Food and Chemical Toxicology最新文献

{"title":"Mechanistic insights into Thymol's anticancer activity in breast cancer: Evidence from in silico, in vitro and in vivo studies.","authors":"Ali Mohammad, Luna Sakr, Aziz Habib, Issam Mahfoud, Abraham Yazbeck, Maria Younes, Mohamad Rima, Brigitte Wex, Sandra Rizk","doi":"10.1016/j.fct.2026.116488","DOIUrl":"https://doi.org/10.1016/j.fct.2026.116488","url":null,"abstract":"<p><p>Thymol, a monoterpenoid phenol from Mediterranean thyme species, is a well-characterized food-associated chemical with documented cytotoxic activity against breast cancer cells. This review critically evaluates mechanisms underlying thymol's selective cytotoxic and antiproliferative effects on breast cancer cells across in silico, in vitro, and in vivo studies. A targeted keyword-based search of Scopus using \"thymol\" and \"breast cancer\" identified 114 eligible studies, supplemented by 12 mechanism-relevant references. Computational analyses predicted favorable binding to oncogenic targets with low predicted toxicity. In vitro, thymol, whether purified, an essential oil constituent, a synthetic derivative, or nano-formulated, induced dose- and time-dependent cytotoxicity across breast cancer cell lines while largely sparing normal cells. Mechanistically, this was primarily driven by intrinsic apoptosis via Reactive Oxygen Species generation, mitochondrial membrane depolarization, and caspase activation, alongside cell cycle arrest and suppression of proliferation, migration, invasion, and angiogenesis. In vivo, thymol-rich essential oils reduced tumor volume without reported hepatotoxicity. By integrating in silico, in vitro, and in vivo mechanistic evidence on thymol's cytotoxic activity in breast cancer, we further highlight under-explored alternative cell death pathways. Altogether, these findings position thymol as a multi-targeted, selectively toxic natural compound, warranting mechanistic validation and eventual clinical exploration.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"116488"},"PeriodicalIF":3.2,"publicationDate":"2026-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149369772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RIFM fragrance ingredient safety assessment, 1,3-dioxane, 2-(2,4-dimethyl-3-cyclohexene-1-yl)-5-methyl-5-(1-methylpropyl)-, CAS Registry Number 117933-89-8.","authors":"A M Api, A Bartlett, D Belsito, D Botelho, M Bruze, A Bryant-Friedrich, G A Burton, M A Cancellieri, H Chon, M Cronin, S Crotty, M L Dagli, W Dekant, C Deodhar, K Farrell, A D Fryer, M Guttenberg, L Jones, K Joshi, A Lapczynski, D L Laskin, M Lavelle, I Lee, H Moustakas, J Muldoon, T M Penning, A H Piersma, G Ritacco, N Sadekar, I Schember, T W Schultz, F Siddiqi, I G Sipes, G Sullivan, Y Thakkar","doi":"10.1016/j.fct.2026.116486","DOIUrl":"https://doi.org/10.1016/j.fct.2026.116486","url":null,"abstract":"<p><p>1,3-Dioxane, 2-(2,4-dimethyl-3-cyclohexene-1-yl)-5-methyl-5-(1-methylpropyl)- was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data show that 1,3-dioxane, 2-(2,4-dimethyl-3-cyclohexene-1-yl)-5-methyl-5-(1-methylpropyl)- is not genotoxic and provide a calculated Margin of Exposure (MOE) >100 for the repeated dose toxicity endpoint. The reproductive toxicity and local respiratory toxicity endpoints were evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class III material, and the exposure to 1,3-dioxane, 2-(2,4-dimethyl-3-cyclohexene-1-yl)-5-methyl-5-(1-methylpropyl)- is below the TTC (0.0015 mg/kg/day and 0.47 mg/day, respectively). Data show that there are no safety concerns for 1,3-dioxane, 2-(2,4-dimethyl-3-cyclohexene-1-yl)-5-methyl-5-(1-methylpropyl)- for skin sensitization under the current declared levels of use. The photoirritation/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; 1,3-dioxane, 2-(2,4-dimethyl-3-cyclohexene-1-yl)-5-methyl-5-(1-methylpropyl)- is not expected to be photoirritating/photoallergenic. The environmental endpoints were evaluated; 1,3-dioxane, 2-(2,4-dimethyl-3-cyclohexene-1-yl)-5-methyl-5-(1-methylpropyl)- was found not to be Persistent, Bioaccumulative, and not Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use (VoU) in Europe (EU), North America (NA), South America (SA), Japan (JP), and Asia Pacific (AP) (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"116486"},"PeriodicalIF":3.2,"publicationDate":"2026-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149369774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nutrient-mediated protection against environmental pollutant-induced heart defects: mechanisms and opportunities.","authors":"Mingxuan Zhang, Xinyue Yang, Xu Nie, Lei Wu, Yan Jiang, Tao Chen","doi":"10.1016/j.fct.2026.116489","DOIUrl":"https://doi.org/10.1016/j.fct.2026.116489","url":null,"abstract":"<p><p>Congenital heart disease (CHD) is the most prevalent birth defect worldwide, yet effective prevention strategies remain limited. Accumulating evidence implicates environmental pollutants as significant contributors to abnormalities in cardiac development. The molecular initiating events encompass xenobiotic-receptor-mediated signalling and direct toxicant-biomolecule interactions. These initial events trigger a series of downstream pathogenic cascades that ultimately result in cardiac developmental defects. Nutrients with biological activity and generally favorable safety profiles at recommended dietary intake levels offer considerable potential as preventive agents against pollutant-induced cardiac malformations. Notably, combined nutrient interventions may exert superior synergistic protective effects relative to single-nutrient approaches. This narrative review comprehensively summarizes the molecular initiating events and subsequent pathogenic pathways involved in pollutant-induced cardiac developmental abnormalities. We further critically evaluate the preclinical evidence and signalling targets of nutrients, and propose a scientific framework for the development of precision prenatal nutritional strategies to reduce the burden of environment-related CHD.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"116489"},"PeriodicalIF":3.2,"publicationDate":"2026-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149369773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Berberine attenuates cigarette smoke extract-induced stress and senescence-associated changes in human brain microvascular endothelial cells.","authors":"Haochen Wang, Bingbing Lin, Yajie Zhang, Yutong Liu, Yu Kuang, Kai Li, Huanwen Tang, Qian Sun","doi":"10.1016/j.fct.2026.116487","DOIUrl":"https://doi.org/10.1016/j.fct.2026.116487","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study is to investigate the protective effects of berberine (BBR) against cigarette smoke extract (CSE)-induced injury in human brain microvascular endothelial cells and to identify candidate molecules and associated candidate molecules.</p><p><strong>Methods: </strong>hCMEC/D3 cells were exposed to 4% CSE and/or 7.5 μM BBR for 24 h. Inflammation, oxidative stress, and senescence-associated phenotypes were assessed. Previously generated CSE-responsive transcriptomic data were integrated with ChEMBL-derived candidates, followed by enrichment, weighted prioritization, protein-protein interaction (PPI) analysis, and docking.</p><p><strong>Results: </strong>Compared with CSE alone, BBR co-treatment increased cell viability (P < 0.001), attenuated NF-κB-associated inflammation. IL-1β and TNF-α levels were significantly reduced (P < 0.05). BBR also reduced reactive oxygen species (ROS) accumulation, and increased the reduced/oxidized glutathione (GSH/GSSG) ratio from 8.74 to 12.74 (P < 0.001). Senescence-associated β-galactosidase positivity decreased from 15.00% to 1.39% (P < 0.001), accompanied by reduced p16/p21 expression and G0/G1 accumulation (P < 0.01). Integrated analysis identified 23 overlapping candidates and prioritized GDF15, HMOX1, NQO1, IL1B, and CDKN1A. Docking predicted potential interactions with BBR; RT-qPCR and Western blot showed differential expression responses to BBR.</p><p><strong>Conclusion: </strong>BBR attenuates CSE-induced oxidative stress, inflammation, and senescence-associated alterations in hCMEC/D3 cells. These effects may be associated with modulation of interconnected cellular stress responses.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"116487"},"PeriodicalIF":3.2,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149357027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RIFM fragrance ingredient safety assessment, N,2-dimethyl-N-phenylbutyramide, CAS Registry Number 84434-18-4.","authors":"A M Api, A Bartlett, D Belsito, D Botelho, M Bruze, A Bryant-Friedrich, G A Burton, M A Cancellieri, H Chon, M Cronin, S Crotty, M L Dagli, W Dekant, C Deodhar, K Farrell, A D Fryer, M Guttenberg, L Jones, K Joshi, A Lapczynski, D L Laskin, M Lavelle, I Lee, H Moustakas, J Muldoon, T M Penning, A H Piersma, G Ritacco, N Sadekar, I Schember, T W Schultz, F Siddiqi, I G Sipes, G Sullivan, Y Thakkar","doi":"10.1016/j.fct.2026.116485","DOIUrl":"https://doi.org/10.1016/j.fct.2026.116485","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"116485"},"PeriodicalIF":3.2,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149357028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RIFM Natural Complex Substance (NCS) fragrance ingredient safety assessment, caraway seed oil, CAS Registry Number 8000-42-8, RIFM ID 326-H2.12.","authors":"A M Api, A Bartlett, D Belsito, D Botelho, M Bruze, A Bryant-Friedrich, G A Burton, M A Cancellieri, H Chon, M Cronin, S Crotty, M L Dagli, W Dekant, C Deodhar, K Farrell, A D Fryer, M Guttenberg, L Jones, K Joshi, A Lapczynski, D L Laskin, M Lavelle, I Lee, H Moustakas, J Muldoon, T M Penning, A H Piersma, G Ritacco, N Sadekar, I Schember, T W Schultz, F Siddiqi, I G Sipes, G Sullivan, Y Thakkar","doi":"10.1016/j.fct.2026.116479","DOIUrl":"https://doi.org/10.1016/j.fct.2026.116479","url":null,"abstract":"<p><p>Caraway seed oil was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data for the components of the NCS do not show a concern for genotoxicity. caraway seed oil was evaluated for the repeated dose and reproductive toxicity endpoints on the basis of component analysis using a combination of target data, read-across data, and the threshold of toxicological concern (TTC); caraway seed oil is safe for use under the conditions described in this safety assessment for the repeated dose and reproductive toxicity endpoints. Data for the components of the NCS do not show a concern for skin sensitization under the current, declared levels of use. The photoirritation endpoint was evaluated based on data on the whole NCS and ultraviolet/visible (UV/Vis) absorption spectra for the components of the NCS; caraway seed oil is not photoirritating. The photoallergenicity endpoint was evaluated based on UV/Vis absorption spectra for the components of the NCS; caraway seed oil is not expected to be photoallergenic. The local respiratory toxicity endpoint for this NCS was evaluated using the inhalation TTC for a Cramer Class II material, and the inhalation exposure to caraway seed oil is below the TTC (0.47 mg/day). Based on the component assessment, caraway seed oil does not contain Persistent, Bioaccumulative, and Toxic (PBT) or very Persistent, very Bioaccumulative (vPvB) components as per the International Fragrance Association (IFRA) Environmental Standards. In addition, following the RIFM Environmental Framework and based on individual component assessment, caraway seed oil does not present a risk to the aquatic environment (i.e., its screening-level PEC/PNEC <1) at the current reported volumes of use (VoU).</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"116479"},"PeriodicalIF":3.2,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149331957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Update to RIFM fragrance ingredient safety assessment, valencene, CAS Registry Number 4630-07-3.","authors":"A M Api, A Bartlett, D Belsito, D Botelho, M Bruze, A Bryant-Friedrich, G A Burton, M A Cancellieri, H Chon, M Cronin, S Crotty, M L Dagli, W Dekant, C Deodhar, K Farrell, A D Fryer, M Guttenberg, L Jones, K Joshi, A Lapczynski, D L Laskin, M Lavelle, I Lee, H Moustakas, J Muldoon, T M Penning, A H Piersma, G Ritacco, N Sadekar, I Schember, T W Schultz, F Siddiqi, I G Sipes, G Sullivan, Y Thakkar","doi":"10.1016/j.fct.2026.116480","DOIUrl":"https://doi.org/10.1016/j.fct.2026.116480","url":null,"abstract":"<p><p>Valencene was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Target data show that valencene is not genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class I material, and the exposure to valencene is below the TTC (0.03 mg/kg/day, 0.03 mg/kg/day, and 1.4 mg/day, respectively). The skin sensitization endpoint was completed using the Dermal Sensitization Threshold (DST) for non-reactive materials (900 μg/cm²); exposure is below the DST. The photoirritation/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; valencene is not expected to be photoirritating/photoallergenic. The environmental endpoints were evaluated; valencene was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients (RQs), based on its current volume of use (VoU) in Europe (EU), North America (NA), Asia-Pacific (AP), Japan (JP), and South America (SA) (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"116480"},"PeriodicalIF":3.2,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149331958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Safety Evaluation of D-Glucuronolactone Derived from Inositol.","authors":"Wenwei Zheng, Qixin Chen, Yin Wang","doi":"10.1016/j.fct.2026.116477","DOIUrl":"https://doi.org/10.1016/j.fct.2026.116477","url":null,"abstract":"<p><p>D-glucuronolactone is a natural compound that is a basic structural component of most connective tissues. It has found applications in various products, such as food formulations and cosmetic preparations. As part of safety assessment for this D-glucuronolactone, a series of toxicological tests have been implemented. Acute oral toxicity test showed that no mortality occurred in rats administered up to 10.0 g/kg BW or in mice given up to 20.0 g/kg BW of D-glucuronolactone, classifying it as actual non-toxic. D-glucuronolactone also showed no evidence of genotoxic potential across a range of genotoxicity tests. During 90-day oral toxicity test, there were no adverse findings observed related to the experimental factors, and the no observed adverse effect levels (NOAEL) were 7.66 and 5.61 g/kg BW for females and males. No significant differences in any indicators were indicated in the teratogenicity test between the control group and dose groups, maternal toxicity was absent at all tested doses. The result showed no potential teratogenic or other developmental effects of D-glucuronolactone in rats at the high dose level (5.0 g/kg BW). These findings confirm that D-glucuronolactone is non-toxic, non-genotoxic, well-tolerated at high dose, with no teratogenic effects observed, supporting its safety for use in foods.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"116477"},"PeriodicalIF":3.2,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149331956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methylparaben Exposure and Keratoconus: A Mechanistic Study Integrating Mendelian Randomization, Network Toxicology, Molecular Docking, and Experimental Validation.","authors":"Yumiao Pan, Wanju Yang, Shangcao Wu, Xianyi Bao, Xinlan Lei, Lan Yu, Xiaoyu Wu, Yanning Yang","doi":"10.1016/j.fct.2026.116482","DOIUrl":"https://doi.org/10.1016/j.fct.2026.116482","url":null,"abstract":"<p><p>Parabens are widely used preservatives, yet their association with keratoconus (KC) remains unclear. Here, we combined Mendelian randomization (MR), network toxicology, molecular docking, molecular dynamics simulations, and cell-based assays to investigate this relationship. MR analysis indicated that, among the four parabens evaluated, only methylparaben (MPB) was genetically associated with KC. Network toxicology identified 139 overlapping database-derived candidate genes potentially linking MPB and KC, with AKT1 and FN1 prioritized as computational hub candidates, enriched in pathways linked to hypoxia, ECM organization, and estrogen signaling. Molecular docking and dynamics simulations predicted favorable binding poses of MPB to both AKT1 and FN1. In cultured corneal stromal cells, MPB dose-dependently increased oxidative stress, suppressed AKT phosphorylation, and reduced FN1 and collagen I levels, recapitulating several features of a KC-associated cellular phenotype. Our findings suggest MPB as a potential risk factor for KC and identify AKT1 and FN1 as candidate molecular targets. These results offer a hypothesis-generating basis for evaluating the ocular safety of MPB-containing products and point to a previously overlooked environmental contributor to KC.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"116482"},"PeriodicalIF":3.2,"publicationDate":"2026-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of Concern: \"Estimation of TiO2 nanoparticle-induced genotoxicity persistence and possible chronic gastritis-induction in mice\" [Food chem. Toxicol. 83 (2015) 76-83 10.1016/j.fct.2015.05.018].","authors":"","doi":"10.1016/j.fct.2026.116323","DOIUrl":"10.1016/j.fct.2026.116323","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"217 ","pages":"116323"},"PeriodicalIF":3.2,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}