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

宾夕法尼亚州立大学 TCORS：烟草产品成分对毒性和成瘾性的影响

• 批准号: 10665895
• 负责人: JONATHAN FOULDS
• 金额: $ 399.02万
• 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/10665895
• 关键词: Address; Aerosols; Affect; Analytical Chemistry; Area; Authorization documentation; Basic Science; Biological; Biological Markers; Biometry; Career Mobility; Characteristics; Chemicals; Cigar; Cigarette; Clinical Research; Collaborations; Communication; Communities; Data; Development; Devices; Education; Electronic cigarette; Emerging Tobacco Products; Flavoring; Free Radicals; Harm Reduction; Health; Inhalation; Knowledge; Laboratory Animal Models; Laboratory Study; Length; Marketing; Measurement; Measures; Mentors; Methodology; Methods; Mission; Nicotine; Nitrates; Oral; Oxidants; Oxidative Stress; Persons; Pilot Projects; Placebos; Production; Randomized Controlled Clinical Trials; Regulation; Research; Research Design; Research Infrastructure; Research Methodology; Research Project Grants; Research Support; Resource Development; Resources; Risk; Role; Sampling; Science; Scientist; Senior Scientist; Series; Smoke; Smoker; Source; System; Temperature; Testing; Time; Tobacco; Tobacco smoke; Tobacco use; Toxic effect; Translational Research; United States Food and Drug Administration; Work; addiction; authority; base; career development; combustible tobacco; data management; design; electronic cigarette user; electronic liquid; epidemiologic data; experience; exposed human population; multidisciplinary; non-cigarette tobacco product; novel; novel marker; programs; research and development; stem; student training; tobacco exposure; tobacco products; tobacco regulation; tobacco regulatory science; tobacco toxicant; translational study; ventilation

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.

项目概要/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依据 减少烟草产品的危害。我们的中心将通过以下合作来实现这一目标： 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转化研究 各种烟草产品的毒性和成瘾性。这包括开发新的研究方法， 有可能用于超出宾夕法尼亚州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，但我们的重点将是对 烟草烟雾和气溶胶中的氧化剂及其对烟草制品使用者的生物效应。 我们将研究几种烟草产品，包括电子烟（EC），小雪茄和尼古丁袋。 总的来说，这些研究是我们以前关于可燃物产生的氧化剂的工作的逻辑延伸， 不燃烟草产品及其产品设计特征对其生产的影响。在 此外，这些建议是基于我们先前就降低香烟尼古丁标准的可行性进行的研究， 最低成瘾或非成瘾水平。这些研究表明，一些吸烟者将继续使用 降低尼古丁产品，需要采取额外的策略来减少烟草危害，包括提供 为吸烟成瘾者提供安全的尼古丁替代来源，并确定烟草产品的特性 与更大的伤害有关。因此，我们中心的整体综合主题是更好地了解如何 不同和替代烟草产品的产品设计特征影响其毒性， 上瘾。我们建议的中心将解决几个CTP科学领域，包括毒性， 成瘾和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，我们将在实验室动物模型和EC用户中进行转化研究，以解决 吸入EC氧化剂及其潜在危害受产品设计特征影响的假设 这些氧化剂的生物效应可以通过暴露和危害的生物标志物来测量。 在项目2中，我们将研究与吸烟者产生氧化剂有关的潜在毒性， 使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接触的特征。 在项目3中，我们将通过进行一项随机研究， 对照临床试验，以测试这一假设，即生物标志物的伤害，包括那些有关氧化 压力，在提供高尼古丁袋的吸烟者中显着减少。PSTCORS还将 继续大力支持烟草监管科学的职业发展， 通过职业发展核心提供多学科系列教育计划和研究支持。 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： 核心，生物统计学和数据管理核心和生物标志物和分析化学核心。