Frontiers in toxicology最新文献

{"title":"Correction: Hypoxia-induced metabolic shifting and AHR/BCRP axis impairment drive placental dysfunction in early-onset preeclampsia and FGR.","authors":"Jingjing Shi, Wenxuan Zhu, Haixia Liu, Ping Yang, Yongzhong Gu, Wen Peng, Jinlai Meng","doi":"10.3389/ftox.2026.1953267","DOIUrl":"https://doi.org/10.3389/ftox.2026.1953267","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/ftox.2026.1782187.].</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1953267"},"PeriodicalIF":5.1,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Pregnancy and lactation exposure to bisphenol S induces ferroptosis via disrupted hepatic lipid metabolism in offspring mice.","authors":"Mengfen Pan, Xinxin Guo, Caiyun Wei, Nuo Xu, Yan Su, Zhensong Ma, Huaicai Zeng","doi":"10.3389/ftox.2026.1911506","DOIUrl":"https://doi.org/10.3389/ftox.2026.1911506","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/ftox.2026.1753029.].</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1911506"},"PeriodicalIF":5.1,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13594692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149026809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota responses to two-dimensional materials: insights from <i>in vivo</i> models and <i>in vitro</i> antibacterial studies.","authors":"Wen Xu, Guotao Peng","doi":"10.3389/ftox.2026.1865240","DOIUrl":"10.3389/ftox.2026.1865240","url":null,"abstract":"<p><p>Two-dimensional (2D) materials are increasingly applied in environmental and biomedical fields, raising concerns about their interactions with the gut microbiota following oral exposure. In this review, we summarize current understanding of the effects of 2D materials, ranging from graphene-based materials (GBMs) to emerging 2D materials such as transition metal dichalcogenides (TMDs) and transition metal carbides and nitrides (MXenes), on the gut microbiota and the associated biological outcomes. We first summarize <i>in vivo</i> studies, mainly using mouse and zebrafish models and focusing on GBMs, demonstrating that 2D materials exposure can induce gut microbiota dysbiosis, often in association with local and systemic host responses. To provide mechanistic insights, we further examine how key physicochemical properties, particularly nanosheet dimensions, surface chemistry, and material transformation, determine the interactions between 2D materials and bacterial cells, drawing from the extensive body of <i>in vitro</i> antibacterial research. Finally, we highlight future research directions beyond the need for more efforts on emerging 2D materials, including linking physicochemical properties of 2D materials to microbial responses <i>in vivo</i> and analyzing the temporal response patterns of the gut microbiota. We also emphasize the development of community-relevant <i>in vitro</i> models and the need to dissect the potential biotransformation of 2D materials by the gut microbiota. A deeper understanding of the interactions between 2D materials and the gut microbiota will not only advance the safety assessment of these materials but also foster the development of safer-by-design 2D materials.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1865240"},"PeriodicalIF":5.1,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13590223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149013417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative <i>in vitro</i> safety assessments of synthetized and plant-derived cannabidiol (CBD), and pharmacokinetics of synthetized CBD: evidence of similar toxicological profiles and accumulation upon repeated oral administration.","authors":"E T Wong, D Bovard, W K Schlage, W Xia, H Isa, O Sirbu, A R Kolli, G N Nikolajsen, S S Jensen, J Ho, B Phillips, J Hoeng","doi":"10.3389/ftox.2026.1844643","DOIUrl":"10.3389/ftox.2026.1844643","url":null,"abstract":"<p><p>Comparative toxicology between synthetized and plant-derived cannabidiol (CBD) remains underexplored, as most previous research has focused on a single type of CBD. This leaves uncertainties regarding whether differences in origin, purity, or extraction methods affect the safety profiles or metabolic outcomes of CBD. This study assessed the <i>in vitro</i> safety, <i>in vitro</i> hepatotoxicity, and repeated oral dose pharmacokinetics (PK) of CBD in rats. Two brands of synthetized CBD were evaluated alongside two plant-derived CBD (a high-purity isolate and a lower-purity distillate) in vitro. These findings indicated no meaningful in vitro safety differences among the CBD sources and therefore supported selection of a single synthetized CBD source for an in vivo PK study in male Sprague-Dawley rats dosed orally once daily at 26.5 mg/kg for 21 days. Blood samples were collected at multiple time points on days 1 and 21, and pre-dose samples on selected days to assess baseline accumulation. CBD and its metabolites (7-COOH-CBD, 7-OH-CBD, 6-OH-CBD) were measured in plasma and tissues using liquid chromatography-tandem mass spectrometry. All CBD samples showed comparable safety profiles, with no evidence of genotoxicity or mutagenicity in micronucleus and Ames assays, similar cytotoxicity in HepaRG monolayer cultures, and comparable cytochrome P450 (CYP) inhibition. Over 21 days, repeated dosing increased plasma CBD (AUC_INF_D 567 vs. 209 h*kg*ng/mL/mg; Day 21 vs. 1), 7-COOH-CBD (AUC_last_D 1006 vs. 581), 6-OH-CBD (AUC_last_D 33 vs. 13) and 7-OH-CBD (AUC_last_D 43 vs. 31) exposure, and prolonged CBD half-life (41.9 h vs. 5.9 h). The steady-state plasma CBD concentration was achieved by Day 6. Tissue analysis showed marked CBD accumulation in adipose tissue (70,124 ng/g, 1470-fold relative to plasma level) and mesenteric lymph nodes (10,018 ng/g, 201-fold relative to plasma level). Notably, 7-OH-CBD accumulated in adipose tissue (42 ng/g, 21-fold relative to plasma level) and mesenteric lymph nodes (136 ng/g, 73-fold relative to plasma level). Overall, high-purity synthetized and plant-derived CBD showed similar <i>in vitro</i> safety outcomes, while oral administration produced distinct accumulation of CBD and metabolites in plasma and tissue. These findings support flexible CBD source selection for standardized nonclinical research while highlighting the need to consider accumulation dynamics during repeated dosing.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1844643"},"PeriodicalIF":5.1,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149009459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Organ-specific apoptotic pathways induced by micro- and nanoplastics: a systematic review of <i>in vitro</i> toxicological evidence.","authors":"Laura Maria Messina, Maria Concetta Scuto, Gabriella Lupo, Cinzia Maria Grazia Lombardo, Caterina Ledda, Angela Trovato Salinaro","doi":"10.3389/ftox.2026.1908508","DOIUrl":"10.3389/ftox.2026.1908508","url":null,"abstract":"<p><p>The widespread presence of micro- and nanoplastics (MNPs) in environmental matrices and consumer products has raised increasing concern about their potential effects on human health. Due to their small size, persistence, and heterogeneous physicochemical properties, MNPs may interact with biological barriers, reach different cellular compartments, and trigger organ-specific toxic responses. Among the cellular events involved, apoptosis has emerged as a recurrent mechanism linking MNP exposure to tissue injury and functional impairment. This systematic review aimed to synthesize the available <i>in vitro</i> evidence on apoptosis-related toxicity induced by MNPs across different cell models and organoids, with particular attention to organ-specific patterns and underlying molecular pathways. Following a PECOS-based strategy and PRISMA guidance, a literature search was conducted in PubMed, Scopus, and Web of Science on 6 September 2024. Studies were screened using Rayyan, and 80 studies were included in the qualitative synthesis. Overall, the evidence indicates that MNP exposure induces cytotoxic effects in a wide range of cellular models representing the gastrointestinal tract, liver, lung, kidney, reproductive system, placenta, brain, cardiovascular system, skin, and blood-related compartments. Across these models, recurrent mechanisms included oxidative stress, mitochondrial dysfunction, loss of mitochondrial membrane potential, endoplasmic reticulum stress, calcium imbalance, activation of MAPK and PI3K/AKT-related signaling, dysregulation of Bcl-2 family proteins, caspase activation, and crosstalk with inflammatory, autophagic, and ferroptotic pathways. Particle size, surface chemistry, concentration, exposure time, and co-exposure with other contaminants influenced the magnitude and pattern of toxic responses. In conclusion, apoptosis represents a central mechanistic node in the organ-specific toxicity of MNPs <i>in vitro</i>. However, the translational relevance of current evidence remains limited by heterogeneity in particle characteristics, exposure conditions, and experimental models. Future studies should prioritize standardized protocols, environmentally relevant exposure scenarios, and advanced human-based models to better define the implications of MNP exposure for human health.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1908508"},"PeriodicalIF":5.1,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149009449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A practical approach for regulatory acceptance of virtual control groups: vehicle pooling and biological relevance assessment.","authors":"Jiwon Kim, Yoongi Kim, Daeui Park, Sang Kyum Kim, Myung-Gyun Kang","doi":"10.3389/ftox.2026.1888158","DOIUrl":"10.3389/ftox.2026.1888158","url":null,"abstract":"<p><p>The implementation of virtual control groups (VCG) to replace concurrent control groups (CCG) in toxicity studies is challenged by the need for strict covariate matching. This is particularly true in diverse administration vehicles, which severely fragment historical control data (HCD). To overcome this limitation, this study consolidated region-specific HCD from physicochemically similar aqueous vehicles (saline, distilled water, and 0.5% methylcellulose) into a site-specific pool for 13-week rat studies in the Republic of Korea, thus securing a sufficiently powered VCG pool. To rigorously evaluate VCG reproducibility beyond strict statistical thresholds (e.g., p < 0.05), a category-based assessment framework was introduced as a validation methodology focusing on the direction and magnitude (e.g., percentage change) of alterations. Although body and organ weights showed high statistical agreement between VCGs and CCGs, the exact reproduction of statistical significance for clinical pathology parameters was relatively low (25%-40%) owing to limited sample sizes and inherent biological noise. Nevertheless, the category-based assessment demonstrated 100% reproducibility based on the biological relevance of all evaluated clinical pathology parameters. Crucially, the VCG-based analysis confirmed that the study director's fundamental toxicological interpretations and target organ signals remained robustly preserved. Overall, pooling HCD across similar vehicles resolves sample size constraints, and assessing VCG reproducibility via biological relevance provides a practical framework to enhance regulatory acceptance.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1888158"},"PeriodicalIF":5.1,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13585411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148992769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The importance of the life cycle perspective for safety assessment in the European Commission's Safe and Sustainable by Design Framework.","authors":"Irantzu Garmendia Aguirre, Irini Furxhi, Agnieszka Mech, Kirsten Rasmussen, Hubert Rauscher","doi":"10.3389/ftox.2026.1909986","DOIUrl":"10.3389/ftox.2026.1909986","url":null,"abstract":"<p><p>The European Commission Safe and Sustainable by Design (SSbD) framework represents a paradigm shift in innovation by integrating safety and sustainability considerations from the earliest stages of development, guided by a life cycle perspective. A key driver of this shift is the extension of safety beyond siloed considerations towards a comprehensive life cycle approach. However, this extension of safety to the entire life cycle remains insufficiently understood and is often underestimated or even neglected by practitioners, largely due to a lack of understanding of its practical implications. The life cycle perspective in SSbD is closely linked to another novelty that the framework brings to innovation, the sustainability dimension, which is traditionally addressed through life cycle assessment (LCA) and which inherently captures all life cycle stages of a product for the impact assessment. Likewise, adopting a life cycle perspective in safety requires moving beyond the traditional context-specific safety (substance safety, process safety or product safety). Instead, it requires a more holistic view that considers value chain complexity and safety across all chemicals, processes, products and receptors involved in the SSbD life cycle. This shift requires breaking down long-standing disciplinary silos that were originally developed to manage this value chain complexity. It calls for greater collaboration, building bridges across these disciplines and transparent information sharing across value chains. This paper highlights and explores the importance of the life cycle perspective for safety in the EC SSbD framework. It presents the Scoping Analysis as a central methodological component in the revised framework that strengthens the life cycle thinking in safety.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1909986"},"PeriodicalIF":5.1,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149009488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pollutants regulate changes in pathological markers of neurodegenerative diseases: a new perspective in environmental toxicology.","authors":"Xingbo Kou, Qianqian Hu, Yibo Kou, Dinghao An","doi":"10.3389/ftox.2026.1814795","DOIUrl":"https://doi.org/10.3389/ftox.2026.1814795","url":null,"abstract":"<p><p>Neurodegenerative diseases are major global health challenges, with their pathogenesis closely linked to the abnormal aggregation of pathological proteins. Beyond genetic factors, environmental pollutants play key roles in disease onset and progression. Conventional reviews often focus on associations between specific pollutants and particular diseases. This review innovatively concentrates on the common pathogenic mechanisms of core pathological markers (e.g., Aβ, Tau, α-syn, TDP-43), systematically detailing how various pollutants, including air pollutants, metals, and persistent organic pollutants, modulate the generation, aggregation, propagation, and toxicity of pathological proteins, thereby accelerating neurodegenerative processes. We propose an integrated framework of 'pollutants-pathogenic links-neural network failure,' bridging environmental toxicology and molecular neurology to offer a unified novel perspective and theoretical foundation for molecular mechanism-based environmental risk assessment and targeted interventions.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1814795"},"PeriodicalIF":5.1,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13581437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148992827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rewriting paracelsus: linking chemical assessment to public health.","authors":"Ana Fernandez-Agudo, María Del Carmen González-Caballero, Jose V Tarazona","doi":"10.3389/ftox.2026.1872816","DOIUrl":"https://doi.org/10.3389/ftox.2026.1872816","url":null,"abstract":"<p><p>Human health is continuously challenged by exposure to complex mixtures of chemicals present in food, products, and the environment. Traditional risk assessment (TRA), rooted in mid-20th-century paradigms, relies on deterministic thresholds and animal testing to define safe exposure levels. This approach, while useful for regulatory simplicity, fails to represent real-world variability, mixture effects, and lifelong events, limiting its relevance for public health protection. Here we show that a probabilistic Next-Generation Risk Assessment (NGRA) framework integrating quantitative modelling, mechanistic biology, and New Approach Methodologies (NAMs), can transform toxicological evidence into probability distributions, estimating the likelihood of adverse outcomes under realistic exposure scenarios. Central to this approach are Health Impact Pathways (HIPs), which connect molecular perturbations to population-level health indicators, bridging toxicology and epidemiology. The framework explicitly distinguishes susceptible groups, such as individuals in physiologically sensitive stages like pregnancy, from vulnerable groups, including those with pre-existing diseases or higher exposure burdens, poorly covered in TRA. By covering these groups, probabilistic NGRA enables more inclusive, relevant, and informative evaluations that align with FAIR (Findable, Accessible, Interoperable, Reusable) data principles and minimize animal testing, offering a scientifically grounded framework for improving chemical safety evaluations and public health protection.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1872816"},"PeriodicalIF":5.1,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148992822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards test guidelines and standards for advanced materials: scientific insights and recommendations from the MACRAMÉ project.","authors":"Anna Pohl, Daniel Haase, Eric A J Bleeker, Samia Ouhajji, Klaus-Michael Weltring, Martin Wiemann, Alberto Katsumiti, Christian Seitz, Govind Gupta, Luis Mauricio Ortiz-Galvez, Tina Buerki-Thurnherr, Peter Wick, Thomas Eckart Exner, Blanca Suarez-Merino, Rayén Mentler, Tommaso Serchi, Katie Reilly, Iseult Lynch, Steffi Friedrichs, Elisabeth Heunisch","doi":"10.3389/ftox.2026.1895021","DOIUrl":"10.3389/ftox.2026.1895021","url":null,"abstract":"<p><p>The Horizon Europe Project MACRAMÉ developed twelve recommendations towards Test Guidelines and Standards for safety assessment of advanced materials (AdMas) that capture the identified needs in characterisation and identification, safety testing, transformation and release as well as information flow along the AdMas lifecycle. MACRAMÉ highlights challenges posed by complex structures and transformations of AdMas and AdMas-enabled products for regulation and industry drawn on research on graphene-related materials, carbon nanotubes and poly(lactic-co-glycolic) acid in realistic use cases. MACRAMÉ translates advances in characterisation, transformation and release assessment, and New Approach Methodologies into actionable recommendations and calls on regulators, funding bodies, researchers and industry to develop and validate fit-for-purpose test methods, standards and guidance with the aim to enable safe and sustainable deployment of AdMas for societal challenges.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1895021"},"PeriodicalIF":5.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13574966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}