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.

项目摘要 /摘要：总体 宾夕法尼亚州TCOR的总体目标是为FDA提供科学基础，以采取监管行动 减少烟草产品的危害。我们的中心将通过合作 经验丰富的新型烟草监管科学家专注于最先进的基础和转化研究 关于多种烟草产品的毒性和成瘾。这包括开发新的研究方法 有可能在宾夕法尼亚州TCOR的范围之外的烟草监管场中使用 研究计划。尽管毒性是一个非常广泛的科学领域，但我们的重点将是 烟草烟雾和气溶胶中的氧化剂及其在使用烟草产品的人中的生物学作用。 我们将检查几种烟草产品，包括电子烟​​（EC），小雪茄和尼古丁小袋。 总体而言，这些研究是我们以前关于可燃和生产的氧化剂研究的逻辑扩展 不可耐燃的烟草产品及其产品设计特征对其生产的影响。在 此外，它们源于我们先前关于降低烟气标准的香烟可行性的研究 最小化或非副词的水平。这些研究表明，一些吸烟者将继续使用 降低了尼古丁产品，需要其他策略来减少烟草伤害，包括提供 尼古丁的安全替代来源是上瘾的吸烟者并确定哪些烟草产品特征 与更大的伤害有关。因此，我们中心的总体综合主题是更好地了解 各种烟草产品的产品设计特征会影响其毒性和 上瘾性。我们拟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方法。 在项目1中，我们将在实验室动物模型和EC使用者中进行转化研究以解决 吸入的EC氧化剂及其损害潜力受产品设计特征的影响的假设 这些氧化剂的生物学作用可以通过暴露和伤害的生物标志物来测量。 在项目2中，我们将调查与小雪茄吸烟者和 使用流行病学数据以及临床和实验室研究可能影响人类暴露的设计特征。 在项目3中，我们将通过进行随机的烟草袋作为替代的烟草产品。 对照临床试验，以检验该假设，即危害的生物标志物，包括与氧化有关的危害。 在提供高尼古丁小袋的吸烟者中，压力大大减少。 PSTCOR也将 通过综合和 通过职业发展核心的多学科系列教育计划和研究支持。 最后，为了支持所有中心活动，将是一个成熟且经验丰富的核心系统：行政 核心，生物统计学和数据管理核心和生物标志物以及分析化学核心。