{"title":"Comprehensive investigation into the discrete toxicity of curcumin on β-cell viability and insulin secretion","authors":"Rania Derguine , Abdelmalek Rezgui , Rechda Amel Tachour , Imène Zenbout , Rym Agred , Anfel Benmanseur , Fatma-Zahra Hab , Abdelhalim Khenchouche , Widad Sobhi","doi":"10.1016/j.fct.2025.115429","DOIUrl":"10.1016/j.fct.2025.115429","url":null,"abstract":"<div><h3>Background</h3><div>Curcumin possesses several therapeutic benefits. However, the precise mechanisms underlying these actions have not been fully elucidated. The aim of this study was to highlight the toxic effects on β-cells and islets.</div></div><div><h3>Methods</h3><div>The toxic effects of curcumin were investigated on cell viability in ALB/c mouse-isolated Langerhans islets and NIT1 cells (CRL-2055™, a NOD mouse β cell line), and insulin secretion. We evaluated its effects on oxidative stress markers, ROS production, and its role in ER stress through the stimulation of three genes involved in the UPR response. In silico and in vitro studies were conducted to extract a set of genes and curcumin-PPI using a multistep pipeline.</div></div><div><h3>Results</h3><div>Curcumin increases cell viability and insulin secretion in islets of Langerhans. At 60 μg/mL (0,163 μM), curcumin affected β-cell viability, reducing it by up to 70–75 %, and significantly reduced insulin secretion. It also induces oxidative stress and increases the expression of NFKB1, ATF4, and CHOP. These effects were enhanced when curcumin was combined with STZ. Bioinformatic studies have indicated that curcumin interacts with 14 proteins, including Jund, Ddit3, Dapk3, Cebpa, and the NF<em>k</em>B pathway through NFkBia.</div></div><div><h3>Conclusion</h3><div>At high concentrations, curcumin is cytotoxic. It induces β-cell apoptosis associated with UPR-ER and oxidative stress, implicating the NF<em>k</em>B pathway and its associated proteins.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"200 ","pages":"Article 115429"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784068","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}
Gabriely F. Groto Militão , Anjaína F. de Albuquerque , Nelson R. Vinueza , Marina Tenório Botelho , Gisela de Aragão Umbuzeiro
{"title":"The importance of the YG1041 Salmonella strain in the mutagenicity characterization of azo dyes","authors":"Gabriely F. Groto Militão , Anjaína F. de Albuquerque , Nelson R. Vinueza , Marina Tenório Botelho , Gisela de Aragão Umbuzeiro","doi":"10.1016/j.fct.2025.115427","DOIUrl":"10.1016/j.fct.2025.115427","url":null,"abstract":"<div><div>Azo dyes, classified by the functional group (-N<img>N-) are widely used in various industries. Among them, disperse dyes are particularly important because of their low cost, colour versatility, and compatibility with polyester, the most popular synthetic fiber. Because several azo dyes are known to be mutagenic and therefore potentially carcinogenic, new dyes from this class need to have their genotoxic hazard characterized. This study aimed to assess the mutagenicity of five high-purity disperse azo dyes (≥97 %) using a miniaturized, Microplate agar (MPA) version of the Salmonella/microsome assay (Ames test). The MPA with Salmonella strains YG1041, TA98, and TA100 was used to reduce the amount of dyes needed. All five dyes were mutagenic in YG1041, but only one was mutagenic with TA98, and none were positive in TA100. Based on our data and the literature reviewed, we recommend the inclusion of YG1041 in the battery of strains used to evaluate azo dyes. This work also demonstrates the efficacy of the MPA for characterizing mutagenicity of substances with small amounts of test sample.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"200 ","pages":"Article 115427"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787470","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}
A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , M. Lavelle , I. Lee , H. Moustakas , Y. Tokura
{"title":"RIFM Natural Complex Substance (NCS) fragrance ingredient safety assessment, clove bud absolute, CAS Registry Number 8000-34-8, RIFM ID 583-F2.1","authors":"A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , M. Lavelle , I. Lee , H. Moustakas , Y. Tokura","doi":"10.1016/j.fct.2025.115415","DOIUrl":"10.1016/j.fct.2025.115415","url":null,"abstract":"<div><div>Clove bud absolute was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data for components of the NCS do not show a concern for genotoxicity. Clove bud absolute 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 Threshold of Toxicological Concern (TTC); clove bud absolute is safe for use under the conditions described in this safety assessment for the repeated dose and reproductive toxicity endpoints. Data for 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 ultraviolet/visible (UV/Vis) absorption spectra for the components of the NCS; clove bud absolute is not expected to be photoirritating. The photoallergenicity endpoint was evaluated based on UV/Vis absorption spectra for the components of the NCS; clove bud absolute is not expected to be photoallergenic. The local respiratory toxicity endpoint for this NCS was evaluated using the inhalation TTC for a Cramer Class III material, and the inhalation exposure to clove bud absolute is below the TTC (0.47 mg/day). Based on the component assessment, clove bud absolute does not contain Persistent, Bioaccumulative, and Toxic (PBT) or (very) Persistent, (very) Bioaccumulative (vPvB) components as per the IFRA Environmental Standards and does not present a risk to the aquatic environment at the current reported VoU.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115415"},"PeriodicalIF":3.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778560","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}
Fuad M. Alzahrani , Aqsa Bibi , Muhammad Faisal Hayat , Khalid J. Alzahrani , Khalaf F. Alsharif , Adnan Ali
{"title":"Sorbitol induces sub-chronic nephrotoxicity via escalating JAK1/STAT3, oxidative stress and inflammation in Sprague Dawley rats","authors":"Fuad M. Alzahrani , Aqsa Bibi , Muhammad Faisal Hayat , Khalid J. Alzahrani , Khalaf F. Alsharif , Adnan Ali","doi":"10.1016/j.fct.2025.115422","DOIUrl":"10.1016/j.fct.2025.115422","url":null,"abstract":"<div><div>Sorbitol (SOR) is a natural food sweetener that is widely used in candies, chocolates, biscuits, and jams. SOR showed toxic impacts on different body organs except renal tissues. Therefore, the present investigation was conducted to assess the sub-chronic nephrotoxic effects of SOR on renal tissue. Thirty-six Sprague Dawley rats were apportioned into control, SOR (20 mg/kg), SOR (45 mg/kg) and SOR (90 mg/kg) treated group. SOR intoxication showed upregulation in the gene expression of <em>JAK1, STAT3, NF-κB, TNF-α, IL-18, IL-6, IL-1β,</em> and <em>COX-2</em>. The levels of ROS and MDA were promoted while the enzymatic activities of HO-1, SOD, GPx, GSR, CAT and GST were reduced after SOR administration. SOR exposure showed elevation in the levels of cystatin C, BUN, KIM-1, urea, creatinine, uric acid, NAG, while a reduction in creatinine clearance in dose-dependent manners. Besides, SOR intoxication escalated the levels of Caspase-9, Caspase-3 and Bax while reducing the levels of Bcl-2. Moreover, SOR administration distorted the renal histology at all the tested doses. These findings suggest the nephrotoxic effects of SOR in dose-dependent manners as 90 mg/kg > 45 mg/kg > 20 mg/kg owing to its pro-oxidative, pro-inflammatory and pro-apoptotic attributes.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"200 ","pages":"Article 115422"},"PeriodicalIF":3.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143767684","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}
A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar
{"title":"RIFM fragrance ingredient safety assessment, 1-decanol, CAS registry number 112-30-1","authors":"A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar","doi":"10.1016/j.fct.2025.115418","DOIUrl":"10.1016/j.fct.2025.115418","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115418"},"PeriodicalIF":3.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778552","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}
A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar
{"title":"RIFM fragrance ingredient safety assessment, nonyl alcohol, CAS Registry Number 143-08-8","authors":"A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar","doi":"10.1016/j.fct.2025.115417","DOIUrl":"10.1016/j.fct.2025.115417","url":null,"abstract":"<div><div>Nonyl alcohol was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog heptyl alcohol (CAS # 111-70-6) show that nonyl alcohol is not expected to be genotoxic and provide a calculated Margin of Exposure (MOE) >100 for the repeated dose toxicity and reproductive toxicity endpoints. Data from read-across analog 1-decanol (CAS # 112-30-1) provided nonyl alcohol a No Expected Sensitization Induction Level (NESIL) of 10000 μg/cm<sup>2</sup> for the skin sensitization endpoint. The photoirritation/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; nonyl alcohol is not expected to be photoirritating/photoallergenic. The local respiratory toxicity endpoint was evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class I material, and the exposure to nonyl alcohol is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; nonyl alcohol was found not to be Persistent, Bioaccumulative, and 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 and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115417"},"PeriodicalIF":3.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778556","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}
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 , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar
{"title":"Update to RIFM fragrance ingredient safety assessment, methoxy dicyclopentadiene carboxaldehyde, CAS Registry Number 86803-90-9","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 , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar","doi":"10.1016/j.fct.2025.115414","DOIUrl":"10.1016/j.fct.2025.115414","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115414"},"PeriodicalIF":3.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750343","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}
A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar
{"title":"RIFM fragrance ingredient safety assessment, octahydro-4,7-methano-1H-indenecarbaldehyde, CAS Registry Number 30772-79-3","authors":"A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar","doi":"10.1016/j.fct.2025.115412","DOIUrl":"10.1016/j.fct.2025.115412","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115412"},"PeriodicalIF":3.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750163","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}
A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar
{"title":"Update to RIFM fragrance ingredient safety assessment, acetophenone, CAS Registry number 98-86-2","authors":"A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar","doi":"10.1016/j.fct.2025.115416","DOIUrl":"10.1016/j.fct.2025.115416","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115416"},"PeriodicalIF":3.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741718","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}
A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , M. Lavelle , I. Lee , H. Moustakas , Y. Tokura
{"title":"RIFM Natural Complex Substance (NCS) fragrance ingredient safety assessment, Sage oil, Spanish, CAS Registry Number 8022-56-8, RIFM ID 479-E2.12","authors":"A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , M. Lavelle , I. Lee , H. Moustakas , Y. Tokura","doi":"10.1016/j.fct.2025.115411","DOIUrl":"10.1016/j.fct.2025.115411","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115411"},"PeriodicalIF":3.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741716","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}
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