Food and Chemical Toxicology最新文献_第2页

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 , Dan Zhao , Ashley Roberts , Robert Peterson , Daniel E. Connors , David B. Mayfield , Mel Lloyd , Thomas Martin , Sabitha Papineni , 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 , Mingzhao Jia , Yinan Liu , Yawen Shi , Xu Zhao , Chen Chen , 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

Acephate exposure during gestation in rats elicits differing placental transcriptomic responses in male and female fetuses 大鼠妊娠期间乙酰甲胺磷暴露可引起雄性和雌性胎儿不同的胎盘转录组反应

IF 3.5 3区医学

Food and Chemical Toxicology Pub Date : 2026-05-01 Epub Date: 2026-01-27 DOI: 10.1016/j.fct.2026.115980

Pedro Vinicius Gonçalves Martins , Vitor Lima Coelho , Mariana de Souza Pomacena , Yasmim Petronilho de Souza , Beatriz Souza da Silva , Luana Lopes de Souza , Iala Milene Bertasso , Egberto Gaspar de Moura , Patricia Cristina Lisboa , Rosiane Aparecida Miranda

{"title":"Acephate exposure during gestation in rats elicits differing placental transcriptomic responses in male and female fetuses","authors":"Pedro Vinicius Gonçalves Martins , Vitor Lima Coelho , Mariana de Souza Pomacena , Yasmim Petronilho de Souza , Beatriz Souza da Silva , Luana Lopes de Souza , Iala Milene Bertasso , Egberto Gaspar de Moura , Patricia Cristina Lisboa , Rosiane Aparecida Miranda","doi":"10.1016/j.fct.2026.115980","DOIUrl":"10.1016/j.fct.2026.115980","url":null,"abstract":"<div><div>Acephate, a broadly applied insecticide with endocrine-disrupting properties, has <em>in utero</em> effects that are still not fully elucidated. We hypothesized that maternal exposure to a low dose of acephate alters placental function and induces sex-specific offspring changes. Wistar rat dams received water (control) or acephate (4.5 mg/kg/day) by gavage from gestation day (GD) 6.5–18.5, and the placentas and fetuses were collected on GD 18.5. Acephate exposure caused intrauterine growth restriction (IUGR) in both sexes, while placental efficiency (g fetus/g placenta) was reduced in males and increased in females. Placental transcriptomics revealed no significant differential expression in placentas bearing male fetuses. In contrast, 135 downregulated genes and 171 upregulated genes enriched for growth and nutrient transport were identified in placentas bearing female fetuses. A reduction in the profile of proinflammatory cytokines in the amniotic fluid was detected in the fetuses of both sexes, especially in males, whereas the plasma concentration of MCP-1 increased in dams. Taken together, these findings reveal that the response to acephate differs according to fetal sex, suggesting a nontranscriptional mechanism of placental failure in placentas bearing male fetuses, as well as a complex, adaptive transcriptional response in those bearing female fetuses.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 115980"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146071010","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

Detoxification of T-2 toxin in human chondrocytes due to its hydroxylation by carboxylesterases and arylacetamide deacetylase in the liver 肝脏中羧酸酯酶和芳基乙酰胺去乙酰化酶对人软骨细胞中T-2毒素的羟基化解毒作用

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.2026.116007

Shiqiang Cheng , Sirong Shi , Bolun Cheng , Chen Liu , Xuena Yang , Li Liu , Huan Liu , Yan Wen , Alexey A. Tinkov , Anatoly V. Skalny , Yumeng Jia , Feng Zhang

{"title":"Detoxification of T-2 toxin in human chondrocytes due to its hydroxylation by carboxylesterases and arylacetamide deacetylase in the liver","authors":"Shiqiang Cheng , Sirong Shi , Bolun Cheng , Chen Liu , Xuena Yang , Li Liu , Huan Liu , Yan Wen , Alexey A. Tinkov , Anatoly V. Skalny , Yumeng Jia , Feng Zhang","doi":"10.1016/j.fct.2026.116007","DOIUrl":"10.1016/j.fct.2026.116007","url":null,"abstract":"<div><div>T-2 toxin, a trichothecene mycotoxin produced by <em>Fusarium</em> species, is a global cereal contaminant and an important environmental risk factor for cartilage damage and Kashin–Beck disease (KBD). Although hydrolysis is a major metabolic pathway of T-2 toxin, the human enzymes responsible and their toxicological relevance remain poorly understood. In this study, human liver microsomes, recombinant hydrolases, and selective inhibitors were used to identify the key enzymes mediating T-2 hydrolysis, and LC–MS/MS was applied to quantify T-2 and its major metabolites. Human chondrocytes were further used to evaluate the cytotoxicity of T-2 and its hydrolytic metabolites (HT-2 toxin, neosolaniol, and T-2 tetraol). T-2 toxin was predominantly hydrolyzed to HT-2 toxin, primarily by carboxylesterases (CES1, CES2), with inhibitor-based evidence supporting a potential role for arylacetamide deacetylase (AADAC). The toxicity ranking was T-2 toxin > HT-2 toxin > neosolaniol > T-2 tetraol. T-2 toxin markedly impaired autophagy and extracellular matrix metabolism in chondrocytes, whereas its metabolites showed weaker cytotoxicity. These findings indicate that human CES1 and CES2, together with other hydrolases including AADAC, contributing to the hydrolysis and detoxification of T-2 toxin and may represent potential targets for mitigating T-2–associated cartilage damage and KBD risk.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 116007"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146163342","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

{"title":"Analytical measurement and human health risk assessment of selected metals from commercial chocolate bars","authors":"Stephanie A. Thornton , Taylor M. Mincin , Oluwadamilare A. Adebambo , Kenny M. Unice , Marisa L. Kreider","doi":"10.1016/j.fct.2026.116011","DOIUrl":"10.1016/j.fct.2026.116011","url":null,"abstract":"<div><div>Potential health risks associated with exposure to heavy metals in milk and dark chocolate bars were evaluated using analytical testing and representative consumption estimates. Across six brands, 36 chocolate samples were purchased and analyzed for the presence of arsenic (As), cadmium (Cd), lead (Pb), and mercury (Hg) using inductively coupled plasma mass spectroscopy (ICP-MS). Concentrations in chocolate were combined with frequency and quantity of U.S. chocolate consumption to estimate exposures for several age groups. Potential risks were characterized by comparing exposures to health-based screening values. No non-cancer risk was observed for any age group under central tendency exposure assumptions, but high-end exposure assumptions resulted in potential risks for non-cancer endpoints from potential Pb exposure in most age groups. Potential increased cancer risks from potential As exposure were identified for some age groups under central tendency exposure assumptions and all groups under high-end assumptions; however, As was only quantified in two samples. Inherent conservatisms in the approach provided confidence that there is low likelihood of risk from Pb or As in chocolate despite potential risks identified, and no risks were identified from Cd or Hg. Overall, health risks from heavy metals are unlikely under typical exposure scenarios for most chocolate bars.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 116011"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146199995","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

Response to the Letter to the Editor: “Translational perspectives on dietary prebiotics and iron for reducing rice cadmium bioavailability" 对致编辑的信的回应：“饮食益生元和铁对降低水稻镉生物利用度的转化观点”。

IF 3.5 3区医学

Food and Chemical Toxicology Pub Date : 2026-05-01 Epub Date: 2026-02-05 DOI: 10.1016/j.fct.2026.115988

Rong-Yue Xue, Hong-Bo Li

引用次数: 0

Translational perspectives on dietary prebiotics and iron for reducing rice cadmium bioavailability 膳食益生元和铁对降低水稻镉生物利用度的转化研究

IF 3.5 3区医学

Food and Chemical Toxicology Pub Date : 2026-05-01 Epub Date: 2026-02-10 DOI: 10.1016/j.fct.2026.115989

Gizem Zorlu Gorgulugil, Muhammed Ali Coskuner, Gokhan Koker

引用次数: 0

Deriving toxicological reference values for dietary inorganic arsenic exposure from epidemiological evidence of cardiovascular disease risk 从心血管疾病风险的流行病学证据中得出膳食无机砷暴露的毒理学参考值。

IF 3.5 3区医学

Food and Chemical Toxicology Pub Date : 2026-05-01 Epub Date: 2026-02-10 DOI: 10.1016/j.fct.2026.116008

Charitha J. Gamlath , Patricia Hsu , Ashish Pokharel , Felicia Wu

{"title":"Deriving toxicological reference values for dietary inorganic arsenic exposure from epidemiological evidence of cardiovascular disease risk","authors":"Charitha J. Gamlath , Patricia Hsu , Ashish Pokharel , Felicia Wu","doi":"10.1016/j.fct.2026.116008","DOIUrl":"10.1016/j.fct.2026.116008","url":null,"abstract":"<div><div>The toxicity of arsenic has been well established for millennia, with epidemiological data demonstrating the association of inorganic arsenic (iAs) to cancers and dermal defects. Recently, epidemiological and mechanistic studies linking dietary iAs exposure to cardiovascular diseases (CVD) have emerged. Despite growing evidence on iAs induced CVD, current toxicological reference values (TRVs) for dietary iAs are largely based on cancer, peripheral vascular (“blackfoot”) disease, diabetes and dermal endpoints. To bridge this gap, the current study estimated TRVs for food borne iAs using the benchmark dose (BMD) approach, by modeling dose-response data of multiple CVD endpoints identified from literature. The estimated TRVs for CVD incidence were in the range of 0.027-0.037 μg/kg bw/day and were lower than TRVs estimated by regulatory bodies. TRVs estimated based on CVD mortality alone were in the range of 0.074-0.729 μg/kg bw/day. A TRV of 0.03 μg/kg bw/day based on coronary heart disease incidence was considered appropriate from a regulatory standpoint. The TRV estimate suggests that iAs induced cardiovascular diseases are an important endpoint from a policymaking perspective on maximum allowable arsenic levels in food.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 116008"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146176861","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

PFHxS is predicted to bind KEAP1 and is associated with NRF2–NQO1 activation in hepatocellular carcinoma 预计PFHxS与KEAP1结合，并在肝细胞癌中与NRF2-NQO1激活相关。

IF 3.5 3区医学

Food and Chemical Toxicology Pub Date : 2026-05-01 Epub Date: 2026-01-31 DOI: 10.1016/j.fct.2026.115986

Chenghao He , Jiaxin Jiang , Shuguang Hou , Runchun Xu , Qinwan Huang

{"title":"PFHxS is predicted to bind KEAP1 and is associated with NRF2–NQO1 activation in hepatocellular carcinoma","authors":"Chenghao He , Jiaxin Jiang , Shuguang Hou , Runchun Xu , Qinwan Huang","doi":"10.1016/j.fct.2026.115986","DOIUrl":"10.1016/j.fct.2026.115986","url":null,"abstract":"<div><div>Perfluorohexanesulfonic acid (PFHxS), a prevalent short-chain per- and polyfluoroalkyl substance, has been implicated in hepatocellular carcinoma (HCC), but mechanisms remain unclear. We integrated transcriptomic analyses of The Cancer Genome Atlas (TCGA) liver cancer cohort and an HCC single-cell dataset with molecular docking and molecular dynamics simulations and in vitro assays to examine a PFHxS-relevant hypothesis involving KEAP1–NRF2 signaling. Across clinical datasets, higher NQO1, an NRF2-associated gene, was linked to adverse clinicopathologic features; NQO1-high tumor cells showed elevated NRF2-activity signatures and computationally inferred increased MIF signaling toward macrophages. Because exposure information is unavailable, these observations indicate association and define a PFHxS-relevant vulnerability axis rather than PFHxS-driven tumor states. Docking/dynamics suggested PFHxS can bind the KEAP1 Kelch domain near the NRF2-binding site. In HepG2 cells, PFHxS modestly increased viability/DNA-synthesis readouts and enhanced NRF2 nuclear localization, NQO1 protein abundance, and MIF secretion; pharmacologic NRF2 inhibition partially attenuated NRF2/NQO1 readouts and reduced MIF secretion. Together, the data support the hypothesis that PFHxS may engage a KEAP1–NRF2-related vulnerability axis, accompanied by NRF2/NQO1 pathway readouts and increased MIF secretion, motivating exposure-characterized and genetic studies to establish causality.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 115986"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146103338","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

Emodin: Its effects are largely due to hormesis 大黄素：它的作用主要是由于激效。

IF 3.5 3区医学

Food and Chemical Toxicology Pub Date : 2026-05-01 Epub Date: 2026-01-29 DOI: 10.1016/j.fct.2026.115984

Edward J. Calabrese , Peter Pressman , A. Wallace Hayes , Evgenios Agathokleous , Gaurav Dhawan , Rachna Kapoor , Vittorio Calabrese

{"title":"Emodin: Its effects are largely due to hormesis","authors":"Edward J. Calabrese , Peter Pressman , A. Wallace Hayes , Evgenios Agathokleous , Gaurav Dhawan , Rachna Kapoor , Vittorio Calabrese","doi":"10.1016/j.fct.2026.115984","DOIUrl":"10.1016/j.fct.2026.115984","url":null,"abstract":"<div><div>This present paper provides the first integrative evaluation of the occurrence of emodin-induced hormetic-biphasic dose responses in the biological and biomedical literature, their study design and dose-response features, underlying adaptive and toxic mechanistic foundations, and generality across biological models, cell types, as well as across different levels of biological organization (i.e., cell, organ, and organism). Emodin-induced hormetic responses have been reported in numerous cellular experimental systems of broad biomedical interest, as well as in <em>in vivo</em> studies with fish and rodent models. Of particular interest was the generality of the <em>in vivo</em> findings across multiple commercial fish models, in which emodin enhanced growth and development and increased resistance to various physical and environmental stressors. While emodin induces hormetic effects via multiple molecular targets and pathways, a general mechanistic adaptive response strategy involves its capacity to activate peroxisome proliferator-activated receptor gamma and the AMPK/Nrf2 pathway.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 115984"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146096801","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