"J. Lipid Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"167945","DOI":"10.1016\/j.scitotenv.2023.167945","article-title":"Dietary Exposure to Per- and Polyfluoroalkyl Substances: Potential Health Impacts on Human Liver","volume":"907","author":"Zhang","year":"2024","journal-title":"Sci. Total Environ."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1007\/s12403-023-00622-4","article-title":"Per- and Polyfluoroalkyl Substances Concentrations Are Associated with an Unfavorable Cardio-Metabolic Risk Profile: Findings from Two Population-Based Cohort Studies","volume":"16","author":"Faquih","year":"2024","journal-title":"Exponential Health"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"108962","DOI":"10.1016\/j.envint.2024.108962","article-title":"A Novel Molecular Pathway of Lipid Accumulation in Human Hepatocytes Caused by PFOA and PFOS","volume":"191","author":"Gou","year":"2024","journal-title":"Environ. Int."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"108138","DOI":"10.1016\/j.envint.2023.108138","article-title":"PPAR\u03b1\/ACOX1 as a Novel Target for Hepatic Lipid Metabolism Disorders Induced by per- and Polyfluoroalkyl Substances: An Integrated Approach","volume":"178","author":"Yang","year":"2023","journal-title":"Environ. Int."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"141723","DOI":"10.1016\/j.chemosphere.2024.141723","article-title":"A Structural Basis for the Activation of Peroxisome Proliferator-Activated Receptor Gamma (PPAR\u03b3) by Perfluorooctanoic Acid (PFOA)","volume":"354","author":"Pederick","year":"2024","journal-title":"Chemosphere"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"107838","DOI":"10.1016\/j.envint.2023.107838","article-title":"Alteration of Hepato-Lipidomic Homeostasis in A\/J Mice Fed an Environmentally Relevant PFAS Mixture","volume":"173","author":"Khan","year":"2023","journal-title":"Environ. Int."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Tancreda, G., Campisi, L., Sarti, M., Pozzo, L., and Vornoli, A. (2025). Perfluoroalkyl Substances (PFAS) and Lipid Metabolism in Experimental Animal Models: A Scoping Review on the Mechanisms Behind the Induced Hepatotoxicity. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47110944"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"110867","DOI":"10.1016\/j.cbi.2024.110867","article-title":"HNF4A as a Potential Target of PFOA and PFOS Leading to Hepatic Steatosis: Integrated Molecular Docking, Molecular Dynamic and Transcriptomic Analyses","volume":"390","author":"Li","year":"2024","journal-title":"Chem. Biol. Interact."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s00204-023-03649-3","article-title":"Impact of Perfluoroalkyl Substances (PFAS) and PFAS Mixtures on Lipid Metabolism in Differentiated HepaRG Cells as a Model for Human Hepatocytes","volume":"98","author":"Sadrabadi","year":"2024","journal-title":"Arch. Toxicol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"136854","DOI":"10.1016\/j.jhazmat.2024.136854","article-title":"Effects of Mixed Exposure to PFAS on Adolescent Non-Alcoholic Fatty Liver Disease: Integrating Evidence from Human Cohorts, Toxicogenomics, and Animal Models to Uncover Mechanisms and Potential Target Sites","volume":"485","author":"Du","year":"2025","journal-title":"J. Hazard. Mater."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1007\/s00204-024-03814-2","article-title":"In Vitro Screening of Understudied PFAS with a Focus on Lipid Metabolism Disruption","volume":"98","author":"Kashobwe","year":"2024","journal-title":"Arch. Toxicol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"176717","DOI":"10.1016\/j.scitotenv.2024.176717","article-title":"Effects of Per- and Polyfluoroalkyl Substances on the Liver: Human-Relevant Mechanisms of Toxicity","volume":"954","author":"Maerten","year":"2024","journal-title":"Sci. Total Environ."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1007\/s00204-020-02732-3","article-title":"Impairment of Bile Acid Metabolism by Perfluorooctanoic Acid (PFOA) and Perfluorooctanesulfonic Acid (PFOS) in Human HepaRG Hepatoma Cells","volume":"94","author":"Behr","year":"2020","journal-title":"Arch. Toxicol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"115001","DOI":"10.1016\/j.ecoenv.2023.115001","article-title":"Perfluorooctanoic Acid (PFOA) and Hexafluoropropylene Oxide-Dimer Acid (GenX): Hepatic Stress and Bile Acid Metabolism with Different Pathways","volume":"259","author":"Yoo","year":"2023","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"175312","DOI":"10.1016\/j.scitotenv.2024.175312","article-title":"Perfluorooctanoic Acid (PFOA) and Its Alternative Perfluorobutanoic Acid (PFBA) Alter Hepatic Bile Acid Profiles via Different Pathways","volume":"950","author":"Wang","year":"2024","journal-title":"Sci. Total Environ."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"118854","DOI":"10.1016\/j.ecoenv.2025.118854","article-title":"Xenobiotic-Induced Liver Injury: Molecular Mechanisms and Disease Progression","volume":"303","author":"Wang","year":"2025","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1093\/toxsci\/kfae061","article-title":"Effects of PFAS on Human Liver Transporters: Implications for Health Outcomes","volume":"200","author":"Vujic","year":"2024","journal-title":"Toxicol. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"De Battistis, F., Djordjevic, A.B., Saso, L., and Mantovani, A. (2025). Constitutive Androstane Receptor, Liver Pathophysiology and Chemical Contaminants: Current Evidence and Perspectives. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1472563"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1093\/toxsci\/kfaf110","article-title":"Synergistic Toxicity in Alcohol-Associated Liver Disease and PFAS Exposure","volume":"208","author":"Stem","year":"2025","journal-title":"Toxicol. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"154167","DOI":"10.1016\/j.tox.2025.154167","article-title":"Per- and Polyfluoroalkyl Substances as Potentiators of Hepatotoxicity in an Exposome Framework: Current Challenges of Environmental Toxicology","volume":"515","author":"Choi","year":"2025","journal-title":"Toxicology"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"141654","DOI":"10.1016\/j.chemosphere.2024.141654","article-title":"Investigating Mouse Hepatic Lipidome Dysregulation Following Exposure to Emerging Per- and Polyfluoroalkyl Substances (PFAS)","volume":"354","author":"Chappel","year":"2024","journal-title":"Chemosphere"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1080\/10937404.2020.1798315","article-title":"Per- and Polyfluoroalkyl Substances and Male Reproductive Health: A Systematic Review of the Epidemiological Evidence","volume":"23","author":"Petersen","year":"2020","journal-title":"J. Toxicol. Environ. Health Part B"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Yi, Y., Feng, Y., Shi, Y., Xiao, J., Liu, M., and Wang, K. (2024). Per- and Polyfluoroalkyl Substances (PFASs) and Their Potential Effects on Female Reproductive Diseases. Toxics, 12.","DOI":"10.3390\/toxics12080539"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Sun, Z., Wen, Y., Wang, B., Deng, S., Zhang, F., Fu, Z., Yuan, Y., and Zhang, D. (2023). Toxic Effects of Per- and Polyfluoroalkyl Substances on Sperm: Epidemiological and Experimental Evidence. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1114463"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"176224","DOI":"10.1016\/j.scitotenv.2024.176224","article-title":"Reproductive and Germ-Cell Mutagenic Effects of Poly-and Perfluoroalkyl Substances (PFAS) to Caenorhabditis Elegans after Multigenerational Exposure","volume":"954","author":"Cao","year":"2024","journal-title":"Sci. Total Environ."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"118485","DOI":"10.1016\/j.envres.2024.118485","article-title":"Reproductive Toxicity of PFOA, PFOS and Their Substitutes: A Review Based on Epidemiological and Toxicological Evidence","volume":"250","author":"Shi","year":"2024","journal-title":"Environ. Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s12940-025-01188-1","article-title":"Per- and Polyfluoroalkyl Substances (PFAS), Thyroid Hormones, Sexual Hormones and Pubertal Development in Adolescents Residing in the Neighborhood of a 3M Factory","volume":"24","author":"Cox","year":"2025","journal-title":"Environ. Health"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"110690","DOI":"10.1016\/j.envres.2020.110690","article-title":"PFAS and Cancer, a Scoping Review of the Epidemiologic Evidence","volume":"194","author":"Steenland","year":"2021","journal-title":"Environ. Res."},{"key":"ref_88","first-page":"e2023040","article-title":"Per- and Poly-Fluoroalkyl Substances (PFAS) Exposure and Risk of Kidney, Liver, and Testicular Cancers: A Systematic Review and Meta-Analysis","volume":"114","author":"Seyyedsalehi","year":"2023","journal-title":"Med. Lav."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1186\/s12967-025-06517-z","article-title":"Decoding Per- and Polyfluoroalkyl Substances (PFAS) in Hepatocellular Carcinoma: A Multi-Omics and Computational Toxicology Approach","volume":"23","author":"Hong","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1093\/aje\/kwae010","article-title":"Exposure to Per- and Polyfluoroalkyl Substances and Breast Cancer Risk: A Systematic Review and Meta-Analysis of Epidemiologic Studies","volume":"193","author":"Chang","year":"2024","journal-title":"Am. J. Epidemiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"115164","DOI":"10.1016\/j.envres.2022.115164","article-title":"Perfluoroalkyl Substances Exposure in Firefighters: Sources and Implications","volume":"220","author":"Rosenfeld","year":"2023","journal-title":"Environ. Res."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Boyd, R.I., Ahmad, S., Singh, R., Fazal, Z., Prins, G.S., Madak Erdogan, Z., Irudayaraj, J., and Spinella, M.J. (2022). Toward a Mechanistic Understanding of Poly- and Perfluoroalkylated Substances and Cancer. Cancers, 14.","DOI":"10.3390\/cancers14122919"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.chemosphere.2014.10.014","article-title":"Perfluoroalkylated Substances (PFAS) Affect Oxidative Stress Biomarkers in Vitro","volume":"129","author":"Long","year":"2015","journal-title":"Chemosphere"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"108250","DOI":"10.1016\/j.envint.2023.108250","article-title":"Plasma Levels of Per- and Polyfluoroalkyl Substances (PFAS) and Cardiovascular Disease\u2014Results from Two Independent Population-Based Cohorts and a Meta-Analysis","volume":"181","author":"Dunder","year":"2023","journal-title":"Environ. Int."},{"key":"ref_95","unstructured":"Pichler, G., Adlbrecht, C., Weber, T., and McGraw, K.E. PFAS and Cardiovascular Risk: The Effects of Exposure to Perfluoroalkyl and Polyfluoroalkyl Substances on Cardiovascular Health. Wien. Klin. Wochenschr., Online ahead of printing."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"119901","DOI":"10.1016\/j.ecoenv.2026.119901","article-title":"Per- and Polyfluoroalkyl Substances and Cardiovascular Disease: A Mechanistic and Epidemiological Synthesis","volume":"313","author":"Yang","year":"2026","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1186\/s12944-025-02811-3","article-title":"Per- and Polyfluoroalkyl Substances (PFAS) Exposure and Cardiovascular Risk: Lipid Profile as a Mediator","volume":"24","author":"Wang","year":"2025","journal-title":"Lipids Health Dis."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"De Toni, L., Radu, C.M., Sabovic, I., Di Nisio, A., Dall\u2019Acqua, S., Guidolin, D., Spampinato, S., Campello, E., Simioni, P., and Foresta, C. (2020). Increased Cardiovascular Risk Associated with Chemical Sensitivity to Perfluoro\u2013Octanoic Acid: Role of Impaired Platelet Aggregation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020399"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1161\/CIRCRESAHA.124.323697","article-title":"Perfluoroalkyl\/Polyfluoroalkyl Substances: Links to Cardiovascular Disease Risk","volume":"134","author":"Schlezinger","year":"2024","journal-title":"Circ. Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"037007","DOI":"10.1289\/EHP9791","article-title":"Per- and Polyfluoroalkyl Substances and Risk of Myocardial Infarction and Stroke: A Nested Case\u2013Control Study in Sweden","volume":"130","author":"Schillemans","year":"2022","journal-title":"Environ. Health Perspect."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"117395","DOI":"10.1016\/j.ecoenv.2024.117395","article-title":"Kidney Function Mediates the Effects of Four Per-and Polyfluoroalkyl Substances (PFAS) on Atherosclerotic Cardiovascular Disease","volume":"288","author":"Wei","year":"2024","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1093\/toxsci\/kfae065","article-title":"PFAS and Their Association with the Increased Risk of Cardiovascular Disease in Postmenopausal Women","volume":"200","author":"Tunc","year":"2024","journal-title":"Toxicol. Sci."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Meneguzzi, A., Fava, C., Castelli, M., and Minuz, P. (2021). Exposure to Perfluoroalkyl Chemicals and Cardiovascular Disease: Experimental and Epidemiological Evidence. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.706352"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"107979","DOI":"10.1016\/j.envint.2023.107979","article-title":"Plasma Levels of Per- and Polyfluoroalkyl Substances (PFAS) Are Associated with Altered Levels of Proteins Previously Linked to Inflammation, Metabolism and Cardiovascular Disease","volume":"177","author":"Dunder","year":"2023","journal-title":"Environ. Int."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1053\/j.ajkd.2024.02.008","article-title":"Klotho and Clinical Outcomes in CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study","volume":"84","author":"Edmonston","year":"2024","journal-title":"Am. J. Kidney Dis."}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/14\/5\/374\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T11:30:09Z","timestamp":1781695809000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/14\/5\/374"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,26]]},"references-count":105,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["toxics14050374"],"URL":"https:\/\/doi.org\/10.3390\/toxics14050374","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,26]]}}}