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Puffing topography: a tool to evaluate vaping behavior and exposure risks. 雾化地形:评估电子烟行为和暴露风险的工具。
IF 2 4区 医学 Q4 TOXICOLOGY Pub Date : 2025-10-01 Epub Date: 2025-07-11 DOI: 10.1080/08958378.2025.2524728
Shaligram Sharma, Maureen Meister, Xiaojia He, Mark Wilson, Qian Zhang, Jin-Ah Park, Travis Goldsmith, Cristi Bell-Huff, Marilyn Black, Jonathan Shannahan, Christa Wright

The ever-changing popularity of electronic nicotine delivery systems (ENDS) among both youth and adults in the United States has been influential in shaping users' perceptions and behaviors. This behavior driven ENDS usage is described as puffing topography (PT) which includes user's puff duration, flow rate, intra puff interval, the volume of e-liquid used and total number of puffs per session. These metrics are not only useful for characterizing individual vaping behaviors but are also critical for assessing the extent of exposure to potentially harmful substances such as nicotine, volatile organic compounds (VOCs), and particulate matter emitted during use. Previous studies have indicated that puff volume and flow rate are distinct but related parameters that determine exposure to hazardous emissions among users and bystanders. However, current evidence suggests that vaping behavior is also influenced by the age at which users first encounter ENDS, the strength of the nicotine present, and whether users develop circadian patterns of ENDS usage. This review article, which is a part of the Special Issue Science Education and Research on Vaping and Interventions for Community Engagement summarizes the critical aspects of PT and explores how various factors including lifestyle, gender, e-liquid composition (such as flavor and nicotine concentration), and device parameters can influence exposure risks. The standardization of puffing topography as a tool to evaluate vaping behavior and exposure risks to toxic emissions could be instrumental in developing consensus standards for ENDS and protecting public health.

电子尼古丁输送系统(ENDS)在美国年轻人和成年人中不断变化的流行程度对塑造用户的观念和行为产生了影响。这种行为驱动的终端使用被描述为雾化地形(PT),其中包括用户的雾化持续时间、流量、内部雾化间隔、使用的电子液体体积和每次会话的总雾化次数。这些指标不仅有助于描述个人的电子烟行为,而且对于评估尼古丁、挥发性有机化合物(VOCs)和使用过程中排放的颗粒物等潜在有害物质的暴露程度也至关重要。先前的研究表明,烟雾量和流量是确定使用者和旁观者接触有害排放物的不同但相关的参数。然而,目前的证据表明,电子烟的行为也受到用户第一次接触电子烟的年龄、尼古丁含量以及用户是否形成电子烟使用的昼夜节律模式的影响。这篇综述文章是《科学教育与研究:电子烟与社区参与干预》特刊的一部分,总结了电子烟的关键方面,并探讨了生活方式、性别、电子烟液体成分(如口味和尼古丁浓度)和设备参数等各种因素如何影响暴露风险。将雾化地形标准化作为评估电子烟行为和有毒排放物暴露风险的工具,可能有助于制定ENDS的共识标准和保护公众健康。
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引用次数: 0
Deconstructing ENDS aerosols: generation and characterization methods. 解构ENDS气溶胶:生成和表征方法。
IF 2 4区 医学 Q4 TOXICOLOGY Pub Date : 2025-10-01 Epub Date: 2025-03-27 DOI: 10.1080/08958378.2025.2481434
Shaligram Sharma, Maureen Meister, David Christiani, Qian Zhang, Mark Wilson, Travis Goldsmith, I Mark Olfert, Anand Ranpara, Cristi Bell-Huff, Marilyn Black, Jonathan Shannahan, Christa Wright

While electronic nicotine delivery systems or ENDS are often marketed as a safer alternative to traditional cigarettes, emissions generated during the operation of these devices contain a complex mixture of toxic substances. ENDS emissions are primarily composed of fine particulate matter (PM2.5, smaller than 2.5 µm in size) and ultrafine particles/nanoparticles (PM0.1, smaller than 100 nm in size), metals (nickel, copper, zinc, tin, lead, and their oxides), carbonyls (formaldehyde, acetaldehyde (a carcinogen), and acrolein), volatile organic compounds (VOCs) (benzene, toluene, and over 70 other VOCs), nicotine, and many unknown chemicals. The levels and composition of these toxic emissions can vary based on factors like device design, e-liquid formulation, device power and temperature levels, and vaping behavior of the user. Within this section of the Special Issue 'Science Education and Research on Vaping and Interventions for Community Engagement', important parameters in defining and characterizing ENDS aerosols will be discussed. Hazardous components of ENDS aerosols including particulate matter, heavy metals, and volatile organic compounds will be delineated and appropriate analytical methods to accurately determine physicochemical properties will be highlighted. Definitions and comparisons of first-hand, second-hand, and third-hand emissions will also be explored alongside pertinent device parameters that influence each type of ENDS emission.

虽然电子尼古丁输送系统(ENDS)通常被宣传为比传统香烟更安全的替代品,但这些设备在运行过程中产生的排放物含有复杂的有毒物质混合物。ENDS的排放物主要由细颗粒物(PM2.5,尺寸小于2.5微米)和超细颗粒/纳米颗粒(PM0.1,尺寸小于100纳米)、金属(镍、铜、锌、锡、铅及其氧化物)、羰基(甲醛、乙醛(一种致癌物质)和丙烯醛)、挥发性有机化合物(VOCs)(苯、甲苯和70多种其他VOCs)、尼古丁和许多未知化学物质组成。这些有毒排放物的水平和成分可能会因设备设计、电子烟液体配方、设备功率和温度水平以及用户的吸烟行为等因素而有所不同。在特刊“电子烟的科学教育和研究以及社区参与的干预措施”的这一部分中,将讨论定义和表征电子烟气溶胶的重要参数。将描述ENDS气溶胶的有害成分,包括颗粒物质,重金属和挥发性有机化合物,并强调准确确定物理化学性质的适当分析方法。还将探讨一手、二手和三手排放的定义和比较,以及影响每种终端排放类型的相关设备参数。
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引用次数: 0
Introduction to science education and research on vaping and interventions for community engagement. 介绍有关电子烟的科学教育和研究,以及社区参与的干预措施。
IF 2 4区 医学 Q4 TOXICOLOGY Pub Date : 2025-10-01 Epub Date: 2026-01-19 DOI: 10.1080/08958378.2025.2609719
Christa Wright, J Shannahan, S Sharma, J Zelikoff
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引用次数: 0
A review of popular vaping misconceptions: redefining ENDS safety and usage risks. 流行的电子烟误解综述:重新定义电子烟的安全性和使用风险。
IF 2 4区 医学 Q4 TOXICOLOGY Pub Date : 2025-10-01 Epub Date: 2025-10-15 DOI: 10.1080/08958378.2025.2571918
Shaligram Sharma, Laura Crotty Alexander, Maureen Meister, Cassandra Ross, Joseph Hess, Kenneth Ray, Alexandra Noël, Jonathan Shannahan, Christa Wright

The widespread use of electronic nicotine delivery systems (ENDS) among youth and adults has become a significant public health concern. Approximately 19.6% of middle and high school students in the United States have reported using ENDS containing nicotine. Factors contributing to their popularity include social and recreational appeal, sensory satisfaction, ease of accessibility, and aggressive marketing strategies including influencer-driven promotions and youth-targeted campaigns through social media platforms. The variety of available flavors and modifiable features of ENDS devices further enhances their acceptance, often overshadowing their potential health risks. Despite their perceived advantages, misconceptions about ENDS persist, including beliefs that emissions are harmless, vaping is safer than smoking, and secondhand exposure is inconsequential. These misunderstandings contribute to the normalization of ENDS use, hindering public awareness of the associated health and environmental hazards. This manuscript addresses seven prevalent misconceptions about ENDS ranging from their safety during pregnancy to their environmental impact, highlighting the need for comprehensive education and community engagement to mitigate the risks of ENDS usage and promote informed decision-making. In the following section of the Special Issue Science Education and Research on Vaping and Interventions for Community Engagement (SERVICE), we will explore how these misconceptions not only encourage the societal acceptance and use of ENDS but also contribute to potential health risks.

电子尼古丁输送系统(ENDS)在青少年和成年人中的广泛使用已成为一个重大的公共卫生问题。大约19.6%的美国中学生和高中生报告使用含有尼古丁的电子烟。影响其受欢迎程度的因素包括社交和娱乐吸引力、感官满意度、易用性以及积极的营销策略,包括通过社交媒体平台进行的有影响力的促销和针对年轻人的活动。ENDS设备的各种可用口味和可修改特性进一步提高了它们的接受度,往往掩盖了它们潜在的健康风险。尽管它们有明显的优势,但对电子烟的误解仍然存在,包括认为排放物是无害的,电子烟比吸烟更安全,二手接触是无关紧要的。这些误解助长了终端使用的正常化,阻碍了公众对相关健康和环境危害的认识。本文阐述了关于终端使用的七个普遍误解,从孕期安全性到环境影响,强调了全面教育和社区参与的必要性,以减轻终端使用的风险,促进知情决策。在下一期《电子烟与社区参与干预科学教育与研究》特刊中,我们将探讨这些误解如何不仅鼓励社会接受和使用电子烟,而且还会导致潜在的健康风险。
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引用次数: 0
Building awareness and harm reduction strategies to address vaping risks. 建立意识和减少危害的策略,以解决电子烟的风险。
IF 2 4区 医学 Q4 TOXICOLOGY Pub Date : 2025-10-01 Epub Date: 2025-12-19 DOI: 10.1080/08958378.2025.2591032
Shaligram Sharma, Xiaojia He, Maureen Meister, Joseph Hess, Haylee Young, Cristi Bell-Huff, Jonathan Shannahan, Christa Wright

Electronic nicotine delivery systems (ENDS) have become a growing health concern among both youth and adults. Rise in vaping-associated lung injury underscores the consequences of the ENDS usage under certain conditions. In response, stakeholders including researchers and public health regulators have launched awareness initiatives to highlight the hazards of vaping and promote harm reduction strategies. Within harm reduction frameworks, several strategies exist including vaping behavior assessments and monitoring, engineering controls, and limiting the variety of ENDS and e-liquid formats and formulations. From an engineering perspective, controls could be implemented to limit puff size, monitor e-liquid consumption, and explore attachable filters to reduce inhalation risks. Additionally, reducing the availability of flavored e-liquids and restricting modifications could minimize their appeal to youth. Marketing strategies should clearly communicate the harms of vaping devices through informative text, images, and digital campaigns. Additionally, warning labels should be placed directly on the devices, not just on packaging, to constantly remind users of the associated risks. This review which is a part of the Special Issue Science Education and Research on Vaping and Interventions for Community Engagement examines the challenges of vaping cessation methods and explores how stakeholders, users, manufacturers, and policymakers can contribute to vaping harm reduction.

电子尼古丁输送系统(ENDS)已成为青少年和成年人日益关注的健康问题。电子烟相关肺损伤的增加强调了在某些条件下使用ENDS的后果。作为回应,包括研究人员和公共卫生监管机构在内的利益相关者发起了提高认识的举措,以强调电子烟的危害,并促进减少危害的战略。在减少危害的框架内,存在几种策略,包括电子烟行为评估和监测、工程控制,以及限制终端和电子烟液体形式和配方的多样性。从工程角度来看,可以实施控制措施来限制雾化尺寸,监测电子液体的消耗,并探索附加过滤器以降低吸入风险。此外,减少调味电子液体的可用性和限制修改可以最大限度地减少它们对年轻人的吸引力。营销策略应该通过翔实的文字、图片和数字活动,清楚地传达电子烟设备的危害。此外,警告标签应该直接贴在设备上,而不仅仅是在包装上,以不断提醒用户相关的风险。这篇综述是《电子烟科学教育与研究和社区参与干预特刊》的一部分,它研究了电子烟戒烟方法的挑战,并探讨了利益相关者、用户、制造商和政策制定者如何为减少电子烟的危害做出贡献。
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引用次数: 0
The beginning of ENDS (electronic nicotine delivery systems): origins, trends, and regulatory considerations. 电子尼古丁输送系统的开始:起源、趋势和监管考虑。
IF 2 4区 医学 Q4 TOXICOLOGY Pub Date : 2025-10-01 Epub Date: 2025-03-27 DOI: 10.1080/08958378.2025.2479518
Shaligram Sharma, Maureen Meister, Scott Weaver, Judith Zelikoff, Cristi Bell-Huff, Marilyn Black, Jonathan Shannahan, Christa Wright

Electronic nicotine delivery systems (ENDS), commonly known as e-cigarettes, are battery-operated devices that produce aerosols by vaporizing e-liquids, which typically contain propylene glycol and/or vegetable glycerin, nicotine, and flavorings. Since their launch in the U.S. in 2007, ENDS have evolved significantly to meet consumer demands, prompting federal regulation in 2016 under the Family Smoking Prevention and Tobacco Control Act. The first ENDS resembled conventional tobacco cigarettes and were initially marketed as smoking cessation tools. While their smoking cessation efficacy under advantageous conditions has been supported by randomized clinical trials, observational cohort studies have raised doubt about their utility for smoking cessation under more typical real-world use conditions. In 2018, the U.S. Surgeon General declared youth vaping a national epidemic as prevalence of current ENDS use rose to 27.5% among high school. The youth vaping trend alongside injury reports and deaths related to e-cigarette or vaping product use-associated lung injury (EVALI) raised public health alarms in 2019. Although youth vaping has since declined, over 1.6 million high school students and 410, 000 middle school students reported ENDS usage in 2024. Thus, the ongoing challenges surrounding vaping including adolescent usage and smoking cessation efficacy continue to attract public health concern and debate. Within this section of the Special Issue "Science Education and Research on Vaping and Interventions for Community Engagement", an overview of the history of the vaping epidemic, current formats and ENDS generations, usage statistics across various demographics along with market trends and regulatory guidelines will be discussed.

电子尼古丁输送系统(ENDS),通常被称为电子烟,是一种电池供电的设备,通过蒸发电子液体产生气溶胶,电子液体通常含有丙二醇和/或植物甘油、尼古丁和调味剂。自2007年在美国推出以来,ENDS已经发生了重大变化,以满足消费者的需求,并于2016年根据《家庭吸烟预防和烟草控制法》制定了联邦法规。第一批ENDS类似于传统香烟,最初作为戒烟工具销售。虽然它们在有利条件下的戒烟效果得到了随机临床试验的支持,但观察性队列研究对它们在更典型的现实使用条件下的戒烟效用提出了质疑。2018年,美国外科医生宣布青少年吸电子烟是一种全国性的流行病,因为目前电子烟在高中生中的使用率上升到了27.5%。2019年,青少年吸电子烟的趋势,以及与电子烟或电子烟产品使用相关的肺损伤(EVALI)相关的伤害报告和死亡,引发了公共卫生警报。尽管青少年吸电子烟的人数已经下降,但到2024年,仍有超过160万高中生和41万中学生报告使用电子烟。因此,围绕电子烟的持续挑战,包括青少年使用和戒烟功效,继续引起公共卫生关注和辩论。在特刊“电子烟的科学教育和研究以及社区参与的干预措施”的这一部分中,将概述电子烟流行的历史、当前的形式和ENDS世代、不同人口统计学的使用统计数据以及市场趋势和监管指南。
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引用次数: 0
Effect of single inhalation of hypochlorous acid on the activity of cysteine cathepsins in rat blood plasma. 单次吸入次氯酸对大鼠血浆半胱氨酸组织蛋白酶活性的影响。
IF 2 4区 医学 Q4 TOXICOLOGY Pub Date : 2025-08-01 Epub Date: 2025-09-11 DOI: 10.1080/08958378.2025.2558569
Bohdan Murashevych, Olha Abraimova, Olha Netronina, Dmitry Girenko, Tetiana Herhel, Hanna Maslak

Objective: Gaseous hypochlorous acid HOCl(g) is a promising agent for continuous complex disinfection of premises, but the toxic effect of its inhalation has been practically not studied. In this study, the effect of inhalation of 0.75 and 1.79 ppm HOCl(g) on ​​the activity of cysteine ​​cathepsins B, H and L, and alpha-1 antitrypsin in the blood plasma of rats was studied to assess the extent of lysosome damage as an element of oxidative stress.

Materials and methods: the inhalation exposure was carried out in the 'whole-body' mode during a single 4-hour treatment of animals of two age groups in inhalation chamber equipped with a specially designed evaporative unit. Biochemical parameters were analyzed 2 h and 24 h after the procedure.

Results and discussion: it was found that the activity of cathepsin L did not change in any of the animal groups, while the activities of cathepsins B and H significantly increased. Inhalation had the greatest effect on cathepsin H, which increased by 1.6-6.4 times in different groups, and the reaction of young animals was more intense. Alpha-1 antitrypsin levels were also elevated both 2 and 24 h after exposure, but age-dependent differences were not significant. In all cases, an increase in the deviation of biochemical parameters from the norm was noted with an increase in the HOCl(g) concentration.

Conclusions: HOCl(g) inhalation at the concentrations used causes pronounced oxidative stress in animals. More detailed biochemical, histological and immunohistochemical studies are needed to assess the toxic consequences of such exposure.

目的:气态次氯酸HOCl(g)是一种很有前途的场所连续复合消毒剂,但其吸入的毒性作用尚未进行实际研究。在本研究中,研究了吸入0.75和1.79 ppm HOCl(g)对大鼠血浆中半胱氨酸组织蛋白酶B、H和L以及α -1抗胰蛋白酶活性的影响,以评估作为氧化应激因素的溶酶体损伤程度。材料和方法:两个年龄组的动物在配有专门设计的蒸发装置的吸入室中以“全身”模式进行单次4小时的吸入暴露。术后2 h、24 h进行生化指标分析。结果与讨论:发现各动物组组织蛋白酶L活性没有变化,而组织蛋白酶B和H活性明显升高。吸入对组织蛋白酶H的影响最大,各组组织蛋白酶H升高1.6 ~ 6.4倍,幼龄动物反应更为强烈。暴露后2和24 h α -1抗胰蛋白酶水平也升高,但年龄依赖性差异不显著。在所有情况下,随着HOCl(g)浓度的增加,生化参数与标准的偏差增加。结论:吸入所使用浓度的HOCl(g)会引起动物明显的氧化应激。需要更详细的生化、组织学和免疫组织化学研究来评估这种接触的毒性后果。
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引用次数: 0
A positive pressure system for selective human exposure to gas and particulate mixed atmospheres. 一种正压系统,供人类选择性地暴露于气体和颗粒混合大气中。
IF 2 4区 医学 Q4 TOXICOLOGY Pub Date : 2025-08-01 Epub Date: 2025-09-29 DOI: 10.1080/08958378.2025.2565730
Jacob S Griffin, S Thorne Gregory, Thomas E Austin, Ingrid George, Joseph Martin, Lauren Slaber, Jon Berntsen, Steven E Prince, James M Samet

Introduction: Exposure to air pollution containing particulates (PM) and gas-phase volatile organic compounds (VOCs), is a leading cause of human morbidity and mortality globally. Devising effective protective public health strategies requires an assessment of the relative contribution of PM and VOCs to the health effects of air pollution exposure.

Methods: To enable studies of VOCs isolated from mixed atmospheres, we developed a positive air pressure exposure system that permits the subject to breathe unimpeded by the pressure drop imposed by filtering respirators. This system uses pumps to draw air through respirator filters and delivers it to a modified positive pressure respirator at a flow rate that exceeds the ventilatory requirements of the wearer, while preventing infiltration of the surrounding atmosphere.

Results: Tests showed negligible leaks (<5% flow reduction) and minimal VOC losses (95% recovery) to the system. When tested using an atmosphere containing woodsmoke, PM filters showed effective exclusion of particulates but minimal losses of VOCs, while activated carbon based cartridges effectively removed gaseous compounds and PM. A team member exercising moderately in a woodsmoke atmosphere for 2-hours reported no perveivable odors and experienced no discomfort during an exposure using charcoal filter cartridges.

Discussion: We report the development and validation of a novel human exposure system that allows selective exposure to the gaseous fraction of a mixed atmosphere. This system allows for moderate to vigorous exercise of the study subject and can be used in place of an exposure chamber, making it compatible with clinical and field studies.

导言:暴露于含有颗粒物(PM)和气相挥发性有机化合物(VOCs)的空气污染中,是全球人类发病和死亡的主要原因。制定有效的保护性公共卫生战略需要评估可吸入颗粒物和挥发性有机化合物对接触空气污染的健康影响的相对贡献。方法:为了研究从混合大气中分离出的挥发性有机化合物,我们开发了一种正压暴露系统,该系统允许受试者不受过滤式呼吸器施加的压降的阻碍呼吸。该系统使用泵通过呼吸器过滤器吸入空气,并以超过佩戴者通气要求的流速将其输送到改良的正压呼吸器,同时防止周围大气的渗透。结果:测试显示可以忽略不计的泄漏(讨论:我们报告了一种新型人体暴露系统的开发和验证,该系统允许选择性暴露于混合大气的气态部分。该系统允许研究对象进行中度到剧烈的运动,可以代替暴露室使用,使其与临床和现场研究兼容。
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引用次数: 0
Fragrance inhalation toxicity assessment: a proactive testing strategy using ex vivo precision cut lung slices (PCLuS) for the prioritization of selected aroma ingredients candidates for in vivo testing. 香味吸入毒性评估:一种主动测试策略,使用离体精确切割肺片(PCLuS)对选定的香气候选成分进行体内测试的优先级。
IF 2 4区 医学 Q4 TOXICOLOGY Pub Date : 2025-08-01 Epub Date: 2025-10-07 DOI: 10.1080/08958378.2025.2566446
Tizia Thoma, Olga Lemke, Lan Ma-Hock, Lars Hareng, Markus Wahl

Objective: To date, exposure thresholds for fragrance chemicals are most often extrapolated from oral administration data. Due to limited inhalation toxicity data, the potentially high exposure levels toward fragrances - especially in air care applications - are sometimes perceived as potentially critical. Herein, we assessed the potential inhalation toxicity of various commonly used fragrances with main focus on respiratory tract effects.

Methods: 19 high volume fragrances were screened for their cytotoxic potential by using rat precision cut lung slices (PCLuS). Based on the screening data, chemicals were categorized into low, mid, and high cytotoxicity groups. From these groups, five fragrances were selected for further in vivo investigation. In a 14-day inhalation study, male 7-week old Wistar rats were exposed to geraniol, geranyl acetate, citral, L-menthol, and p-tert-butyl-alpha-methylhydro-cinnamic aldehyde (BMHCA) to investigate the respiratory and sensory irritation potential.

Results: Ex vivo screening allowed for a preliminary classification of the cytotoxic potential, facilitating the selection of candidates for in vivo inhalation assessments. Local respiratory irritation was observed for liquid aerosol fractions of citral and geraniol, but not for other substances or vapor only exposure. Overall, no systemic effects related to treatment were observed. Sensory irritation was only observed for citral and BMHCA but not for other fragrance chemicals.

Discussion: While PCLuS and further model development could not fully replace animal testing at this stage, this study's findings contribute to the reduction and refinement according to 3 R principles and might serve as a foundation for future testing strategies aiming toward a complete replacement.

目的:迄今为止,芳香化学品的暴露阈值通常是从口服给药数据中推断出来的。由于有限的吸入毒性数据,对香水的潜在高暴露水平-特别是在空气护理应用中-有时被认为是潜在的关键。在此,我们评估了各种常用香水的潜在吸入毒性,主要关注呼吸道效应。方法:采用大鼠精密肺切片法对19种大剂量香精进行细胞毒性筛选。根据筛选数据,化学物质被分为低、中、高细胞毒性组。从这些组中,选择了五种香水进行进一步的体内研究。在一项为期14天的吸入研究中,7周龄雄性Wistar大鼠暴露于香叶醇、香叶乙酸酯、柠檬醛、l-薄荷醇和对叔丁基- α -甲基氢肉桂醛(BMHCA)中,研究其呼吸和感觉刺激电位。结果:体外筛选允许对细胞毒性潜力进行初步分类,促进体内吸入评估的候选物的选择。对柠檬醛和香叶醇的液体气溶胶组分观察到局部呼吸道刺激,但对其他物质或仅蒸汽暴露没有观察到局部呼吸道刺激。总的来说,没有观察到与治疗相关的全身效应。只观察到柠檬醛和BMHCA的感官刺激,而没有观察到其他香精化学物质。讨论:虽然PCLuS和进一步的模型开发在现阶段不能完全取代动物实验,但本研究的发现有助于根据3r原则减少和改进动物实验,并可能为未来旨在完全取代动物实验的测试策略奠定基础。
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引用次数: 0
Episodic ozone exposure over two weeks alters pulmonary inflammation and gene expression in Long-Evans rats. 两周的臭氧暴露会改变Long-Evans大鼠的肺部炎症和基因表达。
IF 2 4区 医学 Q4 TOXICOLOGY Pub Date : 2025-08-01 Epub Date: 2025-10-23 DOI: 10.1080/08958378.2025.2576492
Janice A Dye, Makala M Moore, Helen H Nguyen, Mette C Schladweiler, Victoria R Adams, Judy H Richards, Wanda C Williams, Rachel D Grindstaff, Urmila P Kodavanti, Colette N Miller

Objective: Elevated exposure to ozone (O3) may occur episodically over short windows of time. However, laboratory investigations have consistently shown that repeated ozone exposures produce an adaptation response, reducing the effects of O3 on ventilatory function. To better understand these responses, we developed a rodent model of episodic O3 exposure to characterize differing exposure patterns on pulmonary toxicity.

Methods: Male, Long-Evans rats were exposed for either two days or two weeks of episodic exposure to 0.4 or 0.8 ppm O3 (4 h/day). Rats in the two-week group were exposed for a total of five nonconsecutive days, with one- to four-day periods of recovery between each exposure. Whole body plethysmography was performed following each exposure. Markers of lung injury and inflammation in the bronchoalveolar lavage fluid were measured, and lung expression of select genes were assessed using qPCR ∼24 h after the final exposure.

Results: Concentration-dependent effects of O3 on breathing parameters and lung injury were observed following two days of exposure. However, these responses were less evident in rats exposed episodically over two weeks. Comparable increases in bronchoalveolar lavage fluid inflammatory cells and cytokine concentrations were observed irrespective of exposure duration. Furthermore, reduced expression of genes involved in neuroendocrine signaling was detected only following two weeks of episodic exposure (Adrb2, Nr3c1, Dusp1, Glccl1).

Conclusions: Aspects of the adaptation response were still present in rats episodically exposed to O3 over two weeks. On the other hand, O3-mediated alterations in pulmonary immune populations show continued responsiveness in this model, suggesting that adaptation may be endpoint specific.

目的:高暴露于臭氧(O3)可能会在短时间内偶然发生。然而,实验室研究一致表明,反复暴露于臭氧会产生适应反应,从而降低臭氧对通气功能的影响。为了更好地理解这些反应,我们开发了一种偶发性臭氧暴露的啮齿动物模型,以表征不同的暴露模式对肺毒性的影响。方法:雄性Long-Evans大鼠暴露于0.4或0.8 ppm的O3中2天或2周(4小时/天)。两周组的大鼠暴露在非连续的五天中,每次暴露之间有一到四天的恢复期。每次暴露后进行全身体积脉搏描记。测量支气管肺泡灌洗液中肺损伤和炎症标志物,并在最终暴露后约24小时使用qPCR评估选定基因的肺表达。结果:O3暴露2天后,观察其对呼吸参数和肺损伤的浓度依赖性影响。然而,这些反应在连续暴露超过两周的大鼠中不太明显。支气管肺泡灌洗液炎症细胞和细胞因子浓度的增加与暴露时间无关。此外,仅在两周的间歇性暴露后,检测到参与神经内分泌信号传导的基因表达减少(Adrb2, Nr3c1, Dusp1, Glccl1)。结论:在连续暴露于O3超过两周的大鼠中,适应性反应的各个方面仍然存在。另一方面,在该模型中,肺免疫群体中臭氧介导的改变显示出持续的反应性,这表明适应可能是终点特异性的。
{"title":"Episodic ozone exposure over two weeks alters pulmonary inflammation and gene expression in Long-Evans rats.","authors":"Janice A Dye, Makala M Moore, Helen H Nguyen, Mette C Schladweiler, Victoria R Adams, Judy H Richards, Wanda C Williams, Rachel D Grindstaff, Urmila P Kodavanti, Colette N Miller","doi":"10.1080/08958378.2025.2576492","DOIUrl":"10.1080/08958378.2025.2576492","url":null,"abstract":"<p><strong>Objective: </strong>Elevated exposure to ozone (O<sub>3</sub>) may occur episodically over short windows of time. However, laboratory investigations have consistently shown that repeated ozone exposures produce an adaptation response, reducing the effects of O<sub>3</sub> on ventilatory function. To better understand these responses, we developed a rodent model of episodic O<sub>3</sub> exposure to characterize differing exposure patterns on pulmonary toxicity.</p><p><strong>Methods: </strong>Male, Long-Evans rats were exposed for either two days or two weeks of episodic exposure to 0.4 or 0.8 ppm O<sub>3</sub> (4 h/day). Rats in the two-week group were exposed for a total of five nonconsecutive days, with one- to four-day periods of recovery between each exposure. Whole body plethysmography was performed following each exposure. Markers of lung injury and inflammation in the bronchoalveolar lavage fluid were measured, and lung expression of select genes were assessed using qPCR ∼24 h after the final exposure.</p><p><strong>Results: </strong>Concentration-dependent effects of O<sub>3</sub> on breathing parameters and lung injury were observed following two days of exposure. However, these responses were less evident in rats exposed episodically over two weeks. Comparable increases in bronchoalveolar lavage fluid inflammatory cells and cytokine concentrations were observed irrespective of exposure duration. Furthermore, reduced expression of genes involved in neuroendocrine signaling was detected only following two weeks of episodic exposure (<i>Adrb2</i>, <i>Nr3c1</i>, <i>Dusp1</i>, <i>Glccl1</i>).</p><p><strong>Conclusions: </strong>Aspects of the adaptation response were still present in rats episodically exposed to O<sub>3</sub> over two weeks. On the other hand, O<sub>3</sub>-mediated alterations in pulmonary immune populations show continued responsiveness in this model, suggesting that adaptation may be endpoint specific.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"343-356"},"PeriodicalIF":2.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Inhalation Toxicology
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