Food and Chemical Toxicology最新文献_第3页

Multi-matrix HPLC investigation of preservatives employing a recent validated method: A Monte Carlo simulation approach to health risks in Bangladeshi processed foods and healthcare

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2025-02-03 DOI: 10.1016/j.fct.2025.115282

Mohammad Nasir Uddin , Suman Das , Mohammad Rafiul Omar Khan Noyon , Md Samrat Mohay Menul Islam , Abu Saleh Mohammad Khaled , Md Ashraful Islam , Dipankar Chakraborty , Monir Uddin , Md Nurun Nabi , Sreebash Chandra Bhattacharjee

To determine the amounts of benzoic acid, sorbic acid, methylparaben, and propylparaben in an assortment of products, this study provides a validated HPLC-PDA method. Linearity, recovery, accuracy, precision, sensitivity, specificity, system suitability, and robustness were all examined throughout validation in compliance with ICH criteria. The method of measurement showed high reliability, precision, and linear calibration curves (5–50 mg/L) with correlation values over 0.999, demonstrating that it is suitable for consistent analysis. Reliability across various matrices was validated by robustness testing. Goods such as fruit juices, ketchup, cakes, herbal goods, and pharmaceuticals were subjected to health risk assessments including CDI, THQ, and HI. Significant sorbate and high benzoate levels, in particular in herbal products (up to 6636 mg/kg), were found in processed meals, while methylparaben surpassed the recommended limit in some herbal and pharmaceutical products. Levels of propylparaben remain low. Risk evaluations revealed that consumption of herbal products was the main cause of significant worry, especially for children with lower body weights. THQ levels below the threshold were found in Monte Carlo simulations (5th, median, and 95th percentiles), indicating that food preservatives provide little non-carcinogenic risk to the majority of the population.

{"title":"Multi-matrix HPLC investigation of preservatives employing a recent validated method: A Monte Carlo simulation approach to health risks in Bangladeshi processed foods and healthcare","authors":"Mohammad Nasir Uddin , Suman Das , Mohammad Rafiul Omar Khan Noyon , Md Samrat Mohay Menul Islam , Abu Saleh Mohammad Khaled , Md Ashraful Islam , Dipankar Chakraborty , Monir Uddin , Md Nurun Nabi , Sreebash Chandra Bhattacharjee","doi":"10.1016/j.fct.2025.115282","DOIUrl":"10.1016/j.fct.2025.115282","url":null,"abstract":"<div><div>To determine the amounts of benzoic acid, sorbic acid, methylparaben, and propylparaben in an assortment of products, this study provides a validated HPLC-PDA method. Linearity, recovery, accuracy, precision, sensitivity, specificity, system suitability, and robustness were all examined throughout validation in compliance with ICH criteria. The method of measurement showed high reliability, precision, and linear calibration curves (5–50 mg/L) with correlation values over 0.999, demonstrating that it is suitable for consistent analysis. Reliability across various matrices was validated by robustness testing. Goods such as fruit juices, ketchup, cakes, herbal goods, and pharmaceuticals were subjected to health risk assessments including CDI, THQ, and HI. Significant sorbate and high benzoate levels, in particular in herbal products (up to 6636 mg/kg), were found in processed meals, while methylparaben surpassed the recommended limit in some herbal and pharmaceutical products. Levels of propylparaben remain low. Risk evaluations revealed that consumption of herbal products was the main cause of significant worry, especially for children with lower body weights. THQ levels below the threshold were found in Monte Carlo simulations (5th, median, and 95th percentiles), indicating that food preservatives provide little non-carcinogenic risk to the majority of the population.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"197 ","pages":"Article 115282"},"PeriodicalIF":3.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254241","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

RIFM fragrance ingredient safety assessment, 4,5-dihydro-3(2H)thiophenone, CAS Registry Number 1003-04-9

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2025-02-03 DOI: 10.1016/j.fct.2025.115307

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

Oral exposure to nanoplastics altered lipid profiles in mouse intestine

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2025-02-02 DOI: 10.1016/j.fct.2025.115304

Sihuan Luo , Xiaomei Zhao , Yijin Wang , Miao Jiang , Yi Cao

The wide uses of plastics lead to nanoplastic exposure in reality. Previous studies reported that micro- and nano-plastics (MNPs) disrupted metabolism, but few studies investigated lipid profile changes. Hereby, we exposed mice to vehicles (control), 0.05 or 0.5 mg/kg 20 or 100 nm nanoplastics via gavage, once a day, for 14 days. Albeit no obvious tissue damage, lipidomics data revealed 76 up-regulated and 29 down-regulated lipid molecules in mouse intestines. Further analysis revealed that a number of up-regulated lipid molecules belong to glycerophospholipid (GP). Among GP, we noticed an up-regulation of 9 phosphatidylserine (PS) molecules, and we further verified the presence of autophagosomes and co-localization of typical autophagic lipolysis proteins in intestinal sections, as well as decreased lysosomal associated protein 2 (LAMP2) and increased adipose triglyceride lipase (ATGL) in intestinal homogenates, indicating perturbed autophagic pathway. The exposure also up-regulated 9 phosphatidylinositol (PI) molecules, and we verified a significant decrease of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), indicating altered PI3K-signaling pathway. Besides GP, nanoplastics also significantly up-regulated some sphingolipids (SP), such as ceramide (Cer), and some sterol lipids, such as cholesterol derivatives. Combined, these results suggested that oral exposure to nanoplastics altered lipid profiles and related signaling pathway in mouse intestines.

{"title":"Oral exposure to nanoplastics altered lipid profiles in mouse intestine","authors":"Sihuan Luo , Xiaomei Zhao , Yijin Wang , Miao Jiang , Yi Cao","doi":"10.1016/j.fct.2025.115304","DOIUrl":"10.1016/j.fct.2025.115304","url":null,"abstract":"<div><div>The wide uses of plastics lead to nanoplastic exposure in reality. Previous studies reported that micro- and nano-plastics (MNPs) disrupted metabolism, but few studies investigated lipid profile changes. Hereby, we exposed mice to vehicles (control), 0.05 or 0.5 mg/kg 20 or 100 nm nanoplastics via gavage, once a day, for 14 days. Albeit no obvious tissue damage, lipidomics data revealed 76 up-regulated and 29 down-regulated lipid molecules in mouse intestines. Further analysis revealed that a number of up-regulated lipid molecules belong to glycerophospholipid (GP). Among GP, we noticed an up-regulation of 9 phosphatidylserine (PS) molecules, and we further verified the presence of autophagosomes and co-localization of typical autophagic lipolysis proteins in intestinal sections, as well as decreased lysosomal associated protein 2 (LAMP2) and increased adipose triglyceride lipase (ATGL) in intestinal homogenates, indicating perturbed autophagic pathway. The exposure also up-regulated 9 phosphatidylinositol (PI) molecules, and we verified a significant decrease of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), indicating altered PI3K-signaling pathway. Besides GP, nanoplastics also significantly up-regulated some sphingolipids (SP), such as ceramide (Cer), and some sterol lipids, such as cholesterol derivatives. Combined, these results suggested that oral exposure to nanoplastics altered lipid profiles and related signaling pathway in mouse intestines.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"197 ","pages":"Article 115304"},"PeriodicalIF":3.9,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143163117","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

Chemical characterization, antibacterial and antifungal activity of honey pots and pollen pots obtained from the stingless bee Tetragonisca angustula (Latreille, 1811)

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2025-02-02 DOI: 10.1016/j.fct.2025.115305

Nair Silva Macêdo , Zildene de Sousa Silveira , Débora Menezes Dantas , Cristina Rodrigues dos Santos Barbosa , Antonia Thassya Lucas dos Santos , Thiago Araújo de Medeiros Brito , Josean Fechine Tavares , Débora Odília Duarte Leite , Priscilla Ramos Freitas Alexandre , José Galberto Martins da Costa , Cícera Datiane de Morais Oliveira-Tintino , Henrique Douglas Melo Coutinho , Maria Flaviana Bezerra Morais-Braga , Francisco Assis Bezerra da Cunha

This study aimed to determine the chemical composition of the ethanolic extracts of honey pots (EEHPTa) and pollen pots (EEPPTa) from the stingless bee Tetragonisca angustula, as well as to evaluate their antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans, and Candida tropicalis. The chemical composition was determined using HPLC-Q-TOF-MS/MS and HPLC-DAD, while antimicrobial assays were performed using the broth microdilution method. Eleven compounds were identified in EEHPTa and nine in EEPPTa, including cirsimaritin, 3ʹ-prenylnaringenin, xanthohumol, lespedezaflavanone B, and 19α-hydroxyursolic acid. The extracts enhanced the action of norfloxacin against S. aureus (MIC reduced from 256 to 128 μg/mL). With gentamicin, EEHPTa reduced the MIC from 17.95 to 11.31 μg/mL, while EEPPTa reduced it to 12.69 μg/mL. Only EEHPTa was effective with ampicillin, reducing the MIC from 71.83 to 31.7 μg/mL. Against P. aeruginosa, EEHPTa decreased the MIC of gentamicin from 8 to 4 μg/mL, whereas EEPPTa exhibited an antagonistic effect. For E. coli, only EEPPTa reduced the MIC from 64 to 57.01 μg/mL. EEHPTa exhibited lower IC₅₀ values against yeast (C. albicans: 65.47 μg/mL; C. tropicalis: 29.79 μg/mL) compared to EEPPTa (C. albicans: 820.7 μg/mL; C. tropicalis: 809.9 μg/mL). Both extracts enhanced the effect of fluconazole against C. albicans but showed no effect on the C. tropicalis strain. These findings highlight the therapeutic potential of the secondary metabolites in these extracts, reinforcing their importance in the development of new antimicrobial and antifungal strategies.

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引用次数: 0

Black phosphorus nanomaterials mediate size-dependent acute lung injury by promoting macrophage polarization 黑磷纳米材料通过促进巨噬细胞极化介导大小依赖性急性肺损伤。

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2025-02-01 DOI: 10.1016/j.fct.2024.115219

Mingtao Wu , Jie Zeng , Wanru Huang , Fengkai Ruan, Zhenghong Zuo, Liang Bu, Chengyong He

Black phosphorus nanomaterials (BPNM) exhibit excellent properties and potential applications in electronics, but workers may face inhalation exposure during BPNM production. In addition, there is a lack of biosafety assessments regarding respiratory exposure to BPNM of different sizes. In this study, we investigated the lung toxicity in mice exposed to 5, 50, 500 μg/kg of black phosphorus quantum dots (BPQDs) and black phosphorus nanosheet (BPNS) via single tracheal instillation. The average diameter of the BPQDs and BPNS were 13.48 ± 4.82 nm and 325.53 ± 165.17 nm, respectively. Twenty-four hours after exposure, both BPQDs and BPNS caused acute lung injury, characterized by bronchial wall thickening, alveolar collapse, increased lamellar bodies, and immune cell infiltration. BPNS exposure resulted in reduced gene expression of pulmonary surfactant proteins Spb and Spc. Additionally, both BPQDs and BPNS increased inflammatory factors gene expression and induced lung macrophages polarization, with BPNS demonstrating a more significant effect. This study is the first to show that BPQDs and BPNS induced acute lung injury and inflammation in mice, with BPNS being more toxic. These findings are crucial for enhancing the biosafety assessment of BPNM and advancing technologies to improve the safety of nanomaterials.

黑磷纳米材料（BPNM）具有优异的性能和在电子领域的潜在应用，但在生产过程中工人可能面临吸入暴露。此外，缺乏关于呼吸接触不同大小的BPNM的生物安全性评估。本实验研究了5、50、500 μg/kg黑磷量子点（BPQDs）和黑磷纳米片（BPNS）单次气管灌注对小鼠肺毒性的影响。bpqd和BPNS的平均直径分别为13.48±4.82 nm和325.53±165.17 nm。暴露24小时后，BPQDs和BPNS均可引起急性肺损伤，表现为支气管壁增厚、肺泡塌陷、板层体增多、免疫细胞浸润。BPNS暴露导致肺表面活性蛋白Spb和Spc基因表达降低。此外，BPQDs和BPNS均能增加炎症因子基因表达，诱导肺巨噬细胞极化，其中BPNS的作用更为显著。本研究首次证实BPQDs和BPNS诱导小鼠急性肺损伤和炎症，且BPNS毒性更大。这些发现对于加强BPNM的生物安全性评价和推进纳米材料的安全性研究具有重要意义。

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引用次数: 0

Single and combined effect of chrysin and N-acetylcysteine against deltamethrin exposure in rats 黄菊花素和n -乙酰半胱氨酸对溴氰菊酯暴露大鼠的单独和联合作用。

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2025-02-01 DOI: 10.1016/j.fct.2024.115191

Ahmet Eker , Gökhan Eraslan

Effects of chrysin and N-acetylcysteine on deltamethrin exposure in rats were investigated. Eighty male Wistar Albino rats, weighing between 150 and 200 g and aged 2–3 months, were used and evenly allocated into eight groups. The control group of rats received a corn oil vehicle. Chrysin (50 mg/kg.bw), N-acetylcysteine (50 mg/kg.bw), a combination of chrysin and N-acetylcysteine, deltamethrin (10 mg/kg.bw), deltamethrin combined with chrysin, deltamethrin combined with N-acetylcysteine, and a combination of deltamethrin, chrysin, and N-acetylcysteine were administered via oral gavage for a duration of 21 days. Tissue (liver, kidney, brain, testis, heart, lung) and blood of oxidative stress markers (MDA, NO, GSH, SOD, CAT, GSH-Px, GR, GST, G6PD), hepatic caspase 3, 9 and p53 protein levels, biochemical parameters (glucose, triglyceride, cholesterol, BUN, creatinine, uric acid, total protein, albumin, LDH, AST, ALT, ALP, PChE activities/levels), as well as rat body/organ weights and plasma/liver deltamethrin concentrations. The administration of chrysin and N-acetylcysteine independently did not alter the assessed parameters. Significant differences were observed in most parameters assessed in the deltamethrin-alone group compared to the control group, whereas the parameter values in the groups treated with chrysin, NAC, or their combination with deltamethrin were similar to those of the control.

研究了菊花素和n -乙酰半胱氨酸对大鼠溴氰菊酯暴露的影响。选用体重150 ~ 200 g、2 ~ 3月龄雄性Wistar白化大鼠80只，平均分为8组。对照组大鼠给予玉米油灌胃。菊素（50 mg/kg.bw）、n -乙酰半胱氨酸（50 mg/kg.bw）、菊素与n -乙酰半胱氨酸联用、溴氰菊酯（10 mg/kg.bw）、菊素与菊素联用、菊素与n -乙酰半胱氨酸联用、菊素与n -乙酰半胱氨酸联用、菊素与n -乙酰半胱氨酸联用、菊素与n -乙酰半胱氨酸联用，连续灌胃21 d。组织（肝、肾、脑、睾丸、心、肺）和血液中的氧化应激标志物（MDA、NO、GSH、SOD、CAT、GSH- px、GR、GST、G6PD），肝脏caspase 3、9和p53蛋白水平，生化参数（葡萄糖、甘油三酯、胆固醇、BUN、肌酐、尿酸、总蛋白、白蛋白、LDH、AST、ALT、ALP、PChE活性/水平），以及大鼠体/器官重量和血浆/肝脏溴氰菊酯浓度。单独给药菊花素和n -乙酰半胱氨酸没有改变评估参数。与对照组相比，单独使用溴氰菊酯组的大部分参数均有显著差异，而单独使用菊花素、NAC或与溴氰菊酯联用组的参数值与对照组相似。

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引用次数: 0

Exploring the therapeutic potential of lupeol: A review of its mechanisms, clinical applications, and advances in bioavailability enhancement 探索鹿皮醇的治疗潜力：其机制，临床应用和生物利用度提高的进展综述。

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2025-02-01 DOI: 10.1016/j.fct.2024.115193

Xia Luo , Ji Li , Zhifeng Cen , Gang Feng , Meiqi Hong , Lizhen Huang , Qinqiang Long

Lupeol, a naturally occurring triterpenoid, has garnered significant attention for its diverse range of biological activities and potential therapeutic applications. This comprehensive review delves into the various aspects of lupeol, including its sources, extraction methods, chemical characteristics, pharmacokinetics, safety evaluation, mechanisms of action, and applications in disease treatment. We highlight the compound's unique carbon skeleton and its role in inflammation regulation, antioxidant activity, and broad-spectrum antimicrobial effects. The review also underscores lupeol's potential in cancer therapy, cardiovascular protection, metabolic disease management, and wound healing. Furthermore, we discuss the challenges and future perspectives of lupeol's clinical application, emphasizing the need for further research to improve its bioavailability and explore its full therapeutic potential. The review concludes by recognizing the significance of lupeol in drug development and healthcare, with expectations for future breakthroughs in medical applications.

Lupeol是一种天然存在的三萜，因其多种生物活性和潜在的治疗应用而受到广泛关注。本文对芦皮醇的来源、提取方法、化学特性、药代动力学、安全性评价、作用机制及其在疾病治疗中的应用等方面进行了综述。我们强调该化合物独特的碳骨架及其在炎症调节、抗氧化活性和广谱抗菌作用中的作用。该综述还强调了lupeol在癌症治疗、心血管保护、代谢性疾病管理和伤口愈合方面的潜力。此外，我们讨论了lupeol临床应用的挑战和未来前景，强调需要进一步研究以提高其生物利用度并发掘其全部治疗潜力。综述总结了lupeol在药物开发和医疗保健方面的重要意义，并对未来在医疗应用方面的突破进行了展望。

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引用次数: 0

From food-to-human microplastics and nanoplastics exposure and health effects: A review on food, animal and human monitoring data 从食物到人类的微塑料和纳米塑料暴露及其健康影响：对食品、动物和人类监测数据的审查。

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2025-02-01 DOI: 10.1016/j.fct.2024.115209

Flavia Ruggieri , Beatrice Battistini , Angela Sorbo , Marta Senofonte , Veruscka Leso , Ivo Iavicoli , Beatrice Bocca

This review figures out the overall status on the presence of microplastics (MPs) and nanoplastics (NPs) in food and their bioaccumulation in animal and human tissues, providing critical insights into possible human health impacts. Data are discussed on both in-vivo and ex-vivo animal and human studies, and the role of physicochemical properties in determining the biological fate and toxicological effects of MPs and NPs. Particular attention is given to dietary exposure assessments, specifically evaluating daily intake through the consumption of contaminated food items. The current limitations in the body of knowledge and some considerations for future assessments are also reported. Overall, there is a pressing need to establish more robust biomarker research and develop standardized methodologies, for a better understanding of MPs and NPs fate and associated effects in more realistic scenarios for their safe consumption. The review underscores the importance of integrating the human biomonitoring into monitoring programs and interdisciplinary research to ultimately inform on MPs and NPs real burden in the human body.

本文综述了食品中微塑料（MPs）和纳米塑料（NPs）存在的总体状况及其在动物和人体组织中的生物积累，为可能对人类健康产生的影响提供了重要见解。讨论了体内和离体动物和人体研究的数据，以及物理化学性质在决定MPs和NPs的生物学命运和毒理学效应中的作用。对饮食暴露评估给予了特别关注，特别是评估通过食用受污染食品而获得的每日摄入量。还报告了目前知识体系的局限性和对未来评估的一些考虑。总的来说，迫切需要建立更强大的生物标志物研究和开发标准化的方法，以便更好地了解MPs和NPs的命运和在更现实的情况下安全食用的相关影响。该综述强调了将人体生物监测纳入监测计划和跨学科研究的重要性，以最终了解MPs和NPs在人体中的真正负担。

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引用次数: 0

Dietary exposure to mixtures of chemicals in the first year of life and allergic and respiratory diseases up to 8 years in the French EDEN mother-child cohort 在法国EDEN母婴队列中，在生命的第一年饮食暴露于化学混合物以及长达8年的过敏和呼吸系统疾病。

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2025-02-01 DOI: 10.1016/j.fct.2024.115167

Manel Ghozal , Rosalie Delvert , Karine Adel-Patient , Muriel Tafflet , Isabella Annesi-Maesano , Amélie Crépet , Véronique Sirot , Marie Aline Charles , Barbara Heude , Manik Kadawathagedara , Blandine de Lauzon-Guillain

Exposure to environmental chemicals has been associated with higher risk of childhood allergies. This study aimed to examine the association between infant's dietary exposure to mixtures of chemicals and allergic and respiratory multimorbidity in childhood.

Dietary exposures were assessed at 8 and 12 months in 724 and 745 children of the EDEN cohort. Allergic and respiratory multimorbidity clusters were identified using latent class analyses. Associations between dietary exposure to mixtures of chemicals and allergic clusters were assessed by adjusted multinomial logistic regressions.

At 8 months, higher exposure to a mixture of furans, trace elements, dioxins and PAHs was positively associated with the “asthma only” cluster, while moderate exposure to a mixture of PAHs, pesticides, PCBs and acrylamide was negatively associated with this cluster. A mixture of PCBs and BFRs was positively associated with the “multi-morbidity” cluster. Exposure to a mixture of pesticides and trace elements was positively associated with the “allergy without asthma” cluster. At 12-months, higher exposure to a mixture of trace elements and pesticides was positively associated with “multi-morbidity” cluster.

The differences in findings between the two ages suggest the need for further studies to explore this critical window of chemical exposure and its impact on children's health.

接触环境中的化学物质会增加儿童过敏的风险。本研究旨在研究婴儿饮食中接触化学物质混合物与儿童时期过敏和呼吸道疾病之间的关系。在EDEN队列中，724名和745名儿童在8个月和12个月时进行了饮食暴露评估。使用潜在分类分析确定过敏性和呼吸性多发病群。通过调整后的多项逻辑回归评估饮食中化学物质混合物暴露与过敏簇之间的关系。在8个月时，较高程度地暴露于呋喃、微量元素、二恶英和多环芳烃的混合物与“仅哮喘”群呈正相关，而中度暴露于多环芳烃、农药、多氯联苯和丙烯酰胺的混合物与这一群呈负相关。多氯联苯和BFRs的混合与“多发病”群呈正相关。暴露于农药和微量元素的混合物与“过敏无哮喘”群呈正相关。在12个月时，较高的微量元素和农药混合物暴露与“多发病”群集呈正相关。这两个年龄段研究结果的差异表明，需要进一步的研究来探索化学物质暴露的这一关键窗口期及其对儿童健康的影响。

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引用次数: 0

Cathinone metabolism and biliary excretion in an ex-vivo pig liver model: Example of 4-Cl-PVP and eutylone 离体猪肝模型中卡西酮代谢和胆汁排泄：以4-Cl-PVP和真tyone为例。

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology

Pub Date : 2025-02-01 DOI: 10.1016/j.fct.2024.115217

Romain Pelletier , Brendan Le Daré , Thomas Kerforne , Nicolas Patou Parvedy , Florian Lemaitre , Camille Tron , Kevin Maunand , Anne Corlu , Isabelle Morel , Michel Rayar , Thomas Gicquel

Objective

Recently, the pig liver model perfused ex vivo using a normothermic machine perfusion (NMP) has been proposed as a suitable model to study xenobiotic metabolism and biliary excretion. The aim of our study is to describe the metabolism of NPS such as cathinones (with a focus on 4-Cl-PVP and eutylone) in blood and bile, using a normothermic perfused pig liver model.

Methods

Livers (n = 4) from male large white pigs, 3–4 months of age and weighing approximately 75–80 kg, were harvested and reperfused onto an NMP (LiverAssist®, XVIVO) using autologous whole blood at 38 °C. 4-Cl-PVP and eutylone were administered as a bolus in the circulating blood at T0 with the aim of achieving a concentration of 1 μg/mL in the reperfusion system. The assays were carried out on plasma and bile between 0 and 120 min after cathinone administration using an targeted and untargeted approaches based on liquid chromatography coupled with high resolution mass spectrometry (Q-Exactive Thermo Scientific®).

Results

In plasma, the concentration of 4-Cl-PVP and eutylone decreased rapidly with elimination half-lives of 4 min and 0.25 min, respectively. Their phase I and phase II metabolites were detected in plasma as early as 1 min. In bile, 4-Cl-PVP and eutylone were detected with maximum intensity between 0 and 30 min post-administration, and the main metabolites found in plasma were found in bile. Phase II derivatives showed increasing biliary excretion over time up to 120 min.

Conclusion

The pig liver model perfused ex vivo using an NMP represent a promising model in pharmaco-toxicology, particularly for toxicokinetic investigations of cathinones. This model may be of interest in the absence of authentic cases of cathinone consumption or other NPS consumption to identify relevant metabolites consumption markers. In addition, the possibility of collecting bile in this model represents an additional advantage for studying biliary excretion of NPS and their metabolites in forensic toxicology.

目的：近年来，采用恒温机器灌注（NMP）体外灌注猪肝模型被提出作为研究外源代谢和胆汁排泄的合适模型。我们的研究目的是描述NPS如卡西酮（重点是4-Cl-PVP和真tyone）在血液和胆汁中的代谢，使用恒温灌注猪肝模型。方法：取3-4月龄、体重约75- 80kg的雄性大型白猪肝脏（n = 4），在38°C下用自体全血再灌注到NMP （LiverAssist®，XVIVO）中。4-Cl-PVP和真tylone在T0时给药于循环血液中，再灌注系统浓度达到1 μg/mL。在卡西酮给药后0 - 120分钟内，使用基于液相色谱-高分辨率质谱（Q-Exactive Thermo Scientific®）的靶向和非靶向方法对血浆和胆汁进行检测。结果：血浆中4- cl - pvp和真tylone浓度迅速下降，消除半衰期分别为4 min和0.25 min。它们的I期和II期代谢物早在给药后1 min就可在血浆中检测到。在给药后0 ~ 30 min， 4-Cl-PVP和真tylone的检测强度最大，血浆中主要代谢物在胆汁中检测到。结论：用NMP体外灌注猪肝模型是一种很有前途的药物毒理学模型，特别是在卡西酮的毒代动力学研究中。在缺乏卡西酮消费或其他NPS消费的真实案例中，该模型可能对识别相关代谢物消费标记物感兴趣。此外，在该模型中收集胆汁的可能性为法医毒理学研究NPS及其代谢物的胆汁排泄提供了额外的优势。

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引用次数: 0