Project 1: Translational Studies on Temperature and Solvent Effects on Electronic Cigarette-Derived Oxidants

项目1：温度和溶剂对电子烟氧化剂影响的转化研究

• 批准号: 10665896
• 负责人: JOHN P RICHIE
• 金额: $ 52.66万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10665896
• 关键词: Acute; Address; Aerosols; Affect; Animal Model; Animals; Biological; Biological Markers; Blood; Characteristics; Chemicals; Cigarette; Cigarette Smoker; Crossover Design; Data; Development; Devices; Electronic cigarette; Epithelium; Exhalation; Exposure to; Flavoring; Free Radicals; Future; Health; Health Personnel; High temperature of physical object; Home; Human; In Vitro; Individual; Inflammation; Inhalation; Inhalation Exposure; Link; Liquid substance; Lung; Mainstreaming; Marketing; Measures; Mus; Nicotine; Normal Range; Nose; Oxidants; Oxidative Stress; Participant; Perception; Physical condensation; Policy Maker; Population Study; Production; Propylene Glycols; Pulmonary Inflammation; Randomized; Recommendation; Research; Research Personnel; Risk; Safety; Sampling; Site; Smoker; Solvents; Temperature; Testing; Tobacco smoke; Toxic effect; Toxicant exposure; Translating; Urine; Variant; Visit; addiction; animal data; biomarker development; biomarker validation; cold temperature; combustible cigarette; design; e-cigarette aerosols; electronic cigarette user; electronic liquid; in vivo; innovation; lipidomics; mouse model; novel; novel marker; oxidant stress; recruit; specific biomarkers; tobacco exposure; tobacco products; translational approach; translational study

Project Summary / Abstract: Project 1 Electronic cigarettes (EC) have gained increasing popularity due, in part, to the perception of them as a less harmful nicotine delivery device as compared to cigarettes. However, EC aerosols contain a number of harmful or potentially harmful constituents including free radicals and other oxidants that may impact the safety of EC. The diversity of products and rapidly evolving EC market poses a challenge for researchers seeking to understand the potential harms associated with their use, and for regulators who are asked to make determinations regarding their safety and seek data on device characteristics that impact EC harm. Our in vitro data show that EC temperature and e-liquid propylene glycol (PG) concentration are the major factors regulating the production of highly reactive free radicals and other oxidants. Further, our preliminary in vivo animal data suggest that these oxidants increase biomarkers of oxidative stress and inflammation. These data suggest the potential for harm in EC users and a potential link with specific EC design features. This proposed research provides valuable data for regulatory product standard development related to current and future ECs. It addresses our overall TCORS theme to better understand how the physical design and chemical constituents affect the toxicity and addictiveness of tobacco products with a focus on harm generated from oxidants. In Aim 1 we will conduct controlled animal exposure studies to determine the effects of temperature and PG concentration on biomarkers of exposure and harm, focusing on inflammation and oxidant stress. In Aim 2 we will conduct studies of current EC users, performing controlled inhalation exposure studies as well as naturalistic studies to determine the effects of EC temperature and e- liquid PG concentration on biomarkers of exposure and harm. We will use a randomized 4-treatment 4-period crossover design to compare low and high temperature and low and high PG e-liquid concentration. Acute effects including biomarkers of exposure, inflammation, oxidant stress and cardiorespiratory function will be measured before and immediately after rigidly controlled inhalation sessions, after a two-week period of naturalistic use and after on-site ad libitum use. In Aim 3 we will test for associations between solvent PG content and free radical production and biomarkers of exposure & harm in popular commercially available pod- type EC devices. Given the popularity of these devices, it is critical that the impact of important design features on free radical production and oxidative stress-related biomarkers in individuals using these products be investigated. Overall, this project addresses the well-established need for research regarding how variation in EC product design characteristics impact constituent exposure and toxicity and development of biomarkers to assess EC-related exposure and related harm or toxicity. As such, this research directly addresses the Toxicity domain of the TCORS 3.0 RFA.

项目摘要 /摘要：项目1 电子香烟（EC）的普及程度越来越多，部分原因是它们的感知 与香烟相比，有害的尼古丁递送装置较少。但是，EC气溶胶包含一个数字 可能影响的有害或潜在有害成分，包括自由基和其他可能影响的氧化剂 EC的安全。产品的多样性和快速发展的EC市场对 寻求了解与使用相关的潜在危害的研究人员以及 要求确定其安全性，并寻求有关设备特征的数据 影响EC伤害。我们的体外数据表明，EC温度和电子液体丙烯（PG） 浓度是调节高反应性自由基和其他其他的主要因素 氧化剂。此外，我们的初步体内动物数据表明，这些氧化剂增加了生物标志物 氧化应激和炎症。这些数据表明，EC用户有可能受到伤害和潜力 与特定的EC设计功能链接。这项拟议的研究为监管提供了宝贵的数据 产品标准开发与当前和未来EC有关。它解决了我们的整体TCOR主题 更好地了解物理设计和化学成分如何影响毒性和 烟草产品的上瘾性，重点是氧化剂产生的伤害。在目标1中，我们将 进行受控动物暴露研究以确定温度和PG的影响 集中于暴露和伤害的生物标志物，重点是炎症和氧化应激。目标 2我们将对当前的EC使用者进行研究，还进行受控的吸入暴露研究 作为确定EC温度和E-液体PG浓度对的自然研究 暴露和伤害的生物标志物。我们将使用随机的4处理4期跨界设计 比较低温和高温以及低和高PG电子液体浓度。急性影响包括 将测量暴露，炎症，氧化应激和心肺功能的生物标志物 在经过两周的自然主义时期之后，在严格控制的吸入课程之前和之后 使用和自由使用之后。在AIM 3中，我们将测试溶剂PG内容之间的关联 以及在流行的市售豆荚中的自由基生产和暴露和伤害的生物标志物 键入EC设备。考虑到这些设备的流行，至关重要的是重要设计的影响 使用这些的自由基生产和氧化应激相关的生物标志物的特征 产品可以研究。总体而言，该项目解决了公认的研究需求 关于EC产品设计特征的变化如何影响组成的暴露和毒性 和开发生物标志物以评估与EC相关的暴露和相关危害或毒性。像这样， 这项研究直接解决了TCOR 3.0 RFA的毒性领域。