Toxicology letters最新文献

{"title":"Mixed exposure to brominated flame retardants adversely affects vaccine-induced antibody titers: Risk prioritization and benchmark dose modeling.","authors":"Zihui Zhao, Chi Zhang, Xueyu Chen, Yongheng Yan, He Jiao, Xianhao Wang, Ruxu Yan, Yiqian Wang, Meng Liu, Xianfeng Yue, Yuqian Sui, Xia Li, Shuting Wang, Rongqian Sun, Qian He, Daiyu Song, Long Ji, Dong Li","doi":"10.1016/j.toxlet.2026.111910","DOIUrl":"https://doi.org/10.1016/j.toxlet.2026.111910","url":null,"abstract":"<p><p>The association between brominated flame retardant (BFRs) exposure and measles, mumps, and rubella vaccine (MMR) antibody responses was investigated using the National Health and Nutrition Examination Survey (2003-2004). Using multivariate linear regression and restricted cubic spline (RCS) model, we found significant inverse association between single BFR exposure (BB-153 and BDE-100) and mumps antibody levels (P < 0.05). Mixed BFR exposure synergistically reduced antibody levels across mumps and rubella vaccines, with BB-153 identified as the dominant contributor for mumps (PIP = 0.460). Benchmark dose modeling revealed immunotoxicity thresholds for a 10% antibody reduction: BB-153 (BMDL₁₀ = 46.73pg/g serum) for mumps, BDE-153 (BMDL₁₀ = 258.27pg/g serum) for rubella. While the exposure levels of most people in this study were below these thresholds, dose-response trends were still observed at sub-threshold concentrations. Enrichment analyses via Comparative Exploratory functional enrichment analysis suggested that BFR exposure may be associated with immune-related pathways. However, these findings are hypothesis-generating and do not represent definitive mechanistic evidence. Further experimental studies are needed to validate these potential biological mechanisms. Sensitivity analyses confirmed robust associations, and independent toxic effects were observed in females. This is the first study to examine the relationship between BFR exposure and MMR vaccine effects, highlighting the need for enhanced monitoring and a revised framework for assessing immunotoxicity.</p>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":" ","pages":"111910"},"PeriodicalIF":2.9,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicological Potential of Nanomaterials by Concentration-dependent Transcriptomics of Human Cells.","authors":"Wendi Fang, Mingming Tian, Xiao Gou, Pu Xia, Xiaowei Zhang","doi":"10.1016/j.toxlet.2026.111909","DOIUrl":"https://doi.org/10.1016/j.toxlet.2026.111909","url":null,"abstract":"<p><p>Biological pathways altered by nanomaterials can be used to predict potential hazards to humans and wildlife. However, the impacts of particle size, charge, and chemical composition of nanomaterials on biological pathways in the cellular system are largely unknown. Here, the biological pathway profiles of ten typical metal oxide nanomaterials were obtained in A549 cells by using concentration-dependent transcriptomic analysis with reduced human transcriptome (RHT) technology. We further analysed the influence of particle size, charge, and chemical composition on the biological pathways affected by nanomaterials. All pathways activated by the ten metal oxide nanomaterials were related to inflammation, DNA damage, and apoptosis; however, the transcriptomic potencies of this group of materials differed by more than two orders of magnitude. Furthermore, nanomaterials with similar chemical compositions, particle sizes, and charges are more likely to cluster together based on profiles of altered pathways. In addition, small-sized manganese oxide nanomaterials are more likely to interfere with metabolic, cell component, and developmental pathways, whereas high-charge manganese oxide nanomaterials are more likely to activate pathways such as stress response, DNA damage, and hormone signalling. Concentration-dependent transcriptomic analysis can provide information on the biological pathways and associated potency, which can then provide references for future nanomaterial toxicity assessment and green metal oxide nanoparticle design.</p>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":" ","pages":"111909"},"PeriodicalIF":2.9,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tributyltin exposure disrupts intestinal barrier and enteric nervous system in the ileum of Wistar rats.","authors":"Gabriela Pustiglione Marinsek, Isabelly Cristina Correia Dos Santos de Oliveira, Manuela Agulló Tagliamento, Lucas Correia Villas Boas, Ítalo Braga de Castro, Regina Cláudia Barbosa da Silva, Renata de Britto Mari","doi":"10.1016/j.toxlet.2026.111906","DOIUrl":"10.1016/j.toxlet.2026.111906","url":null,"abstract":"<p><p>Tributyltin (TBT) is a lipophilic compound known to damage biological membranes and is associated with neurotoxic and inflammatory effects. This study evaluated the impact of TBT (20 ng/g and 600 ng/g) on the gastrointestinal tract (GIT) barrier and morphology and enteric nervous system (ENS) of Wistar rats exposed for 30 days via gavage. We observed a significant reduction in goblet cell density in the group 20 ng/g, and an increase in goblet cells in the group 600 ng/g. There was also an increase in intraepithelial lymphocytes (IELs) in both exposed groups, indicating an activated immune response and potential tissue injury. In the enteric nervous system, neuronal metabolism decreased without affecting overall neuronal density, in the group 20 ng/g, while the group exposed to 600 ng/g showed an increase in total neuronal density with the maintenance of metabolic activity. TBT exposure also induced an increase in peroxiredoxin-2 (Prx2) in both groups and altered occludin expression. Integrated biomarker response (IBR) analysis confirmed that TBT disrupted intestinal homeostasis and neuronal integrity, affecting cellular functions and causing immunological and oxidative dysfunctions.</p>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":" ","pages":"111906"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147820627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Acanthoic acid protectsagainst ethanol-induced liver injury: Possible role of AMPK activation and IRAK4 inhibition\" [Toxicol. Lett. 281 (2017) 127-138].","authors":"You-Li Yao, Xin Han, Jian Song, Jing Zhang, Ya-Mei Li, Li-Hua Lian, Yan-Ling Wu, Ji-Xing Nan","doi":"10.1016/j.toxlet.2026.111897","DOIUrl":"https://doi.org/10.1016/j.toxlet.2026.111897","url":null,"abstract":"","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":" ","pages":"111897"},"PeriodicalIF":2.9,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enantioselective CYP inhibition by diclofop, the active metabolite of diclofop-methyl: Mechanism and relevance for human exposure","authors":"Maike Felipe Santos Barbetta ,&nbsp;Giovanni Stoppa Baviera ,&nbsp;Leandro Oka-Duarte ,&nbsp;Icaro Salgado Perovani ,&nbsp;Anderson Rodrigo Moraes de Oliveira","doi":"10.1016/j.toxlet.2026.111844","DOIUrl":"10.1016/j.toxlet.2026.111844","url":null,"abstract":"<div><div>Diclofop (DF) is the main chiral metabolite of diclofop-methyl (DFM), a widely used herbicide for grass weed control. While DFM toxicity is documented, little is known about DF, despite its persistence. This study evaluated the enantioselective inhibition by racemic DF and its enantiomers over the major cytochrome P450 (CYP) isoforms present in human liver microsomes. The inhibition screening showed that (+)-DF preferentially inhibited CYP1A2, CYP2C9, CYP2E1, and CYP3A4/5, whereas (−)-DF was more active against CYP2C19 and CYP3A4/5. IC₅₀ and kinetic studies confirmed moderate inhibition without time-dependent effect. DF competitively inhibited CYP2C9 with a K_i value of 2.13 µmol L⁻¹. Finally, R₁ factor estimations indicated that <em>in vivo</em> inhibition is unlikely even at exposure levels up to 100-fold above the acceptable daily intake. These results highlight the enantioselective inhibitory potential of a pesticide metabolite and its relevance for pesticide–drug interactions and human toxicity.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"417 ","pages":"Article 111844"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146094273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triclosan’s interference with endocrine signalling: A mechanistic investigation","authors":"Deepa Sharma ,&nbsp;Tarang Kumar Shah ,&nbsp;Reshma Sinha","doi":"10.1016/j.toxlet.2026.111851","DOIUrl":"10.1016/j.toxlet.2026.111851","url":null,"abstract":"<div><div>The triclosan (TCS) has been widely used as an antimicrobial and antibacterial agent in personal care products, medical, acrylic, veterinary, and household items. Owing to its capacity to interfere with hormone-regulated pathways, it has been evidenced as a potential endocrine-disrupting chemical. This review summarizes the existing data on the mechanistic basis of TCS-induced endocrine disruption, emphasizing its impacts on steroidogenesis, receptor-based signalling, thyroid hormone regulation, crosstalk with metabolic hormones, and transformation product hazards. Consolidating molecular and cellular studies, this review highlights TCS-altered major endocrine functions and identifies areas of concern requiring further investigation for risk assessment and regulatory decisions.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"417 ","pages":"Article 111851"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146120220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bisphenol S and F disrupt cerebellar functions and neuronal health: The role of estrogen receptor and BMP2 signaling","authors":"Uttara Das ,&nbsp;Neetu Shukla ,&nbsp;Deeksha Ojha ,&nbsp;Garima Sagar ,&nbsp;Somendu Kumar Roy ,&nbsp;Sanghamitra Bandyopadhyay","doi":"10.1016/j.toxlet.2026.111850","DOIUrl":"10.1016/j.toxlet.2026.111850","url":null,"abstract":"<div><div>Bisphenol S (BPS) and bisphenol F (BPF) have gained attention as endocrine disruptors that affect brain functions, with their specific impact on the cerebellum being less thoroughly explored. Estrogen receptors (ERs) are crucial in maintaining neuronal health in the cerebellum, which participates in motor coordination. Additionally, bone morphogenetic proteins (BMPs) participate in various neuronal processes and are influenced by ER signaling. This study investigated how environmentally relevant doses of BPS and BPF (0.4–40 μg/kg) affect cerebellar functions in adult female rats, with a particular emphasis on ER and BMP signaling. Our assessments of motor coordination, conducted using rota-rod and grip strength tests, indicated that exposure to BPS/BPF significantly compromised balance and muscle strength. Investigation of cerebellar tissue revealed decreased levels of estrogen receptors ERα and ERβ, along with reduced BMP2 at both mRNA and protein levels. BMP2 signaling was also diminished, marked by lower BMPR2 and downstream components like p-Smad. Notably, ER agonists PPT and DPN restored BMP2 levels, while BMP2 administration enhanced ERα and ERβ levels, highlighting a reciprocal relationship between these signaling pathways. Moreover, treatments with PPT, DPN, and BMP2 led to improvements in neuronal survival, NeuN levels, and overall motor coordination performance. In conclusion, BPS and BPF disrupt cerebellar functions and neuronal health by interfering with the interplay between ER and BMP2 signaling, suggesting that targeting these pathways may help mitigate the adverse effects of these chemicals.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"417 ","pages":"Article 111850"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of non-dietary human health risk based on concentration of multiresidue pesticides in soil of irrigated farmland around Lake Ziway, Ethiopia","authors":"Asrat Fekadu Demsie","doi":"10.1016/j.toxlet.2026.111855","DOIUrl":"10.1016/j.toxlet.2026.111855","url":null,"abstract":"<div><div>Soil samples collected from irrigated farmlands around Lake Ziway were thoroughly analyzed for 35 different pesticides, yielding significant insights into contamination profiles and the non-dietary health risks associated with these substances in the region. The analysis utilized gas chromatography-mass spectrometry (GC-MS) techniques. To assess non-dietary health risks, the study employed metrics such as the hazard index (HI) and Incremental Lifetime Cancer Risk (ILCR), considering various exposure pathways, including ingestion, dermal contact, and inhalation for both children and adults. The results revealed a concerning level of pesticide contamination in the agricultural soils of the area. Propargite was identified as the most prevalent contaminant, with a concentration of 62.463 ± 21.963 µg/kg, followed by p,p’-DDE at 46.85 ± 10.052 µg/kg. Other pesticides were detected at significantly lower levels. Risk estimates based on HI values indicated a non-carcinogenic risk for children and adults at 1.08E-02 and 1.35E-03, respectively, suggesting that the non-carcinogenic risk remains within acceptable limits (HI &lt;1). The ILCR for children across all exposure levels, as well as for adults in terms of ingestion was found to be range from 1.59E-08–3.38E-16, suggesting that there is no significant cancer risk to humans through these pathways. However, the ILCRs associated with dermal contact for adults indicate a potential cancer risk, with estimates ranging from 10⁻⁴ to 10⁻⁶. Furthermore, model estimates indicate that adults face a greater cancer risk of non-dietary pesticide exposure compared to children. These findings highlight the urgent need for enhanced monitoring programs that address both currently used and banned pesticides.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"417 ","pages":"Article 111855"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146174583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal dibutyl benzene-1,2-dicarboxylate exposure accelerates bone marrow mesenchymal stem cells senescence to induce skeletal retardation in male offspring mice","authors":"Yao Zhang ,&nbsp;Kehan Wang ,&nbsp;Jingzhu Lu ,&nbsp;Ruicheng Wang ,&nbsp;Chun Pan ,&nbsp;Tan Ma ,&nbsp;Fuyuan Ma","doi":"10.1016/j.toxlet.2026.111843","DOIUrl":"10.1016/j.toxlet.2026.111843","url":null,"abstract":"<div><div>Dibutyl benzene-1,2-dicarboxylate (DBP), a ubiquitous plasticizer, readily crosses the placenta, posing a risk to male offspring development. Previous studies have found that maternal DBP exposure leads to multiple organ development disorders in male offspring, but the effect on skeletal development in male offspring mice is unclear. In this study, pregnant mice were orally administered corn oil from day 12 of pregnancy or given different doses of DBP by gavage. Our results showed that prenatal DBP exposure induced dose-dependent deterioration in the male offspring's femoral bone microarchitecture, as revealed by micro-CT. <em>In vitro</em>, we found that the primary metabolite MBP disrupted the osteogenic-adipogenic balance in bone marrow mesenchymal stem cells (BMSCs) by suppressing osteogenic differentiation while promoting adipogenic differentiation. Mechanistically, MBP treatment induced a premature senescent phenotype in BMSCs, as evidenced by heightened senescence-associated β-galactosidase (SA-β-Gal) activity, upregulation of senescence markers (γH2AX, p16, p21), and increased secretion of senescence-associated inflammatory factors. Critically, treatment with rapamycin prevented MBP-induced senescence and restored the osteogenic-adipogenic balance in BMSCs. This study identifies BMSCs senescence as a pivotal mechanism underlying DBP-induced skeletal retardation, providing novel insights into the environmental bone toxicity of phthalate exposure.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"417 ","pages":"Article 111843"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146081064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcript-protein discrepancy of glutamatergic receptor subunits in human iPSC-derived neurons: Implications for neurotoxicity testing","authors":"Melania Maria Serafini ,&nbsp;Miriam Midali ,&nbsp;Giacomo Grumelli ,&nbsp;Alessandro Cutarelli ,&nbsp;Marina Marinovich ,&nbsp;Luciano Conti ,&nbsp;Barbara Viviani","doi":"10.1016/j.toxlet.2026.111834","DOIUrl":"10.1016/j.toxlet.2026.111834","url":null,"abstract":"<div><div>The development of robust human in vitro models is crucial for advancing neurotoxicology and reducing animal testing. Human-induced pluripotent stem cell (hiPSC)-derived neuronal models hold great promise, but still show limitations in recapitulating certain neurodevelopmental processes. Currently, rodent primary cultures remain the gold standard for studying complex processes such as synaptogenesis. A key mechanism in glutamatergic synapse maturation is the GluN2B/GluN2A switch, which promotes the recruitment of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, increasing the structural and functional complexity of the synaptic spines. This study characterizes the development of the glutamatergic machinery in hiPSC-derived neurons, focusing on the expression and maturation of N-methyl-<span>D</span>-aspartate (NMDA) and AMPA receptors. The increase of neuronal markers and the reduction of progenitor markers confirmed the differentiation efficiency. However, discrepancies emerged between transcriptional and protein profiles of key receptor subunits. GluN2A mRNA levels increased over time, while protein levels remained similar to those of neural progenitor cells (NPCs). Conversely, the GluN3A transcript increased at 30 and 60 days in vitro (DIV), while protein abundance decreased. Similar transcript–protein mismatches were observed for some AMPA receptor subunits. These results suggest that this model does not reach full glutamatergic maturity within the tested timeframe. Therefore, optimizing differentiation conditions (such as extending culture duration or adding maturation cues) may be necessary to better reproduce receptor dynamics. Finally, this study highlights the need to integrate protein-level analyses with transcriptional data to improve the reliability of hiPSC-derived neuronal models for neurotoxicity and NMDA receptor–mediated excitotoxicity studies.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"417 ","pages":"Article 111834"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146067245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}