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 电子烟 (EC) 越来越受欢迎，部分原因是人们将其视为一种 与香烟相比，尼古丁输送装置危害更小。然而，EC 气溶胶含有许多 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的安全性。产品的多样性和快速发展的 EC 市场对 研究人员试图了解与其使用相关的潜在危害，以及监管机构 被要求做出有关其安全性的决定并寻求有关设备特征的数据 影响EC的危害。我们的体外数据显示 EC 温度和电子烟液丙二醇 (PG) 浓度是调节高活性自由基和其他物质产生的主要因素 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 用户可能受到伤害以及潜在的 与特定 EC 设计功能相关。这项拟议的研究为监管提供了有价值的数据 与当前和未来 EC 相关的产品标准开发。它解决了我们的总体 TCORS 主题 更好地了解物理设计和化学成分如何影响毒性和 烟草制品的成瘾性，重点关注氧化剂产生的危害。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 专注于暴露和伤害的生物标志物，重点关注炎症和氧化应激。瞄准 2 我们将对当前 EC 用户进行研究，同时进行受控吸入暴露研究 作为自然主义研究，以确定 EC 温度和电子液体 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 周期交叉设计来 比较低温和高温以及低和高PG烟油浓度。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 在严格控制的吸入课程之前和之后，在两周的自然主义时期之后 使用时和现场随意使用后。在目标 3 中，我们将测试溶剂 PG 含量之间的关联 以及流行的市售豆荚中自由基的产生以及暴露和伤害的生物标志物- EC 型设备。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中自由基产生和氧化应激相关生物标志物的特征 产品进行调查。总体而言，该项目解决了既定的研究需求 关于 EC 产品设计特性的变化如何影响成分暴露和毒性 开发生物标志物以评估 EC 相关暴露和相关危害或毒性。像这样， 这项研究直接涉及 TCORS 3.0 RFA 的毒性领域。