Toxicology Reports最新文献

Heated tobacco product aerosol emission compared to cigarette smoke: A scoping review 加热烟草制品气溶胶排放与香烟烟雾的比较：范围综述

Q1 Environmental Science

Toxicology Reports

Pub Date : 2026-01-27 DOI: 10.1016/j.toxrep.2026.102209

Stefano Bellosta , Alberto Corsini , Gabriele Catena

Heated tobacco products (HTPs) are promoted as reduced-risk alternatives to combustible tobacco cigarettes (TCs), yet toxicant exposure reduction and associated health benefits remain uncertain. We evaluated preclinical and interventional clinical studies comparing HTPs with TCs, focusing on aerosol composition, toxicological exposure, and harm biomarkers. A systematic PubMed search identified 1105 peer-reviewed articles published between January 2017 and October 2024. Studies were screened using validated MeSH terms and commercial brand names. Forty-three articles met inclusion criteria, reporting standardized aerosol characterization, in vivo or in vitro toxicology, or biomarker assessments. Data were extracted by independent reviewers. Clinical studies were categorized by exposure duration (acute, short, medium, or long-term). HTP aerosols contained up to 95 % lower levels of regulated toxicants and exhibited substantially reduced mutagenic, toxic, genotoxic, carcinogenic, and proinflammatory activities (85–95 % reduction) compared with TC smoke. Among 24 interventional clinical studies, 20 reported 40–97 % reductions in toxicant biomarkers of exposure (BoE)—including tobacco-specific nitrosamines, carboxyhemoglobin, volatile organic compounds, and mutagenic metabolites—among smokers who switched completely to HTPs. These reductions were observed from minutes to 24 months and occurred largely independently of systemic nicotine concentrations. Four independent studies reported no significant improvement or detected adverse effects. International health authorities acknowledge that HTP aerosols contain carcinogenic and mutagenic constituents, albeit at substantially lower concentrations than TC smoke, suggesting a potential—though unconfirmed—risk reduction. Overall, HTP users experience lower toxicant exposure than TC smokers; however, additional independent, long-term investigations are required to determine the actual health impact of sustained HTP use.

加热烟草制品被宣传为可燃烟草卷烟（tc）的低风险替代品，但减少毒物接触和相关的健康益处仍不确定。我们评估了比较HTPs和tc的临床前和介入性临床研究，重点关注气溶胶成分、毒理学暴露和危害生物标志物。一项系统的PubMed搜索确定了2017年1月至2024年10月期间发表的1105篇同行评议文章。研究使用经过验证的MeSH术语和商业品牌名称进行筛选。43篇文章符合纳入标准，报告了标准化的气溶胶特性、体内或体外毒理学或生物标志物评估。数据由独立审稿人提取。临床研究按暴露时间（急性、短期、中期或长期）进行分类。与TC烟雾相比，HTP气溶胶含有的受管制毒物含量降低了95% %，并表现出显著降低的致突变、毒性、基因毒性、致癌和促炎活性（降低85 - 95% %）。在24项干介性临床研究中，20项报告在完全转向HTPs的吸烟者中，毒性暴露生物标志物（BoE）减少了40 - 97% %，包括烟草特异性亚硝胺、羧化血红蛋白、挥发性有机化合物和致突变代谢物。从几分钟到24个月观察到这些减少，并且在很大程度上与全身尼古丁浓度无关。四项独立研究报告没有显著改善或发现不良反应。国际卫生当局承认，高温高压气溶胶含有致癌和致突变成分，尽管其浓度远低于高温高压烟雾，这表明有潜在的（尽管未经证实的）风险降低。总体而言，HTP使用者比TC吸烟者接触到的有毒物质更少；然而，需要进行额外的独立长期调查，以确定持续使用HTP对健康的实际影响。

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引用次数: 0

Polycyclic aromatic hydrocarbon exposure in battlefield and beyond: Implications for environmental- and human health 战场内外的多环芳烃暴露：对环境和人类健康的影响

Q1 Environmental Science

Toxicology Reports

Pub Date : 2026-01-24 DOI: 10.1016/j.toxrep.2026.102208

Markis’ D. Hamilton , Ritu Chauhan , Anthony E. Archibong , Aramandla Ramesh

Polycyclic aromatic hydrocarbons (PAHs) are combustion pollutants that are released into the environment through natural events and anthropogenic activities. Exposures to PAHs occur in military personnel during garrison (non-combat) and active deployment (combat) environments. Exposures that occur at low levels during deployment could lead to health issues, post-deployment. A scoping review was conducted to address the pathways of exposure, and the adverse effects caused by PAHs in active-duty personnel and veterans. Out of 50,171 scientific publications screened from 5 databases, 296 studies were identified that focused on the relationship between exposure to PAHs from various point sources and debilitating health issues reported in veterans. The findings revealed that in combat conditions, PAHs are released into the environment through explosions caused by bombing, artillery fire, and missile attacks on military installations, petrochemical industries, oil well fires set by saboteurs, and burn pits used to incinerate ammunition waste and military base refuse. Significant exposure of troops to PAHs occurred during active combat in the Operation Desert Shield, Operation Desert Storm, and Operation Enduring Freedom campaigns launched against hostile forces. The PAH releases contaminated not only the affected service personnel and staff, but also the surrounding environment. The coastal environment, including its flora and fauna, were affected by oil tanker fires, petroleum storage tanks that caught fire during conflict and subsequent release of PAHs into the marine environment. The human health effects resulting from PAH exposures included severe lung-, kidney-, and reproductive dysfunctions, as well as an increased risk of cancer, mostly manifested in Veterans as part of the Gulf War Syndrome. The Exposome approach utilizing the omics-based biomarkers to characterize individual service member profile with wearable monitors (wrist bands and sensors) to characterize the external environment when combined with biomonitoring studies holds significant promise for treatment of troops during combat and post deployment.

多环芳烃（PAHs）是通过自然事件和人为活动释放到环境中的燃烧污染物。军事人员在驻军（非战斗）和积极部署（战斗）环境中暴露于多环芳烃。部署期间低水平的暴露可能导致部署后的健康问题。针对多环芳烃在现役人员和退伍军人中的暴露途径和不良影响进行了范围审查。从5个数据库筛选的50,171份科学出版物中，确定了296项研究，重点关注从各种点源接触多环芳烃与退伍军人报告的衰弱健康问题之间的关系。调查结果显示，在作战条件下，多环芳烃通过轰炸、炮击和导弹袭击军事设施、石化工业、破坏分子纵火油井以及焚烧弹药废物和军事基地垃圾的火坑释放到环境中。在“沙漠盾牌”行动、“沙漠风暴”行动和对抗敌对势力的“持久自由”行动中，部队大量暴露于多环芳烃。多环芳烃的释放不仅污染了受影响的服务人员和工作人员，而且污染了周围的环境。沿海环境，包括其动植物，受到油轮火灾、冲突期间着火的石油储罐以及随后向海洋环境释放多环芳烃的影响。多环芳烃暴露对人体健康的影响包括严重的肺、肾和生殖功能障碍，以及癌症风险的增加，主要表现在退伍军人身上，是海湾战争综合症的一部分。暴露方法利用基于组学的生物标志物来表征单个服务成员的特征，可穿戴监视器（腕带和传感器）来表征外部环境，与生物监测研究相结合，为战斗期间和部署后的部队治疗带来了重大希望。

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引用次数: 0

Acute and subacute oral toxicity assessment of Karanjin in Sprague Dawley rats 卡兰金对大鼠急性和亚急性口服毒性评价

Q1 Environmental Science

Toxicology Reports

Pub Date : 2026-01-16 DOI: 10.1016/j.toxrep.2026.102207

Natasha Sura Anak Lubau , Vinod Balasubramaniam , Christina Gertrude Yap , Alina Arulsamy , Vetriselvan Subramaniyan

Karanjin (KRN) is a benzofuran flavonoid derived from Pongamia pinnata seeds, known for its antihyperglycemic and anti-inflammatory properties. Despite its traditional use, comprehensive toxicological data are limited. This study evaluated the acute and subacute oral toxicity of KRN in Sprague Dawley rats. In the acute study, single doses of 5, 500, or 2000 mg/kg were administered, and animals were observed for 14 days. In the subacute study, daily doses of 5, 50, or 250 mg/kg were given for 28 days. Clinical signs, body weight, food and water intake were monitored throughout. At termination, organs (liver, kidney, heart, etc.) were weighed, blood was analysed for biochemical parameters (ALT, AST, ALP, total protein, albumin, lipids), and tissues were examined histopathologically. No mortality or treatment-related clinical signs occurred at any dose. Body weight, food/water intake, and organ weights did not differ significantly between treated and control groups. Serum biochemical values remained within normal limits, showing only minor, non-dose-dependent variations. Histopathology revealed normal architecture of major organs without evidence of necrosis, inflammation, or degeneration. These findings demonstrate a wide margin of safety for oral KRN and support its potential for further pharmacological development.

Karanjin （KRN）是一种苯并呋喃类黄酮类化合物，从羽状石榴籽中提取，以其抗高血糖和抗炎特性而闻名。尽管其传统用途，但全面的毒理学数据有限。本研究评价了KRN对大鼠的急性和亚急性口服毒性。在急性研究中，单次给药5500 mg/kg或2000 mg/kg，观察动物14天。在亚急性研究中，每天给药5、50或250 mg/kg，持续28天。在整个过程中监测临床症状、体重、食物和水的摄入量。终止时，称重各器官（肝、肾、心等），分析血液生化参数（ALT、AST、ALP、总蛋白、白蛋白、脂质），并对组织进行组织病理学检查。在任何剂量下均未发生死亡或与治疗相关的临床症状。治疗组和对照组的体重、食物/水摄入量和器官重量没有显著差异。血清生化值保持在正常范围内，仅显示轻微的非剂量依赖性变化。组织病理学显示主要器官结构正常，无坏死、炎症或变性。这些发现表明口服KRN具有广泛的安全性，并支持其进一步药理开发的潜力。

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引用次数: 0

Genotoxicity risk assessment of a 7-hydroxymitragynine-enriched Kratom preparation: An integrated in silico and in vitro approach 富含7-羟基米特拉甘氨酸的Kratom制剂的遗传毒性风险评估：一种集成的体外和体外方法

Q1 Environmental Science

Toxicology Reports

Pub Date : 2026-01-14 DOI: 10.1016/j.toxrep.2026.102206

Nathaphat Harnkit , Tiyanee Sahad , Ittiya Noonate , Phatiphan Primpai , Sarayut Radapong , Weerachai Pipatrattanaseree , Pornchai Sincharoenpokai , Pramote Chamnanpuen

The increasing global use of Mitragyna speciosa (Kratom) necessitates a thorough safety assessment, particularly regarding the genotoxic potential of its key alkaloids. This study employed an integrated in silico and in vitro approach to evaluate the genotoxicity of a well-characterized, semi-synthetically enhanced Kratom preparation (SKP) enriched in 7-hydroxymitragynine (7-OHMG; 56.31 % of total composition). Computational predictions using the OECD QSAR Toolbox and VEGA-QSAR platform indicated a lack of genotoxic activity for the major Kratom alkaloids (mitragynine, paynantheine, speciogynine, 7-hydroxymitragynine, and speciociliatine) across various in vitro and in vivo endpoints. However, several DNA-binding structural alerts were identified, particularly under metabolic activation, and prediction reliability ranged from low to moderate. To empirically verify these findings, an in vitro cytokinesis-block micronucleus (CBMN) assay was conducted in human TK6 cells following OECD Test Guideline 487. The extract induced concentration-dependent cytotoxicity. A statistically significant increase in micronucleus frequency was observed only at the highest concentration tested (125 µg/mL) under short-term (4 h) exposure conditions, both with and without S9 metabolic activation. Excessive cytotoxicity prevented analysis at high concentrations during long-term (24 h) exposure. Importantly, a complementary bacterial reverse mutation assay (Ames test) conducted on the identical extract showed no mutagenic activity up to 5000 µg/plate across five strains. In conclusion, while a weak positive chromosomal effect was noted at a highly cytotoxic concentration, the overall weight of evidence—including negative in silico predictions, negative Ames results, and limited in vitro micronucleus response—suggests that this 7-OHMG-enriched Kratom preparation does not present a significant genotoxic hazard under the conditions tested. This study underscores the value of a combined computational and experimental workflow for the robust genotoxicity assessment of complex natural products.

随着米特拉基纳（Kratom）在全球的使用日益增加，需要对其进行彻底的安全性评估，特别是对其主要生物碱的遗传毒性潜力进行评估。本研究采用硅内和体外结合的方法，对一种表征良好、富含7-羟基米特ragynine （7-OHMG；占总成分56.31 %）的半合成增强Kratom制剂（SKP）的遗传毒性进行了评价。使用OECD QSAR工具箱和VEGA-QSAR平台的计算预测表明，Kratom主要生物碱（米特拉吉碱、paynantheine、特特拉吉碱、7-羟基米特拉吉碱和特特拉吉碱）在各种体外和体内终点缺乏遗传毒性活性。然而，几个dna结合结构警报被确定，特别是在代谢激活下，预测可靠性范围从低到中等。为了从经验上验证这些发现，根据OECD试验指南487，在人TK6细胞中进行了体外细胞动力学阻断微核（CBMN）测定。提取物诱导浓度依赖性细胞毒性。在短期（4 h）暴露条件下，无论是否有S9代谢激活，仅在最高浓度（125µg/mL）下观察到微核频率有统计学意义的增加。在长期（24 h）暴露期间，过量的细胞毒性阻止了高浓度的分析。重要的是，在相同的提取物上进行的互补细菌反向突变试验（Ames试验）显示，在5000 μ g/板的情况下，5株菌株没有诱变活性。总之，虽然在高细胞毒性浓度下发现了微弱的阳性染色体效应，但证据的总体重量-包括阴性的硅预测，阴性的Ames结果和有限的体外微核反应-表明，在测试条件下，这种富含7- ohmg的Kratom制剂不存在显著的遗传毒性危害。这项研究强调了计算和实验相结合的工作流程对复杂天然产物的强大遗传毒性评估的价值。

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引用次数: 0

Phytochemical composition and anti-Alzheimer potential of medicinal plants from Central and West Africa: Systematic review 中非和西非药用植物的化学成分和抗阿尔茨海默病潜能：系统综述

Q1 Environmental Science

Toxicology Reports

Pub Date : 2026-01-14 DOI: 10.1016/j.toxrep.2026.102205

Protais Mukunzi , Ben Shalom Byishimo , Ekom Monday Etukudo , Hyppolyte Iradukunda , Darius Benimana , Ibe Michael Usman , Augustin Oviosun , Comfort Ojochenemi Usman , David Ikwuka , Wusa Makena , Victor Bassey Archibong

In recent time, the use of medicinal plants in the management of human disease conditions has gained immense attention. The aim of the present review was to explore the phytochemical composition and anti-Alzheimer potential of medicinal plants from Central and West Africa. A structured systematic approach was used to conduct the present systematic review of articles. Scopus, PubMed, and Web of Science were searched using the following search terms combined by Boolean operators: (“Alzheimer’s disease” OR “Neurodegenerative disease” OR "Nervous system diseases") AND (“Extract” OR "herbs" OR “Plant”) AND (“West Africa” OR “Central Africa” OR “Africa”) on the 6th of July 2024 without any filters. Following the conclusion of the title, abstract, and full text screening, only 13 articles were included. Most of the included studies (10/13, 77 %) were conducted between 2014 and 2024. Geographically, 9 (69 %) studies were conducted in Nigeria. Plants identified in the present study include: Solanum macrocarpon, Solanum nigru, Pteleopsis suberosa, Macrosphyra longistyl, Beta vulgaris, Persea americana, Syzygium aromaticum, Citrullus lanatus, Cucumeropsis mannii, Lagenaria siceraria, Achyranthes aspera Linn., Tithonia diversifolia. These plants were found to contain Luteolin, Catechin, Decanoic acid methyl ester, 11,14-Eicosadienoic acid methyl ester, Caffeic acid, Syringic acid, Azelaic acid. The plant-derived phytochemicals were reported to modulate critical Alzheimer’s disease (AD) pathways, notably oxidative stress, acetylcholinesterase (AChE) inhibition, and neuroinflammation. In conclusion, Central and West African medicinal plants represent a rich reservoir of multifunctional neuroprotective metabolites capable of targeting diverse AD pathways.

近年来，药用植物在人类疾病状况管理中的应用获得了极大的关注。本综述旨在探讨中非和西非药用植物的植物化学成分及其抗阿尔茨海默病的潜力。采用结构化的系统方法对文章进行系统评价。Scopus， PubMed和Web of Science在2024年7月6日使用布尔运算符组合的以下搜索词进行搜索：（“阿尔茨海默病”或“神经退行性疾病”或“神经系统疾病”）和（“提取物”或“草药”或“植物”）和（“西非”或“中非”或“非洲”），没有任何过滤器。在结束题目、摘要和全文筛选之后，只有13篇文章被纳入。大多数纳入的研究（10/13,77 %）是在2014 - 2024年间进行的。从地理上看，在尼日利亚进行了9项（69 %）研究。本研究鉴定的植物包括：大龙葵、黑龙葵、羽绒拟南芥、长柱大龙葵、甜菜、美洲波斯、香薷、瓜柳、甘露黄瓜、木犀草、牛膝牛膝。，金银花。这些植物含有木犀草素、儿茶素、癸酸甲酯、11,14-二十二烯酸甲酯、咖啡酸、丁香酸、壬二酸。据报道，植物源性植物化学物质可调节阿尔茨海默病（AD）的关键途径，特别是氧化应激、乙酰胆碱酯酶（AChE）抑制和神经炎症。综上所述，中非和西非药用植物具有丰富的多功能神经保护代谢物，能够靶向不同的AD通路。

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引用次数: 0

Azilsartan as a novel anti-ferriptotic agent via the upregulation of the Nrf2/HO-1/SLC7A11/GPX4 axis and downregulation of inflammatory pathways in folic acid-induced acute kidney injury in male mice 阿兹沙坦通过上调叶酸诱导的雄性小鼠急性肾损伤的Nrf2/HO-1/SLC7A11/GPX4轴和下调炎症通路，作为一种新型抗铁肽剂

Q1 Environmental Science

Toxicology Reports

Pub Date : 2026-01-08 DOI: 10.1016/j.toxrep.2026.102204

Elaf Mahmood Shihab , Saba Naseer Abbas , Saja Majeed Shareef , Rana Jawad Hasan , Khulood Majid Alsaraf , Hayder Adnan Fawzi

Purpose

Azilsartan, a unique angiotensin II receptor blocker (ARB) with an oxo-oxadiazole ring, exhibits antioxidant and anti-inflammatory properties, but its role in ferroptosis-mediated AKI remains unexplored. This study investigates whether azilsartan protects against FA-induced AKI in male mice by attenuating ferroptosis, modulating iron metabolism, and suppressing inflammatory signaling.

Methods

42 male C57BL/6 J mice were randomized into six groups: control, FA-induced AKI, three azilsartan doses (1, 3, 5 mg/kg), and ferrostatin-1 (Fer-1) as a positive control. Azilsartan or Fer-1 was administered for 7 days before FA injection (250 mg/kg, i.p.) and continued for 3 days post-induction. Renal function (serum urea, creatinine), ferroptosis markers (GPX4, MDA, Nrf2, SLC7A11, HO-1), iron-handling proteins (ferritin, TfR1), inflammatory mediators (TNF-α, NF-κB p65), and histopathology were assessed.

Results

FA-AKI caused marked renal dysfunction, elevated KIM-1, lipid peroxidation, depletion of GPX4, downregulation of Nrf2/HO-1/SLC7A11 and TfR1, reduction of transferrin levels, and inflammatory activation. Azilsartan improved renal function and histology in a dose-dependent manner, restored GPX4, reduced MDA, upregulated Nrf2/HO-1/SLC7A11 and TfR1, increased ferritin levels, and suppressed TNF-α/NF-κB. High-dose azilsartan achieved effects comparable to those of Fer-1.

Conclusion

Azilsartan confers potent protection against FA-induced AKI by activating the Nrf2/HO-1/SLC7A11/GPX4 axis, reducing lipid peroxidation, normalizing iron metabolism, and attenuating inflammation. These findings support azilsartan’s potential as a repurposed therapy for ferroptosis-driven renal injury.

目的阿兹沙坦是一种独特的血管紧张素II受体阻滞剂（ARB），具有氧-恶二唑环，具有抗氧化和抗炎特性，但其在铁中毒介导的AKI中的作用尚不清楚。本研究探讨阿齐沙坦是否通过减轻铁下垂、调节铁代谢和抑制炎症信号传导来预防fa诱导的雄性小鼠AKI。方法42只雄性C57BL/6 J小鼠随机分为对照组、fa诱导AKI组、阿齐沙坦3个剂量组（1、3、5 mg/kg）和他汀铁素-1 （fe -1）阳性对照组。阿齐沙坦或fe -1在FA注射前给予7天（250 mg/kg, ig），诱导后持续3天。评估肾功能（血清尿素、肌酐）、上铁标志物（GPX4、MDA、Nrf2、SLC7A11、HO-1）、铁处理蛋白（铁蛋白、TfR1）、炎症介质（TNF-α、NF-κB p65）和组织病理学。结果fa - aki引起明显的肾功能障碍、kim1升高、脂质过氧化、GPX4缺失、Nrf2/HO-1/SLC7A11和TfR1下调、转铁蛋白水平降低和炎症激活。阿兹沙坦以剂量依赖的方式改善肾功能和组织学，恢复GPX4，降低MDA，上调Nrf2/HO-1/SLC7A11和TfR1，升高铁蛋白水平，抑制TNF-α/NF-κB。大剂量阿兹沙坦的效果与fe -1相当。结论阿兹沙坦通过激活Nrf2/HO-1/SLC7A11/GPX4轴，减少脂质过氧化，使铁代谢正常化，减轻炎症，对fa诱导的AKI具有有效的保护作用。这些发现支持阿兹沙坦作为铁中毒所致肾损伤的再用途治疗的潜力。

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引用次数: 0

Toxicity and health effects of delta-8, delta-9, and delta-10-tetrahydrocannabinol and unregulated cannabinoids in vaping products 电子烟产品中δ -8、δ -9和δ -10四氢大麻酚和不受管制的大麻素的毒性和健康影响

Q1 Environmental Science

Toxicology Reports

Pub Date : 2026-01-08 DOI: 10.1016/j.toxrep.2026.102202

Karen Lin, Yehao Sun, Rhea Raghu, Parth Suharu, Felix Effah, Irfan Rahman

Hemp-derived cannabinoids (CBDs) such as Δ8- and Δ10-tetrahydrocannabinol (THC) in cannabis e-cigarettes have been growing in popularity among youth, causing great concern for their health effects. Previous novel lung injury outbreaks, such as E-cigarette or Vaping Use-Associated Lung Injury (EVALI), were associated with the rising use of e-cigarettes and vaping products. Toxicological studies have revealed that chronic exposure to cannabis vapor can cause adverse brain and pulmonary effects. Hemp products are classified as cannabis and set a limit of no more than 0.3 % Δ9-THC, while products containing more than 0.3 % are defined as ‘marijuana.’ This has led to the proliferation of hemp-derived intoxicating cannabinoids, such as Δ8- and Δ10-THC, in addition to cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), and Δ9-THC appearing in combination products. CBD frequently serves as a significant component of hemp-derived formulations, making it a central consideration for toxicological and regulatory evaluation as well. This phenomenon poses significant health risks to youth because these newer THC isomers and products are currently unregulated and not well-researched, yet they are still widely available. Therefore, we have examined the pharmacology, toxicity, potential therapeutic uses and possible health risks of several THC and hemp-derived cannabinoids. This review draws insightful highlights to the public health consequences of secondary exposures to CBD and THC, and their molecular mechanisms of action. It underscores the urgency for a regulatory oversight over unregulated cannabinoid markets to prevent toxicity of vaping-related health crises and other rapidly emerging cannabis health disorders, like the cannabinoid hyperemesis syndrome (CHS).

大麻电子烟中的大麻衍生大麻素（cbd），如Δ8-和Δ10-tetrahydrocannabinol (THC)，在年轻人中越来越受欢迎，引起了人们对其健康影响的极大关注。以前新型肺损伤的爆发，如电子烟或电子烟使用相关肺损伤（EVALI），与电子烟和电子烟产品使用的增加有关。毒理学研究表明，长期接触大麻蒸汽会对大脑和肺部造成不良影响。大麻产品被归类为大麻，并设定了不超过0.3 % Δ9-THC的限制，而含有超过0.3 %的产品则被定义为“大麻”。“这导致了大麻衍生的令人陶醉的大麻素的增殖，除了大麻二酚（CBD）、大麻酚（CBN）、大麻二酚（CBG）和Δ9-THC出现在组合产品中，还包括Δ8-和Δ10-THC。”CBD经常作为大麻衍生制剂的重要组成部分，使其成为毒理学和监管评估的中心考虑因素。这一现象给年轻人带来了重大的健康风险，因为这些较新的四氢大麻酚异构体和产品目前不受监管，也没有得到充分的研究，但它们仍然广泛存在。因此，我们研究了几种四氢大麻酚和大麻衍生大麻素的药理学、毒性、潜在治疗用途和可能的健康风险。这篇综述对二次暴露于CBD和THC的公共卫生后果及其分子作用机制进行了有见地的强调。它强调了对不受监管的大麻素市场进行监管的紧迫性，以防止与电子烟相关的健康危机和其他迅速出现的大麻健康疾病的毒性，如大麻素剧吐综合征（CHS）。

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引用次数: 0

Acute polyneuropathy associated with Kambo poisoning: An unusual case report 急性多神经病变与康博中毒：一个不寻常的病例报告

Q1 Environmental Science

Toxicology Reports

Pub Date : 2026-01-05 DOI: 10.1016/j.toxrep.2026.102200

Julio César Mantilla-Pardo , Juan David García-Valencia , Juan Pablo Fernández-Cubillos

Kambo is a natural secretion obtained from the Amazonian frog Phyllomedusa bicolor, traditionally used in ritualistic and alternative medicine practices for its purported purifying and immunostimulatory effects. Acute intoxication has been associated with neuropsychiatric manifestations, electrolyte disturbances, and systemic complications; however, involvement of the peripheral nervous system has not been previously confirmed by electrodiagnostic studies. We report the case of a 40-year-old man with no prior medical history who developed rapidly progressive quadriparesis and facial diparesis four days after subcutaneous self-application of Kambo venom. Cerebrospinal fluid analysis demonstrated albuminocytologic dissociation, and nerve conduction studies revealed an acute demyelinating motor polyneuropathy with conduction block and preserved sensory conduction. Due to clinical deterioration and risk of respiratory failure, the patient required intensive care management. He initially underwent five sessions of plasmapheresis with limited improvement, followed by intravenous immunoglobulin at a dose of 0.4 g/kg/day for five days, resulting in partial neurological recovery. At three-month follow-up, he persisted with residual motor deficits without sensory involvement. This case represents, to our knowledge, the first electrodiagnostically confirmed report of acute polyneuropathy associated with Kambo poisoning. Clinicians should be aware that Kambo intoxication may extend beyond central neuropsychiatric effects to involve the peripheral nervous system, and early recognition with consideration of immunomodulatory therapy may be warranted.

Kambo是一种从亚马逊蛙Phyllomedusa bicolor中提取的天然分泌物，传统上用于仪式和替代医学实践，因为它具有据称的净化和免疫刺激作用。急性中毒与神经精神表现、电解质紊乱和全身并发症有关；然而，周围神经系统的受累尚未被先前的电诊断研究证实。我们报告的情况下，一个40岁的男子没有先前的病史，谁发展迅速进行性四肢瘫和面部重瘫的四天后，皮下自我应用坎博毒液。脑脊液分析显示白蛋白细胞分离，神经传导研究显示急性脱髓鞘运动多发性神经病伴传导阻滞和感觉传导保留。由于临床恶化和呼吸衰竭的风险，患者需要重症监护管理。他最初接受了5次血浆置换治疗，改善有限，随后静脉注射免疫球蛋白，剂量为0.4 g/kg/天，持续5天，导致神经系统部分恢复。在三个月的随访中，他仍然存在残余的运动缺陷，没有感觉受累。据我们所知，这是首例电诊断证实的与Kambo中毒相关的急性多神经病变报告。临床医生应该意识到Kambo中毒可能会超越中枢神经精神影响，涉及周围神经系统，并且考虑免疫调节治疗的早期识别可能是有保证的。

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引用次数: 0

Prediction of primary human targets and toxicity mechanisms of imidacloprid using integrative In Silico approaches 应用集成计算机方法预测吡虫啉的主要人体靶点和毒性机制

Q1 Environmental Science

Toxicology Reports

Pub Date : 2026-01-02 DOI: 10.1016/j.toxrep.2026.102199

Cherdsak Boonyong , Pannapa Powthong

Imidacloprid is frequently detected as a residue in food commodities, raising concerns about potential human health risks. Previous findings remain fragmented, and no study has systematically elucidated the primary human target organs and underlying mechanisms using an integrative systems toxicology framework. We applied a human-specific network toxicology approach to characterize imidacloprid-induced toxicity comprehensively. By integrating target prediction and ADME/toxicity models (ADMETlab 3.0, admetSAR 3.0, and ProTox 3.0), the study identified three primary human-relevant toxicity endpoints (respiratory toxicity, liver injury, and genotoxicity/carcinogenicity). Protein-protein interaction, GO, and KEGG pathway analyses revealed that MAPK, NF-κB, JAK-STAT, UPR-ER stress, and Wnt signaling networks may be key pathways involved in oxidative stress, inflammatory signaling, cell-cycle dysregulation, and apoptosis. Molecular docking analysis further supported relatively stronger predicted binding of imidacloprid to several upstream regulatory proteins, including PTGS2 (COX-2), NOS3 (eNOS), APC, CDH1 (cadherin-1 or E-cadherin), AR, HSPA5 (GRP78 or BiP), HSP90AA1 (HSP90α), JAK2, and RELA (p65), whereas downstream signaling proteins such as MAPK14 (p38α), MAPK1 (ERK2), MAPK3 (ERK1), NFKB1 (p50/p105), WNT3A (Wnt), TNF (TNF-α), ESR1 (ERα), and BCL2 exhibited moderate predicted binding. Although these findings are derived from computational analyses and do not establish functional disruption, the coordinated involvement of upstream and downstream signaling hubs suggests possible mechanisms through which imidacloprid exposure may influence multiple organ systems. Taken together, this study provides a systems-level, hypothesis-generating framework to support future experimental validation and human health risk assessment.

吡虫啉经常被检测为食品商品中的残留物，引起人们对潜在人类健康风险的关注。以前的研究结果仍然是碎片化的，没有研究系统地阐明了主要的人体靶器官和潜在的机制，使用综合系统毒理学框架。我们应用人类特异性网络毒理学方法来全面表征吡虫啉诱导的毒性。通过整合靶标预测和ADME/毒性模型（ADMETlab 3.0、admetSAR 3.0和ProTox 3.0），该研究确定了三个主要的人类相关毒性终点（呼吸毒性、肝损伤和遗传毒性/致癌性）。蛋白-蛋白相互作用、GO和KEGG通路分析显示，MAPK、NF-κB、JAK-STAT、UPR-ER应激和Wnt信号网络可能是参与氧化应激、炎症信号、细胞周期失调和细胞凋亡的关键通路。分子对接分析进一步支持吡虫啉与上游调节蛋白PTGS2 （COX-2）、NOS3 （eNOS）、APC、CDH1 （cadherin-1或E-cadherin）、AR、HSPA5 （GRP78或BiP）、HSP90AA1 （HSP90α）、JAK2和RELA （p65）的结合预测，而下游信号蛋白MAPK14 （p38α）、MAPK1 （ERK2）、MAPK3 （ERK1）、NFKB1 （p50/p105）、WNT3A （Wnt）、TNF （TNF-α）、ESR1 （ERα）和BCL2的结合预测相对较强。虽然这些发现来源于计算分析，并没有确定功能破坏，但上游和下游信号中枢的协调参与表明，吡虫啉暴露可能影响多个器官系统的可能机制。综上所述，本研究提供了一个系统级的假设生成框架，以支持未来的实验验证和人类健康风险评估。

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引用次数: 0

Activated carbon from pistachio shells: A promising approach to improve health metrics in mice with zearalenone exposure 开心果壳活性炭：一种有希望改善玉米赤霉烯酮暴露小鼠健康指标的方法

Q1 Environmental Science

Toxicology Reports

Pub Date : 2025-12-26 DOI: 10.1016/j.toxrep.2025.102197

Faezeh Oskoueian , Kimia Asadi , Zeinab Javanshir , Saeed Heidarisani , Samira Bozorgi Kasgari , Helia Ghafaripour , Ehsan Karimi , Ehsan Oskoueian

Zearalenone (ZEN), an estrogenic mycotoxin produced by Fusarium species, poses persistent challenges to food and feed safety due to its potent toxicological effects and widespread occurrence in cereal-based products. This study investigated the protective efficacy of activated carbon (AC) derived from pistachio shells, an abundant agricultural by-product against ZEN-induced toxicity in mice. Pistachio shell carbon was prepared through chemical activation and comprehensively characterized using SEM, FTIR spectroscopy, and BET surface area analysis. Activation increased surface area from 4.1 to 275.9 m²/g and enhanced pore volume from 0.009 to 0.26 cm³/g, confirming substantial improvements in adsorptive architecture. Forty BALB/c mice were assigned to four dietary treatments: control, ZEN-contaminated diet, and ZEN diets supplemented with non-activated or activated carbon (0.5 g/kg). ZEN exposure markedly reduced weight gain, feed intake, antioxidant enzyme activity (GPx, SOD, CAT), and jejunal villus morphology, while elevating serum ALT, AST, and ALP activities. Supplementation with activated carbon significantly ameliorated these adverse effects, restoring growth performance, improving antioxidant status, normalizing liver enzymes, and enhancing intestinal integrity. Histopathological observations corroborated reduced mucosal damage in AC-treated mice. These findings demonstrate that pistachio shell–based activated carbon is a potent, sustainable, and low-cost mycotoxin adsorbent capable of mitigating ZEN toxicity. The study highlights a promising strategy for simultaneous agricultural waste valorization and enhancement of food and feed safety systems.

玉米赤霉烯酮（ZEN）是一种由镰刀菌产生的雌激素性真菌毒素，由于其强大的毒理学效应和广泛存在于谷类产品中，对食品和饲料安全构成了持续的挑战。本研究研究了从开心果壳中提取的活性炭（AC）对小鼠禅致毒性的保护作用。采用化学活化法制备了开心果壳碳，并利用SEM、FTIR光谱和BET表面积分析对其进行了综合表征。活化使比表面积从4.1增加到275.9 m²/g，孔隙体积从0.009增加到0.26 cm³/g，证实了吸附结构的实质性改善。40只BALB/c小鼠被分配到四种饮食处理中：对照组、ZEN污染饮食、ZEN饮食中添加非活性炭或活性炭（0.5 g/kg）。ZEN暴露显著降低了仔猪增重、采食量、抗氧化酶活性（GPx、SOD、CAT）和空肠绒毛形态，同时提高了血清ALT、AST和ALP活性。补充活性炭可显著改善这些不良反应，恢复生长性能，改善抗氧化状态，使肝酶正常化，并增强肠道完整性。组织病理学观察证实ac处理小鼠粘膜损伤减轻。这些发现表明，开心果壳活性炭是一种有效的、可持续的、低成本的霉菌毒素吸附剂，能够减轻ZEN毒性。该研究强调了一项有希望的战略，可以同时对农业废物进行评估并加强食品和饲料安全系统。

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引用次数: 0