Pub Date : 2025-11-19DOI: 10.1016/j.fct.2025.115847
Roser Fabrés, Ivonne M.C.M. Rietjens, Frances Widjaja-van den Ende
Pyrrolizidine alkaloids (PAs) and their N-oxides (PA-N-oxides) are phytotoxins which raise safety concerns when present in food. This study analyzes trends in their levels and associated risks in selected samples of food items (n = 3752) from 2011 to 2023, a period marked by risk management actions following evaluations by EFSA and others. Contamination levels and temporal trends were assessed, followed by risk evaluations using the margin of exposure (MOE) approach, both without and with consideration of relative potency, applying available interim relative potency (iREP) values.
The findings indicate that PA and PA-N-oxide levels in herbal infusions and herbal food supplements significantly declined after 2017, coinciding with the publication of EFSA's risk assessment. Additionally, the proportion of herbal food supplement samples raising health concerns decreased significantly when comparing data from before and after 2017.
However, overall, a high incidence of samples raising concern is still observed in borage- and other naturally PA-containing foods. The specific PA and PA-N-oxide profiles in the samples, along with consumption levels, have a major influence on risk assessment outcomes. It is concluded that further risk management actions are still indicated.
吡咯利西啶生物碱（PAs）及其n -氧化物（pa - n -氧化物）是植物毒素，在食品中存在时引起安全问题。本研究分析了2011年至2023年（欧洲食品安全局和其他机构评估后采取风险管理行动的时期）选定食品样品（n= 3752）中其水平和相关风险的趋势。对污染水平和时间趋势进行了评估，然后使用暴露边际（MOE）方法进行风险评估，不考虑或考虑相对效力，应用可用的临时相对效力（iREP）值。研究结果表明，2017年之后，草药注射剂和草药食品补充剂中的PA和PA- n -氧化物水平显著下降，与欧洲食品安全局发布的风险评估结果一致。此外，与2017年前后的数据相比，引起健康问题的草药食品补充剂样本比例显著下降。然而，总的来说，在琉璃苣和其他天然含pa的食品中仍然观察到高发生率的样品引起关注。样品中特定的PA和PA- n -氧化物特征，以及消费水平，对风险评估结果有重大影响。结论是，仍需采取进一步的风险管理措施。
{"title":"Exploring time dependent trends and risks of pyrrolizidine alkaloids and their N-oxides in food","authors":"Roser Fabrés, Ivonne M.C.M. Rietjens, Frances Widjaja-van den Ende","doi":"10.1016/j.fct.2025.115847","DOIUrl":"10.1016/j.fct.2025.115847","url":null,"abstract":"<div><div>Pyrrolizidine alkaloids (PAs) and their N-oxides (PA-N-oxides) are phytotoxins which raise safety concerns when present in food. This study analyzes trends in their levels and associated risks in selected samples of food items (n = 3752) from 2011 to 2023, a period marked by risk management actions following evaluations by EFSA and others. Contamination levels and temporal trends were assessed, followed by risk evaluations using the margin of exposure (MOE) approach, both without and with consideration of relative potency, applying available interim relative potency (<sub>i</sub>REP) values.</div><div>The findings indicate that PA and PA-N-oxide levels in herbal infusions and herbal food supplements significantly declined after 2017, coinciding with the publication of EFSA's risk assessment. Additionally, the proportion of herbal food supplement samples raising health concerns decreased significantly when comparing data from before and after 2017.</div><div>However, overall, a high incidence of samples raising concern is still observed in borage- and other naturally PA-containing foods. The specific PA and PA-N-oxide profiles in the samples, along with consumption levels, have a major influence on risk assessment outcomes. It is concluded that further risk management actions are still indicated.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"208 ","pages":"Article 115847"},"PeriodicalIF":3.5,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145572650","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 : 2025-11-19DOI: 10.1016/j.fct.2025.115859
Paul R. Hanlon , Paul A. Hepburn , Joseph A. Scimeca , Brian T. Schaneberg
As new sources of food emerge and technologies advance, the concepts of safe food and risk assessment have evolved. New Approach Methods (NAMs) are appearing at a pivotal point in toxicology and provide an opportunity to adopt improved science (from a sensitivity and specificity perspective), which is more human relevant, is quicker and is ethically sounder (does not employ animals). The safety standard for any substance added to food in the United States is that there is a reasonable certainty of no harm under the intended conditions of use and applies to food additives and substances that are Generally Recognized as Safe (GRAS). This means that the use of NAMs must have a wide acceptability amongst the scientific community, including the regulatory authorities. The demand for new sources of protein ingredients is increasing, and is one category of food to which NAMs can be applied to determine safety. Safety considerations for proteins are described and for this purpose have been grouped into i) biosynthetic proteins produced by precision fermentation, ii) protein concentrates from traditional foods, and iii) total protein extracts. NAMs can be used to support the safety determination of proteins by: i) addressing mechanistic questions; ii) demonstrating equivalence to foods already in the food supply; iii) comparing intake to the amount traditionally consumed; iv) potential allergenicity. Confidence now needs to be built amongst stakeholders in food safety, with more food case studies in which NAMs are used in GRAS determinations and food additive petitions.
{"title":"Application of new approach methods (NAMs) in food safety with considerations for new proteins","authors":"Paul R. Hanlon , Paul A. Hepburn , Joseph A. Scimeca , Brian T. Schaneberg","doi":"10.1016/j.fct.2025.115859","DOIUrl":"10.1016/j.fct.2025.115859","url":null,"abstract":"<div><div>As new sources of food emerge and technologies advance, the concepts of safe food and risk assessment have evolved. New Approach Methods (NAMs) are appearing at a pivotal point in toxicology and provide an opportunity to adopt improved science (from a sensitivity and specificity perspective), which is more human relevant, is quicker and is ethically sounder (does not employ animals). The safety standard for any substance added to food in the United States is that there is a reasonable certainty of no harm under the intended conditions of use and applies to food additives and substances that are Generally Recognized as Safe (GRAS). This means that the use of NAMs must have a wide acceptability amongst the scientific community, including the regulatory authorities. The demand for new sources of protein ingredients is increasing, and is one category of food to which NAMs can be applied to determine safety. Safety considerations for proteins are described and for this purpose have been grouped into i) biosynthetic proteins produced by precision fermentation, ii) protein concentrates from traditional foods, and iii) total protein extracts. NAMs can be used to support the safety determination of proteins by: i) addressing mechanistic questions; ii) demonstrating equivalence to foods already in the food supply; iii) comparing intake to the amount traditionally consumed; iv) potential allergenicity. Confidence now needs to be built amongst stakeholders in food safety, with more food case studies in which NAMs are used in GRAS determinations and food additive petitions.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"208 ","pages":"Article 115859"},"PeriodicalIF":3.5,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145572715","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 : 2025-11-18DOI: 10.1016/j.fct.2025.115856
Borja Peris-Camarasa , Olga Pardo , Vincenzo Nava , Giuseppa di Bella , Cristina Aleixandre , Clara Coscollà
Acrylamide (AA) is a low-molecular-weight compound formed primarily through the Maillard reaction in carbohydrate-rich, low-protein foods subjected to high temperatures under low-moisture conditions. Since its classification as a “probable human carcinogen”, AA has attracted substantial scientific attention. Although non-dietary sources of AA exposure exist, dietary intake remains the predominant route, accounting for approximately 38 % of total caloric consumption from foods potentially containing this compound. In Europe, the principal dietary sources of AA have been identified as fried potato products, coffee, and crackers. To assess dietary AA exposure within the European Mediterranean framework, 85 food samples were collected across Spain and Italy. Measured AA content exhibited considerable variability, ranging from 30 to 1905 μg kg−1. Based on these findings, dietary exposure estimated and associated health risks were calculated. The Estimated Daily Intakes (EDIs) represented to approximately 20–28 % of the lowest EDI value reported by the European Food Safety Authority (EFSA) for the European population (0.4 μg·kg-bw−1·day−1), highlighting their potential relevance. Risk assessment outcomes suggest that dietary AA exposure may pose a health concern. Consequently, periodic monitoring and surveillance of AA levels in food products including the assessment of its dietary exposure are essential to protect public health.
{"title":"Presence of acrylamide in key food sources within the European Mediterranean framework","authors":"Borja Peris-Camarasa , Olga Pardo , Vincenzo Nava , Giuseppa di Bella , Cristina Aleixandre , Clara Coscollà","doi":"10.1016/j.fct.2025.115856","DOIUrl":"10.1016/j.fct.2025.115856","url":null,"abstract":"<div><div>Acrylamide (AA) is a low-molecular-weight compound formed primarily through the Maillard reaction in carbohydrate-rich, low-protein foods subjected to high temperatures under low-moisture conditions. Since its classification as a “probable human carcinogen”, AA has attracted substantial scientific attention. Although non-dietary sources of AA exposure exist, dietary intake remains the predominant route, accounting for approximately 38 % of total caloric consumption from foods potentially containing this compound. In Europe, the principal dietary sources of AA have been identified as fried potato products, coffee, and crackers. To assess dietary AA exposure within the European Mediterranean framework, 85 food samples were collected across Spain and Italy. Measured AA content exhibited considerable variability, ranging from 30 to 1905 μg kg<sup>−1</sup>. Based on these findings, dietary exposure estimated and associated health risks were calculated. The Estimated Daily Intakes (EDIs) represented to approximately 20–28 % of the lowest EDI value reported by the European Food Safety Authority (EFSA) for the European population (0.4 μg·kg-bw<sup>−1</sup>·day<sup>−1</sup>), highlighting their potential relevance. Risk assessment outcomes suggest that dietary AA exposure may pose a health concern. Consequently, periodic monitoring and surveillance of AA levels in food products including the assessment of its dietary exposure are essential to protect public health.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"207 ","pages":"Article 115856"},"PeriodicalIF":3.5,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562204","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 : 2025-11-17DOI: 10.1016/j.fct.2025.115854
Anastasia Kariagina, Elena Morozova, Kloma Cardoza, Kristin Knickerbocker, Molly McSween, Richard C. Schwartz
We previously found benzophenone-3, an endocrine disrupting chemical and common sunscreen ingredient, has promotional and protective effects on mammary tumorigenesis dependent upon dietary fat. The current study examines mammary correlates to the protective effect of benzophenone-3 in mice fed low-fat diet versus the promotional effect in mice fed high-fat diet during adulthood. Benzophenone-3 treatment of mice fed low-fat diet resulted in broad activation of Th1, Th2, and Th17 cells, a shift toward M2 macrophage polarization, and elevated Areg, Ereg, and TGFa RNAs. Benzophenone-3 treatment in mice fed adult high-fat diet resulted in decreased Tc cells, and elevated Rankl RNA. Mice fed adult high-fat diet by itself showed a shift toward M2 macrophage polarization and elevated Areg and Egf RNAs. The tumor protective effect of benzophenone-3 in low-fat diet mice plausibly results from heightened Th activity with expression of IL-21 sparing Tc activity. The tumor promoting effect of benzophenone-3 in mice fed adult high-fat diet plausibly results from reduced Tc activity and increased RANKL expression interacting with high-fat diet increased expression of mammary growth factors and M2 macrophage polarization. Dietary fat and benzophenone-3 have immunomodulatory consequences that may interact in affecting mammary tumorigenesis in either a protective or promotional fashion.
{"title":"Diet-dependent BP-3 modulation of immune function in murine mammary tumorigenesis","authors":"Anastasia Kariagina, Elena Morozova, Kloma Cardoza, Kristin Knickerbocker, Molly McSween, Richard C. Schwartz","doi":"10.1016/j.fct.2025.115854","DOIUrl":"10.1016/j.fct.2025.115854","url":null,"abstract":"<div><div>We previously found benzophenone-3, an endocrine disrupting chemical and common sunscreen ingredient, has promotional and protective effects on mammary tumorigenesis dependent upon dietary fat. The current study examines mammary correlates to the protective effect of benzophenone-3 in mice fed low-fat diet versus the promotional effect in mice fed high-fat diet during adulthood. Benzophenone-3 treatment of mice fed low-fat diet resulted in broad activation of Th1, Th2, and Th17 cells, a shift toward M2 macrophage polarization, and elevated <em>Areg</em>, <em>Ereg</em>, and <em>TGFa</em> RNAs. Benzophenone-3 treatment in mice fed adult high-fat diet resulted in decreased Tc cells, and elevated <em>Rankl</em> RNA. Mice fed adult high-fat diet by itself showed a shift toward M2 macrophage polarization and elevated <em>Areg</em> and <em>Egf</em> RNAs. The tumor protective effect of benzophenone-3 in low-fat diet mice plausibly results from heightened Th activity with expression of IL-21 sparing Tc activity. The tumor promoting effect of benzophenone-3 in mice fed adult high-fat diet plausibly results from reduced Tc activity and increased RANKL expression interacting with high-fat diet increased expression of mammary growth factors and M2 macrophage polarization. Dietary fat and benzophenone-3 have immunomodulatory consequences that may interact in affecting mammary tumorigenesis in either a protective or promotional fashion.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"207 ","pages":"Article 115854"},"PeriodicalIF":3.5,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556084","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 : 2025-11-15DOI: 10.1016/j.fct.2025.115852
A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar
3,7-Dimethyl-1,6-nonadien-3-ol was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Target data and data from read-across analog linalool (CAS # 78-70-6) show that 3,7-dimethyl-1,6-nonadien-3-ol is not expected to be genotoxic. Data on read-across analog linalool (CAS # 78-70-6) provide a calculated Margin of Exposure (MOE) > 100 for the repeated dose toxicity, reproductive toxicity, and local respiratory toxicity endpoints and show that there are no safety concerns for 3,7-dimethyl-1,6-nonadien-3-ol for skin sensitization under the current declared levels of use. The photoirritation/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; 3,7-dimethyl-1,6-nonadien-3-ol is not expected to be photoirritating/photoallergenic. The environmental endpoints were evaluated; 3,7-dimethyl-1,6-nonadien-3-ol 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":"2nd update to RIFM fragrance ingredient safety assessment, 3,7-dimethyl-1,6-nonadien-3-ol, CAS Registry Number 10339-55-6","authors":"A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M. Cronin , S. Crotty , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , D.L. Laskin , Y. Thakkar","doi":"10.1016/j.fct.2025.115852","DOIUrl":"10.1016/j.fct.2025.115852","url":null,"abstract":"<div><div>3,7-Dimethyl-1,6-nonadien-3-ol was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Target data and data from read-across analog linalool (CAS # 78-70-6) show that 3,7-dimethyl-1,6-nonadien-3-ol is not expected to be genotoxic. Data on read-across analog linalool (CAS # 78-70-6) provide a calculated Margin of Exposure (MOE) > 100 for the repeated dose toxicity, reproductive toxicity, and local respiratory toxicity endpoints and show that there are no safety concerns for 3,7-dimethyl-1,6-nonadien-3-ol for skin sensitization under the current declared levels of use. The photoirritation/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; 3,7-dimethyl-1,6-nonadien-3-ol is not expected to be photoirritating/photoallergenic. The environmental endpoints were evaluated; 3,7-dimethyl-1,6-nonadien-3-ol was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use (VoU) in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"206 ","pages":"Article 115852"},"PeriodicalIF":3.5,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145538240","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 : 2025-11-15DOI: 10.1016/j.fct.2025.115848
Ayca Aktas Sukuroglu , Sevda Ildan Ozmen
Hookah, also known as a water pipe, is a popular form of tobacco smoking and one of the most widely used nicotine-containing products in Asia and Africa today, particularly in Turkiye. As hookah use among adolescents is increasing globally, health problems associated with exposure to high concentrations of heavy metals are also becoming more significant. Therefore, the amount of heavy metals in the fresh and waste tobacco flavours (cola, dominic, gum, two apples and cranberry melon) and in the wastewater of hookahs, which are most commonly used in hookah cafes in Turkiye, were analysed using inductively coupled plasma mass spectrometry (ICP-MS). Based on the heavy metal results obtained, a risk assessment was conducted using best-case and worst-case scenarios to evaluate the health risks that may arise from exposure through inhalation and oral exposure. A risk assessment has revealed that, in the worst-case scenario, the levels of non-carcinogenic metals such as cobalt, antimony, copper and lead found in tobacco flavours pose a risk, while, in the best-case scenario, lead and copper pose a risk. The presence of risk is a consequence of aluminium in both scenarios.
{"title":"Risk assessment of exposure to heavy metals from hookah consumption in Turkiye","authors":"Ayca Aktas Sukuroglu , Sevda Ildan Ozmen","doi":"10.1016/j.fct.2025.115848","DOIUrl":"10.1016/j.fct.2025.115848","url":null,"abstract":"<div><div>Hookah, also known as a water pipe, is a popular form of tobacco smoking and one of the most widely used nicotine-containing products in Asia and Africa today, particularly in Turkiye. As hookah use among adolescents is increasing globally, health problems associated with exposure to high concentrations of heavy metals are also becoming more significant. Therefore, the amount of heavy metals in the fresh and waste tobacco flavours (cola, dominic, gum, two apples and cranberry melon) and in the wastewater of hookahs, which are most commonly used in hookah cafes in Turkiye, were analysed using inductively coupled plasma mass spectrometry (ICP-MS). Based on the heavy metal results obtained, a risk assessment was conducted using best-case and worst-case scenarios to evaluate the health risks that may arise from exposure through inhalation and oral exposure. A risk assessment has revealed that, in the worst-case scenario, the levels of non-carcinogenic metals such as cobalt, antimony, copper and lead found in tobacco flavours pose a risk, while, in the best-case scenario, lead and copper pose a risk. The presence of risk is a consequence of aluminium in both scenarios.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"207 ","pages":"Article 115848"},"PeriodicalIF":3.5,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145538299","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 : 2025-11-14DOI: 10.1016/j.fct.2025.115844
Parth Aphale, Shashank Dokania, Himanshu Shekhar
{"title":"Beyond monitoring: Integrating risk, benefit, and biomonitoring in Greek dietary exposure to dioxins and PCBs.","authors":"Parth Aphale, Shashank Dokania, Himanshu Shekhar","doi":"10.1016/j.fct.2025.115844","DOIUrl":"10.1016/j.fct.2025.115844","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115844"},"PeriodicalIF":3.5,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145533924","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 : 2025-11-13DOI: 10.1016/j.fct.2025.115851
Jingyan Wang , Yinhua Liu , Chengsheng Zhu , Zhiying Wang , Sijia Wang , Shuguang Fang , Fei Xu
Lactobacillus delbrueckii subsp. bulgaricus is a traditional yogurt starter widely recognized for its safety and gut health benefits. This study evaluated the safety and functional potential of Lactobacillus delbrueckii subsp. bulgaricus LB42 through genomic analysis, in vitro assays, and a randomized placebo-controlled clinical trial. Genomic screening confirmed the absence of pathogenic, resistance, or virulence genes. LB42 exhibited no cytotoxicity or hemolysis, showed broad antibiotic sensitivity, and adhered strongly to Caco-2 cells. Acute oral toxicity testing revealed no adverse effects in mice. In humans, LB42 was well tolerated without biochemical or hematological abnormalities, and no adverse events or allergic reactions were reported. LB42 supplementation significantly reduced Gastrointestinal Symptom Rating Scale and Pittsburgh Sleep Quality Index scores (p < 0.05), indicating improved gastrointestinal function and sleep quality, and lowered fecal calprotectin. Immune analyses demonstrated enhanced IgA and IgG responses (p < 0.05). Microbiota profiling revealed enrichment of short-chain fatty acid-producing genera (e.g., Lachnospira, Parabacteroides) and suppression of pro-inflammatory taxa (Enterococcus, Fusobacterium, Bilophila). Collectively, LB42 is genetically safe, well tolerated, and exerts dual benefits in enhancing host immunity and supporting microbial balance, supporting its potential as a clinically valuable probiotic strain with multifunctional benefits.
{"title":"Gut microbiota and immune regulation by Lactobacillus delbrueckii subsp. bulgaricus LB42: From preclinical safety assessment to clinical evidence","authors":"Jingyan Wang , Yinhua Liu , Chengsheng Zhu , Zhiying Wang , Sijia Wang , Shuguang Fang , Fei Xu","doi":"10.1016/j.fct.2025.115851","DOIUrl":"10.1016/j.fct.2025.115851","url":null,"abstract":"<div><div><em>Lactobacillus delbrueckii</em> subsp. <em>bulgaricus</em> is a traditional yogurt starter widely recognized for its safety and gut health benefits. This study evaluated the safety and functional potential of <em>Lactobacillus delbrueckii</em> subsp. <em>bulgaricus</em> LB42 through genomic analysis, in vitro assays, and a randomized placebo-controlled clinical trial. Genomic screening confirmed the absence of pathogenic, resistance, or virulence genes. LB42 exhibited no cytotoxicity or hemolysis, showed broad antibiotic sensitivity, and adhered strongly to Caco-2 cells. Acute oral toxicity testing revealed no adverse effects in mice. In humans, LB42 was well tolerated without biochemical or hematological abnormalities, and no adverse events or allergic reactions were reported. LB42 supplementation significantly reduced Gastrointestinal Symptom Rating Scale and Pittsburgh Sleep Quality Index scores (<em>p</em> < 0.05), indicating improved gastrointestinal function and sleep quality, and lowered fecal calprotectin. Immune analyses demonstrated enhanced IgA and IgG responses (<em>p</em> < 0.05). Microbiota profiling revealed enrichment of short-chain fatty acid-producing genera (e.g., <em>Lachnospira</em>, <em>Parabacteroides</em>) and suppression of pro-inflammatory taxa (<em>Enterococcus</em>, <em>Fusobacterium</em>, <em>Bilophila</em>). Collectively, LB42 is genetically safe, well tolerated, and exerts dual benefits in enhancing host immunity and supporting microbial balance, supporting its potential as a clinically valuable probiotic strain with multifunctional benefits.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"207 ","pages":"Article 115851"},"PeriodicalIF":3.5,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530333","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 : 2025-11-13DOI: 10.1016/j.fct.2025.115850
Cindi S. Zimmermann , Sujatha Rajeev Thundivalappil , Brittany Wilson-Mifsud , Sydney Boyle , Yiwei Wang , Ian Lamb , Matthew Merrell , Carey A. Mathesius , Melissa N. Fallers , JoAnna Bultman , Brenda L. Smith , Anne B. Carlson , Katie L. Stewart , Mark Nelson , Bryan P. Hurley
Hazard assessment of proteins using human-derived intestinal epithelial cell (IEC) lines has been investigated previously. The purpose of this work was to a) reduce occurrences of false positives by including a non-hazardous protein (BSA) negative control while redesigning statistical analyses; and b) consider the potential of the IEC assay as a component of a weight of evidence approach in the hazard assessment of four different structural/functional classes of insecticidal proteins. The protein classes evaluated included: Mpf (Mpf2Ba1); Cyt (IPD084Aa); Cry (IP3-H9); and uncharacterized (IPD072Aa). Using BSA as the negative control comparator paired with a statistical method correcting for false positives, it was determined that three of the four proteins evaluated did not reveal any indications of hazard. Statistically significant effects on barrier integrity and cytotoxicity endpoints were observed for intact (non-digested) IPD072Aa protein, however, no adverse effects were observed in acute and repeated dose oral toxicity studies with IPD072Aa. Use of the IEC assay featuring refinements to better distinguish between false negatives and effects that are significant and reproducible may serve as a useful component within a weight of evidence approach to inform the level of downstream in vivo testing warranted to identify potentially hazardous proteins.
{"title":"Hazard assessment of insecticidal proteins representing different structural classes using an in vitro experimental platform of human intestinal epithelial monolayers","authors":"Cindi S. Zimmermann , Sujatha Rajeev Thundivalappil , Brittany Wilson-Mifsud , Sydney Boyle , Yiwei Wang , Ian Lamb , Matthew Merrell , Carey A. Mathesius , Melissa N. Fallers , JoAnna Bultman , Brenda L. Smith , Anne B. Carlson , Katie L. Stewart , Mark Nelson , Bryan P. Hurley","doi":"10.1016/j.fct.2025.115850","DOIUrl":"10.1016/j.fct.2025.115850","url":null,"abstract":"<div><div>Hazard assessment of proteins using human-derived intestinal epithelial cell (IEC) lines has been investigated previously. The purpose of this work was to a) reduce occurrences of false positives by including a non-hazardous protein (BSA) negative control while redesigning statistical analyses; and b) consider the potential of the IEC assay as a component of a weight of evidence approach in the hazard assessment of four different structural/functional classes of insecticidal proteins. The protein classes evaluated included: Mpf (Mpf2Ba1); Cyt (IPD084Aa); Cry (IP3-H9); and uncharacterized (IPD072Aa). Using BSA as the negative control comparator paired with a statistical method correcting for false positives, it was determined that three of the four proteins evaluated did not reveal any indications of hazard. Statistically significant effects on barrier integrity and cytotoxicity endpoints were observed for intact (non-digested) IPD072Aa protein, however, no adverse effects were observed in acute and repeated dose oral toxicity studies with IPD072Aa. Use of the IEC assay featuring refinements to better distinguish between false negatives and effects that are significant and reproducible may serve as a useful component within a weight of evidence approach to inform the level of downstream <em>in vivo</em> testing warranted to identify potentially hazardous proteins.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"207 ","pages":"Article 115850"},"PeriodicalIF":3.5,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530339","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 : 2025-11-11DOI: 10.1016/j.fct.2025.115842
Suraj Singh , Ishvarchandra Parmar
Bioanalytical chemistry has become an essential part of modern toxicological research, offering the sensitivity and precision needed to detect chemical exposures in biological systems. This review highlights the critical role of bioanalytical techniques in identifying toxic substances, studying their behaviour in complex biological environments, and connecting these exposures to harmful health effects. As toxicology becomes more predictive and mechanistic, advanced tools like mass spectrometry, chromatography, and electron microscopy have significantly improved the analysis of toxicokinetic and toxicodynamic methods in environmental, pharmaceutical, and forensic fields.
This work also explains current innovations such as GC-MS, LC-MS, and other hyphenated techniques, along with emerging tools like mass spectrometry imaging, microfluidic systems, and AI-driven data analysis. It emphasizes the structural assessment of nanomaterials through electron microscopy and the monitoring of biochemical changes using vibrational spectroscopy. Furthermore, it addresses important aspects of sample preparation, automation technologies, and multi-omics integration for enhanced risk assessment and biomonitoring.
Looking forward, the future of toxicology lies in cross-disciplinary collaboration. The continued development of bioanalytical techniques, combined with computational models and systems biology, will be vital in overcoming key challenges and improving the accuracy of toxicological evaluations to a better protection of human and environmental health.
{"title":"Advances in bioanalytical techniques for toxicological applications: Emerging techniques, challenges, and future directions","authors":"Suraj Singh , Ishvarchandra Parmar","doi":"10.1016/j.fct.2025.115842","DOIUrl":"10.1016/j.fct.2025.115842","url":null,"abstract":"<div><div>Bioanalytical chemistry has become an essential part of modern toxicological research, offering the sensitivity and precision needed to detect chemical exposures in biological systems. This review highlights the critical role of bioanalytical techniques in identifying toxic substances, studying their behaviour in complex biological environments, and connecting these exposures to harmful health effects. As toxicology becomes more predictive and mechanistic, advanced tools like mass spectrometry, chromatography, and electron microscopy have significantly improved the analysis of toxicokinetic and toxicodynamic methods in environmental, pharmaceutical, and forensic fields.</div><div>This work also explains current innovations such as GC-MS, LC-MS, and other hyphenated techniques, along with emerging tools like mass spectrometry imaging, microfluidic systems, and AI-driven data analysis. It emphasizes the structural assessment of nanomaterials through electron microscopy and the monitoring of biochemical changes using vibrational spectroscopy. Furthermore, it addresses important aspects of sample preparation, automation technologies, and multi-omics integration for enhanced risk assessment and biomonitoring.</div><div>Looking forward, the future of toxicology lies in cross-disciplinary collaboration. The continued development of bioanalytical techniques, combined with computational models and systems biology, will be vital in overcoming key challenges and improving the accuracy of toxicological evaluations to a better protection of human and environmental health.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"207 ","pages":"Article 115842"},"PeriodicalIF":3.5,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145511435","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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