Archives of Toxicology最新文献

{"title":"Hepatic cytochrome P450 induction following Kashin-Beck disease-related selenium deficiency and T-2 toxin exposure in mice.","authors":"Tong Zhao, Yichen Zhao, Tingting Mao, Weixuan Da, Lina Qin, Li Liu, Huan Liu, Bolun Cheng, Yan Wen, Feng Zhang, Yumeng Jia","doi":"10.1007/s00204-026-04532-7","DOIUrl":"https://doi.org/10.1007/s00204-026-04532-7","url":null,"abstract":"<p><p>Kashin-Beck disease (KBD) is a multifactorial endemic osteoarthropathy that has been associated with nutritional and environmental factors, including selenium deficiency and T-2 toxin exposure. However, whether combined selenium deficiency and T-2 toxin exposure affects hepatic xenobiotic metabolism has not been systematically investigated. Male C57BL/6 mice were fed a selenium-adequate or selenium-deficient diet for 4 weeks, followed by another 4 weeks with or without daily oral T-2 toxin (0.2 mg/kg). Plasma selenium and glutathione peroxidase (GPx) activity were measured. Hepatic histology, activities of major mouse cytochrome P450 (Cyp450) isoforms, and corresponding mRNA and protein expression were assessed. RNA sequencing was performed using liver samples from four biological replicates per group to identify differentially expressed genes (DEGs) and enriched pathways. Selenium deficiency was confirmed by significantly reduced plasma selenium levels and GPx activity. Histological examination revealed marked hepatic steatosis. Transmission electron microscopy further showed prominent ultrastructural alterations including endoplasmic reticulum dilation. The activities of five hepatic Cyp450 isoforms, Cyp1a2, Cyp2b10, Cyp2c29, Cyp2c50, and Cyp3a11, were significantly increased to 1.64-2.51 times the control levels, consistent with increased mRNA and protein expression. Combined selenium deficiency and T-2 toxin exposure was associated with increased hepatic Cyp450 enzyme activity and expression, identifying the liver as a responsive target of KBD-related exposures. These findings suggest the need to further evaluate hepatic xenobiotic metabolism in populations from KBD-endemic areas.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Micro- and nanoplastics-induced neurotoxicity: a CNS-centered, evidence-graded adverse outcome pathway framework based on systematic weight-of-evidence assessment.","authors":"Kexin Zheng, Jun Xie, Yong Hu, Zhen Zhou, Changjian Quan, Hongwei Xie, Hua Zou, Lifang Zhou, Xiangjing Gao","doi":"10.1007/s00204-026-04528-3","DOIUrl":"https://doi.org/10.1007/s00204-026-04528-3","url":null,"abstract":"<p><p>Micro- and nanoplastics (MPs/NPs) are ubiquitous anthropogenic particulate pollutants posing emerging threats to human neurological health. Severe heterogeneity in particle physicochemical properties, environmental aging status, exposure paradigms and experimental platforms has created persistent mechanistic uncertainties in MP/NP neurotoxicology, hindering reliable hazard characterization and risk translation. Here, we systematically consolidate empirical toxicological evidence and construct a dedicated central nervous system (CNS)-targeted adverse outcome pathway (AOP) network integrated with rigorous weight-of-evidence (WoE) grading to elucidate the hierarchical, particle-specific toxic cascades underlying MP/NP-induced neural injury. Our synthesis overturns the conventional linear toxicity paradigm, demonstrating that MPs/NPs trigger neurotoxicity via a complex multi-input mechanistic network. We definitively establish oxidative stress as a robust early convergent key event-rather than a universal molecular initiating event-orchestrating ROS overproduction, lipid peroxidation, mitochondrial dysfunction, and neuroinflammation to propagate neuronal damage. This core module is driven by five distinct particulate upstream triggers: particle-biomolecule interfacial perturbation, corona-facilitated cellular internalization, plastic-associated chemical leaching, aging-derived free radical reactivity, and gut-borne systemic neurotoxic signaling. Downstream pathogenic outcomes encompass glial overactivation, neurotransmitter dyshomeostasis, autophagy-lysosome dysfunction, metabolic reprogramming, regulated neuronal cell death, and behavioral impairments. Tiered WoE analysis confirms strong validation for early oxidative/inflammatory cascades, moderate support for gut-brain axis crosstalk and intracellular trafficking disruption, and nascent evidence for synaptic dysfunction and neurodegeneration-linked proteostatic defects. Extrapolation to human health risk remains constrained by the frequent use of high-dose exposure paradigms, limited validated data on internal dosimetry in the human brain, discrepancies between effective concentrations in experimental models and environmentally relevant human tissue burdens, and insufficient causal validation of distal adverse outcomes. We highlight key research priorities including aged mixed-particle exposure systems, leachate-controlled assays, quantitative internal dose evaluation, and mechanistic intervention verification. This evidence-stratified AOP framework resolves longstanding mechanistic ambiguities in particulate neurotoxicity, providing a standardized, causality-based foundation for future mechanistic exploration and health risk assessment of global plastic pollution.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diet modulates metabolic and hepatic responses to chronic pesticide mixture exposure in mice.","authors":"C Rives, N Poirier-Jaouen, Y Malaisé, C M P Martin, M Huillet, S Ellero-Simatos, P Perrier, A Polizzi, F Lasserre, V Alquier-Bacquié, C Guyon, Y Lippi, C Naylies, C Comera, H Budzinski, K Le Menach, E L Jamin, N K Dieng, R Vuillaume, C Orlandi, J Gomez, S Costes, A Arrar, A Lucas, S Fried, E Boutet-Robinet, J Guillermet-Guibert, E Kesse-Guyot, H Guillou, N Loiseau, A Fougerat, L Gamet-Payrastre","doi":"10.1007/s00204-026-04533-6","DOIUrl":"https://doi.org/10.1007/s00204-026-04533-6","url":null,"abstract":"<p><p>Chronic exposure to pesticide mixtures through diet is common, yet their combined metabolic effects and interactions with dietary factors remain unclear. We identified four pesticides prevalent in human exposure (imazalil, thiabendazole, boscalid, lambda-cyhalothrin) and assessed their combined impacts on hepatic metabolism and metabolic homeostasis using human liver cells and male mice fed standard chow or western diets. We found that the pesticide mixture induced metabolic perturbations in human hepatocytes. In addition, the pesticide mixture altered hepatic gene expression in chow-fed mice and exacerbated western diet-induced glucose intolerance, fasting hyperglycemia, and insulin resistance without affecting body weight or liver steatosis. These findings reveal that dietary context influences the metabolic consequences of pesticide mixtures, highlighting the need to consider nutritional status when evaluating environmental contaminant risks. Our results suggest that pesticide mixtures at reference doses may contribute to metabolic dysregulation, particularly under obesogenic dietary conditions.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current status of human biomonitoring of beauvericin and enniatins.","authors":"Gsela H Degen, Anamarija Romac","doi":"10.1007/s00204-026-04527-4","DOIUrl":"https://doi.org/10.1007/s00204-026-04527-4","url":null,"abstract":"<p><p>Beauvericin (BEA) and enniatins (ENNs) are Fusarium mycotoxins found in cereals and cereal-based foods as reported in several studies. But information on human internal exposure remains scattered. Human biomonitoring (HBM) enables the investigation of exposure to these nonregulated contaminants. This review summarizes data from studies published since 2014 on occurrence of BEA and ENNs in human urine, blood, breast milk, tissues and hair. Most studies from Europe, Africa, Asia and North America applied state-of-art methodologies for biomarker analysis. ENN B was the most frequently detected compound and was found in a high proportion of blood samples across different populations. Although BEA was reported less frequently, measurable levels were found in plasma, breast milk, tissues and, more recently, in urine. Both BEA and ENNs were found in human milk, indicating transfer from mother to infant, but generally at low concentrations. Data for human tissues suggest differences in distribution, with BEA occurring mainly in adipose tissue and ENN B reaching the highest concentrations in liver. Some studies reported phase-I metabolites of ENNs in urine, demonstrating that biotransformation contributes to their elimination in humans. Available HBM data indicate widespread dietary exposure to BEA and ENNs in several human populations. Concentrations measured in blood and tissues are much lower than those associated with their cytotoxic effects in vitro. Uncertainties remain regarding human toxicokinetics and the toxicological relevance of their metabolites. Further studies addressing these gaps will improve interpretation of biomonitoring data and support the human health risk assessment of these emerging mycotoxins.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Between evidence and allegation: factual accuracy in discussions on fluoride toxicity and research integrity.","authors":"Andrea Buettner, Patrick Diel, Gerhard Eisenbrand, Bernd Epe, Petra Först, Tilman Grune, Sabine Guth, Dirk Haller, Volker Heinz, Michael Hellwig, Hans-Ulrich Humpf, Henry Jäger, Sabine E Kulling, Alfonso Lampen, Marcel Leist, Angela Mally, Doris Marko, Ute Nöthlings, Elke Röhrdanz, Angelika Roth, Joachim Spranger, Stefan Vieths, Wim Wätjen, Jan G Hengstler","doi":"10.1007/s00204-026-04531-8","DOIUrl":"https://doi.org/10.1007/s00204-026-04531-8","url":null,"abstract":"","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pregnane X receptor-mediated liver growth: a controlled clinical trial in healthy volunteers and identification of the role of AKT-MTOR pathway in mouse.","authors":"Piia Lassila, Mikko Karpale, Outi Kummu, Aaron Stahl, Aki Käräjämäki, Eija Pääkkö, Helen Sophie Hammer, Albert Braeuning, Oliver Pötz, Markus Templin, Janne Hukkanen, Jukka Hakkola","doi":"10.1007/s00204-026-04526-5","DOIUrl":"https://doi.org/10.1007/s00204-026-04526-5","url":null,"abstract":"<p><p>Pregnane X receptor (PXR) is a nuclear receptor acting as a master xenobiotic receptor for many exogenous chemicals. Activation of PXR has been linked to liver growth in mice, usually via interaction with Yes-associated protein (YAP), but this adaptive response has not been observed in humans. We investigated the effect of human PXR agonist, rifampicin, on liver size in a controlled clinical trial in healthy volunteers. Moreover, we developed a novel protocol to reveal mechanisms of PXR-mediated liver growth in mice. One-week rifampicin treatment caused a 2.7% mean increase in liver volume-to-body weight ratio without affecting liver fat content in human volunteers (n=16). Pxr^-/- mice were transduced with adenovirus carrying either murine PXR or green fluorescent protein and both groups were treated with pregnenolone-16α-carbonitrile (PCN) for 0 to 4 days. In this setup, activation of PXR with PCN significantly increased liver size in male mice already after 1-day PCN treatment and the liver growth was further enhanced after 4 days. No significant liver enlargement was observed in female mice. 4-day PCN treatment also improved glucose tolerance in the male mice. RNA-sequencing revealed upregulation of genes and pathways involved in proliferation. DigiWest protein profiling and immunoblotting revealed increased activity of AKT-mammalian target of rapamycin (MTOR) pathway in the male mice. In contrast, we did not observe YAP activation. Our results indicate that PXR activation induces liver growth and activates proliferative AKT-MTOR pathway in male mice and may also induce liver growth in humans.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148824387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated water temperatures enhance 2,4,6-trinitrotoluene induced stress response of carbonyl reductase in blue mussels (Mytilus edulis): Another environmental impact of climate change?","authors":"Jacqueline Lindemeyer, Romina Marietta Schuster, Lili Hartmann, Lillian Tabea Hannah Bünning, Matthias Brenner, Edmund Maser, Jennifer Susanne Strehse","doi":"10.1007/s00204-026-04520-x","DOIUrl":"https://doi.org/10.1007/s00204-026-04520-x","url":null,"abstract":"<p><p>Toxic explosives leaking from submerged munitions appear as an emerging marine pollutant in recent years. The nitroaromatic compound 2,4,6-trinitrotoluene (TNT) is of particular interest in this context. TNT poses a threat to marine environments and organisms. Previous studies showed that TNT and its metabolites are incorporated in mussel tissue thereby causing adverse effects through cellular oxidative stress. Recently, the impact of TNT on mRNA expression of the enzyme carbonyl reductase (CR) in blue mussels was discovered. This enzyme plays a key part in the cellular antioxidative system. A factor that should be taken into account is the increase in water temperature caused by anthropogenic climate change. To investigate potential synergistic effects of TNT in combination with elevated water temperatures on CR expression, blue mussels were exposed to concentrations of 0.1 µg/L, 50 µg/L, and 500 µg/L TNT and water temperatures of 11 °C, 15 °C and 18 °C, respectively, in the present study. Semiquantitative PCR analysis of CR mRNA expression in different tissues confirmed that TNT leads to increased mRNA expression levels, especially in gill tissue even at lower concentrations than tested in previous studies. Furthermore, varying water temperatures apparently influenced CR gene expression. Our study suggests a higher vulnerability to xenobiotic-induced oxidative stress in case of simultaneous presence of pollution from munitions and elevated water temperature. Our findings also underline the importance of molecular biomarkers like CR as a method for assessment of the impact of environmental stressors on the marine ecosphere.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148811871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A human PBMC-based new approach method reveals PFAS-driven T-cell proliferation and immune dysregulation.","authors":"Allison Loan, Lauren M Bradford, Andrée Nunnikhoven, Gong Zhang, Emily Dupuis, Eunnara Cho, Matthew J Meier, Rocio Aranda-Rodriguez, Azam Tayabali, Kristin M Eccles, David Prescott","doi":"10.1007/s00204-026-04525-6","DOIUrl":"https://doi.org/10.1007/s00204-026-04525-6","url":null,"abstract":"<p><p>Immunotoxicity has emerged as a key health concern for per- and polyfluoroalkyl substances (PFAS), with animal studies showing reduced T-dependent antibody responses (TDAR) and epidemiological studies reporting decreased vaccine antibody titres. Notably, immunotoxicity is considered one of the most sensitive endpoints for PFAS exposure and has been used to inform regulatory guidance and health-based values. Given that more than 14,000 PFAS exist and are highly environmentally persistent, evaluating the immunotoxicity of individual compounds is critical but impractical, highlighting the need for efficient, human-relevant test systems that provide mechanistically informative, immune-relevant endpoints. Here, we assessed immunomodulatory effects of six PFAS analogues using an in vitro human peripheral blood mononuclear cell (PBMC) model. Two immune stimuli were applied, including lipopolysaccharide (LPS) to trigger innate responses and phytohemagglutinin (PHA) to simulate T-cell-mediated adaptive immune activation. Critically, several PFAS analogues enhanced T-cell proliferation following PHA activation, while a non-inclusive but overlapping subset of analogues suppressed cytokine secretion in response to PHA and LPS. Transcriptomic analyses indicate reduced B-cell identity and immunoglobulin gene expression alongside increased expression of genes associated with T-cell activation and proliferation. These findings implicate a dysregulated coordination between T- and B-cell responses as a potential mechanism underlying PFAS-associated immunotoxicity. Overall, the human PBMC model demonstrated that it is a cost-effective and ethical method for identifying and characterizing key events (KEs) in the adverse outcome pathway (AOP) for PFAS-induced immunotoxicity and has the potential to be refined and incorporated into a robust new approach method (NAM) to assess the next generation of commercial PFAS.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148811881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of toll-like receptors in tributyltin-, dibutyltin-, and pentachlorophenol-induced stimulation of tumor necrosis factor-alpha (TNFα) production in human immune cells.","authors":"Latoya M Daniel, Aleshia Seaton-Terry, Ellie Bray, Meaghan Lewis, Zinia Hunter, Sophia Fisher, Brian Townsend, Margaret M Whalen","doi":"10.1007/s00204-026-04522-9","DOIUrl":"10.1007/s00204-026-04522-9","url":null,"abstract":"<p><p>Tributyltin (TBT), Dibutyltin (DBT), and Pentachlorophenol (PCP) are persistent environmental contaminants that increase immune-cell production of pro-inflammatory cytokines and thus have the capacity to cause chronic inflammation and its associated pathologies such as cancer, cardiovascular disorders, and autoimmune conditions. TBT has been detected in human blood at concentrations up to 260 nM, DBT up to 0.3 µM, and PCP between 0.15 and 5 µM. Tumor necrosis factor-alpha (TNF-α) is a pro-inflammatory cytokine produced by immune cells in response to pathogen- or damage-associated molecular patterns (PAMPs/DAMPs) via Toll-like receptors (TLRs). Dysregulated TNF-α production contributes to chronic inflammatory pathology. Previous studies have shown that TBT, DBT, and PCP increase pro-inflammatory cytokine production by immune cells and that these increases depend on mitogen-activated protein kinases (MAPKs), which are downstream components of TLR activation. The current study indicates that TLR4 plays a role in TBT-, DBT-, and PCP-induced production of TNF-α. Additionally, TBT-induced TNF-α production was, at least in part, dependent on TLR2, DBT-induced TNF-α production on TLR1/2 and PCP-induced TNF-α production on TLR3 and TLR8. Blocking the initial component of TLR1/2, TLR2, TLR4, and TLR8 signaling, MyD88, led to very significant blockade of TBT- and PCP-induced TNF-α production. These findings provide additional understanding as to how compounds that are persistent pollutants activate production of a crucial regulator of inflammation, TNF-α, potentially contributing to chronic inflammation and its associated diseases.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148811907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PFAS: challenges and scientific perspectives in human health risk assessment.","authors":"Janine Kowalczyk, Klaus Abraham, Christina August, Runa S Boeddinghaus, James C Y Chan, Alexander Eckhardt, Tony Fletcher, Finnian Freeling, Bernd Göckener, Thorhallur I Halldórsson, Dorte Herzke, Ron L A P Hoogenboom, Kristina Jakobsson, Christian Jung, Federica Madia, Bernhard Monien, Jorge Numata, Louise Ramhøj, Greet Schoeters, Katharina Sommerkorn, Xenia Trier, Periklis Tsiros, Christian Unkelbach, Stefan P J van Leeuwen, Thorsten Buhrke","doi":"10.1007/s00204-026-04523-8","DOIUrl":"https://doi.org/10.1007/s00204-026-04523-8","url":null,"abstract":"<p><p>To review recent advances in research on per- and polyfluoroalkyl substances (PFAS) and outline priority steps for risk assessment in consumer health protection, the German Federal Institute for Risk Assessment (BfR) organized the 'International PFAS Conference' in Berlin in October 2025. Building on the European Food Safety Authority's (EFSA) opinion in 2020, global research activities on PFAS have intensified. The conference was attended by 200 participants from 18 countries and covered topics such as analytical methods, human exposure, toxicokinetics, toxicity, and future perspectives. Given that there are more than 21,000 different PFAS in use, discussions highlighted the need for further data collection and a basis for prioritizing substances. Robust exposure assessment requires improved analytical methods combined with newly developed predictive tools to quantify, identify, and make better use of non-target data. Hazard characterization may benefit from the combined use of classic experimental data sets, epidemiological data, and new approach methodologies (NAMs) data. The participants emphasized the continuous need for refined data and proposed a systematic consolidation of global data on shared data platforms, accompanied by corresponding guidelines for data usage. In the final panel discussion, effective risk communication was identified as a critical challenge, necessitating clear and consistent messaging for the public and policymakers. The conference concluded with five key recommendations for future health risk assessments: prioritizing PFAS; improving analytical methods; promoting generation of robust data and data gap filling; promoting open science, including the development of shared data infrastructure and cross-institutional knowledge exchange; and strengthening risk communication. These recommendations aim to support transparent, evidence-based and effective PFAS consumer health risk management in the decades ahead.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148811936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}