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

项目摘要/摘要：项目1 电子烟(EC)越来越受欢迎，部分原因是人们认为电子烟是一种 与香烟相比，尼古丁输送装置的危害更小。然而，欧共体气雾剂中含有一些 有害或潜在有害成分，包括自由基和其他氧化剂，可能会影响 EC的安全性。产品的多样性和快速发展的电子商务市场对以下方面提出了挑战 寻求了解与使用它们相关的潜在危害的研究人员，以及 被要求对它们的安全性做出决定，并寻找关于设备特征的数据，这些数据 影响EC危害。我们的体外数据显示，EC温度和e-液体丙二醇(PG) 浓度是调节高活性自由基和其他自由基产生的主要因素 氧化剂。此外，我们在活体动物中的初步数据表明，这些氧化剂增加了 氧化应激和炎症。这些数据表明了EC用户的潜在危害和潜在的 与特定的EC设计功能相关联。这项拟议的研究为监管部门提供了宝贵的数据 制定与当前和未来ECS相关的产品标准。它解决了我们的总体TCORS主题 为了更好地了解物理设计和化学成分如何影响毒性和 烟草产品的成瘾性，重点是氧化剂产生的危害。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 关注暴露和危害的生物标志物，重点关注炎症和氧化应激。在AIM 2我们将对目前的EC使用者进行研究，并进行受控吸入暴露研究 作为自然主义研究，以确定EC温度和e-液体PG浓度对 暴露和伤害的生物标志物。我们将使用随机4处理4期交叉设计来 比较了低温和高温以及PG电子液的低浓度和高浓度。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记物。 在严格控制的吸入期之前和之后，在两周的自然主义时期之后 使用和现场随意使用后。在目标3中，我们将测试溶剂PG含量之间的关联 和自由基的产生以及暴露和伤害的生物标志物在流行的商业豆荚- 输入EC设备。鉴于这些设备的普及，重要设计的影响至关重要 使用这些药物的个体的自由基产生和氧化应激相关生物标志物的特征 对产品进行调查。总体而言，该项目满足了公认的研究需求 关于EC产品设计特征的变化如何影响成分暴露和毒性 以及开发生物标志物，以评估EC相关的暴露和相关的伤害或毒性。因此， 这项研究直接针对TCORS 3.0 RFA的毒性领域。

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.