Pub Date : 2025-12-16DOI: 10.1016/j.fct.2025.115902
Silje M. Johanson , Thea H. Kleiven , Lada Ivanova , Oscar D. Rangel-Huerta , Caroline P. Åkesson , Agnieszka A. Niklas , Kit Granby , Erik Ropstad , Jan E. Paulsen , Mette H.B. Müller
Processed meat contains multiple substances with mutagenic properties, but there is limited knowledge about the combined effect of polycyclic aromatic hydrocarbons (PAHs) and N-nitroso compounds (NOCs). This study characterized the carcinogenic potential of single or combined dietary exposure to Benzo[a]pyrene (BaP, a PAH) and a mixture of six food-derived NOCs in the A/J Min/+ mouse model for human colorectal cancer. Mice were given diets containing low or high concentrations of BaP and/or NOCs for nine weeks. The concentrations were based on estimated daily intake levels in the European population. A sex-dependent increased CRC initiation was detected after combined exposure to the high doses of BaP and NOCs. No effects were seen on CRC following exposure to the low doses of BaP or NOCs individually or in combination. Targeted plasma metabolomics revealed alterations in cellular membranes, lipid and energy metabolism in mice exposed to the high doses of BaP and NOCs. An alteration of plasma metabolites was also seen in mice exposed to the low dose of BaP, but not in mice exposed to the low dose of NOCs or to the combined low doses of BaP and NOCs. The study highlights the complex interplay between dietary carcinogens.
{"title":"Colorectal cancer initiation by benzo[a]pyrene and N-nitroso compounds in A/J Min/+ mice","authors":"Silje M. Johanson , Thea H. Kleiven , Lada Ivanova , Oscar D. Rangel-Huerta , Caroline P. Åkesson , Agnieszka A. Niklas , Kit Granby , Erik Ropstad , Jan E. Paulsen , Mette H.B. Müller","doi":"10.1016/j.fct.2025.115902","DOIUrl":"10.1016/j.fct.2025.115902","url":null,"abstract":"<div><div>Processed meat contains multiple substances with mutagenic properties, but there is limited knowledge about the combined effect of polycyclic aromatic hydrocarbons (PAHs) and <em>N</em>-nitroso compounds (NOCs). This study characterized the carcinogenic potential of single or combined dietary exposure to Benzo[<em>a</em>]pyrene (BaP, a PAH) and a mixture of six food-derived NOCs in the A/J Min/+ mouse model for human colorectal cancer. Mice were given diets containing low or high concentrations of BaP and/or NOCs for nine weeks. The concentrations were based on estimated daily intake levels in the European population. A sex-dependent increased CRC initiation was detected after combined exposure to the high doses of BaP and NOCs. No effects were seen on CRC following exposure to the low doses of BaP or NOCs individually or in combination. Targeted plasma metabolomics revealed alterations in cellular membranes, lipid and energy metabolism in mice exposed to the high doses of BaP and NOCs. An alteration of plasma metabolites was also seen in mice exposed to the low dose of BaP, but not in mice exposed to the low dose of NOCs or to the combined low doses of BaP and NOCs. The study highlights the complex interplay between dietary carcinogens.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"209 ","pages":"Article 115902"},"PeriodicalIF":3.5,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145779804","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 : 2025-12-15DOI: 10.1016/j.fct.2025.115898
Gang Chen , Hang Yuan , XiaoPeng Li, Shihui Chen, Xuejun Sun, Junhui Yu
Objective
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.
Methods
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.
Results
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.
Conclusion
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.
{"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":"2025-12-15","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}
Pub Date : 2025-12-13DOI: 10.1016/j.fct.2025.115893
Katarina Baralić , Jovana Jerotijević , Marta Pantelić , Jovana Živanović , Danijela Đukić-Ćosić
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 in silico approach, while also exploring the protective potential of antioxidant vitamins and phytochemicals, including Vitamin C, Vitamin E, sulforaphane, resveratrol, curcumin, naringin, and quercetin. CTD database, GeneMANIA server, and Toppgene portal were used as the main in silico 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.
{"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":"2025-12-13","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}
Pub Date : 2025-12-13DOI: 10.1016/j.fct.2025.115899
Nidal A. Qinna , Bayan Y. Ghanim , Duaa Abuarqoub , Qasem Abdallah , Malak Jaber , Mohammad AlNatoor , Duaa Sabbah , Bayan Alkhawaja , Dong-Hyun Kim
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.
{"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":"2025-12-13","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}
Pub Date : 2025-12-12DOI: 10.1016/j.fct.2025.115890
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
Salicornia ramosissima, 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 S. ramosissima 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 Drosophila melanogaster and no mutagenic activity in the Ames test. Overall, these results indicate that subchronic administration of S. ramosissima 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.
{"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":"2025-12-12","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}
Pub Date : 2025-12-12DOI: 10.1016/j.fct.2025.115901
Qingquan Gong , Dingyu Liang , Yongjin Luo , Chao Yang , Yihua Yang , Shujie Zhang
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.
{"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":"2025-12-12","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}
Pub Date : 2025-12-12DOI: 10.1016/j.fct.2025.115897
Jolanta Charchuła , Grzegorz Dziubanek , Danuta Rogala , Anna Niesler
Seafood may accumulate heavy metals (HMs) from environmental sources, posing potential health risks through dietary intake. This study aimed to assess the health risk associated with dietary intake of Hg, Cd, As and Zn from selected seafood available in Poland. In this study, a total 51 samples of shrimp and squid were analysed. The metals content was determined using such analytical methods as ET-AAS with a graphite furnace in the case of Cd, ICP-OES in the case of As and Zn, and CV-AFS in the case of Hg. The mean content of Cd and Zn were found to be 0.25 and 16.94 mg/kg f. w., respectively. In the case of Hg and As, these metals were detected at concentrations of 0.023 and 11.71 mg/kg f. w. The number of samples exhibiting results higher than the LOQ for Cd, As, Zn and Hg were found to be 24, 1, 50 and 1, respectively. The heavy metals content generally did not exceed the maximum permissible concentrations. Elevated content of Cd were detected in a single shrimp sample. The HI exceeded 1 among adults and children, with arsenic in shrimp identified as the predominant contributor. The ingestion of As from highest contaminated shrimp sample has been associated an elevated cancer risk among adult (2.33 × 10–3) and children (5.44 × 10–3). The findings of this study indicate that, in order to ensure the health safety of consumers, it is necessary to undertake more effective monitoring of the HMs content in seafood available in the Polish market.
{"title":"Health risks associated with the consumption of shrimp and squid contaminated with heavy metals in Poland","authors":"Jolanta Charchuła , Grzegorz Dziubanek , Danuta Rogala , Anna Niesler","doi":"10.1016/j.fct.2025.115897","DOIUrl":"10.1016/j.fct.2025.115897","url":null,"abstract":"<div><div>Seafood may accumulate heavy metals (HMs) from environmental sources, posing potential health risks through dietary intake. This study aimed to assess the health risk associated with dietary intake of Hg, Cd, As and Zn from selected seafood available in Poland. In this study, a total 51 samples of shrimp and squid were analysed. The metals content was determined using such analytical methods as ET-AAS with a graphite furnace in the case of Cd, ICP-OES in the case of As and Zn, and CV-AFS in the case of Hg. The mean content of Cd and Zn were found to be 0.25 and 16.94 mg/kg f. w., respectively. In the case of Hg and As, these metals were detected at concentrations of 0.023 and 11.71 mg/kg f. w. The number of samples exhibiting results higher than the LOQ for Cd, As, Zn and Hg were found to be 24, 1, 50 and 1, respectively. The heavy metals content generally did not exceed the maximum permissible concentrations. Elevated content of Cd were detected in a single shrimp sample. The HI exceeded 1 among adults and children, with arsenic in shrimp identified as the predominant contributor. The ingestion of As from highest contaminated shrimp sample has been associated an elevated cancer risk among adult (2.33 × 10–3) and children (5.44 × 10–3). The findings of this study indicate that, in order to ensure the health safety of consumers, it is necessary to undertake more effective monitoring of the HMs content in seafood available in the Polish market.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"209 ","pages":"Article 115897"},"PeriodicalIF":3.5,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145754825","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 : 2025-12-11DOI: 10.1016/j.fct.2025.115849
Stephen S Hecht, Samuel M Cohen, Gerhard Eisenbrand, Shoji Fukushima, Nigel J Gooderham, F Peter Guengerich, Ivonne M C M Rietjens, Thomas J Rosol, Jeanne M Davidsen, Christie L Harman, Sean V Taylor
As part of the Expert Panel of the Flavor and Extract Manufacturers Association's (FEMA) program to evaluate the safety of flavor ingredients, this publication, thirteenth in the series, details the re-evaluation of natural flavor complexes (NFCs) whose constituent profiles are characterized by mono- and sesquiterpene hydrocarbons. The Panel's constituent-based safety evaluation procedure parses the identified constituents of each NFC into well-defined congeneric groups. For each congeneric group, an evaluation based on the estimated intake is conducted using the conservative Threshold of Toxicological Concern (TTC) approach and a review of available data on absorption, metabolism and toxicity, including genotoxicity, for identified constituents and the NFCs, is conducted. The scope of the safety evaluation of the NFCs contained herein does not include added use in dietary supplements or any products other than food. Thirty-five NFCs, derived from the Angelica, Abies, Cananga, Croton, Apium, Canarium, Erigeron, Ferula, Zingiber, Humulus, Juniperus, Cistus, Commiphora, Boswellia, Piper, Pinus and Schinus genera were determined/affirmed as generally recognized as safe (GRAS) under their conditions of intended use as flavoring ingredients based on an evaluation of each NFC and the constituents and congeneric groups therein.
{"title":"FEMA GRAS assessment of natural flavor complexes: Pepper, ginger, coniferous-derived and related flavoring ingredients.","authors":"Stephen S Hecht, Samuel M Cohen, Gerhard Eisenbrand, Shoji Fukushima, Nigel J Gooderham, F Peter Guengerich, Ivonne M C M Rietjens, Thomas J Rosol, Jeanne M Davidsen, Christie L Harman, Sean V Taylor","doi":"10.1016/j.fct.2025.115849","DOIUrl":"10.1016/j.fct.2025.115849","url":null,"abstract":"<p><p>As part of the Expert Panel of the Flavor and Extract Manufacturers Association's (FEMA) program to evaluate the safety of flavor ingredients, this publication, thirteenth in the series, details the re-evaluation of natural flavor complexes (NFCs) whose constituent profiles are characterized by mono- and sesquiterpene hydrocarbons. The Panel's constituent-based safety evaluation procedure parses the identified constituents of each NFC into well-defined congeneric groups. For each congeneric group, an evaluation based on the estimated intake is conducted using the conservative Threshold of Toxicological Concern (TTC) approach and a review of available data on absorption, metabolism and toxicity, including genotoxicity, for identified constituents and the NFCs, is conducted. The scope of the safety evaluation of the NFCs contained herein does not include added use in dietary supplements or any products other than food. Thirty-five NFCs, derived from the Angelica, Abies, Cananga, Croton, Apium, Canarium, Erigeron, Ferula, Zingiber, Humulus, Juniperus, Cistus, Commiphora, Boswellia, Piper, Pinus and Schinus genera were determined/affirmed as generally recognized as safe (GRAS) under their conditions of intended use as flavoring ingredients based on an evaluation of each NFC and the constituents and congeneric groups therein.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115849"},"PeriodicalIF":3.5,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751459","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 : 2025-12-11DOI: 10.1016/j.fct.2025.115900
Ting Shao, Yue-Lei Chen
Immortalized cell lines function as invaluable tools in life science and preclinical studies. Poor laboratory practices can lead to cell line misidentification, cross-contamination, and mislabelling, resulting in invalid, misleading, and unrepeatable results. The issue of nonhuman-derived cell misidentification was once discovered timely, but it received less attention than the misidentification of human cells. Consequently, problematic murine cell lines still appear frequently in the literature. For instance, ImKC cells have been applied as a mouse Kupffer cell line in the last decade. In this report, we revealed that the ImKC cell line was a RAW 264.7 derivative through STR analysis, and further determined that it was not an SV40-transformed cell line by PCR and western blotting assays. Moreover, we outlined the relevant publications using the ImKC cell line. This study aims to prevent further researchers from employing the problematic cell line in their studies.
{"title":"Multiple approaches revealed ImKC cells as a RAW 264.7 derivative rather than a Kupffer cell line","authors":"Ting Shao, Yue-Lei Chen","doi":"10.1016/j.fct.2025.115900","DOIUrl":"10.1016/j.fct.2025.115900","url":null,"abstract":"<div><div>Immortalized cell lines function as invaluable tools in life science and preclinical studies. Poor laboratory practices can lead to cell line misidentification, cross-contamination, and mislabelling, resulting in invalid, misleading, and unrepeatable results. The issue of nonhuman-derived cell misidentification was once discovered timely, but it received less attention than the misidentification of human cells. Consequently, problematic murine cell lines still appear frequently in the literature. For instance, ImKC cells have been applied as a mouse Kupffer cell line in the last decade. In this report, we revealed that the ImKC cell line was a RAW 264.7 derivative through STR analysis, and further determined that it was not an SV40-transformed cell line by PCR and western blotting assays. Moreover, we outlined the relevant publications using the ImKC cell line. This study aims to prevent further researchers from employing the problematic cell line in their studies.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"209 ","pages":"Article 115900"},"PeriodicalIF":3.5,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751465","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 : 2025-12-09DOI: 10.1016/j.fct.2025.115892
Hui Jiang , Junhua Yang , Xichun Wang , Lihui Zhu
Deoxynivalenol (DON) and copper (Cu) are crucial food-related contaminants associated with health risks in both animals and humans. This study investigated the individual and combined effects of DON and Cu on a mouse hepatocyte line NCTC1469 cells. The results demonstrated that both DON and Cu induced ultrastructural damage, promoted mitochondrial vacuolization, increased pro-inflammatory cytokine levels, such as interleukin-1β (IL-1β) and tumor necrosis factor-alpha, reduced cell viability, and suppressed antioxidant enzyme activity, including glutathione and superoxide dismutase. Notably, DON + Cu enhanced cell viability compared to DON alone. In addition, co-treatment significantly reduced IL-1β levels relative to DON alone at 0.625, 1.25, and 2.5 μM. Transcriptome sequencing revealed that both DON alone and DON-Cu co-exposure triggered numerous differentially expressed genes, which were notably enriched in autophagy related pathways, such as ribosome biogenesis in eukaryotes, lysosome, spliceosome, and cell cycle. Meanwhile, the relative protein ratio of LC3-II/LC3-I was elevated at 0.65 μM DON, while the p62 expression was decreased in a dose-dependent manner compared to the control. In summary, DON exerts toxic effects on mouse hepatocytes, while Cu can mitigate DON-induced cellular damage at low concentrations, likely through involvement in Beclin-1/p62 related autophagic regulation.
{"title":"Interaction of deoxynivalenol and copper: Cellular and molecular insights in mouse liver cells","authors":"Hui Jiang , Junhua Yang , Xichun Wang , Lihui Zhu","doi":"10.1016/j.fct.2025.115892","DOIUrl":"10.1016/j.fct.2025.115892","url":null,"abstract":"<div><div>Deoxynivalenol (DON) and copper (Cu) are crucial food-related contaminants associated with health risks in both animals and humans. This study investigated the individual and combined effects of DON and Cu on a mouse hepatocyte line NCTC1469 cells. The results demonstrated that both DON and Cu induced ultrastructural damage, promoted mitochondrial vacuolization, increased pro-inflammatory cytokine levels, such as interleukin-1β (IL-1β) and tumor necrosis factor-alpha, reduced cell viability, and suppressed antioxidant enzyme activity, including glutathione and superoxide dismutase. Notably, DON + Cu enhanced cell viability compared to DON alone. In addition, co-treatment significantly reduced IL-1β levels relative to DON alone at 0.625, 1.25, and 2.5 μM. Transcriptome sequencing revealed that both DON alone and DON-Cu co-exposure triggered numerous differentially expressed genes, which were notably enriched in autophagy related pathways, such as ribosome biogenesis in eukaryotes, lysosome, spliceosome, and cell cycle. Meanwhile, the relative protein ratio of LC3-II/LC3-I was elevated at 0.65 μM DON, while the p62 expression was decreased in a dose-dependent manner compared to the control. In summary, DON exerts toxic effects on mouse hepatocytes, while Cu can mitigate DON-induced cellular damage at low concentrations, likely through involvement in Beclin-1/p62 related autophagic regulation.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"208 ","pages":"Article 115892"},"PeriodicalIF":3.5,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145740296","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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