Inhalation Toxicology最新文献

{"title":"Spatially distinct molecular and immune responses to ozone exposure during mutant surfactant protein-C-induced lung injury.","authors":"Claire B Montgomery-Bowie, Jenna R Cheminant, Meghan Buddy, Yerim Lee, Jessica Noll, Alessandro Venosa","doi":"10.1080/08958378.2026.2738562","DOIUrl":"https://doi.org/10.1080/08958378.2026.2738562","url":null,"abstract":"<p><strong>Objective: </strong>Environmental exposure and genetic mutations are key factors in the pathogenesis and exacerbation of fibrosis. This work maps the distribution ozone (O₃) signals and examines the impact of exposure in lung remodeling.</p><p><strong>Materials and methods: </strong>Spatial transcriptomic and proteomic analyses were performed on CD68⁺ macrophages and CD45^- non-immune cells from histologically distinct regions of air- or O₃-exposed (0.8 ppm, 3 h) SP-C mutant lungs. Fibrosis was initiated by tamoxifen-mediated induction of a disease-linked Surfactant Protein (SP)-C gene mutation. The effects of O₃ exposure prior or after SP-C induction were assessed <i>via</i> histology, flow cytometry, and immunohistochemistry.</p><p><strong>Results: </strong>Multi-omics analysis of O₃ injury revealed spatially restricted and cell-specific responses, characterized by mitochondrial metabolism and antioxidant pathway enrichment in injured-region macrophages, while peri-injured cells displayed pro-survival and lipid metabolism signatures. O₃ exposure induced senescence and cell-cycle regulatory signals in all CD45^- cells, with peri-injured exhibiting additional metabolic and collagen remodeling pathways. Proteomics showed widespread phospho-signaling in CD45^- cells, an effect restricted to peri-injured areas in CD68⁺ macrophages. O₃ exposure in fibrosing SP-C mutant mice caused Ly6C^hi monocyte influx at 3 days but dampened the expansion of CD4⁺/CD8⁺ T cell observed in the O₃ exposed uninduced lung. Fibrotic remodeling, cell proliferation (Ki67), and immune composition were not influenced by O₃ exposure at 7 days, though their combination increased mouse mortality and inflammatory cell activation (iNOS).</p><p><strong>Conclusion: </strong>These data identify O₃ exposure as a modifier of regional inflammatory and stress-response pathways with modest effects on disease progression in the SP-C mutant lung.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"1-16"},"PeriodicalIF":2.1,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concerns about methodology and inference in Davigo and colleagues' review of heated tobacco products.","authors":"Red Thaddeus D Miguel, Isabella Steffensen","doi":"10.1080/08958378.2026.2683422","DOIUrl":"10.1080/08958378.2026.2683422","url":null,"abstract":"","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"524-525"},"PeriodicalIF":2.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148194702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N-acetylcysteine multifaceted activity in the control of toxicity induced in C57BL/6 mice by long-term inhalation of low-dose formaldehyde.","authors":"Elena Cecilia Marcano-Gómez, Pedro Alves Machado-Junior, Ana Beatriz Farias de Souza, João Pedro Oliveira Rezende, Vitoria Louise Texeira, Renata Rebeca Pereira, André Talvani, Daniela Caldeira Costa, Frank Silva Bezerra","doi":"10.1080/08958378.2026.2678376","DOIUrl":"10.1080/08958378.2026.2678376","url":null,"abstract":"<p><strong>Objective: </strong>This study investigated whether N-acetylcysteine (NAC) protects against the harmful effects induced by long-term inhalation of low-dose formaldehyde (FA).</p><p><strong>Materials and methods: </strong>Male C57BL/6 mice were divided into six groups: control (CG), vehicle (VG), FA-exposed (1% FA by inhalation), and three FA-exposed groups treated with NAC (100, 150, or 200 mg/kg; FN100, FN150, and FN200, respectively) administered by orogastric gavage during six months. Ventilatory and biometric parameters were assessed; biological samples were collected for analysis.</p><p><strong>Results: </strong>FA exposure reduced body mass and increased relative lung mass. Total and differential leukocyte counts in peripheral blood were reduced, whereas inflammatory cell influx to the airways was increased. Oxidative stress was evidenced by elevated carbonyl protein and TBARS levels. There was an increased superoxide dismutase activity, and reduced catalase activity. Redox imbalance was further characterized by increased sulfhydryl group levels, and there was a decreased reduced glutathione system. FA exposure also induced a marked inflammatory response, with elevated levels of IL-6, IL-15, IL-13, and IL-10. Structural lung damage was indicated by decreased alveolar airspace volume density and mean linear intercept, along with increased septal volume density, and it was associated with altered ventilatory parameters, including reduced respiratory rate and increased tidal volume. MMP-9 activity was reduced following FA exposure. NAC administration attenuated oxidative stress, inflammatory mediator release, pulmonary inflammation, and lung tissue damage.</p><p><strong>Conclusion: </strong>These findings demonstrate that NAC exerts protective effects by modulating redox imbalance and inflammatory responses, thereby preventing lung injury and respiratory dysfunction induced by long-term FA inhalation.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"496-512"},"PeriodicalIF":2.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of exposure to environmental heavy metals with markers of sepsis susceptibility: a population-based study from NHANES.","authors":"Duo Li, Zhu Yue, Genshen Zhen","doi":"10.1080/08958378.2026.2687782","DOIUrl":"10.1080/08958378.2026.2687782","url":null,"abstract":"<p><strong>Background: </strong>Sepsis is a life-threatening syndrome of immune dysregulation; preexisting lymphopenia and an elevated neutrophil-to-lymphocyte ratio (NLR) heighten host susceptibility. Chronic low-dose exposure to lead (Pb), cadmium (Cd), and mercury (Hg) is immunotoxic, but its association with these pre-sepsis markers in the general population remains unclear.</p><p><strong>Methods: </strong>We analyzed 12,580 adults from NHANES 2011-2018. Outcomes were lymphopenia (absolute lymphocyte count <1.0 × 10⁹/L) and high NLR (top quartile). Survey-weighted logistic and Weighted Quantile Sum (WQS) regressions evaluated individual and joint mixture effects. Restricted cubic splines modeled dose-response relationships. Continuous exposure models were also constructed to minimize information loss.</p><p><strong>Results: </strong>Fully adjusted models showed higher quartiles of Pb, Cd, and Hg were each associated with greater odds of lymphopenia and high NLR. Comparing highest to lowest quartiles, ORs for lymphopenia were 1.85 (95% CI 1.42-2.41) for Pb, 1.66 (95% CI 1.28-2.15) for Cd, and 1.52 (95% CI 1.15-2.01) for Hg. Continuous models confirmed that each log2-fold increase in blood metals was associated with significantly reduced absolute lymphocyte counts and elevated NLR (all <i>p</i> < 0.05). The WQS index was positively associated with lymphopenia (OR 1.63) and high NLR (OR 1.48).</p><p><strong>Conclusion: </strong>In a nationally representative sample, chronic low-level exposure to Pb, Cd, and Hg was independently associated with an immune profile linked to sepsis susceptibility, suggesting environmental metal reduction as a potential population-level strategy to reduce sepsis risk.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"513-523"},"PeriodicalIF":2.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of alveoli-distributed lung geometry for ferrets to predict particle deposition in the respiratory tract.","authors":"Bahman Asgharian, Owen T Price, Michael J Oldham","doi":"10.1080/08958378.2026.2675448","DOIUrl":"10.1080/08958378.2026.2675448","url":null,"abstract":"<p><strong>Objective: </strong>Ferrets have long served as an important animal model for the study of respiratory infections, inhalation toxicology, and aerosolized therapeutics because of their anatomical and physiological similarities to humans. Despite their widespread use, quantitative models describing particle deposition within the ferret lung remain limited. In this study, we developed a mechanistic dosimetry model to predict total and regional deposition of inhaled inert particles in the ferret lower respiratory tract (LRT).</p><p><strong>Materials and methods: </strong>Two anatomically based lung geometries were constructed using available morphometric data: a modified typical-path symmetric lung geometry and a more physiologically representative 2-path symmetric lung geometry. Both models were designed to yield realistic lung volumes and airway counts while accommodating the limited availability of airway measurements. Airway dimensions were derived from published morphometric data and extended using sigmoidal curve fits to represent the complete tracheobronchial (TB) and pulmonary (PUL) regions. Lung ventilation was modeled assuming uniform pleural pressure, with airflow distributed proportionally to distal lung volume. Particle transport and deposition were simulated using a one-dimensional (1D) advection-diffusion framework incorporating gravitational settling, inertial impaction, and Brownian diffusion.</p><p><strong>Results and discussion: </strong>The 2-path symmetric lung geometry enables more realistic predictions of particle deposition throughout the lung, particularly with respect to deposition as a function of lung depth, allowing direct comparison of predicted deposition with <i>in vivo</i> imaging measurements.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"483-495"},"PeriodicalIF":2.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148211233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of PTCH1 receptor polymorphisms in the SHH signalling pathway as determinants of COPD severity and functional impairment.","authors":"Nidhi Mahajan, Vishal Chopra, Kranti Garg, Siddharth Sharma","doi":"10.1080/08958378.2026.2728395","DOIUrl":"https://doi.org/10.1080/08958378.2026.2728395","url":null,"abstract":"<p><strong>Background: </strong>Chronic Obstructive Pulmonary Disease (COPD) is a multifactorial disorder influenced by environmental exposures and genetic factors. The Hedgehog signaling pathway, particularly the PTCH1 receptor, plays a critical role in lung development, epithelial repair, and airway remodeling. However, its genetic contribution to COPD remains unclear.</p><p><strong>Objective: </strong>To evaluate the association of <i>PTCH1</i> polymorphic variants (rs56161606 and rs41313327) with COPD susceptibility and clinical phenotypes in a North Indian population.</p><p><strong>Methodology: </strong>A case-control study was conducted involving 500 COPD patients and 500 controls. Genotyping was performed on <i>PTCH1</i> polymorphic variants (rs56161606 and rs41313327) using PCR-RFLP. Logistic regression was applied, adjusting for age, sex, and smoking. Genotype-phenotype associations were assessed using spirometric parameters, GOLD-COPD classification, and COPD symptoms.</p><p><strong>Results: </strong><i>PTCH1</i> variants were not associated with overall COPD susceptibility. However, rs41313327 demonstrated an age-dependent effect, with the TT genotype increasing COPD risk in individuals aged ≥57 years (aOR = 1.8, <i>p</i> = 0.03). The rs56161606 variant was significantly associated with prolonged disease duration, increased mucus hypersecretion (aOR = 1.6, <i>p</i> = 0.04), exacerbation risk (aOR = 2.4, <i>p</i> = 0.02), and a genotype-dependent decline in the FEV₁/FVC ratio (<i>p</i> < 0.05), suggesting its role in airflow obstruction. Furthermore, rs56161606 exhibited phenotype-specific associations with dyspnea and physical activity, highlighting its potential influence on the clinical heterogeneity of COPD.</p><p><strong>Conclusion: </strong>The <i>PTCH1</i> rs56161606 polymorphism did not correlate with overall COPD susceptibility but appeared to be a possible genetic modulator of disease severity, affecting pulmonary function and phenotype-specific clinical symptoms. These results highlight the significance of Hedgehog signaling in airway remodeling and tissue repair mechanisms that contribute to the clinical heterogeneity of COPD.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"1-12"},"PeriodicalIF":2.1,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148911888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Respiratory health outcomes following co-exposure to subchronic high temperature, episodic wildfire smoke exposure, and high-cholesterol diet.","authors":"Thomas W Jackson, Devin I Alewel, Samuel A Vance, Stephen H Gavett, Mette C Schladweiler, Paul M Evansky, Michael Monsees, Danielle Freeborn, Joseph Martin, Ingrid J George, Nina Warren, Rachel D Grindstaff, Prasada Kodavanti, Torrie A Crabbs, Renee Fisher, Quashana Brown, Charan K Ganta, Robert C Sills, Ronald A Herbert, Urmila P Kodavanti","doi":"10.1080/08958378.2026.2697433","DOIUrl":"10.1080/08958378.2026.2697433","url":null,"abstract":"<p><strong>Background: </strong>Increased ambient temperature alongside concomitant heatwaves and wildfire smoke imperil human health. We examined whether long-term episodic exposure to wildfire smoke induced greater respiratory injury/inflammation in male rats subchronically housed at elevated temperature or consuming unhealthy, cholesterol-rich diets. Respiratory effects of wildfire eucalyptus smoke exposure (WFES; ∼7mg/m3 particulate matter) were assessed 2h and 24h post-exposure in rats housed at 22 °C (room temperature; RT) consuming normal diet (ND) and exposed to filtered air (FA) or WFES for 1h.</p><p><strong>Methods: </strong>To determine effects of ongoing exposure, 4-5-week-old rats were subchronically housed at RT or high temperature (HT; 30-31°C) and fed ND or high-cholesterol (2%) diet (HCD). Rats were episodically exposed to FA or WFES 1h/d, 1d/wk, for 12-13wk. 48h after final exposure, bronchoalveolar lavage fluid (BALF) lung injury and inflammation, gene expression, and lung/nasal pathology were assessed.</p><p><strong>Results: </strong>Acute WFES exposure increased BALF markers of lung injury and neutrophilic inflammation. Subchronic HT resulted in >30% lower weight gain and decreased body fat relative to RT; effects were greater in episodically WFES-exposed rats. Whole body plethysmography revealed HT-induced changes in breathing parameters; WFES exacerbated these effects. Small effects were observed on BALF markers of lung injury/inflammation, consistent with minimal pathological findings in lung and nasal cavity. All three stressors, individually and in combination, inhibited gene expression of proteins involved in glucocorticoid-mediated regulation of neuroendocrine stress response and peripheral homeostatic physiology.</p><p><strong>Conclusion: </strong>These findings suggest functional impairment at HT, exacerbated by WFES, linked to dysregulation of stress without affecting structural integrity of respiratory tract.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"433-454"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the toxicity of polystyrene micro- and nanoplastics in human bronchial epithelial cells: differences and challenges using aerosol and suspension exposures.","authors":"I F Gosselink, P Leonhardt, M J Drittij, E M Höppener, R J Smelt, F J van Schooten, A H V Remels","doi":"10.1080/08958378.2026.2695089","DOIUrl":"10.1080/08958378.2026.2695089","url":null,"abstract":"<p><strong>Objective: </strong>Studies investigating toxicity of airborne micro- and nanoplastics (MNPs) are mostly based on conventional submerged cell cultures while limited studies utilize air-liquid interface (ALI) systems. Inherent differences in these culture/exposure modalities, such as particle behavior and deposited dose, likely affect cellular responses. To investigate this, we exposed submerged human bronchial epithelial cells (BEAS-2B) to polystyrene (PS) MNPs <i>vs.</i> aerosol exposure of ALI cultures.</p><p><strong>Methods: </strong>First, submerged bronchial epithelial cells (BEAS-2B) were exposed to suspensions of PS particles (50 nm or 1 µm) in four different applied concentrations (0.79-50 µg/cm²; 24 h). Second, BEAS-2B cells were cultured at ALI and exposed in a cloud system to PS 1 µm particles (deposited dose: 55.4 µg/cm²; 24 h). Toxicity readouts focused on cytotoxicity (LDH release), inflammation (IL-8 release and transcriptional activation of inflammatory genes), and oxidative stress (DCFH-DA assay, antioxidant gene expression, and assessment of reduced/oxidized glutathione).</p><p><strong>Results: </strong>In both models, PS exposure did not induce cell death, or an antioxidant response. However, NF-κB transcriptional activity was strongly upregulated in submerged cells in response to both sizes of PS particles in a dose-dependent manner. Gene expression of <i>CXCL1</i>, <i>CXCL2</i>, and <i>CXCL8</i> increased up to 7-fold after PS microplastic exposure (50 µg/cm²) in the submerged model (which was less pronounced in response to PS nanoplastics) and 2-fold in the ALI model. In contrast, IL-8 secretion increased 1.6-fold for the ALI, but not the submerged model.</p><p><strong>Conclusions: </strong>Overall, both exposure modalities revealed an inflammatory response toward PS MNPs although with differences, likely due to significant differences in deposited dose.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"469-481"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148404547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of exposure to asbestos from the cutting of cement pipe with a powered saw.","authors":"Quincy Perry, Karmen Kissell, Dennis Paustenbach","doi":"10.1080/08958378.2026.2697434","DOIUrl":"10.1080/08958378.2026.2697434","url":null,"abstract":"<p><strong>Objective: </strong>This study characterized occupational asbestos exposure during the cutting of asbestos-containing cement (A/C) pipe using a gas-powered abrasive saw. Seven pipe sections (25% chrysotile, 10% crocidolite) were cut during two scenarios: above ground and within a shored trench.</p><p><strong>Materials and methods: </strong>Airborne fiber concentrations were quantified by phase contrast microscopy (PCM) and transmission electron microscopy (TEM), with TEM results converted to PCM-equivalent (PCME) concentrations. Mean 30-minute PCME concentrations were 0.81 f/cc during above-ground operations and 10.55 f/cc during in-trench cutting.</p><p><strong>Results: </strong>Eight-hour time-weighted averages (TWAs) and cumulative lifetime exposures were estimated assuming one eight-minute cutting event per week over a 45-year career. Above-ground cutting yielded eight-hour TWAs of 0.010 f/cc (chrysotile) and 0.004 f/cc (crocidolite); in-trench cutting produced 0.16 and 0.021 f/cc, respectively.</p><p><strong>Discussion and conclusions: </strong>All calculated TWAs were well below contemporaneous OSHA permissible exposure limits of 2 f/cc and higher. Estimated cumulative exposures were 0.061 f/cc-years (chrysotile) and 0.023 f/cc-years (crocidolite) for above-ground cutting, and 0.98 f/cc-years (chrysotile) and 0.13 f/cc-years (crocidolite) for trench conditions. These doses were below published no-observed-adverse-effect levels (NOAELs) for both fiber types. Chrysotile exposures were substantially lower than reported NOAEL ranges (100-300 f/cc-years), while crocidolite exposures approached but did not exceed estimated acceptable levels of exposure as derived from epidemiology studies (0.3-0.8 f/cc-years). Although abrasive saw use represents a worst-case scenario, findings indicate that historical occupational risks associated with A/C pipe cutting for the vast majority of workers were overestimated, particularly where manual methods for cutting or exposure controls were implemented.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"455-468"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhalation exposure to heat-not-burn tobacco aerosol versus combustible cigarette smoke: comparative assessment of respiratory and systemic toxicity in an experimental rat model.","authors":"Sena Nur Armağan, Hamza Ogun, Abdurrahim Koçyiğit, Eray Metin Güler, Muhammed Emin Akkoyunlu, Ali Toprak, Ali Gelir, Ömer Faruk Kadı, Kadir Berat Yıldırım","doi":"10.1080/08958378.2026.2686703","DOIUrl":"10.1080/08958378.2026.2686703","url":null,"abstract":"<p><strong>Objective: </strong>Heat-not-burn tobacco products (IQOS) have emerged as potentially reduced-risk alternatives to combustible cigarettes (CSs), yet their inhalation toxicity profile remains incompletely characterized.</p><p><strong>Materials and methods: </strong>This study evaluated the comparative respiratory and systemic effects of IQOS aerosol vs. CS smoke through whole-body inhalation exposure in an experimental rat model. Twenty-one male Wistar albino rats (8-10 weeks, 250-300 g) were randomly assigned to three groups (n = 7): control (ambient air), CS exposure (10 mg nicotine/day, ∼6 cigarettes/session), and IQOS exposure (equivalent nicotine dose, ∼8 HeatSticks/session). A custom-designed whole-body inhalation exposure system, developed in collaboration with Istanbul Technical University, delivered standardized aerosols following Health Canada Intense puffing parameters (55 mL puff volume, 27.5 mL/s flow rate, 2-s puff duration, 30-s inter-puff interval) during daily 1.5-h sessions over 21 consecutive days. Peripheral blood samples were collected on Days 7, 14, and 21 for assessment of plasma inflammatory markers (IL-1β, IL-6, TNF-α, and hs-CRP), oxidative stress parameters (total oxidant status [TOS], total antioxidant status, oxidative stress index), and DNA damage in isolated mononuclear leukocytes using the alkaline comet assay. Plasma cotinine was quantified as the primary biomarker of systemic nicotine absorption. Terminal lung tissue analysis on Day 21 evaluated local respiratory oxidative stress, inflammatory cytokine concentrations, and tissue cotinine deposition. .</p><p><strong>Results: </strong>Plasma TOS increased progressively in both exposure groups (CS: 9.2 ± 1.82 to 14.71 ± 1.65 µmol H2O2 Eq/L; IQOS: 6.81 ± 1.25 to 11.49 ± 1.30 µmol H2O2 Eq/L), with CS demonstrating significantly higher oxidative burden. DNA damage in circulating cells escalated markedly (CS: 21.74 ± 2.51% to 47.76 ± 3.67% tail DNA; IQOS: 16.22 ± 1.87% to 33.44 ± 2.41% tail DNA). Lung tissue analysis revealed significant 'elevation of inflammatory markers and oxidative stress parameters' in both exposure groups. While IQOS inhalation induced less severe toxicity than CS smoke, it produced significant respiratory and systemic adverse effects including oxidative stress, inflammatory responses, and DNA damage.</p><p><strong>Discussion and conclusion: </strong>These findings challenge claims of substantially reduced harm for heat-not-burn products and support continued regulatory oversight of inhaled tobacco delivery systems.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"417-432"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148375629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}