Pub Date : 2026-01-13DOI: 10.1016/j.fct.2026.115950
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, 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
{"title":"Update to RIFM fragrance ingredient safety assessment, citral, CAS Registry Number 5392-40-5.","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, 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.2026.115950","DOIUrl":"https://doi.org/10.1016/j.fct.2026.115950","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115950"},"PeriodicalIF":3.5,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145987495","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}
Pub Date : 2026-01-13DOI: 10.1016/j.fct.2026.115937
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, 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
1,6-Octadien-3-ol, 3,7-dimethyl-, acid-isomerized was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data show that 1,6-octadien-3-ol, 3,7-dimethyl-, acid-isomerized is not genotoxic. Data on 1,6-octadien-3-ol, 3,7-dimethyl-, acid-isomerized provide a calculated Margin of Exposure (MOE) >100 for the repeated dose toxicity and reproductive toxicity endpoints. Data show that there are no safety concerns for 1,6-octadien-3-ol, 3,7-dimethyl-, acid-isomerized for skin sensitization under the current declared levels of use. The photoirritation/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; 1,6-octadien-3-ol, 3,7-dimethyl-, acid-isomerized 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 III material, and the exposure to 1,6-octadien-3-ol, 3,7-dimethyl-, acid-isomerized is below the TTC (0.47 mg/day). The environmental endpoints were evaluated; 1,6-octadien-3-ol, 3,7-dimethyl-, acid-isomerized 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.
{"title":"Update to RIFM fragrance ingredient safety assessment, 1,6-octadien-3-ol, 3,7-dimethyl-, acid-isomerized, CAS Registry Number 73018-51-6.","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, 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.2026.115937","DOIUrl":"https://doi.org/10.1016/j.fct.2026.115937","url":null,"abstract":"<p><p>1,6-Octadien-3-ol, 3,7-dimethyl-, acid-isomerized was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data show that 1,6-octadien-3-ol, 3,7-dimethyl-, acid-isomerized is not genotoxic. Data on 1,6-octadien-3-ol, 3,7-dimethyl-, acid-isomerized provide a calculated Margin of Exposure (MOE) >100 for the repeated dose toxicity and reproductive toxicity endpoints. Data show that there are no safety concerns for 1,6-octadien-3-ol, 3,7-dimethyl-, acid-isomerized for skin sensitization under the current declared levels of use. The photoirritation/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; 1,6-octadien-3-ol, 3,7-dimethyl-, acid-isomerized 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 III material, and the exposure to 1,6-octadien-3-ol, 3,7-dimethyl-, acid-isomerized is below the TTC (0.47 mg/day). The environmental endpoints were evaluated; 1,6-octadien-3-ol, 3,7-dimethyl-, acid-isomerized 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.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115937"},"PeriodicalIF":3.5,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145987674","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}
Pub Date : 2026-01-12DOI: 10.1016/j.fct.2026.115929
Simone Baldi , Sara Bertorello , Francesco Cei , Antonino Iurato La Rocca , Valentina Scianaro , Gianluca Bartolucci , Guido Mannaioni , Amedeo Amedei , Elisabetta Gerace
Fetal Alcohol Spectrum Disorder (FASD), caused by prenatal alcohol exposure (PAE), produces lasting physical, cognitive, and behavioral impairments. The present study examined effects of early PAE on the gut microbiome (GM) in adolescent mice to identify targets for early intervention. Female C57Bl/6 dams received 10 % ethanol during the first 10 days of gestation while controls received water. Fecal and blood samples from adolescent offspring were profiled by 16S rRNA sequencing and gas chromatography-mass spectrometry to characterize microbial composition and short-chain fatty acids (SCFAs). PAE reduced microbial alpha diversity and produced distinct beta diversity patterns versus controls. Metabolomic profiling revealed increased fecal acetate and reduced anti-inflammatory SCFAs in PAE mice, though circulating SCFA levels remained unchanged. Sex-stratified analyses showed that these alterations were driven predominantly by males, who exhibited greater microbial and metabolic disruptions, enrichment of pro-inflammatory genera (Parasutterella, Parabacteroides, Clostridioides), and elevated serum medium-chain fatty acids. Cluster analysis of PAE males identified a dysbiotic subgroup with severe alpha diversity loss, increased pro-inflammatory taxa, diminished beneficial SCFAs, and enrichment of catabolic and fatty acid biosynthesis pathways. Together, the results reveal sex- and individual-specific susceptibility to PAE-induced GM dysbiosis and justify further mechanistic studies to develop sex-tailored microbiota-targeted strategies for FASD.
{"title":"Gender-specific gut microbiota alterations in adolescent C57BL/6 mice following prenatal alcohol exposure","authors":"Simone Baldi , Sara Bertorello , Francesco Cei , Antonino Iurato La Rocca , Valentina Scianaro , Gianluca Bartolucci , Guido Mannaioni , Amedeo Amedei , Elisabetta Gerace","doi":"10.1016/j.fct.2026.115929","DOIUrl":"10.1016/j.fct.2026.115929","url":null,"abstract":"<div><div>Fetal Alcohol Spectrum Disorder (FASD), caused by prenatal alcohol exposure (PAE), produces lasting physical, cognitive, and behavioral impairments. The present study examined effects of early PAE on the gut microbiome (GM) in adolescent mice to identify targets for early intervention. Female C57Bl/6 dams received 10 % ethanol during the first 10 days of gestation while controls received water. Fecal and blood samples from adolescent offspring were profiled by 16S rRNA sequencing and gas chromatography-mass spectrometry to characterize microbial composition and short-chain fatty acids (SCFAs). PAE reduced microbial alpha diversity and produced distinct beta diversity patterns versus controls. Metabolomic profiling revealed increased fecal acetate and reduced anti-inflammatory SCFAs in PAE mice, though circulating SCFA levels remained unchanged. Sex-stratified analyses showed that these alterations were driven predominantly by males, who exhibited greater microbial and metabolic disruptions, enrichment of pro-inflammatory genera (<em>Parasutterella</em>, <em>Parabacteroides</em>, <em>Clostridioides</em>), and elevated serum medium-chain fatty acids. Cluster analysis of PAE males identified a dysbiotic subgroup with severe alpha diversity loss, increased pro-inflammatory taxa, diminished beneficial SCFAs, and enrichment of catabolic and fatty acid biosynthesis pathways. Together, the results reveal sex- and individual-specific susceptibility to PAE-induced GM dysbiosis and justify further mechanistic studies to develop sex-tailored microbiota-targeted strategies for FASD.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"210 ","pages":"Article 115929"},"PeriodicalIF":3.5,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973040","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}
Pub Date : 2026-01-09DOI: 10.1016/j.fct.2025.115915
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, 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
{"title":"RIFM fragrance ingredient safety assessment, 1,1-dimethoxycyclododecane, CAS Registry Number 950-33-4.","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, 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.2025.115915","DOIUrl":"https://doi.org/10.1016/j.fct.2025.115915","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115915"},"PeriodicalIF":3.5,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951015","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}
Cancer-associated fibroblasts (CAFs), as key stromal components of the tumor microenvironment (TME), exert profound influences on tumor progression by secreting cytokines, exosomes, and remodeling the extracellular matrix (ECM). Cadmium (Cd), a hazardous heavy metal, is strongly associated with lung carcinogenesis through environmental and occupational exposure. However, the molecular mechanisms underlying Cd-induced activation of fibroblasts and their functional contributions to lung cancer development remain poorly understood. Our study demonstrated that acute Cd exposure promoted the transformation of normal fibroblasts (MRC-5 cells) into an inflammatory CAFs-like (iCAFs) phenotype through upregulation of fibroblast activation protein (FAP). This Cd-driven FAP overexpression was accompanied by upregulated IL-6 and CCL2 release. Functionally, Cd-activated iCAFs-like cells significantly promoted the proliferation, migration, and invasion of lung cancer cell lines (H460 and A549) via paracrine signaling. Notably, FAP knockdown in MRC-5 cells using siRNA abrogated Cd-induced secretion of inflammatory factors and reversed the tumor-promoting effects of Cd-activated fibroblasts on cancer cells, establishing FAP as a central mediator of Cd-driven stromal reprogramming. These findings uncover a novel mechanism by which environmental Cd exposure exacerbates lung cancer progression through FAP-dependent fibroblast activation. Furthermore, they identify FAP as a potential therapeutic target for mitigating Cd-induced carcinogenesis, with implications for environmental toxin-associated cancer prevention and treatment.
{"title":"Cadmium-induced activation of inflammatory cancer-associated fibroblasts-like cells enhances malignant phenotypes of lung cancer cells","authors":"Qi Jiang , Lujiao Wang , Biyun Chen, Tianyi Dong, Wanyou Shen, Xue Zhou","doi":"10.1016/j.fct.2026.115927","DOIUrl":"10.1016/j.fct.2026.115927","url":null,"abstract":"<div><div>Cancer-associated fibroblasts (CAFs), as key stromal components of the tumor microenvironment (TME), exert profound influences on tumor progression by secreting cytokines, exosomes, and remodeling the extracellular matrix (ECM). Cadmium (Cd), a hazardous heavy metal, is strongly associated with lung carcinogenesis through environmental and occupational exposure. However, the molecular mechanisms underlying Cd-induced activation of fibroblasts and their functional contributions to lung cancer development remain poorly understood. Our study demonstrated that acute Cd exposure promoted the transformation of normal fibroblasts (MRC-5 cells) into an inflammatory CAFs-like (iCAFs) phenotype through upregulation of fibroblast activation protein (FAP). This Cd-driven FAP overexpression was accompanied by upregulated IL-6 and CCL2 release. Functionally, Cd-activated iCAFs-like cells significantly promoted the proliferation, migration, and invasion of lung cancer cell lines (H460 and A549) via paracrine signaling. Notably, FAP knockdown in MRC-5 cells using siRNA abrogated Cd-induced secretion of inflammatory factors and reversed the tumor-promoting effects of Cd-activated fibroblasts on cancer cells, establishing FAP as a central mediator of Cd-driven stromal reprogramming. These findings uncover a novel mechanism by which environmental Cd exposure exacerbates lung cancer progression through FAP-dependent fibroblast activation. Furthermore, they identify FAP as a potential therapeutic target for mitigating Cd-induced carcinogenesis, with implications for environmental toxin-associated cancer prevention and treatment.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"210 ","pages":"Article 115927"},"PeriodicalIF":3.5,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948334","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}
In this study, pregnant mice were exposed to dietary Di(2-ethylhexyl) phthalate (DEHP) (0.1% or 0.2%) from gestational day (GD) 0 to GD18, and maternal liver metabolomes were profiled by GC-MS/MS-based metabolomics followed by bioinformatics analysis using our PiTMaP platform. Multivariate analysis revealed clear separation between the control and DEHP groups, indicating substantial metabolic alterations in maternal liver. Among the metabolites contributing to group separation, 20 compounds, including malic acid, tryptophan, niacinamide, cysteine, and hypotaurine, showed significant differences (FDR < 0.05), suggesting mitochondrial dysfunction and alterations in the tryptophan-niacinamide and hypotaurine metabolic pathways. In addition, a machine learning-based Random Forest classifier demonstrated that these significantly altered metabolites could accurately discriminate among the three groups. Further network analysis identified hypotaurine as the top network hub in the liver. These results demonstrate tissue-specific rewiring of metabolic networks under DEHP exposure, with mitochondrial and tryptophan-niacinamide pathways being prominently affected in the liver. Overall, this study provides novel mechanistic insights into maternal metabolic disturbances induced by DEHP exposure during pregnancy and contributes to the identification of organ-specific biomarkers relevant to such exposure.
{"title":"Metabolic Profiling of the Maternal Liver in Pregnant Mice Exposed to Di(2-ethylhexyl) Phthalate (DEHP).","authors":"Tomomi Asano, Yuto Ohtani, Shinnosuke Sugiura, Masaru Taniguchi, Kei Zaitsu","doi":"10.1016/j.fct.2026.115928","DOIUrl":"https://doi.org/10.1016/j.fct.2026.115928","url":null,"abstract":"<p><p>In this study, pregnant mice were exposed to dietary Di(2-ethylhexyl) phthalate (DEHP) (0.1% or 0.2%) from gestational day (GD) 0 to GD18, and maternal liver metabolomes were profiled by GC-MS/MS-based metabolomics followed by bioinformatics analysis using our PiTMaP platform. Multivariate analysis revealed clear separation between the control and DEHP groups, indicating substantial metabolic alterations in maternal liver. Among the metabolites contributing to group separation, 20 compounds, including malic acid, tryptophan, niacinamide, cysteine, and hypotaurine, showed significant differences (FDR < 0.05), suggesting mitochondrial dysfunction and alterations in the tryptophan-niacinamide and hypotaurine metabolic pathways. In addition, a machine learning-based Random Forest classifier demonstrated that these significantly altered metabolites could accurately discriminate among the three groups. Further network analysis identified hypotaurine as the top network hub in the liver. These results demonstrate tissue-specific rewiring of metabolic networks under DEHP exposure, with mitochondrial and tryptophan-niacinamide pathways being prominently affected in the liver. Overall, this study provides novel mechanistic insights into maternal metabolic disturbances induced by DEHP exposure during pregnancy and contributes to the identification of organ-specific biomarkers relevant to such exposure.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115928"},"PeriodicalIF":3.5,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145942079","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}
Pub Date : 2026-01-02DOI: 10.1016/j.fct.2025.115926
Jianhui Liu , Shaofei Su , Ruixia Liu , Shuanghua Xie , Chenghong Yin , Enjie Zhang , Lihua Ren
Polystyrene nanoplastics (PS-NPs) exposure can induce testosterone decline, but the underlying mechanism remains elusive. In the present study, prepubertal PS-NPs exposure caused testicular injury and reduced testosterone levels. RNA sequence analysis indicated that cholesterol homeostasis and PPARα signaling pathways may be involved in the disruption of testosterone biosynthesis. Compared with the control group, exposure to PS-NPs resulted in no significant change in serum cholesterol levels but a marked reduction in testicular and TM3 cell cholesterol levels. Western blot analysis revealed prepubertal PS-NPs exposure activated the PPARα pathway, with a consequent significant downregulation in the expression of cholesterol uptake receptors SCARB1 and LDLR. Using immunoprecipitation, we found that PS-NPs disrupted cholesterol uptake by facilitating the ubiquitin-dependent degradation of FTO. Ultimately, we observed that PS-NPs exposure markedly upregulated Smurf1 protein expression. Knocking down Smurf1 repressed PS-NPs caused the ubiquitin-dependent degradation of FTO protein, thereby alleviating cholesterol and testosterone decline. Overall, our study elucidated a novel mechanism by which prepubertal PS-NPs exposure disrupted cholesterol/testosterone homeostasis via Smurf1-dependent FTO degradation.
{"title":"Polystyrene nanoplastics disrupted cholesterol/testosterone homeostasis via Smurf1-dependent FTO degradation","authors":"Jianhui Liu , Shaofei Su , Ruixia Liu , Shuanghua Xie , Chenghong Yin , Enjie Zhang , Lihua Ren","doi":"10.1016/j.fct.2025.115926","DOIUrl":"10.1016/j.fct.2025.115926","url":null,"abstract":"<div><div>Polystyrene nanoplastics (PS-NPs) exposure can induce testosterone decline, but the underlying mechanism remains elusive. In the present study, prepubertal PS-NPs exposure caused testicular injury and reduced testosterone levels. RNA sequence analysis indicated that cholesterol homeostasis and PPARα signaling pathways may be involved in the disruption of testosterone biosynthesis. Compared with the control group, exposure to PS-NPs resulted in no significant change in serum cholesterol levels but a marked reduction in testicular and TM3 cell cholesterol levels. Western blot analysis revealed prepubertal PS-NPs exposure activated the PPARα pathway, with a consequent significant downregulation in the expression of cholesterol uptake receptors SCARB1 and LDLR. Using immunoprecipitation, we found that PS-NPs disrupted cholesterol uptake by facilitating the ubiquitin-dependent degradation of FTO. Ultimately, we observed that PS-NPs exposure markedly upregulated Smurf1 protein expression. Knocking down Smurf1 repressed PS-NPs caused the ubiquitin-dependent degradation of FTO protein, thereby alleviating cholesterol and testosterone decline. Overall, our study elucidated a novel mechanism by which prepubertal PS-NPs exposure disrupted cholesterol/testosterone homeostasis via Smurf1-dependent FTO degradation.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"209 ","pages":"Article 115926"},"PeriodicalIF":3.5,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145898892","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}
Pub Date : 2025-12-31DOI: 10.1016/j.fct.2025.115923
Dina A. AbdElrazek , Neven H. Hassan , Marwa A. Ibrahim , Eman I. Hassanen , Khaled Y. Farroh , H.I. Abass
{"title":"Corrigendum to “Ameliorative effects of rutin and rutin-loaded chitosan nanoparticles on testicular oxidative stress and histological damage induced by cyclophosphamide in male rats” [Food and Chemical Toxicology 184 (2024) 114436]","authors":"Dina A. AbdElrazek , Neven H. Hassan , Marwa A. Ibrahim , Eman I. Hassanen , Khaled Y. Farroh , H.I. Abass","doi":"10.1016/j.fct.2025.115923","DOIUrl":"10.1016/j.fct.2025.115923","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"209 ","pages":"Article 115923"},"PeriodicalIF":3.5,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881379","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}
Pub Date : 2025-12-30DOI: 10.1016/j.fct.2025.115924
Mohammed I.A. Ibrahim , Antoinette V. Lensink , Christo J. Botha
Deoxynivalenol (DON) and zearalenone (ZEA) are among the most prevalent mycotoxins synthesized by Fusarium species, with 60 % and 80 % prevalence in grains containing mycotoxins, respectively. These mycotoxins often co-contaminate feedstuffs and induce male reproductive toxicity. This study investigated in vitro cytotoxicity, the structure of selected cytoskeletal proteins, mitochondrial morphology, lysosomal activity, and ultrastructural changes associated with individual and combined DON and ZEA exposure in rat Leydig cells (LC-540). Deoxynivalenol (IC50: 2.66, 0.50, and 0.44 μM) induced higher cytotoxicity than ZEA (IC50: 117.0, 69.1, and 34.4 μM) after 24, 48, and 72 h, respectively. Combined DON + ZEA exposure revealed concentration- and time-dependent cytotoxic effects that were synergistic at low concentrations (0.125 + 10 μM), but additive or antagonistic at higher concentrations (2 + 30 and 5 + 50 μM). Microscopic analysis revealed both mycotoxins disrupted F-actin and β-tubulin, impaired mitochondrial morphology, and increased lysosomal acidification. Ultrastructurally, marked cellular alterations included mitochondrial damage, autophagosome formation, and apoptosis. The observed cytotoxicity, disruption of cytoskeletal proteins, and mitochondrial damage in the Leydig cells may play a role in clarifying the male reproductive toxicity induced by DON and ZEA or their co-exposure.
{"title":"The cytotoxic effects of a single and combined exposure to the mycotoxins, deoxynivalenol and zearalenone, on a rat Leydig cell line (LC-540)","authors":"Mohammed I.A. Ibrahim , Antoinette V. Lensink , Christo J. Botha","doi":"10.1016/j.fct.2025.115924","DOIUrl":"10.1016/j.fct.2025.115924","url":null,"abstract":"<div><div>Deoxynivalenol (DON) and zearalenone (ZEA) are among the most prevalent mycotoxins synthesized by <em>Fusarium</em> species, with 60 % and 80 % prevalence in grains containing mycotoxins, respectively. These mycotoxins often co-contaminate feedstuffs and induce male reproductive toxicity. This study investigated <em>in vitro</em> cytotoxicity, the structure of selected cytoskeletal proteins, mitochondrial morphology, lysosomal activity, and ultrastructural changes associated with individual and combined DON and ZEA exposure in rat Leydig cells (LC-540). Deoxynivalenol (IC<sub>50</sub>: 2.66, 0.50, and 0.44 μM) induced higher cytotoxicity than ZEA (IC<sub>50</sub>: 117.0, 69.1, and 34.4 μM) after 24, 48, and 72 h, respectively. Combined DON + ZEA exposure revealed concentration- and time-dependent cytotoxic effects that were synergistic at low concentrations (0.125 + 10 μM), but additive or antagonistic at higher concentrations (2 + 30 and 5 + 50 μM). Microscopic analysis revealed both mycotoxins disrupted F-actin and β-tubulin, impaired mitochondrial morphology, and increased lysosomal acidification. Ultrastructurally, marked cellular alterations included mitochondrial damage, autophagosome formation, and apoptosis. The observed cytotoxicity, disruption of cytoskeletal proteins, and mitochondrial damage in the Leydig cells may play a role in clarifying the male reproductive toxicity induced by DON and ZEA or their co-exposure.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"209 ","pages":"Article 115924"},"PeriodicalIF":3.5,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881318","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}
Pub Date : 2025-12-29DOI: 10.1016/j.fct.2025.115925
Leeseon An , Jung-Eun Kim , Eunseo Park , Hyo-Jeong Lee
Legal limits and toxic thresholds for histamine levels in food have been established by the Codex Alimentarius Commission as well as by national food safety authorities in various countries In this study, we found that mast cell degranulation was increased in a histamine concentration-dependent manner, and this degranulation was found to be associated with MRGPRX2, a receptor involved in non-IgE-mediated allergic reactions, as demonstrated by molecular docking analysis and mRNA expression. A strong positive correlation was observed between MRGPRX2 and mast cell degranulation, indicating that higher MRGPRX2 mRNA levels were associated with increased degranulation activity. We analyzed histamine concentrations, MRGPRX2 mRNA expression, and mast cell degranulation for fermented soy sauce and shrimp sauce (FSS, used as a positive control). DS, FS, and JS demonstrated a histamine concentration below 200 μg/mL and showed no significant effect on mast cell degranulation and MRGPRX2 mRNA levels in HMC-1.2 cells. Especially, FS contained high GABA concentrations. A strong negative correlation and the expression of MRGPRX2 mRNA as well as mast cell degranulation. Finally, this assay, anchored to the histamine limits recommended by the Codex, enables routine screening of biogenic amine-containing foods to verify regulatory compliance and help ensure a safe food supply.
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