Marina Romero-Bernal , Ángela González-Díaz , Maria Tripodi , Alba Zheli Álvarez , Jara Rodríguez , David Núñez-Jurado , María de la Luz Cádiz-Gurrea , Ana I. Prieto , Leticia Diez-Quijada , Irene Cantarero , Carmen del Río , Joan Montaner
{"title":"Subchronic 90-days toxicity profile of Salicornia ramosissima extract in rats","authors":"Marina Romero-Bernal , Ángela González-Díaz , Maria Tripodi , Alba Zheli Álvarez , Jara Rodríguez , David Núñez-Jurado , María de la Luz Cádiz-Gurrea , Ana I. Prieto , Leticia Diez-Quijada , Irene Cantarero , Carmen del Río , Joan Montaner","doi":"10.1016/j.fct.2025.115890","DOIUrl":"10.1016/j.fct.2025.115890","url":null,"abstract":"<div><div><em>Salicornia ramosissima</em>, a halophytic plant rich in bioactive compounds, has gained attention for its potential health benefits. However, its long-term safety profile remains underexplored. This study aimed to evaluate the subchronic 90-day toxicity of <em>S. ramosissima</em> extract in Wistar rats. Animals received daily oral doses of 100, 500 or 1.000 mg/kg/day of the extract or placebo, and key physiological, biochemical, and histopathological parameters were assessed. Results indicated no significant adverse effects on body weight, food and water intake, or organ weights. Hematological and biochemical analyses revealed no major toxicological concerns. Histopathological examination did not indicate any extract-induced lesions in any of the examined organs, which included gastrointestinal, respiratory, lymphoid, urinary, nervous, circulatory and reproductive systems. Complementary assays demonstrated absence of developmental toxicity in <em>Drosophila melanogaster</em> and no mutagenic activity in the Ames test. Overall, these results indicate that subchronic administration of <em>S. ramosissima</em> extract is well tolerated in rats and does not elicit genotoxic or developmental toxicity, supporting its potential safe use as a functional food or nutraceutical ingredient.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"209 ","pages":"Article 115890"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145754012","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}
Leeseon An , Jung-Eun Kim , Eunseo Park , Hyo-Jeong Lee
{"title":"Effective in vitro evaluation of biogenic amines in fermented food using mast cells","authors":"Leeseon An , Jung-Eun Kim , Eunseo Park , Hyo-Jeong Lee","doi":"10.1016/j.fct.2025.115925","DOIUrl":"10.1016/j.fct.2025.115925","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"209 ","pages":"Article 115925"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877324","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}
Jianhui Liu , Shaofei Su , Ruixia Liu , Shuanghua Xie , Chenghong Yin , Enjie Zhang , Lihua Ren
{"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":"2026-03-01","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}
Gang Chen , Hang Yuan , XiaoPeng Li, Shihui Chen, Xuejun Sun, Junhui Yu
{"title":"Decipher the molecular network of PFOA in inflammatory bowel disease through integrating machine learning, molecular docking strategies, and validation in vitro","authors":"Gang Chen , Hang Yuan , XiaoPeng Li, Shihui Chen, Xuejun Sun, Junhui Yu","doi":"10.1016/j.fct.2025.115898","DOIUrl":"10.1016/j.fct.2025.115898","url":null,"abstract":"<div><h3>Objective</h3><div>Perfluorooctanoic Acid (PFOA), widely recognized as an enduring environmental pollutant, is associated with immune system disruption and potential cancer-causing effects. Epidemiological findings show that serum power is significantly associated with inflammatory bowel disease (IBD). However, the specific mechanisms driving these effects remain poorly understood.</div></div><div><h3>Methods</h3><div>Possible targets associated with PFOA were obtained from various sources. Transcriptomic data from IBD patients were sourced through GEO. To delve into the binding interactions of PFOA with its target proteins, we employed machine learning techniques, network toxicology approaches, as well as molecular docking strategies.</div></div><div><h3>Results</h3><div>This study reveals that PFOA has the potential to promote the development of IBD by affecting certain genes and signaling pathways. ABCB1, HSD17B11, PDK2, LCN2, SETD7, and MMP1 were identified as six pivotal genes via machine learning, and molecular docking verified that PFOA has a strong binding affinity with important goals. In validation, we found that the expression of LCN2 is elevated by PFOA in NCM460 and HT29 cells, with higher concentrations leading to a corresponding increase in expression levels.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that PFOA has the potential to promote development of IBD. The results may offer important insights into the advancement of understanding IBD mechanisms associated with PFOA.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"209 ","pages":"Article 115898"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773116","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}
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":"2026-03-01","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}
Katarina Baralić , Jovana Jerotijević , Marta Pantelić , Jovana Živanović , Danijela Đukić-Ćosić
{"title":"Computational profiling of toxic mixtures associated with type 2 diabetes mellitus development: identification of key protective agents","authors":"Katarina Baralić , Jovana Jerotijević , Marta Pantelić , Jovana Živanović , Danijela Đukić-Ćosić","doi":"10.1016/j.fct.2025.115893","DOIUrl":"10.1016/j.fct.2025.115893","url":null,"abstract":"<div><div>The aim of the current research was to assess the association between the exposure to plastic-related chemicals and toxic metals with the development of type 2 diabetes mellitus using an <em>in silico</em> approach, while also exploring the protective potential of antioxidant vitamins and phytochemicals, including Vitamin C, Vitamin E, sulforaphane, resveratrol, curcumin, naringin, and quercetin. <em>CTD</em> database, <em>GeneMANIA</em> server, and <em>Toppgene</em> portal were used as the main <em>in silico</em> tools in this study. Six common genes (BAX, CASP3, CAT, IL6, SOD1, TNF) were identified for all toxic substances, indicating potential shared mechanisms of toxicity (apoptosis, inflammation, oxidative stress). Additionally, phthalates and bisphenols affected cell growth, lipid and energy metabolism, and vascular functions, while toxic metals were linked to apoptosis regulation, DNA repair, insulin regulation, and glucose uptake. All tested protective substances, except naringin, affected all six common genes for all toxic substances, with vitamin C, vitamin E, and sulforaphane showing the most consistent protective effects. This study highlights the complex mechanisms in type 2 diabetes pathogenesis induced by toxic substances and provides a foundation for further research on the preventive effects of tested protective substances, emphasizing their varying protective potentials depending on the toxic compounds.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"209 ","pages":"Article 115893"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145754013","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}
Qingquan Gong , Dingyu Liang , Yongjin Luo , Chao Yang , Yihua Yang , Shujie Zhang
{"title":"Aspartame promotes ovarian cancer progression: A multi-omics study integrating mendelian randomization, network toxicology, and in vitro validation","authors":"Qingquan Gong , Dingyu Liang , Yongjin Luo , Chao Yang , Yihua Yang , Shujie Zhang","doi":"10.1016/j.fct.2025.115901","DOIUrl":"10.1016/j.fct.2025.115901","url":null,"abstract":"<div><div>The causal relationship between the artificial sweetener aspartame and ovarian cancer (OC), a highly lethal malignancy, remains unclear. This study, therefore, employed a multi-omics approach to investigate this causal link and its potential mechanisms. First, a Mendelian Randomization (MR) analysis indicated that genetically predicted aspartame intake is associated with an increased risk of OC (OR = 2.10, 95 % CI: 1.06–4.18). Next, by integrating network toxicology with machine learning algorithms (LASSO, SVM, and Random Forest), we identified AURKA, CCND1, and RAD51 as potential core target genes. Further validation using multi-omics data from bulk and single-cell RNA sequencing confirmed that these three genes are upregulated in OC tissues. A subsequent MR analysis also provided causal evidence that high expression of CCND1 increases the risk of OC. Furthermore, molecular docking simulations showed that aspartame could form stable bonds with all three target proteins. Finally, in vitro experiments demonstrated that aspartame significantly promoted the malignant phenotypes of OC cells and regulated the expression of these core genes. In conclusion, this study suggests that aspartame may promote ovarian cancer development, potentially by upregulating the expression of key genes such as AURKA, CCND1, and RAD51. These findings provide new evidence for evaluating the safety of aspartame.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"209 ","pages":"Article 115901"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145754708","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}
Zofi A. McKenzie, Anne-Sophie Parant, Katy L. Bridgwood, Ewan D. Booth
{"title":"Evaluation of the genotoxic potential of dietary metabolites to support the renewal of an active substance under European Commission Regulation (EC) 1107/2009 – fludioxonil case study","authors":"Zofi A. McKenzie, Anne-Sophie Parant, Katy L. Bridgwood, Ewan D. Booth","doi":"10.1016/j.fct.2025.115872","DOIUrl":"10.1016/j.fct.2025.115872","url":null,"abstract":"<div><div>The evaluation of the genotoxic potential of dietary metabolites of active substances is an important aspect for the (re)registration of pesticides within the European Union. This paper presents a case study evaluating the genotoxic potential of three dietary metabolites (CGA335892, SYN518580 and CGA227731) of the active substance fludioxonil under Regulation (EC)1107/2009. This tiered process started with (Q)SAR and read across, to enable a “grouping” approach, the three metabolites were identified as “exemplar compounds” and evaluated for gene mutation, clastogenicity and aneugenicity. Bacterial reverse mutation tests were conducted on CGA335892 (negative), SYN518580 (negative) and CGA227731 (positive). <em>In vitro</em> micronucleus assays on CGA335892 and SYN518580 were positive whereas CGA227731 was negative. <em>In vivo</em> genotoxicity assays were conducted to follow up the positive <em>in vitro</em> findings. Mouse micronucleus studies (CGA335892, SYN518580) were negative and therefore these compounds were concluded not clastogenic and not aneugenic <em>in vivo</em>. CGA227731 was negative in a rat Comet assay; however, following regulatory review a transgenic rodent gene mutation assay was conducted to investigate the <em>in vivo</em> mutagenicity of this metabolite. CGA227731 is concluded to be non-mutagenic <em>in vivo</em>. Based on this extensive battery of genotoxicity tests, we conclude CGA335892, SYN518580 and CGA227731 to be of no genotoxic concern.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"209 ","pages":"Article 115872"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647058","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}
Nidal A. Qinna , Bayan Y. Ghanim , Duaa Abuarqoub , Qasem Abdallah , Malak Jaber , Mohammad AlNatoor , Duaa Sabbah , Bayan Alkhawaja , Dong-Hyun Kim
{"title":"Effect of single binge alcohol consumption on alcohol-naïve and -exposed drinking mouse models","authors":"Nidal A. Qinna , Bayan Y. Ghanim , Duaa Abuarqoub , Qasem Abdallah , Malak Jaber , Mohammad AlNatoor , Duaa Sabbah , Bayan Alkhawaja , Dong-Hyun Kim","doi":"10.1016/j.fct.2025.115899","DOIUrl":"10.1016/j.fct.2025.115899","url":null,"abstract":"<div><div>Binge alcohol exposure is underestimated compared to chronic intake, particularly in young or alcohol-naïve individuals. This study investigates the effects of single binge drinking, on both alcohol-naïve and alcohol-dependent drinking subjects. C57BL/6J mice received a binge ethanol dose (6 g/kg body weight; 40 % ethanol(v/v)), and subsequent haematological, hepatic, transcriptomic, and metabolomic changes were analyzed. In naïve mice, binge alcohol elevated serum AST levels, indicating acute liver injury. In ethanol-dependent mice (20 g/kg/day; 6 % ethanol(v/v)), single binge episode altered haematological parameters and affected liver-to-body weight ratios. Both naïve and previously exposed animals showed downregulation of hepatic ADH1, Cat, and antioxidant enzyme SOD expression. Liver ROS was triggered across alcohol-drinking groups, more pronounced in binge-treated mice. Additionally, ethanol exposure induced lipid accumulation and ROS generation in liver tissue, upregulated lipogenic and downregulated fatty acid oxidation genes—effects exacerbated in previously exposed animals. Metabolomic analysis revealed alterations in amino acid and energy metabolism pathways following binge exposure. These findings can confirm the hazard of binge drinking on both previously exposed “alcohol-consumers” and “naïve-drinkers”. Moreover, it highlights severe physiological disruptions caused by a single binge episode and the necessity for deeper experimental and clinical exploration of binge drinking, given its prevalence for long-term health consequences.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"209 ","pages":"Article 115899"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145761820","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}
Fangfang Chen , Boshi Xu , Shihui Zhang , Wenqi Shao , Jinhao Wang , Shuo Li , Shirui Wang , Guanchen Liu , Kexiang Liu , Shuchen Zhao , Jiaying Guo , Lijia Zhao
{"title":"Ferroptosis inhibition mitigates glyphosate-induced inflammation and blood–milk barrier disruption in bovine mammary epithelial cells","authors":"Fangfang Chen , Boshi Xu , Shihui Zhang , Wenqi Shao , Jinhao Wang , Shuo Li , Shirui Wang , Guanchen Liu , Kexiang Liu , Shuchen Zhao , Jiaying Guo , Lijia Zhao","doi":"10.1016/j.fct.2025.115904","DOIUrl":"10.1016/j.fct.2025.115904","url":null,"abstract":"<div><div>Glyphosate (GLY), the primary active component in many herbicides, is widely used in agriculture, and it is associated with impaired mammary gland development. However, the molecular mechanisms underlying its toxicity to mammary epithelial cells remain poorly understood. Ferroptosis, a regulated form of cell death characterized by iron overload and excessive lipid peroxidation, has emerged as a crucial driver of inflammation and barrier dysfunction. In the present study, bovine mammary epithelial cells (MAC-T) were used as an <em>in vitro</em> model to investigate the involvement of ferroptosis in GLY-induced cellular injury. GLY exposure increased intracellular ferrous iron (Fe<sup>2+</sup>) accumulation, enhanced lipid peroxidation, and elevated reactive oxygen species levels, all of which are hallmarks of ferroptosis. Furthermore, GLY induced inflammatory responses and downregulated tight junction proteins, including ZO-1, Occludin, and Claudin-3, ultimately compromising the integrity of the blood–milk barrier. Notably, treatment with the ferroptosis inhibitor Ferrostatin-1 (Fer-1) attenuated GLY-induced inflammation and barrier disruption significantly. The findings demonstrate that ferroptosis is a key mediator of GLY-induced inflammatory injury and blood–milk barrier dysfunction in mammary epithelial cells, suggesting that ferroptosis is a potential therapeutic target for preventing GLY-associated mammary toxicity.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"209 ","pages":"Article 115904"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800235","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}