Food and Chemical Toxicology最新文献

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Integrative multi-omics analysis reveals FAAH and LIPE as candidate targets in OBS-induced spermatogenic and fertility impairment. 综合多组学分析显示FAAH和LIPE是obs诱导的生精和生育障碍的候选靶点。
IF 3.2 3区 医学
Food and Chemical Toxicology Pub Date : 2026-10-11 DOI: 10.1016/j.fct.2026.116440
Tao Yin, Chaoyi Bian, Yunxia Cao
{"title":"Integrative multi-omics analysis reveals FAAH and LIPE as candidate targets in OBS-induced spermatogenic and fertility impairment.","authors":"Tao Yin, Chaoyi Bian, Yunxia Cao","doi":"10.1016/j.fct.2026.116440","DOIUrl":"10.1016/j.fct.2026.116440","url":null,"abstract":"<p><strong>Background: </strong>Sodium p-perfluorous nonenoxybenzene sulfonate (OBS) is an emerging polyfluoroalkyl ether sulfonate with environmental persistence and potential biological toxicity. However, its effects on male reproductive health and associated molecular alterations remain poorly understood.</p><p><strong>Methods: </strong>Network toxicology, transcriptomic and single-cell transcriptomic analyses, data-independent acquisition-based proteomics, molecular docking, and mouse experiments were integrated to investigate OBS-associated spermatogenic toxicity.</p><p><strong>Results: </strong>FAAH and LIPE were prioritized as candidate targets potentially associated with OBS-induced spermatogenic impairment. In human non-obstructive azoospermia datasets, FAAH and LIPE were downregulated and showed discriminatory ability between affected and control samples. Molecular docking predicted potentially favorable interaction conformations between OBS and the two proteins. In mice, exposure to 0.5 or 2.5 mg/kg OBS was associated with disrupted seminiferous tubule architecture, impaired sperm quality, reduced testicular FAAH and LIPE expression, and fewer offspring after mating.</p><p><strong>Conclusion: </strong>OBS exposure was associated with impaired spermatogenesis and reduced male reproductive performance in mice. FAAH and LIPE may be involved in OBS-associated testicular injury, although their functional roles and direct interactions with OBS require further experimental validation. These findings provide additional evidence of the male reproductive toxicity of OBS and highlight the need for continued evaluation of emerging PFAS alternatives.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"116440"},"PeriodicalIF":3.2,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163634","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}
引用次数: 0
Update to RIFM fragrance ingredient safety assessment, 2,6-dimethylocta-2,4,6-triene, CAS Registry Number 673-84-7. 更新RIFM香料成分安全性评估,2,6-二甲基二甲基-2,4,6-三烯,CAS注册号673-84-7。
IF 3.2 3区 医学
Food and Chemical Toxicology Pub Date : 2026-10-11 DOI: 10.1016/j.fct.2026.116442
A M Api, A Bartlett, D Belsito, D Botelho, M Bruze, A Bryant-Friedrich, G A Burton, M A Cancellieri, H Chon, M Cronin, S Crotty, M L Dagli, W Dekant, C Deodhar, K Farrell, A D Fryer, M Guttenberg, L Jones, K Joshi, A Lapczynski, D L Laskin, M Lavelle, I Lee, H Moustakas, J Muldoon, T M Penning, A H Piersma, G Ritacco, N Sadekar, I Schember, T W Schultz, F Siddiqi, I G Sipes, G Sullivan, Y Thakkar
{"title":"Update to RIFM fragrance ingredient safety assessment, 2,6-dimethylocta-2,4,6-triene, CAS Registry Number 673-84-7.","authors":"A M Api, A Bartlett, D Belsito, D Botelho, M Bruze, A Bryant-Friedrich, G A Burton, M A Cancellieri, H Chon, M Cronin, S Crotty, M L Dagli, W Dekant, C Deodhar, K Farrell, A D Fryer, M Guttenberg, L Jones, K Joshi, A Lapczynski, D L Laskin, M Lavelle, I Lee, H Moustakas, J Muldoon, T M Penning, A H Piersma, G Ritacco, N Sadekar, I Schember, T W Schultz, F Siddiqi, I G Sipes, G Sullivan, Y Thakkar","doi":"10.1016/j.fct.2026.116442","DOIUrl":"https://doi.org/10.1016/j.fct.2026.116442","url":null,"abstract":"<p><p>2,6-Dimethylocta-2,4,6-triene was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog myrcene (CAS # 123-35-3) show that 2,6-dimethylocta-2,4,6-triene is not expected to be genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class I material, and the exposure to 2,6-dimethylocta-2,4,6-triene is below the TTC (0.03 mg/kg/day, 0.03 mg/kg/day, and 1.4 mg/day, respectively). Data from read-across analog myrcene (CAS # 123-35-3) show that there are no safety concerns for 2,6-dimethylocta-2,4,6-triene for skin sensitization under the current declared levels of use. The photoirritation/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; 2,6-dimethylocta-2,4,6-triene is not expected to be photoirritating/photoallergenic. The environmental endpoints were evaluated; 2,6-dimethylocta-2,4,6-triene was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients (RQs), based on its current volume of use (VoU) in Europe (EU), North America (NA), Asia-Pacific (AP), and South America (SA) (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1. 2,6-Dimethylocta-2,4,6-triene was not able to be risk screened for Japan (JP) as there was no reported VoU for this region in the 2023 IFRA Survey.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"116442"},"PeriodicalIF":3.2,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164096","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}
引用次数: 0
Study on the effects of gestational arsenic exposure on the developmental toxicity of brain tissue in mice offspring using network toxicology and RNA-seq 应用网络毒理学和RNA-seq技术研究妊娠期砷暴露对小鼠后代脑组织发育毒性的影响。
IF 3.5 3区 医学
Food and Chemical Toxicology Pub Date : 2026-05-01 Epub Date: 2026-02-07 DOI: 10.1016/j.fct.2026.116001
Zitong Wang , Wenjin Qiao , Ruigang Liu , Yuan Lv , Binjie Niu , Tianxu Li , Mengling Zhang , Yanhui Xiang , Rui Qiao , Dapeng Tai
{"title":"Study on the effects of gestational arsenic exposure on the developmental toxicity of brain tissue in mice offspring using network toxicology and RNA-seq","authors":"Zitong Wang ,&nbsp;Wenjin Qiao ,&nbsp;Ruigang Liu ,&nbsp;Yuan Lv ,&nbsp;Binjie Niu ,&nbsp;Tianxu Li ,&nbsp;Mengling Zhang ,&nbsp;Yanhui Xiang ,&nbsp;Rui Qiao ,&nbsp;Dapeng Tai","doi":"10.1016/j.fct.2026.116001","DOIUrl":"10.1016/j.fct.2026.116001","url":null,"abstract":"<div><h3>Background</h3><div>Long-term arsenic exposure is associated with health risks, including neurotoxicity, cardiovascular diseases, and cancer, with heightened vulnerability during early development. This study integrates RNA sequencing (RNA-seq) and network toxicology to construct a competing endogenous RNA (ceRNA) network and elucidate molecular mechanisms of prenatal arsenic-induced neurodevelopmental toxicity.</div></div><div><h3>Methods</h3><div>Pregnant ICR mice were exposed to sodium arsenite (NaAsO<sub>2</sub>, 0.5 ppm) through drinking water. Behavioral tests were performed on postnatal day 30 (PND 30). A total of 20 offspring mice (male/female = 1:1) underwent behavioral assessments, including open field, forced swim, and tail suspension tests, to evaluate anxiety- and depression-like behaviors. Neonatal brain tissues were collected on postnatal day 1 (PND 1) and analyzed using RNA sequencing. The results were further integrated with network toxicology analyses and were subsequently validated experimentally.</div></div><div><h3>Results</h3><div>Prenatal arsenic exposure elicited significant anxiety- and depression-like behaviors in offspring. Integrated analyses showed that disrupted ceRNA regulatory axes converge the calcium-signaling pathway, neuroactive ligand–receptor interaction, and synaptic-vesicle cycle, revealing key molecular mechanisms underlying the observed neurodevelopmental impairments.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that prenatal arsenic exposure induces early molecular perturbations in the neonatal brain by altering competing endogenous RNA regulatory networks. More importantly, the integration of transcriptomic data with network-based analyses provides a systematic framework for elucidating the underlying mechanisms of developmental neurotoxicity, highlighting key signaling pathways associated with synaptic function and neuronal communication. This network-oriented approach offers mechanistic insights beyond single-gene analysis and facilitates the identification of critical regulatory processes involved in arsenic-induced neurodevelopmental effects.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 116001"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146148595","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}
引用次数: 0
FEMA GRAS assessment of natural flavor complexes: Pepper, ginger, coniferous-derived and related flavoring ingredients 天然风味复合物的FEMA GRAS评估:胡椒、姜、针叶树衍生及相关调味成分。
IF 3.5 3区 医学
Food and Chemical Toxicology Pub Date : 2026-05-01 Epub Date: 2025-12-11 DOI: 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
{"title":"FEMA GRAS assessment of natural flavor complexes: Pepper, ginger, coniferous-derived and related flavoring ingredients","authors":"Stephen S. Hecht ,&nbsp;Samuel M. Cohen ,&nbsp;Gerhard Eisenbrand ,&nbsp;Shoji Fukushima ,&nbsp;Nigel J. Gooderham ,&nbsp;F. Peter Guengerich ,&nbsp;Ivonne M.C.M. Rietjens ,&nbsp;Thomas J. Rosol ,&nbsp;Jeanne M. Davidsen ,&nbsp;Christie L. Harman ,&nbsp;Sean V. Taylor","doi":"10.1016/j.fct.2025.115849","DOIUrl":"10.1016/j.fct.2025.115849","url":null,"abstract":"<div><div>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 <em>Angelica, Abies, Cananga, Croton, Apium, Canarium, Erigeron</em>, <em>Ferula, Zingiber, Humulus, Juniperus, Cistus, Commiphora, Boswellia, Piper, Pinus</em> and <em>Schinus</em> 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.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 115849"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","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}
引用次数: 0
Proteomic and in silico characterization identifies conarachin as a major IgE-reactive peanut allergen 蛋白质组学和芯片鉴定鉴定花生花生角蛋白是一种主要的ige反应性过敏原。
IF 3.5 3区 医学
Food and Chemical Toxicology Pub Date : 2026-05-01 Epub Date: 2026-02-16 DOI: 10.1016/j.fct.2026.116017
Hanène Djeghim , Ouided Benslama , Ines Bellil , Postigo Idoia , Patricia Sanchez , Douadi Khelifi , Huda Alsaeedi , Mikhael Bechlany , Ahmed Barhoum
{"title":"Proteomic and in silico characterization identifies conarachin as a major IgE-reactive peanut allergen","authors":"Hanène Djeghim ,&nbsp;Ouided Benslama ,&nbsp;Ines Bellil ,&nbsp;Postigo Idoia ,&nbsp;Patricia Sanchez ,&nbsp;Douadi Khelifi ,&nbsp;Huda Alsaeedi ,&nbsp;Mikhael Bechlany ,&nbsp;Ahmed Barhoum","doi":"10.1016/j.fct.2026.116017","DOIUrl":"10.1016/j.fct.2026.116017","url":null,"abstract":"<div><div>Peanut allergy is a major health issue, and detailed molecular insights are essential to understand allergenicity. In this study, an integrated immunoproteomic and in silico docking workflow was applied to characterize allergens from six Algerian peanut varieties. Protein profiling by 2-DE (pI 4.8-10.1, 9-68 kDa), followed by immunoblotting, revealed strong IgE binding to low-molecular-weight proteins (20-25 kDa). Sixteen distinct protein spots were excised and analyzed by LC-MS/MS, identifying key allergens including Ara h 1, Ara h 2, Ara h 3, and Ara h 6, with peptide coverages ranging from 34% (Ara h 1) to 70% (Ara h 2). Four highly reactive allergens were prioritized, and nine were further investigated through molecular docking against the human IgE receptor. Computational analyses uncovered novel epitope interactions, with conarachin (Q647H1) emerging as the strongest binder (cluster score −625.4), showing stable contacts at epitopes 26-50, 112-151, and 185-491. Chain-specific docking highlighted high affinity toward both IgE heavy and light chains, underlining its structural adaptability.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 116017"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218033","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}
引用次数: 0
Arsenic exposure induces stemness in human normal breast epithelial cells via the E2F2/FZD10 axis 砷暴露通过E2F2/FZD10轴诱导人正常乳腺上皮细胞干性
IF 3.5 3区 医学
Food and Chemical Toxicology Pub Date : 2026-05-01 Epub Date: 2026-02-09 DOI: 10.1016/j.fct.2026.116003
Yang Yang , Dexiu Hu , Maoyuan Gong , Xingcan Yang , Ruobi Chen , Jingyuan Lin , Qibing Zeng , Yuyan Xu
{"title":"Arsenic exposure induces stemness in human normal breast epithelial cells via the E2F2/FZD10 axis","authors":"Yang Yang ,&nbsp;Dexiu Hu ,&nbsp;Maoyuan Gong ,&nbsp;Xingcan Yang ,&nbsp;Ruobi Chen ,&nbsp;Jingyuan Lin ,&nbsp;Qibing Zeng ,&nbsp;Yuyan Xu","doi":"10.1016/j.fct.2026.116003","DOIUrl":"10.1016/j.fct.2026.116003","url":null,"abstract":"<div><div>Chronic arsenic exposure is associated with systemic toxicity and carcinogenic risk, yet its mechanistic link to breast cancer remains poorly defined. Here, we demonstrate that long-term exposure of human mammary epithelial cells (MCF-10A) to low-dose sodium arsenite (NaAsO<sub>2</sub>) drives acquisition of a breast cancer stem-like phenotype. NaAsO<sub>2</sub>-exposed cells exhibited enhanced migration (1.34-fold), invasion (2.9-fold), and sphere-formation (1.54-fold) capacities, along with elevated expression of BCSCs markers EpCAM (3.17-fold) and ALDH1 (2.45-fold) and an increased CD44<sup>+</sup>/CD24<sup>-/low</sup> subpopulation (1.63-fold). Transcriptomic profiling identified the transcription factor E2F2 as a key mediator of this transformation. Functional studies established that E2F2 directly regulates FZD10 expression, activating the Wnt/β-catenin pathway to sustain the stem-like state. Collectively, we unveil the E2F2/FZD10 axis as a previously unrecognized molecular conduit through which environmental arsenic reprograms mammary epithelial cells toward a BCSCs-like phenotype, providing mechanistic insight into arsenic-associated breast cancer risk and revealing a potential target for preventive intervention.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 116003"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146163286","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}
引用次数: 0
Limosilactobacillus fermentum LF61: A multidimensional study on safety and functionality from genomics to clinical application 发酵乳酸杆菌LF61:从基因组学到临床应用的安全性和功能性多维研究。
IF 3.5 3区 医学
Food and Chemical Toxicology Pub Date : 2026-05-01 Epub Date: 2026-02-06 DOI: 10.1016/j.fct.2026.116002
Manfei Jin , Fei Xu , Yinhua Liu , Zhao Jiang
{"title":"Limosilactobacillus fermentum LF61: A multidimensional study on safety and functionality from genomics to clinical application","authors":"Manfei Jin ,&nbsp;Fei Xu ,&nbsp;Yinhua Liu ,&nbsp;Zhao Jiang","doi":"10.1016/j.fct.2026.116002","DOIUrl":"10.1016/j.fct.2026.116002","url":null,"abstract":"<div><div>This study presents a comprehensive multidimensional assessment of the safety and functional efficacy of <em>Limosilactobacillus fermentum</em> LF61, a strain isolated from human milk. Genomic analysis revealed no virulence factors (VFDB), drug resistance genes (CARD), or toxin synthesis gene cluster (antiSMASH) within its chromosome (2.04 Mb) and plasmid (15.5 kb), meeting EFSA's QPS safety criteria. In vitro studies demonstrated that LF61 exhibited a 2-h survival rate of &gt;98% in gastric acid (pH 2.0) and a survival rate of 99.66% in intestinal fluid (pH 8.0). LF61 was also nontoxic to Caco-2 cells (metabolic activity at 20% concentration: 100.3 ± 2.1%). An acute oral toxicity test (in ICR mice) demonstrated an LD50 &gt; 2 × 10<sup>10</sup> CFU/kg. In a randomized, double-blind clinical trial (n = 49), daily intake of 3 × 10<sup>10</sup> CFU of LF61 for 8 weeks increased serum levels of the antimicrobial peptide LL-37 by 12.3% (<em>p</em> &lt; 0.05), and IgA, IgG, and IgM by 18.7%, 15.2%, and 9.8%, respectively (<em>p</em> &lt; 0.05). Metagenomic analysis revealed that LF61 promoted colonization by short-chain fatty acid-producing bacteria, such as <em>Mitsuokella</em> and <em>Turicibacter</em> (LDA &gt;3), activated the carbohydrate metabolism pathway (<em>p</em> = 0.002), and maintained stable α-diversity in the microbiome (Shannon index <em>p</em> &gt; 0.05). Collectively, our findings indicate that LF61 exerts beneficial effects via a gut-immune axis bidirectional regulatory mechanism, offering a theoretical basis and clinical evidence for the development of novel immunomodulatory probiotics targeting the gut-immune axis.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 116002"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140567","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}
引用次数: 0
Safety evaluation of honey truffle sweet protein produced from Komagataella phaffii 蜂蜜松露甜蛋白的安全性评价。
IF 3.5 3区 医学
Food and Chemical Toxicology Pub Date : 2026-05-01 Epub Date: 2026-02-02 DOI: 10.1016/j.fct.2026.115987
Susan M. Potter , Dan Zhao , Ashley Roberts , Robert Peterson , Daniel E. Connors , David B. Mayfield , Mel Lloyd , Thomas Martin , Sabitha Papineni , Giulia Tosi
{"title":"Safety evaluation of honey truffle sweet protein produced from Komagataella phaffii","authors":"Susan M. Potter ,&nbsp;Dan Zhao ,&nbsp;Ashley Roberts ,&nbsp;Robert Peterson ,&nbsp;Daniel E. Connors ,&nbsp;David B. Mayfield ,&nbsp;Mel Lloyd ,&nbsp;Thomas Martin ,&nbsp;Sabitha Papineni ,&nbsp;Giulia Tosi","doi":"10.1016/j.fct.2026.115987","DOIUrl":"10.1016/j.fct.2026.115987","url":null,"abstract":"<div><div>Honey truffles (<em>Mattirolomyces terfezioides</em>) contain a natural protein which exhibits intense sweetness. This protein is produced via precision fermentation using <em>Komagataella phaffii</em> (formerly <em>Pichia pastoris</em>) as the chassis and is processed into a spray dried powder referred to as Honey Truffle Sweet Protein (HTSP) and the powder contains at least 50% w/w total protein, of which at least 50% is the active sweet protein, Honey Truffle Active Component (HT-AC). HT-AC is 500–2500 times sweeter than sucrose dependent on food/beverage formulations. A set of genotoxicity assays and oral repeated dose studies were conducted to assess the safety of HTSP for its use as a sweetener in food and beverages. The results of the <em>in vitro</em> bacterial mutagenicity and mammalian cell micronucleus tests demonstrated a lack of genotoxic effects. In the 13-week oral exposure study, male and female Wistar Han rats were dosed by gavage to 1800, 3600, and 5400 mg/kg/day of HTSP (equivalent to approximately 500, 1000 and 1500 mg/kg/day of the HT-AC). Treatment was well tolerated with neither mortality nor HTSP-related adverse clinical pathology findings, organ weight effects, or macroscopic or microscopic observations. Consequently, the no observed adverse effect level (NOAEL) was 5400 mg/kg/day (1500 mg/kg/day HT-AC). The results supports the safety of HTSP for use as a dietary sweetener in food and beverage applications.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 115987"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117115","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}
引用次数: 0
RIPK3/MLKL-mediated necroptosis promotes hepatic inflammation in chronic arsenic exposure through drinking water RIPK3/ mlkl介导的坏死性下垂通过饮用水促进慢性砷暴露的肝脏炎症。
IF 3.5 3区 医学
Food and Chemical Toxicology Pub Date : 2026-05-01 Epub Date: 2026-02-18 DOI: 10.1016/j.fct.2026.116020
Meng Zhang , Mingzhao Jia , Yinan Liu , Yawen Shi , Xu Zhao , Chen Chen , Jinghong Chen
{"title":"RIPK3/MLKL-mediated necroptosis promotes hepatic inflammation in chronic arsenic exposure through drinking water","authors":"Meng Zhang ,&nbsp;Mingzhao Jia ,&nbsp;Yinan Liu ,&nbsp;Yawen Shi ,&nbsp;Xu Zhao ,&nbsp;Chen Chen ,&nbsp;Jinghong Chen","doi":"10.1016/j.fct.2026.116020","DOIUrl":"10.1016/j.fct.2026.116020","url":null,"abstract":"<div><div>Chronic exposure to arsenic-contaminated drinking water is a major environmental risk factor for liver injury, yet its pathogenic mechanisms remain unclear. This study explores the role of RIPK3/MLKL-mediated necroptosis in arsenic-induced hepatotoxicity using a chronic <em>in vivo</em> mouse model. Mice were exposed to sodium arsenite (NaAsO<sub>2</sub>) at concentrations of 2.8, 8.4, and 25.2 mg/L in drinking water for 8 weeks. Arsenic exposure induced dose-dependent hepatocellular necrosis, elevated liver injury markers (ALT, AST, GST-α, GDH), and increased hepatic expression of <em>p</em>-RIPK3, <em>p</em>-MLKL and HMGB1, along with upregulation of the proinflammatory cytokines TNF-α and IL-6. Notably, <em>Mlkl</em><sup>−/−</sup> mice exhibited significantly reduced liver injury and lower levels of ALT, AST, GSHα, and GDH, decreased HMGB1, TNF-α and IL-6 expression, following high-dose arsenic exposure (25.2 mg/L) compared to WT controls. These findings indicate that RIPK3/MLKL-mediated necroptosis contributes to arsenic-induced liver injury by promoting hepatocyte death and inflammation. Inhibiting MLKL alleviates arsenic-induced liver injury by reducing cell death and inflammation in mice. Targeting MLKL may offer a promising therapeutic approach for mitigating chronic arsenic-related hepatotoxicity.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 116020"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146256718","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}
引用次数: 0
Analytical measurement and human health risk assessment of selected metals from commercial chocolate bars 商品巧克力棒中选定金属的分析测量和人体健康风险评估。
IF 3.5 3区 医学
Food and Chemical Toxicology Pub Date : 2026-05-01 Epub Date: 2026-02-13 DOI: 10.1016/j.fct.2026.116011
Stephanie A. Thornton , Taylor M. Mincin , Oluwadamilare A. Adebambo , Kenny M. Unice , Marisa L. Kreider
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