Penn State TCORS: Tobacco Product Composition Effects on Toxicity and Addiction

项目摘要/摘要：总体 宾夕法尼亚州立大学TCORS的总体目标是为FDA采取监管行动提供科学基础 以减少烟草产品的危害。我们的中心将通过合作实现这一目标 经验丰富的和新的烟草监管科学家专注于最先进的基础和翻译研究 关于各种烟草产品的毒性和成瘾性。这包括开发新的研究方法， 有可能被用于超出宾夕法尼亚州立大学TCORS范围的烟草监管领域 研究计划。虽然毒性是一个非常广泛的科学领域，但我们的重点将是表征 烟草烟雾和气雾剂中的氧化剂及其对烟草制品使用者的生物影响。 我们将检查几种烟草产品，包括电子烟(EC)、小雪茄和尼古丁袋子。 总体而言，这些研究是我们之前关于可燃和可燃气体产生的氧化剂的合乎逻辑的扩展。 不可燃烟草制品及其产品设计特点对其生产的影响。在……里面 此外，它们源于我们先前对降低香烟尼古丁标准的可行性的研究，以 最低程度的上瘾或不上瘾的水平。这些研究表明，一些吸烟者将继续使用 降低了尼古丁产品，需要采取更多的战略来减少烟草危害，包括提供 对吸烟者安全的尼古丁替代来源和确定哪些烟草产品特性 与更大的危害有关。因此，我们中心的总体整合主题是更好地了解如何 各种替代烟草产品的产品设计特点会影响其毒性和 上瘾。我们建议的中心将涉及几个CTP科学领域，包括毒性， 上瘾与产品组成和设计使用高度跨学科和综合的方法。 在项目1中，我们将在实验动物模型和EC用户中进行翻译研究，以解决 吸入EC氧化剂及其潜在危害的假设受到产品设计特征的影响 这些氧化剂的生物效应可以通过暴露和伤害的生物标记物来衡量。 在项目2中，我们将调查与少量雪茄吸烟者产生氧化剂有关的潜在毒性和 利用流行病学数据以及临床和实验室研究，设计可能影响人类暴露的特征。 在项目3中，我们将重点关注尼古丁袋子作为替代烟草产品，通过进行随机 对照临床试验，以验证伤害的生物标记物，包括那些与氧化有关的生物标记物 在吸烟者中，给他们提供高尼古丁袋子的人的压力显著减少。PSTCORS还将 继续大力支持烟草监管科学的职业发展，通过综合和 通过职业发展核心提供的一系列多学科教育方案和研究支持。 最后，支持中心所有活动的将是一个成熟和经验丰富的核心系统：行政 核心，生物统计和数据管理核心，生物标记和分析化学核心。

Project Summary / Abstract: Overall The overall objective of the Penn State TCORS is to provide a science base for FDA to take regulatory actions to reduce the harm from tobacco products. Our center will accomplish this through a collaboration of experienced and new tobacco regulatory scientists focusing on state-of-the-art basic and translational research on the toxicity and addiction of diverse tobacco products. This includes developing new research methods that have the potential to be used in the tobacco regulatory field beyond the scope of the Penn State TCORS research program. While toxicity is a very broad scientific field, our focus will be on the characterization of oxidants in tobacco smoke and in aerosols, and their biological effects in persons who use tobacco products. We will examine several tobacco products including e-cigarettes (EC), little cigars and nicotine pouches. Overall, these studies are a logical extension of our previous work on oxidants produced by combustible and non-combustible tobacco products and the impact of product design characteristics on their production. In addition, they stem from our previous research on the feasibility of a reduced nicotine standard for cigarettes to minimally-addicting or nonaddicting levels. These studies indicated that some smokers will continue to use lowered nicotine products and that additional strategies are needed to reduce tobacco harm including providing safe alternative sources of nicotine to addicted smokers and determining which tobacco product characteristics are associated with greater harm. Thus, the overall integrative theme of our center is to better understand how product design characteristics of diverse and alternative tobacco products affect their toxicity and addictiveness. Our proposed Center will address several CTP scientific domains including Toxicity, Addiction and Product Composition and Design using a highly interdisciplinary and integrative approach. In Project 1, we will conduct translational studies in both laboratory animal models and EC users to address the hypothesis that inhaled EC oxidants and their potential for harm are influenced by product design features and the biological effects of these oxidants can be measured through biomarkers of both exposure and harm. In Project 2, we will investigate the potential toxicity related to oxidant production in little cigar smokers and design features that may affect human exposure using epidemiologic data and clinical and laboratory studies. In Project 3, we will focus on the nicotine pouch as an alternative tobacco product by conducting a randomized controlled clinical trial to test that hypothesis that biomarkers of harm, including those related to oxidative stress, are significantly reduced in smokers who are provided high nicotine pouches. The PSTCORS will also continue its strong support of career development in tobacco regulatory science through an integrated and multidisciplinary series of educational programs and research support through the Career Development Core. Finally, in support of all Center activities will be a mature and experienced system of cores: Administrative Core, Biostatistics and Data Management Core and Biomarker and Analytical Chemistry Core.