Frontiers in toxicology最新文献

{"title":"Correction: Epidemiological and clinical analysis of Gelsemium poisoning in Guangxi, Southern China: a decade of surveillance data.","authors":"Yanxu Zhong, Mengmeng Shi, Wei Mao, Huitian Deng, Xiaofeng Huang, Yuyan Jiang","doi":"10.3389/ftox.2026.1974873","DOIUrl":"https://doi.org/10.3389/ftox.2026.1974873","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/ftox.2026.1821880.].</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1974873"},"PeriodicalIF":5.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13574524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148972553","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":"Editorial: The safety assessment of novel foods and new nutrient sources.","authors":"Luisa Pozzo, Maria Glymenaki","doi":"10.3389/ftox.2026.1965747","DOIUrl":"https://doi.org/10.3389/ftox.2026.1965747","url":null,"abstract":"","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1965747"},"PeriodicalIF":5.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13572658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148972535","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":"Polymer-specific nanoplastics trigger oxidative stress, inflammatory activation, and mitoepigenetic remodeling: <i>in vitro</i> and <i>in silico</i> evidence for MT-ND6-mediated mitochondrial complex I perturbation.","authors":"Pradyumna Kumar Mishra, Aneha K Rajan, Apoorva Chouksey, Vikas Gurjar, Ashwani Pathak, Aniket Aglawe, Ravi Prakash Tiwari, Debabrata Dash, Ram Kumar Nema, Rajnarayan Tiwari, Devojit Kumar Sarma, Rupesh K Srivastava","doi":"10.3389/ftox.2026.1916884","DOIUrl":"10.3389/ftox.2026.1916884","url":null,"abstract":"<p><strong>Introduction: </strong>Recent studies have detected nanoplastics (NPs) in human tissues and biological fluids, raising concerns regarding their potential effects on cellular homeostasis. Nevertheless, their effects on mitochondrial regulation and mitoepigenetic processes remain poorly understood. This work aimed to study the polymer-specific effects of NPs, including polystyrene (PS), polypropylene (PP), and polyvinyl chloride (PVC), on mitochondrial function, mitochondrial homeostasis, oxidative stress generation, inflammatory response, and mitoepigenetics.</p><p><strong>Methods: </strong>Cell uptake of NPs was examined using flow cytometry and fluorescence microscopy. Analysis of mitochondrial membrane potential (Δψm), oxidative phosphorylation (OXPHOS), Mitochondrial reactive oxygen species (mtROS) generation, respiratory chain complexes, DNA damage repair enzymes, DNA methylation-related markers, inflammatory cytokines, and mitochondrial gene expression was performed at different time points after NP treatment. Moreover, docking analysis was performed to investigate the potential interactions between oxidized nanoplastic-derived oligomers and mitochondrial Complex I. The relationship between respiratory chain function and mtDNA expression was analyzed using regression.</p><p><strong>Results: </strong>The observed effects of the tested NPs included specific effects of each polymer type, such as increased mtROS production, reduced Δψm, induction of oxidative DNA damage, dysregulation of mitochondrial dynamics, and activation of inflammatory pathways. The stress response was characterized by downregulation of DNA methyltransferases, changes in methylation marker levels, and alterations in mitochondrial gene expression. Functional analysis identified Complex I as particularly vulnerable to the effects of NP treatment. The correlation study demonstrated the coordinated regulation of stress-response mediators in mitochondria, namely, DRP1, OMA1, DELE1, and MT-ND6. Meanwhile, the regression analysis showed a correlation between MT-ND6 expression and Complex I activity.</p><p><strong>Discussion: </strong>Collectively, these findings suggest that environmentally relevant NPs elicit polymer-dependent mitochondrial stress responses, mitoepigenetic remodeling, and inflammatory activation.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1916884"},"PeriodicalIF":5.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13571822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964103","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":"Toxicology of caffeine poisoning: molecular mechanisms, toxicokinetic profiles, and clinical implications.","authors":"Antonia Socias, Rafael Blancas","doi":"10.3389/ftox.2026.1933375","DOIUrl":"10.3389/ftox.2026.1933375","url":null,"abstract":"<p><strong>Background: </strong>Caffeine toxicity represents a growing public health challenge due to the widespread availability of highly potent formulations. Ingestions of 3-10 g can be fatal, with serious toxicity occurring at plasma concentrations 15 mg/L or greater. This review provides a framework explaining its diverse clinical consequences.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted across PubMed, Scopus, and Google Scholar using AI-assisted tools, prioritizing clinical, forensic, toxicokinetic, and molecular mechanism studies while excluding chronic moderate consumption.</p><p><strong>Results: </strong>Caffeine toxicity is dose-dependent, progressing from adenosine receptor antagonism to phosphodiesterase inhibition, intracellular calcium release, and GABA-A antagonism. In overdose, these mechanisms interact synergistically to cause severe neurological, cardiovascular, and metabolic complications. Furthermore, the CYP1A2 metabolic system becomes saturated, prolonging the elimination half-life up to 27 h and causing a disproportionate rise in plasma concentrations. Interactions with drugs like mexiletine drastically reduce clearance.</p><p><strong>Conclusion: </strong>Severe poisoning stems from complex, synergistic molecular interactions. Hypokalemia serves as a promising, actionable clinical biomarker for severity assessment. When massive ingestions saturate endogenous detoxification, hemodialysis becomes essential for survival. Unregulated markets for pure caffeine require stricter regulatory interventions and intensified clinical surveillance.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1933375"},"PeriodicalIF":5.1,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13562836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148957394","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":"Readiness of the <i>in vitro</i> alveolar macrophage assay: an interlaboratory comparison using 12 blinded particles.","authors":"Emanoela Thá, Antje Vennemann, Vanessa Marani, Oliver Gräb, Andreas Verlohner, Lan Ma-Hock, Inka Marie Spyridonov, Pamina Weber, Aline Chary, Tommaso Serchi, Robert Landsiedel, Martin Wiemann","doi":"10.3389/ftox.2026.1844090","DOIUrl":"10.3389/ftox.2026.1844090","url":null,"abstract":"<p><p>Inhaled particles can induce persistent pulmonary inflammation when macrophage-mediated clearance mechanisms are overwhelmed. Distinguishing particles that trigger biological activity through intrinsic toxicity from those acting primarily via particle overload represents a central challenge in inhalation toxicology and regulatory safety assessment. Mechanistically anchored new approach methodologies (NAMs) that capture key macrophage responses may therefore provide valuable tools for particle hazard identification while reducing reliance on animal testing. The alveolar macrophage assay (AMA) was developed as an <i>in vitro</i> method to assess particle-induced macrophage activation using four biological endpoints reflecting oxidative stress, lysosomal activation, cytotoxicity, and inflammatory signaling. Previous work demonstrated predictivity of the AMA for short-term inhalation outcomes of nanomaterials. However, broader application of the method requires evidence that the assay can be reliably transferred across laboratories and produce reproducible results with a wide variety of particles. In the present study, an interlaboratory ring-study was conducted to evaluate the transferability and reproducibility of the AMA. Twelve blinded particles were tested in three independent laboratories using standardized protocols and predefined acceptance criteria. Across laboratories, comparable dose-response patterns were observed for most endpoints, and seven of the twelve particles were consistently classified as either biologically active or passive according to the established data interpretation procedure (DIP). Sources of variability were identified, including differences in assay sensitivity, and limitations related to dose metrics and partially soluble particles. A main source of variability was the fetal bovine serum (FBS), highlighting the urgent need for transition to animal-component-free and chemically defined culture media to improve reproducibility of <i>in vitro</i> methods. Taken together, the results demonstrate that the AMA can be successfully transferred across laboratories and generate reproducible biological responses when strict standardization and quality criteria are applied, which underlines the importance of good <i>in vitro</i> method practice (GIVIMP). These findings represent an important step toward the validation of the AMA and support its use as a NAM for mechanism-based hazard assessment and grouping of particles in inhalation toxicology.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1844090"},"PeriodicalIF":5.1,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13561502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148946153","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":"Toxicological and environmental evaluation of the two-phase immersion cooling fluid HFO-153-10mczz-E.","authors":"Grayson Abele, Sarah Smallets, My Hua, Aryatara Shakya, David Brew, Patricia Underwood, Dennis Paustenbach","doi":"10.3389/ftox.2026.1840120","DOIUrl":"10.3389/ftox.2026.1840120","url":null,"abstract":"<p><p>HFO-153-10mczz-E (decafluoro-3-hexene) is a volatile, nonflammable hydrofluoroolefin (HFO) developed as a dielectric fluid in heat transfer applications, such as two-phase immersion cooling (2-PIC). Its high vapor pressure and low water solubility indicate that inhalation is the primary route of exposure and that if released into the environment, the molecule would primarily partition into the air. The available toxicology dataset primarily comprises studies performed with Good Laboratory Practice (GLP) and under Organisation for Economic Co-operation and Development (OECD) test frameworks. This dataset includes acute, subacute, and subchronic inhalation studies, and reveals low systemic toxicity in rats at concentrations of up to approximately 3,000 ppm, with no treatment-related findings in reproductive or developmental endpoints. An <i>in vitro</i> and <i>in vivo</i> genotoxicity battery yielded no indication of genotoxicity. Additional studies illustrated no cardiac sensitization in dogs up to 5,000 ppm and no evidence of ocular/skin irritation or skin sensitization. Environmental testing across algae, invertebrates, and fish revealed no adverse effects in algae or daphnia, with the exception of acute toxicity in fish. However, interpretation was constrained by substantial volatility-related loss of the test material. Environmental partitioning, modeled bioaccumulation factors, and physicochemical properties collectively indicate a low bioaccumulation potential. Collectively, the empirical data characterize HFO-153-10mczz-E as a highly volatile fluorinated fluid with a well-defined toxicological profile, with available data suggesting a low human-health hazard and limited environmental exposure potential under plausible use conditions, though further studies may be warranted.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1840120"},"PeriodicalIF":5.1,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13553145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148914665","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":"Sex-specific cardiac remodeling and metabolic reprogramming in IUGR F2 fetuses following glyphosate or glyphosate-based herbicide exposure.","authors":"Ailín Almirón, Virginia Lorenz, Javier Adur, Juan Ignacio Etchart, Milena Durando, María Mercedes Milesi","doi":"10.3389/ftox.2026.1870011","DOIUrl":"10.3389/ftox.2026.1870011","url":null,"abstract":"<p><p>We previously demonstrated that perinatal exposure to a glyphosate-based herbicide (GBH) or pure glyphosate (Gly) induces intrauterine growth restriction (IUGR) in second-generation (F2) rats. Given the association between IUGR and fetal cardiac remodeling, we investigated whether ancestral exposure programs structural, mitochondrial, and metabolic alterations in F2 fetal hearts. Pregnant F0 rats received GBH or Gly (3.88 and 3.83 mg glyphosate/kg/day, respectively) from gestational day (GD) 9 to F1 weaning. F1 females were subsequently mated and euthanized at GD19 to collect male and female F2 fetal hearts. Both treatments increased relative heart weight in males, while GBH induced left ventricle dilation in both sexes, compatible with a globular phenotype. In males, Gly reduced cardiomyocyte proliferation and <i>Dio2</i> expression, and both treatments increased <i>Vcam1</i> expression. GBH also decreased mitochondrial DNA copy number while upregulating <i>Nd1</i> and mitochondrial biogenesis markers, suggesting a compensatory response. In females, GBH increased <i>Pdk4</i> and <i>Pgc1-α</i> expression, and Gly increased <i>Pparα</i> and <i>Acadl</i> expression, indicating a metabolic reprogramming. Autofluorescence lifetime imaging revealed sex- and treatment-dependent alterations in NAD(P)H and FAD lifetimes. Overall, effects were more pronounced in GBH-exposed lineage and in males, whereas Gly induced subtler alterations. These findings identify the fetal heart as a multigenerational target of herbicide exposure and highlight the contribution of co-formulants to developmental toxicity.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1870011"},"PeriodicalIF":5.1,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13549480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148907803","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":"Exposome influences: a multi-omics perspective on the combined toxic effects of pharmaceuticals and personal care products in Alzheimer's disease.","authors":"I İpek Boşgelmez, Beyza Mertaş, Hayrunnisa Deliser","doi":"10.3389/ftox.2026.1871830","DOIUrl":"10.3389/ftox.2026.1871830","url":null,"abstract":"<p><p>According to WHO data, approximately 57 million people worldwide were affected by dementia in 2021, with prevalence projected to rise. Alzheimer's disease (AD), responsible for 60%-80% of dementia cases, continues to be a leading cause of mortality, with current treatments offering limited efficacy and disease-modifying therapies lacking widespread adoption or conclusive safety evidence, shifting the focus toward prevention and risk modification. Risk factors for AD include both non-modifiable elements, such as age, genetics, and gender, and modifiable factors, like environmental pollution, health status, and diet. While age remains the primary non-modifiable risk factor, early-onset dementia represents only up to 9% of cases. Addressing modifiable factors is essential, as it could prevent or delay almost half of dementia cases, with interventions-such as increased physical activity, smoking cessation, alcohol limitation, and overall health management-being significantly associated with a reduced risk. In this context, the exposome approach offers a comprehensive, integrative framework in which both modifiable and non-modifiable risk factors interact to influence individual susceptibility. Within the neural exposome, chronic low-dose exposure to xenobiotics-such as industrial chemicals, pesticides, metals, pharmaceuticals and personal care products (PPCPs), and air pollutants-may induce neurodegeneration via mechanisms including oxidative stress, neuroinflammation, proteinopathies, and epigenetic modifications, although establishing causality remains challenging. Integration of genomics, transcriptomics, proteomics, metabolomics, and lipidomics, combined with artificial intelligence (AI) techniques such as machine learning (ML) and deep learning (DL), provides promising avenues for biomarker discovery, enhanced preventive strategies, early non-invasive diagnosis, and therapeutic target identification by integrating multi-layered biological data with exposure profiles. This review highlights emerging AD risk factors-including PPCPs-underscoring complex, multifactorial nature of AD and exposome, and the requirement for an interdisciplinary research approach, while also addressing several critical research gaps and methodological limitations.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1871830"},"PeriodicalIF":5.1,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148901665","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":"Enhancing toxicological interpretation and reporting of <i>in vitro</i> high-throughput screening data.","authors":"Bridgett N Hill, Agnes L Karmaus, Victoria Hull, Aswani Unnikrishnan, Nicole C Kleinstreuer, Helena T Hogberg","doi":"10.3389/ftox.2026.1886801","DOIUrl":"10.3389/ftox.2026.1886801","url":null,"abstract":"<p><strong>Introduction: </strong>A wide variety of in vitro high-throughput screening (HTS) assay data are publicly available and have the potential to serve as the foundation for the development of computational toxicology approaches. However, the sources of these data vary in the format and metadata they provide and the clarity of their relevance to toxicological endpoints. Thus, applying them to decisions about chemical effects remains a challenge. To overcome this challenge and help democratize HTS data, we curated and annotated HTS data specifically for toxicological interpretation within a regulatory endpoint context.</p><p><strong>Methods: </strong>Focusing on data from the publicly available ToxCast/Tox21 HTS program, a curation workflow was developed to identify the most reliable data by integrating metadata such as chemical quality control data, concentration-response curve-fitting robustness, assay-specific limitations, and potential technological interference. To this curated HTS (cHTS) dataset, we then applied structured vocabularies and expert review to develop molecular/cellular process annotations mapping HTS assays to toxicologically relevant regulatory endpoints. These data were also mapped to the Organization for Economic Co-operation and Development's Harmonised Template 201 (OHT 201) reporting format to standardize reporting, rendering outputs amenable to regulatory submission.</p><p><strong>Results: </strong>The curated and annotated cHTS dataset supports data interoperability and allows these data to be searched, grouped, and visualized by regulatory endpoints (e.g., endocrine disruption, carcinogenicity, developmental toxicity, and systemic effects). The robust cHTS data and annotations can be retrieved from the publicly accessible National Institute of Health (NIH) Integrated Chemical Environment (NICE, https://ice.ntp.niehs.nih.gov/). Access through NICE allows these data to be optimally leveraged for a variety of uses, from identifying data gaps and providing mechanistic insights to confidently and reproducibly retrieving data, thus supporting their integration to build weight-of-evidence assessments for regulatory-relevant toxicological endpoints.</p><p><strong>Discussion: </strong>Developing an environment in which HTS data that are structured, accessible, and readily interpretable in a toxicological context, ensures that users can apply these evolving resources. Working toward consistent data summaries by leveraging established reporting formats helps bolster regulatory interpretation and adoption. Overall, the work summarized herein demonstrates how fit-for-purpose standardized curation, annotations, ontologies, ease of accessibility, and structured reporting can support data interoperability and the application of complex HTS data for regulatory application.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1886801"},"PeriodicalIF":5.1,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148901654","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 TRPA1-mediated substance P release assay as an <i>in vitro</i> screening tool for airway irritant potential.","authors":"R Bedford, R Medhane, J Lawrance, M Hollings","doi":"10.3389/ftox.2026.1870419","DOIUrl":"10.3389/ftox.2026.1870419","url":null,"abstract":"<p><p>Environmental exposure to airway irritants can elicit sensory irritation and contribute to various disease outcomes. Although <i>in vitro</i> assays have been developed to measure skin and eye irritation, evaluation of respiratory sensory irritation relies predominately on <i>in vivo</i> testing using the RD₅₀ assay, or Alarie test. Although the RD₅₀ assay aligns well with human responses, various disadvantages, such as low throughput and interspecies differences in receptors responsible for detecting noxious stimuli, highlights a few of the many requirements for alternative, or complementary <i>in vitro</i> approaches. Recently, increased emphasis has been placed on methods that predict human responses at the mechanistic level. In this study, we have developed a human relevant <i>in vitro</i> model for airway irritant detection based around molecular events of airway irritation, including transient receptor potential channel activation and substance P release. Using alveolar- and bronchial-derived cell lines, we demonstrate endogenous TRPA1-driven Substance P release following exposure to prototypical irritants. Calcium response was confirmed by flow cytometry following exposure to irritants, with substance P release demonstrated at both the gene and protein levels by qPCR, immunocytochemistry and ELISA. Furthermore, our model demonstrates some concordance with <i>in vivo</i> RD₅₀ data.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1870419"},"PeriodicalIF":5.1,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148901623","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}