Toxics最新文献

{"title":"Mixture-Dependent Toxicity of E-Cigarette Constituents: Cytotoxicity, Inflammation, and DNA-Repair-Associated Protein Responses in Bronchial Epithelial Cells.","authors":"Ehsanul Kabir, Joshua Furst, Thivanka Muthumalage","doi":"10.3390/toxics14100910","DOIUrl":"10.3390/toxics14100910","url":null,"abstract":"<p><p>Electronic cigarette (e-cigarette) aerosols contain complex mixtures of flavoring chemicals, synthetic cooling agents, and metals derived from device components. The biological effects of these constituents in combination remain incompletely characterized. We evaluated selected flavoring chemicals and nickel oxide (NiO), individually and in combination, in BEAS-2B human bronchial epithelial cells. Cells were exposed for 24 h to vanillin, WS23, ethyl vanillin, or p-anisaldehyde over an experimental concentration range of 10-1000 µM. Vanillin-WS23 and ethyl vanillin-p-anisaldehyde mixtures were evaluated at a fixed total concentration of 1000 µM over multiple component ratios. Separate experiments evaluated 100 µM ethyl vanillin, 50 µg/cm² NiO, and their combination. Vanillin, WS23, ethyl vanillin, and p-anisaldehyde reduced viability-associated metabolic activity and cellular ATP in a concentration-dependent manner. The lowest concentrations associated with significant reductions in the MTT endpoint were 200 µM for vanillin, 50 µM for WS23, 300 µM for ethyl vanillin, and 200 µM for p-anisaldehyde. Chou-Talalay analysis identified synergistic interactions between vanillin and WS23 (combination index [CI] < 1) and antagonistic interactions between ethyl vanillin and p-anisaldehyde (CI > 1). Ethyl vanillin and NiO produced no statistically significant decrease in viability but increased inflammatory cytokines in conditioned medium. Both IL-6 and IL-8 levels were significantly elevated with NiO and the combined ethyl vanillin-NiO exposure. Total H2AX abundance did not differ significantly among groups at 24 h. NEIL2 abundance showed increasing trends following NiO alone (<i>p</i> = 0.0518) and combined ethyl vanillin-NiO exposure (<i>p</i> = 0.0760). PNKP increased significantly after ethyl vanillin (<i>p</i> = 0.0261) and combined ethyl vanillin-NiO (<i>p</i> = 0.0041) treatments. These findings show mixture-dependent biological responses that differed from the effects observed with individual constituents. Flavoring chemical mixtures produced either synergistic or antagonistic effects, and ethyl vanillin-NiO exposure produced inflammatory and DNA-repair-associated protein responses under conditions that did not significantly reduce cell viability. By demonstrating non-additive flavoring chemical interactions together with inflammatory and DNA-repair-associated protein responses to chemical-metal exposure, this study evaluated e-cigarette toxicity beyond single-constituent hazard characterization. The NEIL2 and PNKP findings support altered base-excision repair (BER) pathways but do not establish oxidative DNA lesions or increased DNA repair activity.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 10","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13709782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149273433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subcortical Microstructural Changes Associated with Multiple Metal Exposure.","authors":"Eun-Young Lee","doi":"10.3390/toxics14100911","DOIUrl":"10.3390/toxics14100911","url":null,"abstract":"<p><p>Metal exposure has been associated with neurodegenerative disorders including Parkinson's disease (PD). This study examined microstructural changes in subcortical motor areas associated with chronic metal exposure. Subjects with/without a welding history (metal-exposed subjects; <i>n</i> = 23 and controls; <i>n</i> = 24) were examined. Brain microstructural differences were assessed by MRI diffusion metrics [mean (MD), axial (AD), radial diffusivity (RD) and fractional anisotropy (FA)] in subcortical motor areas [nigro-basal ganglia-thalamic circuit: substantia nigra (SN), caudate nucleus (CN), putamen, globus pallidus (GP), and thalamus; dentatorubral circuit: dentate nucleus (DN) and red nucleus (RN)]. Metal exposure was estimated by lifetime welding years, whole blood metal levels, and T1 and R2* (1/T2*) metrics (estimates of brain metal accumulation). Compared to controls, metal-exposed subjects displayed higher diffusivities in the GP and thalamus (<i>p</i>'s < 0.033) but lower FA values in the putamen, SN, and thalamus (<i>p</i>'s < 0.039) without differences in DN and RN (<i>p</i>'s > 0.115). Blood metal mixtures predicted higher GP and SN T1 metrics (<i>p</i>'s < 0.05). Higher T1 metrics predicted higher GP and TH diffusivities and lower SN and TH FA values (<i>p</i>'s < 0.044). Higher blood vanadium levels predicted lower SN FA values (<i>p</i> = 0.009). Multiple metal exposure may be associated with microstructural compromises within the nigro-basal ganglia-thalamic circuit, while the dentatorubral circuit remains relatively spared, a pattern resembling that of PD at-risk populations.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 10","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13709804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149273645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain Gadolinium Biodistribution, Clearance, and Retention Following High-Dose Contrast-Agent Exposure in Mice: A Multimodal Study.","authors":"Alon Zahavi, Stephen Richard, Olga Girshevitz, Basel Obied, Yoav Vardizer, Hila Kreizman-Shefer, Jacob Bajar, Judith Luckman, Dror Fixler, Nitza Goldenberg-Cohen","doi":"10.3390/toxics14100907","DOIUrl":"10.3390/toxics14100907","url":null,"abstract":"<p><p>We evaluated gadolinium biodistribution, clearance, and long-term brain retention following high-dose gadolinium-based contrast agent (GBCA) exposure in 90 mice. Macrocyclic and linear agents were assessed using particle-induced X-ray emission (PIXE) alongside complementary elemental, imaging, and histological methods. Following intravenous administration, gadolinium was detected in blood and multiple tissues during the acute phase, with declining blood levels and detectable urinary excretion. No brain Gd signal was detected by PIXE at the long-term endpoints following single exposure. Repeated-exposure findings were descriptive because the individual subgroups contained only 1-3 animals. Endpoint MRI showed no apparent persistent signal changes, and H&E examination showed preserved tissue morphology. Metallothionein staining varied qualitatively, whereas Iba1 staining showed no apparent increase in microglial activation. Intraperitoneal administration produced no detectable blood gadolinium at the 1-h sampling timepoint. These findings characterize high-dose experimental exposure and support the feasibility of multimodal assessment of gadolinium biodistribution. Negative findings do not exclude residual Gd below the detection capabilities of the methods used.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 10","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13709646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149273443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surfactant-Enhanced In Situ Remediation Beneath an Occupied Residential Building: Reduction of the BTEX Vapor-Intrusion Source Term and Field Validation in a Single Field Season.","authors":"Gautier Decabooter","doi":"10.3390/toxics14100906","DOIUrl":"10.3390/toxics14100906","url":null,"abstract":"<p><p>Petroleum hydrocarbon contamination beneath occupied buildings poses a chronic BTEX vapor-intrusion risk, yet field-scale evidence for in situ remediation under occupied residential structures remains scarce. We report a full-scale surfactant-enhanced remediation (SER) campaign at a former service-station site in Quebec City (Canada), where 235 m² of contaminated soil extended directly beneath an occupied multi-unit residential building. Through 46 dual-action injection-extraction wells, 15.3 m³ of a biodegradable polysorbate-family washing solution and 31.2 m³ of rinse water were delivered by a stop-and-go protocol over 115 days. Pre-treatment soils reached Criterion C for BTEX (xylenes up to 335 mg kg^-1). Validation sampling at three sectors showed compliance with Quebec Criterion B at two of them, with a single residual xylenes exceedance (9.0 mg kg^-1; Criterion B = 5) at Sector 1. Sector-mean abatement reached >99% for ethylbenzene and xylenes at Sector 2, 79% and 90% at Sector 1, and 60-61% for TPH C₁₀-C₅₀. All validation results complied with the provincial criterion for the methylnaphthalenes, yet 1-methylnaphthalene remained 2.2-5.0 times its inhalation-driven USEPA residential screening level. Biodegradable SER can substantially reduce the BTEX vapor-intrusion source term within a single season without displacing occupants; occupant exposure itself was not measured.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 10","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13709739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149273648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"6PPD-Quinone Induces Anxiety-like Behavior in Mice: A Potential Mechanism Shared Across PPD-Quinones.","authors":"Su Xu, Leyan Gao, Yongquan Yu, Ying Kang, Xinting Chen, Shou-Lin Wang, Zengliang Ruan","doi":"10.3390/toxics14100909","DOIUrl":"10.3390/toxics14100909","url":null,"abstract":"<p><p>The increasing occurrence of anxiety disorders caused by emerging environmental toxicants has become a significant global health concern. While recent evidence indicates that 6PPD-Q can induce anxiety-like behavior, the specific mechanisms connecting 6PPD-Q to anxiety-like behavior are still largely unknown. This gap in understanding restricts our knowledge of their neurotoxic potential and complicates the development of targeted treatment strategies. Here, adverse effects, including neuronal degeneration, synaptic dysfunction, and impaired GABAergic signaling in the amygdala, were observed in mice exhibiting anxiety-like behavior following 6PPD-Q exposure. Integrated network toxicology and transcriptomic analysis revealed that inhibition of the cAMP signaling pathway was associated with PPD-Q-related anxiety-like behavior, and adenosine receptors, particularly ADORA2A, as potential targets of 6PPD-Q. Specifically, molecular docking and molecular dynamics simulations suggested that 6PPD-Q may stably interact with the orthosteric ligand-binding pocket of ADORA2A, potentially interfering with receptor activation. Importantly, the predicted interaction with ADORA2A may represent a potentially shared neurotoxicological feature among PPD-Qs, consistent with the computationally predicted interaction profiles across PPD-Qs. Moreover, pharmacological activation of ADORA2A with the selective agonist significantly alleviated the 6PPD-Q-induced neurobehavioral deficits in mice. Collectively, our research provides evidence supporting the involvement of ADORA2A and the cAMP-related signaling pathway in 6PPD-Q-induced anxiety-like behavior, providing a timely foundation for preventing neuropsychiatric disorders associated with PPD-Q exposure.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 10","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13709583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149273541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"POPs Contamination of Aquatic Sediments of the Cerna River Watershed, Romania-Prevalence, Pollution Sources, and Ecological Risk Assessment.","authors":"Irina Monica Simó, Vlad Alexandru Pănescu, Mihaela Cătălina Popovici, Ye Yang, Jérome Vial, Maria Concetta Bruzzoniti, Mihail Simion Beldean-Galea","doi":"10.3390/toxics14100908","DOIUrl":"10.3390/toxics14100908","url":null,"abstract":"<p><p>This study aims to evaluate the prevalence and pollution sources of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs) in sediments of the Cerna River and its main tributaries, and to assess the associated ecological risk on aquatic ecosystem. The compounds were extracted from the dried sediments by ultrasound-assisted extraction and analyzed by gas chromatography coupled with mass spectrometry for PAHs, and with electron capture detector for PCBs and OCPs. Six isomeric and molecular ratios were used to identify the sources of pollution, three for PAHs, and three for OCPs. Ecological risk was assessed using the effects-range low (ERL) and effects-range median (ERM) methods, and health risk using toxic equivalent factors (TEFs). Twenty sediment samples from ten sampling points in two campaigns (October 2023 and August 2024) were collected. Results revealed high concentrations of ƩPAHs, with concentrations between 3.86 and 4450.75 ng/g dw, with values of the isomeric ratios indicating pyrogenic origins. OCPs concentrations ranged between 4.25 and 129.56 ng/g dw. PAHs presented a low biological risk, having concentrations below ERL. Low biological risk was also observed for ƩPCBs, ƩDDTs with values below ERL, and some between ERL and ERM, indicating occasional possible adverse effects.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 10","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13709422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149273387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simulation of Groundwater Pollutant Transport Characteristics in Mining Areas Driven by Subsurface Flow Velocity Fields.","authors":"Chen Zhao, Qiong Li, Ying Zhang","doi":"10.3390/toxics14100905","DOIUrl":"10.3390/toxics14100905","url":null,"abstract":"<p><p>Groundwater pollution in chemical industrial parks is typically concealed, delayed in onset, and difficult to remediate. Moreover, the long-term migration of typical pollutants in aquifers may threaten the safety of surrounding water sources and river water environments. In this study, a numerical subsurface flow model was constructed for a chemical industrial park in a mining area of Inner Mongolia by generalizing the Quaternary loose-rock pore aquifer system, based on hydrogeological surveys and groundwater monitoring data, using MODFLOW. A solute transport model was then established through coupling with MT3DMS to predict the spatiotemporal evolution of ammonia nitrogen and 1,2-dichloroethane in the absence of new pollution sources, and the influence of subsurface flow velocity on pollutant diffusion was further analyzed. The results show that the contaminant plume area gradually increases over the simulation period: the ammonia nitrogen plume expands from 1.84 km² to 3.98 km², and the 1,2-dichloroethane plume expands from 1.47 km² to 3.05 km². Contaminant concentrations in individual wells generally exhibit a downward trend; nonetheless, long-term exceedance risks persist at specific sites. These findings provide a scientific basis for groundwater pollution risk management, water source protection, and subsequent remediation decisions for chemical industrial parks in arid and semi-arid regions.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 10","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13709667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149273506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Toxic Effects and Mechanism of Acetamiprid Exposure on Testicular Tissue: ALKBH5 Regulates m⁶A Modification to Affect PI3K-AKT-Mediated Apoptosis.","authors":"Xiaoyan Hua, Yubin Li, Lixiang Pang, Huiyuan Zhang, Yuwen Wang, Bing Wu, Haoxuan Gao, Yanan Song, Yucheng Yan, Huifang Yang, Yikai Qiu, Ji Zhao","doi":"10.3390/toxics14100903","DOIUrl":"10.3390/toxics14100903","url":null,"abstract":"<p><p>(1) Background: Acetamiprid, a widely used neonicotinoid insecticide, has increasingly drawn people's attention to its potential reproductive toxicity risks. Although existing studies have shown that exposure to acetamiprid can cause testicular damage, its underlying molecular mechanism has not been fully elucidated. (2) Methods: This study established a mouse model of acetamiprid exposure via free drinking water and combined it with in vitro culture of TM3 cells, aiming to explore the toxic effects of acetamiprid on testicular tissue and its potential mechanism. (3) Results: Acetamiprid exposure induced significant pathological damage to the testicular tissue of mice and significantly reduced sperm quality. Further mechanism studies have shown that acetamiprid down-regulates the expression of RNA demethylase ALKBH5, leading to an overall increase in m⁶A modification levels, thereby inhibiting the activity of the PI3K/AKT signaling pathway and ultimately inducing apoptosis of TM3 cells. (4) Conclusions: In conclusion, this study, by integrating both internal and external models, has revealed a molecular mechanism by which acetamiprid is involved in testicular injury through epigenetic pathways, providing scientific basis and mechanism clues for assessing reproductive hazards caused by exposure to environmental toxins.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 10","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13709516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149273651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does Biofunctionalization Make ZnO and TiO₂ Nanoparticles Safer? A Critical Review of Their Changing Toxicological Identity.","authors":"Liliana Cepoi, Tatiana Chiriac, Ludmila Rudi, Lilit Gabrielyan, Anna Karapetyan","doi":"10.3390/toxics14100904","DOIUrl":"10.3390/toxics14100904","url":null,"abstract":"<p><p>ZnO and TiO₂ nanoparticles are increasingly biofunctionalized to improve stability, biological recognition, targeting, and compatibility. However, whether biofunctionalization inherently makes these nanoparticles safer remains unresolved. Rather than cataloguing biofunctionalization strategies, this critical review evaluates whether toxicological changes can be attributed specifically to deliberate biomolecular surface modification and whether any resulting safety advantage persists during exposure-relevant transformations. A structured literature search identified 60 publications for critical synthesis, including 10 comparative studies providing direct evidence on toxicological changes attributable to deliberate biofunctionalization. The available evidence does not support a uniform toxicity-reducing effect. Depending on the nanoparticle-biointerface combination and exposure context, biofunctionalization can reduce toxicity, produce coating-dependent changes, increase biological accessibility, or redirect reactivity toward selected biological targets. These outcomes arise from changes in surface charge, aggregation, colloidal stability, cellular interactions, and biointerface evolution and are material-specific: ZnO additionally requires consideration of dissolution and Zn²⁺ release, whereas TiO₂ behavior is more strongly influenced by particulate persistence and surface-mediated reactivity. We therefore conceptualize toxicological identity as an evolving, exposure-dependent profile rather than an intrinsic material property. Within a safe-by-design framework, biofunctionalization is advantageous only when it reduces non-target toxicity, preserves or improves the intended function, and maintains this advantage after exposure-relevant transformations.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 10","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13709862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149273407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Smoking-Related Multi-Metal Exposure Associated with Hierarchical Gut Microbiota Alterations in Colorectal Polyp Patients.","authors":"Jiali Long, Di Wu, Yingru Liang, Rong He, Yongxian Li, Lei Tan, Peng He, Jun Yuan, Jichuan Shen, Boheng Liang, Shuxian Chen","doi":"10.3390/toxics14100902","DOIUrl":"10.3390/toxics14100902","url":null,"abstract":"<p><p>Smoking-related metal exposure involves complex mixtures, yet its combined effects on gut microbiota and colorectal polyp progression remain unclear. We constructed a multi-metal disruption index integrating urinary arsenic, cadmium, and zinc concentrations that differed significantly between smokers and non-smokers in 196 colorectal polyp patients in 2023-2024 and examined its associations with gut microbiota and colorectal polyp progression. The index showed dose-dependent increases in detection rates of <i>Limosilactobacillus</i>, <i>Methylovirgula</i> and <i>Peptoclostridium</i>, with the most robust association observed for <i>Limosilactobacillus</i> after adjusting for covariates (OR = 3.39, 95%CI: 1.49-7.76, <i>p</i> = 0.004). Its detection rate was broadly negatively associated with the predicted abundance of pathways such as metabolism and organismal systems. In stratified analyses, the number of pathways with decreased predicted abundance among <i>Limosilactobacillus</i>-positive samples increased significantly as index levels rose (low: 0/27; medium: 15/27; high: 19/27), with 10 pathways significant at both medium and high levels. This dose-dependent genus-level response was observed alongside population-level relative stability, as no significant associations were found between the index and colorectal polyp progression. This multi-Metal Index approach provides a practical framework for assessing the health effects of smoking-related multi-metal mixtures. The dose-dependent increase in Limosilactobacillus colonization, occurring together with the decreased predicted abundance of specific metabolic pathways, suggests a possible association with metal-related stress.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 10","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13709704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149273511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}