Archives of Toxicology最新文献

{"title":"Linking acute exposure to future risk: an omics-to-AOP new approach method for next-generation risk assessment in a human in vitro lung air-liquid interface model.","authors":"Jack Morikka, Ada Taubert, Hanna-Kaarina Juppi, Giorgia Migliaccio, Zeyad Al-Abdulraheem, Lena Möbus, Sanna Peltola, Noora Perho, Maaret Vaani, Antonio Federico, Dario Greco","doi":"10.1007/s00204-026-04563-0","DOIUrl":"https://doi.org/10.1007/s00204-026-04563-0","url":null,"abstract":"<p><p>New approach methodologies (NAMs) are transforming chemical safety assessment by shifting focus from apical toxicity endpoints toward mechanistic, human-relevant prediction of adverse outcomes. Here, we present a human lung air-liquid interface (ALI) alveolar epithelial model coupled to an omics-to-adverse outcome pathway (AOP) analysis, linking acute sublethal exposure to potential long-term toxicity outcomes. A non-tumorigenic, monoclonal lung alveolar epithelial cell line (Arlo), capable of forming a tight monolayer barrier, was basolaterally exposed to sublethal concentrations (0, 20, 60, 100 µg/mL) of the profibrotic compound bleomycin. Dose-dependent modelling of transcriptomic signatures recapitulated known mechanisms of bleomycin-induced epithelial injury, consistent with early key events in fibrotic AOPs, enabling prediction of downstream adverse outcomes. The transcriptomic signature was overlayed on a network-based representation of human pulmonary fibrosis patient biopsies. When compared to a bleomycin exposed mouse lung model, the in vitro Arlo NAM performed comparably, especially for observing effects on extracellular matrix (ECM) restructuring in an acute exposure setting. Epigenomic profiling identified methylation changes associated with epithelial-mesenchymal transition (EMT), suggesting potential long-term gene expression regulation through epigenetic control. By linking functional endpoints with dose-response transcriptomic and epigenetic signatures, this work provides a reproducible schema for omics-to-AOP next-generation safety assessment and demonstrates that acute exposures can be modelled with a resource and time efficient NAM centred on toxicogenomics, informing on longer-term consequences.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human myeloperoxidase-driven activation of skin sensitizing p-phenylenediamine-related aromatic diamines and phenylpropanoids-insights from in chemico and in silico approaches.","authors":"Hannah Deusinger, Philipp Peslalz, Karma C Fussell, Sabine Langhoff, Udo Bock, Carsten Goebel, Brunhilde Blömeke","doi":"10.1007/s00204-026-04549-y","DOIUrl":"https://doi.org/10.1007/s00204-026-04549-y","url":null,"abstract":"<p><p>Skin sensitization is initiated by the covalent binding of low-molecular-weight chemicals to skin proteins. For prehaptens, this requires oxidative activation to generate electrophiles capable of reacting with skin proteins. While abiotic oxidation is established, enzymatic oxidation remains poorly understood. Because neutrophils can infiltrate the skin and release the heme peroxidase myeloperoxidase (MPO), we investigated whether human MPO contributes to the oxidative activation of selected sensitizers. The study included the hair dye precursor p-phenylenediamine (PPD) and its derivatives toluene-2,5-diamine (PTD) and 2-methoxymethyl-PPD (ME-PPD), together with the phenylpropanoid fragrance molecules eugenol and dihydroeugenol, and the aromatic alcohol cinnamyl alcohol. Molecular docking predicted productive binding orientations of all compounds except cinnamyl alcohol, which adopted a non-productive orientation within the MPO active site. Consistent with these predictions, in chemico experiments showed MPO-catalyzed oxidation of the aromatic diamines and phenylpropanoids with comparable catalytic efficiencies (10-25 × 10³mM^-1 × min^-1), whereas cinnamyl alcohol remained unconverted. High-resolution mass spectrometry revealed distinct metabolite profiles, with the aromatic diamines forming mono-, di-, and trimeric oxidation products, including Bandrowski's Base, whereas phenylpropanoids predominantly yielded monomeric quinone methides and dimers. Increased protein-binding potential was predicted for several observed metabolites using the OECD QSAR Toolbox. Collectively, these results demonstrate that MPO catalyzes the oxidation of a subset of the investigated sensitizers, generating metabolites predicted to exhibit increased protein-binding potential. These findings establish MPO-mediated oxidation as an additional enzymatic pathway that complements well-known abiotic oxidation and expands the current understanding of enzymatic activation in the skin.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contact allergies from clothing textiles - is there a cause for growing concern?","authors":"Ralph Pirow, Hermann-Josef Thierse, Christian Riebeling, Suna Nicolai, Patrick Tarnow, Moustapha Sy, Tewes Tralau, Andreas Luch, Andreas Hensel","doi":"10.1007/s00204-026-04556-z","DOIUrl":"https://doi.org/10.1007/s00204-026-04556-z","url":null,"abstract":"<p><p>Allergic contact dermatitis (ACD) due to chemicals in textiles and other clothing has recently been declared to be of growing concern in Europe. An Annex XV dossier proposing a generic ban of skin sensitisers in these products under the European Chemicals legislation REACH estimated the prevalence of clothing-related ACD in the general population to be 0.8-1.0%. The present study took a critical look at the data basis, the methodological approach and the assumptions underlying the calculation of the burden of disease in the Annex XV report. The reported incidence and prevalence estimates were compared with those obtained by our own analyses of the evidence from clinical epidemiological data of the Information Network of Departments of Dermatology (IVDK) and from morbidity statistics on medical diagnoses of ACD in Germany. Additional evidence was taken from the outcomes of two study projects that aimed to characterise the causal link between ACD and the presence of chemicals, including dyes, in clothing. Based on this data, a further assessment suggests that the Annex XV restriction report overestimates the prevalence of clothing-related ACD in Europe. Therefore, the risk reduction potential of the proposed generic ban is considered to be much lower than predicted. Critical points of the proposed generic ban of skin sensitisers in textiles include, among others, 'regrettable substitutions' of dyes that have proven themselves in practice through their extensive and decades-long use by alternatives that might exhibit a different hazard profile as well as poorer perspiration fastness and/or versatility.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mycotoxins modulate oxaliplatin-induced phagocytosis of human colon cancer cells through oxidative stress in vitro.","authors":"Judith Gufler, Doris Marko, Sonja Hager","doi":"10.1007/s00204-026-04558-x","DOIUrl":"https://doi.org/10.1007/s00204-026-04558-x","url":null,"abstract":"<p><p>Phagocytosis of cancer cells is pivotal in the anticancer immune response. To evade phagocytosis, tumor cells express \"don't eat me\" signals or inhibit \"eat me\" signals. This can be overcome by the anticancer drug oxaliplatin, which induces \"eat me\" signals. However, not only anticancer therapies modulate the immune response, but prevalent mycotoxins can also stimulate or suppress immune functions. Consequently, the question arises whether immunomodulating mycotoxins affect the ability of cancer cells to evade phagocytosis and modulate oxaliplatin-induced phagocytosis. Phagocytosis of colon cancer cells treated with oxaliplatin (10-100 µM), alternariol (5-20 µM), deoxynivalenol (1-4 µM), ochratoxin A (OTA) (10-40 µM), or zearalenone (ZEN) (10-40 µM) by immature dendritic cells (DCs) generated from peripheral blood mononuclear cells or THP-1 monocytes was assessed by fluorescence staining and flow cytometry. Expression of \"eat me\" (calreticulin and phosphatidylserine) and \"don't eat me\" signals (CD47 and PDL1) was investigated by flow cytometry. In addition, cell surface patterns in the form of high-mannose N-glycans were analyzed by flow cytometry, and oxidized phospholipids by using fluorescent probes and malondialdehyde content. Our results showed that OTA, ZEN (> 20 µM), and oxaliplatin (> 50 µM) increased phagocytosis of cancer cells, with OTA and ZEN further enhancing oxaliplatin-induced stimulation. This was mainly associated with increased reactive oxygen species and upregulation of oxidized phospholipid patterns. In conclusion, mycotoxin contamination might (over-)stimulate cancer cell phagocytosis by inducing oxidative stress, thereby altering the anticancer immune response. While this might improve therapy outcomes, possible immune exhaustion or tolerogenic phagocytosis might also aggravate them.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive detection of ricin following oral exposure: feces as the key diagnostic matrix.","authors":"Shivani Dixit, Ram Kumar Dhaked, Anjali Yadav, Jagrati Parashar, Nandita Saxena","doi":"10.1007/s00204-026-04535-4","DOIUrl":"https://doi.org/10.1007/s00204-026-04535-4","url":null,"abstract":"<p><p>Ricin is classified as a Schedule 1 toxin under the Chemical Weapons Convention (CWC) and Category B agent under the Biological and Toxin Weapons Convention (BTWC). Its extreme toxicity, lack of an antidote, and potential for deliberate misuse necessitate rapid detection strategies for effective medical and public health responses. However, information on optimal biological matrices and detection windows following ingestion remains limited. This study evaluated optimal biosamples and detection strategies following oral ricin exposure in mice. Crude and purified ricin were isolated from castor seeds and characterized by SDS-PAGE. Following oral LD₅₀ determination, mice were administered 5 × LD₅₀ doses to simulate severe poisoning. Feces, urine, serum, and liver samples were collected at 2, 4, 8, and 18 h post-exposure. Detection was performed using in-house lateral flow assay (LFA), sandwich ELISA, and immunoblotting, with selected samples validated by cytotoxicity assays and LC-MS/MS to confirm toxin integrity and activity. Feces offered the broadest diagnostic window, with biologically active ricin detected at all time points. Urine contained lower toxin levels but consistently enabled detection, supporting its utility as a non-invasive matrix. Serum ricin was transient, peaking at 2-4 h and often required enrichment to overcome matrix interference. Conversely, liver samples exhibited progressive toxin accumulation, peaking at 18 h, emphasizing their forensic value. These findings delineate ricin toxicokinetics following oral exposure and establish feces as the most reliable matrix for sustained detection. By integrating LFA with confirmatory immunoassays, this study provides a practical framework for early identification and public health preparedness in ricin exposure scenarios.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicokinetics and analytical toxicology of four N, N-dimethyltryptamine derivatives studied in human in vitro systems and in vivo by means of zebrafish embryos.","authors":"Gloria Daziani, Lea Wagmann, Matthias D Kroesen, K Simon Wellenberg, Matthias Grill, Jennifer Herrmann, Jérémy Carlier, Francesco Paolo Busardò, Markus R Meyer","doi":"10.1007/s00204-026-04552-3","DOIUrl":"https://doi.org/10.1007/s00204-026-04552-3","url":null,"abstract":"<p><p>N,N-Dimethyltryptamine (DMT) is a naturally occurring substituted tryptamine used as a psychedelic drug for ritual purposes by various cultures. Derivatives were already found on the drug of abuse market, such as N¹-tert-butoxycarbonyl-N,N-dimethyltryptamine (DMT-Boc). The aim of the current study was to investigate the toxicokinetics of DMT-Boc and three related DMT derivatives, by name DMT-isopropylcarbamate, DMT-pivaloylamide, and DMT-THP (N,N-dimethyl-2-[1-(oxan-2-yl)indol-3-yl]ethanamine). In vitro and in vivo metabolism studies with pooled human liver S9 incubations and zebrafish embryos were performed, respectively. Monooxygenase and monoamine oxidase (MAO) isozymes involved in the phase I metabolism were identified. In vitro metabolic stability and plasma protein binding (PPB) were evaluated. A total of 11 metabolites for DMT-Boc, 13 for DMT-isopropylcarbamate, eight for DMT-pivaloylamide and 16 for DMT-THP were identified using high-resolution tandem mass spectrometry. N-Demethylation and hydroxylation were the most relevant metabolic reactions. CYP1A2, CYP2D6, and FMO3 were identified as most active phase I isozymes and MAO-A contributed to DMT-THP metabolism. The in vitro half-lives of DMT-Boc, DMT-isopropylcarbamate, and DMT-pivaloylamide were calculated to be between 74 and 79 min, while that of DMT-THP was found to be > 180 min. All compounds showed high PPB (> 99%) indicating that co-consumption with other drugs might increase the DMT derivatives' toxicity. Combined in vitro and in vivo approaches provided a comprehensive metabolism overview. N, N-bis-Demethylated, N-demethylated and N-oxygenated metabolites along with parent compound were proposed as consumption markers in order to support clinical and forensic toxicologists to identify these substances in biosamples in case of suspected abuse.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of fusaric acid on oxidative stress, ferritinophagy, and ferroptosis pathways: a review.","authors":"Anthia C Govender, Terisha Ghazi","doi":"10.1007/s00204-026-04553-2","DOIUrl":"https://doi.org/10.1007/s00204-026-04553-2","url":null,"abstract":"<p><p>Fusaric acid (FA) is a mycotoxin produced by multiple Fusarium species and is a frequent contaminant of maize and other cereal grains. Its toxicological effects are closely tied to its structural characteristics, particularly its weak acid nature and strong metal-chelating ability, with iron being a critical target. By disrupting iron homeostasis, FA contributes to oxidative stress by enhancing reactive oxygen species (ROS) production and modulating antioxidant defence pathways. Furthermore, FA's interaction with iron positions it as a potential regulator of ferritinophagy and ferroptosis, two interconnected processes that link iron metabolism to cellular survival and death. Although FA has been associated with other cellular pathways, its precise role in iron-dependent pathways remains insufficiently defined. This review seeks to consolidate current knowledge on FA, emphasising its iron-chelating properties and their impact on iron-dependent mechanisms, including oxidative stress, ferritinophagy, and ferroptosis.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149007858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clozapine impairs angiogenic function and cellular bioenergetics in primary human endothelial progenitor cells and zebrafish: involvement of aryl hydrocarbon receptor signaling.","authors":"Chi Chen, Yung-Shuo Kao, Chih-Hsin Tang, Chen-Lin Yu, Kai-Yao Huang, Juei-Yu Yen, Cheng-Yung Lin, Chen-Chen Huang, Der-Yang Cho, Meng-Chiao Chou, Yi-Cheng Wu, Shun-Long Weng, Shih-Wei Wang","doi":"10.1007/s00204-026-04544-3","DOIUrl":"https://doi.org/10.1007/s00204-026-04544-3","url":null,"abstract":"<p><p>Clozapine is indispensable for treatment-resistant schizophrenia, but its effects on endothelial repair and their potential relevance to coronary artery disease remain insufficiently characterized. We combined a propensity score-matched nationwide cohort of 28,802 patients with experiments in primary human endothelial progenitor cells and Tg(fli1:EGFP) zebrafish embryos. Clozapine use was associated with a higher incidence of coronary artery disease during up to 12 years of follow-up (adjusted hazard ratio 1.24, 95% confidence interval 1.13-1.36). In primary human endothelial progenitor cells, clozapine was tested at 1-30 μM for 24-48 h. It concentration-dependently reduced cell growth, migration, tube formation, oxygen consumption, and extracellular acidification. In silico docking predicted a potential interaction with the aryl hydrocarbon receptor (AHR) ligand-binding pocket. Clozapine increased CYP1A1 mRNA expression and reduced AHR protein level. The AHR antagonist CH-223191 (10 μM) partially restored cell growth and shifted extracellular acidification toward control levels, supporting involvement of AHR signaling. Clozapine also increased autophagosome accumulation and LC3-II abundance, while 3-methyladenine intensified growth inhibition, consistent with a potentially compensatory autophagy-associated response. Tg(fli1:EGFP) zebrafish embryos exposed to clozapine (15 or 30 μM) during 12-30 or 30-72 h post-fertilization developed concentration-dependent vascular abnormalities and increased mortality. These findings identify AHR-associated metabolic and angiogenic dysfunction as a plausible vascular effect of clozapine, while further studies are required to determine its contribution to the clinical association and its relevance to chronic therapeutic exposure.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149007800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimisation of in vitro assays for accurate risk assessment of T-cell responses to biologics with potential immune liabilities.","authors":"Liam Farrell, Lonnie MacDonald, Georgia Wells, Sophie Grice, Katy Saide, Xiaoli Meng, Catherine J Betts, Dean J Naisbitt","doi":"10.1007/s00204-026-04557-y","DOIUrl":"https://doi.org/10.1007/s00204-026-04557-y","url":null,"abstract":"<p><p>Biologics are increasingly used to treat disease, but their clinical efficacy is often hindered by anti-drug antibodies and immunological adverse reactions. Accurate prediction of immunogenicity to biologics at a preclinical development stage would improve safety and prevent financial loss to pharmaceutical companies. A stepwise approach to explore immunogenicity to biologics was developed by; (1) assessing the sensitivity of existing PBMC stimulation assays, (2) optimisation of a DC: T-cell co-culture assay, (3) definition of immune epitopes using rituximab MHC class II-binding peptides. Lymphocyte transformation tests and IFN-γ ELISpot assays were performed using healthy donor PBMC to assess the T-cell stimulatory capacity of a panel of biologics. DC: T-cell co-culture methods were optimised for timepoints, cell numbers and immune dysregulation and assessed using the panel of biologics. Sixteen 15-mer peptides derived from the variable region of rituximab were used to generate and characterise T-cell clones. Initial PBMC experiments showed low sensitivity, presenting frequent false negatives. DC: T-cell assays showed increased sensitivity to biologics, however, high background responses were observed in vehicle control cultures. Optimisation of assay conditions reduced the background counts and increased the dynamic range and sensitivity of the assay. CD4 + T-cell clones were responsive to two 15-mer rituximab peptides in proliferation and cytokine release assays. These data indicate that DC: T-cell co-cultures and cloning methods should be used alongside epitope prediction tools to assess T-cell responses to biologics with potential immune liabilities. Implementing the stepwise approach outlined could identify high risk molecules early in development and highlight \"hotspot\" regions of molecules for risk mitigation.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149007842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induction of aneuploidy by the metal-chelating agent neodecanoid acid in mammalian cells in vitro.","authors":"Francesca Marcon, Giorgia Maria Varalda, Carmen Del Franco, Laura Torrieri Di Tullio, Donatella Pietraforte, Serena Cecchetti, Beatrice Bocca, Flavia Ruggieri, Francesca Salani, Ester Siniscalchi, Silvia Bongiorni, Sara Buoni, Ezgi Eyluel Bankoglu, Thomas Tietz, Sebastian Zellmer, Roberta Meschini","doi":"10.1007/s00204-026-04543-4","DOIUrl":"https://doi.org/10.1007/s00204-026-04543-4","url":null,"abstract":"<p><p>Neodecanoic acid (NDA) is an industrial chemical used in food packaging, considered a food contact material. To assess whether its use may pose concern for public health, this study was conducted to investigate in vitro the genotoxicity of NDA, previously identified as a gap-of-knowledge in toxicological risk assessment. No induction of gene mutations was observed in bacterial cells (Ames test) at concentrations ranging from 10 to 1000 µg/plate. Conversely, a statistically significant increase in the frequency of micronuclei was observed in Chinese Hamster Ovary cells, and confirmed in peripheral blood human lymphocytes, in a range from 100 to 500 µg/ml of NDA. An aneugenic mode of action was supported by evidence showing, in the same range of concentrations, a high frequency of chromosome loss in NDA-treated samples associated with mitotic spindle defects, such as multipolar mitotic spindles and cytoskeleton disruption. Study of nuclear lamina organization revealed irregular and deformed nuclei after NDA treatment. Furthermore, the metallomic analysis, performed at 200 and 400 µg/ml NDA, showed that NDA interfered with intracellular metal homeostasis, crucial for the dynamic morphology and mechanics of the cytoskeleton. In conclusion, this study provided evidence showing a thresholded genotoxic activity for NDA in vitro possibly resulting from its property of metal ion chelator affecting microtubule and microfilament network.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}