Food and Chemical Toxicology最新文献_第4页

Update to RIFM fragrance ingredient safety assessment, γ-decalactone, CAS Registry Number 706-14-9 更新RIFM香料成分安全性评估，γ-癸内酯，CAS注册号706-14-9

IF 3.5 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2025-11-25 DOI: 10.1016/j.fct.2025.115864

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

引用次数: 0

Integrated approaches to testing and assessment for the endocrine disrupting activity of tartrazine based on adverse outcome pathways and OECD frameworks 基于不利结果途径和经合组织框架的酒石黄内分泌干扰活性的综合测试和评估方法

IF 3.5 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2025-11-24 DOI: 10.1016/j.fct.2025.115867

Ngoc Minh-Hong Hoang, Kwangsik Park

Tartrazine (TTZ), a widely used synthetic azo dye in processed foods, beverages, and pharmaceuticals, raises various health concerns including hematotoxicity, genotoxicity, carcinogenicity, neurotoxicity, and endocrine activity. Regarding the endocrine disruption, although individual studies has reported estrogenic, androgenic and thyroid effects, a comprehensive and integrated evaluation of across hormonal systems have never been tried. To address this gap, we performed multi-tool in silico approaches covering all nuclear receptors. Docking simulations (Endocrine Disruptome, CB-Dock2, and AutoDock Vina) were employed to estimate receptor–binding propensities. Machine learning–based resources (ADMETlab3.0, ProTox-3.0, CERAPP/CoMPARA, and EDC-Predictor) were used to forecast endocrine activities. Most nuclear receptors exhibited potential effects by TTZ—including AR, ERα, TRα/β, PXR, RXRα, PPARγ, and AhR—except ERβ. Consistently, ToxCast reported active calls for AR, ERα, TR, RXR, and AhR. In addition, SwissTargetPrediction and PharmMapper indicated that TTZ could predominantly influence reproductive and thyroid toxicity via cancer-related pathways. We further aligned in silico outputs with existing in vitro and in vivo findings mapped to AOPs for the estrogen, androgen, and thyroid axes, and summarized evidence across hormonal systems under OECD-relevant considerations to clarify current knowledge and guide future systematic endocrine profiling of TTZ.

酒石黄（TTZ）是一种广泛用于加工食品、饮料和药品的合成偶氮染料，引起了各种健康问题，包括血液毒性、遗传毒性、致癌性、神经毒性和内分泌活性。关于内分泌干扰，虽然个别研究报道了雌激素、雄激素和甲状腺的影响，但从未尝试过对整个激素系统进行全面和综合的评估。为了解决这一差距，我们执行了涵盖所有核受体的多工具硅方法。对接模拟（内分泌干扰、cbdock2和AutoDock Vina）用于估计受体结合倾向。使用基于机器学习的资源（ADMETlab3.0、ProTox-3.0、CERAPP/CoMPARA和EDC-Predictor）预测内分泌活动。除ERβ外，大多数核受体（包括AR、ERα、TRα/β、PXR、RXRα、PPARγ和ahr）均表现出ttz的潜在作用。一致地，ToxCast报告了对AR、ERα、TR、RXR和AhR的活跃呼叫。此外，SwissTargetPrediction和PharmMapper表明，TTZ可能主要通过癌症相关途径影响生殖和甲状腺毒性。我们进一步将计算机输出结果与现有的体外和体内研究结果进行了比对，这些结果与雌激素、雄激素和甲状腺轴的AOPs相关，并在经合组织相关考虑下总结了激素系统的证据，以澄清当前的知识并指导未来TTZ的系统内分泌分析。

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引用次数: 0

Update to RIFM fragrance ingredient safety assessment, isovaleric acid, CAS Registry Number 503-74-2 更新RIFM香料成分安全评估，异戊酸，CAS注册号503-74-2。

IF 3.5 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2025-11-24 DOI: 10.1016/j.fct.2025.115863

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

引用次数: 0

Update to RIFM fragrance ingredient safety assessment, γ-nonalactone, CAS Registry Number 104-61-0 更新RIFM香料成分安全性评估，γ-非内酯，CAS注册号104-61-0。

IF 3.5 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2025-11-24 DOI: 10.1016/j.fct.2025.115865

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

引用次数: 0

Broflanilide impairs cell viability and milk protein secretion in mammary epithelial cells by regulating Akt/mTOR and STAT5 signaling Broflanilide通过调节Akt/mTOR和STAT5信号通路，损害乳腺上皮细胞活力和乳蛋白分泌。

IF 3.5 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2025-11-22 DOI: 10.1016/j.fct.2025.115857

Liang Han , Yuki Yasui , Tamaki Uehara , Hideki Miwa , Ken Kobayashi

Broflanilide is a potent and widely used insecticide that selectively targets γ-aminobutyric acid (GABA) receptors in invertebrates. Recently, emerging evidence suggested its potential toxicity to mammals. Broflanilide and its metabolites are detected in milk fat in Holstein dairy cows. However, it remains unclear whether broflanilide affects milk production in mammary glands. This study investigated the effects of tissue residue–based exposure level of broflanilide on cell survival and milk production in primary mammary epithelial cells (MECs) in vitro. We demonstrated that broflanilide modulates the AKT/mTOR signaling pathway, suppresses cell proliferation, and induces apoptosis, thereby reducing MEC numbers. Additionally, Broflanilide caused the abnormal expression of α- and β-casein, and reduced secretion of α-casein into the culture medium in lactating MECs, while lactoferrin secretion was largely unaffected. Broflanilide markedly inhibited phosphorylation and nuclear translocation of STAT5, a key transcription factor required for expression of milk production-related genes, particularly caseins. Moreover, Broflanilide suppressed the phosphorylation of STAT3, p38, and JNK, while inducing the phosphorylation of NF-κB, indicating dysregulation of inflammation-related signaling pathways. In conclusion, our findings suggest that even at tissue residue level, Broflanilide can negatively affect lactation by reducing MEC viability, inactivating lactogenic signaling, and aberrantly modulating inflammatory pathways.

溴flanilide是一种广泛使用的强效杀虫剂，可选择性靶向γ-氨基丁酸（GABA）受体。最近，新出现的证据表明它对哺乳动物有潜在的毒性。在荷斯坦奶牛的乳脂中检测溴flanilide及其代谢物。然而，溴flanilide是否会影响乳腺的产奶量尚不清楚。本研究探讨了溴flanilide暴露水平对体外原代乳腺上皮细胞（MECs）细胞存活和泌乳量的影响。我们证明了溴flanilide调节AKT/mTOR信号通路，抑制细胞增殖，诱导细胞凋亡，从而减少MEC数量。此外，Broflanilide引起泌乳mec中α-和β-酪蛋白表达异常，α-酪蛋白分泌减少，而乳铁蛋白分泌基本未受影响。溴flanilide显著抑制STAT5的磷酸化和核易位，STAT5是产奶相关基因（尤其是酪蛋白）表达所需的关键转录因子。此外，Broflanilide抑制STAT3、p38和JNK的磷酸化，同时诱导NF-κB的磷酸化，表明炎症相关信号通路失调。总之，我们的研究结果表明，即使在组织残留水平，溴flanilide也会通过降低MEC活力、灭活乳原信号和异常调节炎症途径对泌乳产生负面影响。

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引用次数: 0

Targeting the MLKL–F-actin–NLRP3 axis attenuates arsenic-induced myocardial necroinflammation 靶向MLKL-F-actin-NLRP3轴可减轻砷诱导的心肌坏死炎症。

IF 3.5 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2025-11-21 DOI: 10.1016/j.fct.2025.115861

Yinan Liu , Yixin Cui , Meng Zhang , Yawen Shi , Xu Zhao , Xinhe Zhang , Lian Li , Pinglin Yang , Jinghong Chen

Arsenic, an environmental toxicant, causes myocardial inflammatory injury upon chronic low-dose exposure, though its mechanisms are not fully understood. Necroptosis, mediated by mixed lineage kinase domain-like protein (MLKL), promotes necroinflammation by activating the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. Since F-actin depolymerization may regulate NLRP3, this study investigates its role in arsenite-induced cardiac injury. Wild-type (WT) and Mlkl-knockout (Mlkl ^−/−) C57BL/6 mice were exposed to arsenite (2.8–25.2 mg/L) for 8 weeks, while H9C2 cardiomyocyte were treated with arsenite (8–32 μM) for 24 h. Inhibitors targeting MLKL (Nec-1, GSK-872, NSA), NLRP3 (MCC950), and F-actin stabilization (Jasplakinolide) were employed. Arsenite dose-dependently upregulated p-MLKL and NLRP3 protein expression in myocardial tissues and H9C2 cells. Mlkl knockout or inhibition of necroptosis (Nec-1, GSK-872, and NSA) significantly suppressed NLRP3 activation and attenuated cardiac injury. Arsenite dose-dependently induced F-actin depolymerization and reduced actin expression, which was partially reversed in Mlkl ^−/− mice and necroptosis inhibitors. F-actin stabilizer Jasplakinolide markedly inhibited NLRP3 without affecting MLKL phosphorylation. Thus, chronic arsenite exposure promotes NLRP3 inflammasome activation via p-MLKL-mediated F-actin disruption, forming a “necroptosis-cytoskeletal disruption-inflammation” cascade. Targeting the MLKL-F-actin-NLRP3 axis offers a novel strategy for preventing and treating arsenic-induced myocardial damage.

砷是一种环境毒物，慢性低剂量暴露可引起心肌炎症性损伤，但其机制尚不完全清楚。由混合谱系激酶结构域样蛋白（MLKL）介导的坏死性上睑死亡，通过激活含有3 （NLRP3）炎性体的nod样受体家族pyrin结构域来促进坏死性炎症。由于f -肌动蛋白解聚可能调节NLRP3，本研究探讨其在亚砷酸盐诱导的心脏损伤中的作用。野生型（WT）和Mlkl敲除型（Mlkl-/-） C57BL/6小鼠暴露于亚砷酸盐（2.8 ~ 25.2 mg/L） 8周，H9C2心肌细胞暴露于亚砷酸盐（8 ~ 32 μM） 24小时。使用靶向MLKL (Nec-1, GSK-872， NSA), NLRP3 （MCC950）和F-actin稳定化（Jasplakinolide）的抑制剂。亚砷酸盐剂量依赖性上调心肌组织和H9C2细胞中p-MLKL和NLRP3蛋白表达。Mlkl敲除或抑制坏死下垂（Nec-1、GSK-872和NSA）可显著抑制NLRP3的激活并减轻心脏损伤。亚砷酸盐剂量依赖性诱导f -肌动蛋白解聚并降低肌动蛋白表达，这在Mlkl-/-小鼠和坏死性下垂抑制剂中部分逆转。f -肌动蛋白稳定剂茉莉烯内酯在不影响MLKL磷酸化的情况下显著抑制NLRP3。因此，慢性亚砷酸盐暴露通过p- mlkl介导的f -肌动蛋白破坏促进NLRP3炎性体活化，形成“坏死-细胞骨架破坏-炎症”级联反应。靶向MLKL-F-actin-NLRP3轴为预防和治疗砷诱导的心肌损伤提供了一种新的策略。

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引用次数: 0

Exposure to per- and polyfluoroalkyl substances (PFAS) and phthalate metabolites and their association with low estimated glomerular filtration rates in the US population 美国人群暴露于全氟烷基和多氟烷基物质（PFAS）和邻苯二甲酸酯代谢物及其与肾小球滤过率低的关系

IF 3.5 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2025-11-21 DOI: 10.1016/j.fct.2025.115853

Humairat H. Rahman , Weston R. Stokey , Stuart H. Munson-McGee

Per- and polyfluoroalkyl substances (PFAS) and phthalates are synthetic chemicals widely used in consumer products and polymers. Human exposure occurs through multiple pathways and has been linked to renal, neurologic, and endocrine toxicities. This study examined associations between PFAS and phthalate metabolites and reduced kidney function, as measured by estimated glomerular filtration rate (eGFR), using National Health and Nutrition Examination Survey (NHANES) 2013–2018 data. Participants who were non-Hispanic Black, over 40 years, or with serious heart disease showed higher likelihood of low eGFR. Among PFAS, exposure to MPAH was significantly associated with low eGFR (odds ratio [OR] 2.85; 95 % confidence interval [CI]: 1.31–6.21). Multiple phthalate metabolites were also positively associated with low eGFR, including MCOP, MCNP, MECPP, MBP, MEP, MEHHP, MHNCH, MEHP, MiBP, MEOHP, and MBzP, with ORs ranging from 1.42 to 2.50 across models. These findings suggest both PFAS and phthalate exposures are linked to kidney dysfunction in U.S. adults, with particularly strong associations for several phthalate metabolites. The results highlight the potential nephrotoxic risks of widespread chemical exposures and underscore the need for further studies on cumulative effects and vulnerable subpopulations.

全氟和多氟烷基物质（PFAS）和邻苯二甲酸盐是广泛用于消费品和聚合物的合成化学品。人体暴露通过多种途径发生，并与肾脏、神经系统和内分泌毒性有关。本研究使用2013-2018年国家健康与营养检查调查（NHANES）数据，通过估算肾小球滤过率（eGFR）测量PFAS和邻苯二甲酸酯代谢物与肾功能降低之间的关系。非西班牙裔黑人、40岁以上或患有严重心脏病的参与者更有可能出现eGFR偏低。在PFAS中，暴露于MPAH与低eGFR显著相关（优势比[OR] 2.85； 95%可信区间[CI]: 1.31-6.21）。多种邻苯二甲酸酯代谢物也与低eGFR呈正相关，包括MCOP、MCNP、MECPP、MBP、MEP、MEHHP、MHNCH、MEHP、MiBP、MEOHP和MBzP，各模型的or值为1.42 ~ 2.50。这些发现表明，PFAS和邻苯二甲酸盐暴露与美国成年人肾功能障碍有关，特别是与几种邻苯二甲酸盐代谢物有很强的联系。研究结果强调了广泛接触化学物质的潜在肾毒性风险，并强调了进一步研究累积效应和易感亚群的必要性。

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引用次数: 0

Integrated network toxicology, molecular docking and transcriptomics reveal the mechanistic role of phthalate esters in metabolic disease pathogenesis 综合网络毒理学、分子对接和转录组学揭示邻苯二甲酸酯在代谢性疾病发病机制中的作用。

IF 3.5 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2025-11-21 DOI: 10.1016/j.fct.2025.115855

Yuancheng Shao , Qi Liu , Yicheng Jiang , Gang Zhou, Xihan Gu, Shufan Zhang, Shuai Chen, Jiaming Xue, Liming Tang

Phthalate ester plasticizers (PAEs), common environmental pollutants, are linked to metabolic disorders like obesity, metabolic dysfunction-associated steatotic liver disease (MASLD), and metabolic dysfunction-associated steatohepatitis (MASH), but their multi-target molecular mechanisms remain unclear.

This study integrated network toxicology, transcriptomics, molecular docking, and molecular dynamics simulations to explore metabolic toxicity mechanisms of three common PAEs, including diethyl phthalate (DEP), dimethyl phthalate (DMP), and di-n-octyl phthalate (DNOP). A “plasticizer-target-disease” network was constructed, binding interactions assessed via molecular docking, and transcriptomes of DEP-exposed adipocytes and hepatocytes analyzed.

Common targets of the three PAEs intersecting with diseases enriched in metabolism-related pathways. PPI network identified IL6, PPARG, BCL2, and CASP3 as core targets, with stable binding confirmed by molecular assays. Transcriptomic data showed DEP disrupts metabolic pathways in adipocytes and hepatocytes.

Our findings suggest PAEs may promote metabolic diseases via the PPARG-IL6-BCL2-CASP3 axis, activating lipid accumulation-inflammation-apoptosis-fibrosis cascades. This study not only reveals the potential mechanistic link between plasticizers exposure and metabolic dysfunction, but also demonstrates the utility of network toxicology, molecular docking, and molecular dynamics simulation in evaluating the toxicity of environmental pollutants, laying a theoretical foundation for intervention targets, risk assessment, and prevention strategies.

邻苯二甲酸酯增塑剂（PAEs）是常见的环境污染物，与代谢紊乱如肥胖、代谢功能障碍相关脂肪性肝病（MASLD）和代谢功能障碍相关脂肪性肝炎（MASH）有关，但其多靶点分子机制尚不清楚。本研究综合了网络毒理学、转录组学、分子对接和分子动力学模拟等方法，探讨了三种常见的PAEs的代谢毒性机制，包括邻苯二甲酸二乙酯（DEP）、邻苯二甲酸二甲酯（DMP）和邻苯二甲酸二辛酯（DNOP）。构建了“增塑剂-靶标-疾病”网络，通过分子对接评估结合相互作用，并分析了暴露于dep的脂肪细胞和肝细胞的转录组。三种PAEs的共同靶点与代谢相关途径中丰富的疾病相交。PPI网络鉴定出IL6、PPARG、BCL2和CASP3为核心靶点，并通过分子实验证实其稳定结合。转录组学数据显示，DEP破坏脂肪细胞和肝细胞的代谢途径。我们的研究结果表明PAEs可能通过PPARG-IL6-BCL2-CASP3轴促进代谢性疾病，激活脂质积累-炎症-凋亡-纤维化级联反应。本研究不仅揭示了增塑剂暴露与代谢功能障碍之间潜在的机制联系，而且展示了网络毒理学、分子对接、分子动力学模拟在环境污染物毒性评价中的实用性，为制定干预目标、风险评估和预防策略奠定了理论基础。

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引用次数: 0

Letter to the Editor regarding the assessment of health risks from dietary exposure to natural estrogens in poultry eggs 致编辑的信，内容是评估膳食暴露于禽蛋中的天然雌激素对健康的风险

IF 3.5 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2025-11-20 DOI: 10.1016/j.fct.2025.115860

Justin G. Bendall

引用次数: 0

Food emulsion characteristics influence the release and absorption of 3-chloropropane-1,2-diol esters 食品乳剂特性影响3-氯丙烷-1,2-二醇酯的释放和吸收。

IF 3.5 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2025-11-19 DOI: 10.1016/j.fct.2025.115858

Ayse Nur Akpinar , Selvi Secil Sahin , Busra Moran , Aziz Tekin , Cansu Ekin Bonacina

3-MCPD esters (3-MCPDE) are food processing contaminants that are potentially carcinogenic. This study aimed to determine whether emulsification could enhance the absorption of 3-MCPDE and to investigate strategies for its reduction. Emulsions with fine (369.16 ± 3.72 nm), medium (514.17 ± 2.27 nm), and coarse (1025 ± 11.18 nm) particle sizes were prepared (10 % oil, 90 % aqueous phase). The release of free fatty acids (FFA) and 3-MCPD bioaccessibility were examined using an in vitro digestion model. Cytotoxicity was determined using the cell viability method, also known as the (4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT, Thiazolyl blue) method. The fine emulsion exhibited the highest FFA release (85.27 ± 0.68 %) and 3-MCPDE bioaccessibility (95.03 ± 4.36 %). Incorporating lemon oil, an indigestible oil, into the fine emulsion (up to 30 %) reduced FFA release by up to 30 %. However, bioaccessibility decreased significantly by up to 45 %. The micelle phase of the fine and medium emulsions showed cytotoxicity in fibroblast cells, whereas increasing particle size and including lemon oil improved cell viability. In conclusion, (i) increasing droplet size and (ii) partially replacing digestible oils with indigestible alternatives like lemon oil are promising strategies to mitigate the absorption of 3-MCPD in emulsified food systems.

3-MCPD酯（3-MCPDE）是一种具有潜在致癌性的食品加工污染物。本研究旨在确定乳化是否可以提高3-MCPDE的吸收，并探讨其减少策略。制备了细（369.16±3.72 nm）、中（514.17±2.27 nm）、粗（1025±11.18 nm）粒径（10%油相，90%水相）的乳液。采用体外消化模型检测游离脂肪酸（FFA）的释放和3-MCPD的生物可及性。细胞毒性测定采用细胞活力法，也称为（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四唑（MTT，噻唑蓝）法。细乳剂的FFA释放量最高（85.27±0.68%），3-MCPDE生物可及性最高（95.03±4.36%）。将柠檬油（一种不易消化的油）加入到精细乳剂中（最多30%），可减少30%的FFA释放。然而，生物可及性显著下降高达45%。细、中胶束期乳剂对成纤维细胞表现出细胞毒性，而增加颗粒大小和加入柠檬油可提高细胞活力。总之，(i)增加液滴大小和（ii）用不消化的替代品如柠檬油部分替代可消化的油是减轻乳化食品系统中3-MCPD吸收的有希望的策略。

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引用次数: 0