Impact of sugars on tobacco product toxicity and abuse liability

项目总结 糖，在一些烟草类型中天然存在，也作为烟草填充物添加到卷烟烟草填充物中 添加剂，不包括在FDA的有害和潜在有害成分(HPHC)清单中。现有 研究数据表明，烟草填充物中的糖可能会对香烟的有害特性造成影响 三个关键方法：通过提高烟的适口性和吸引力，以及作为醛和呋喃的前体，在 烟雾会增加烟雾的毒性、致癌性和潜在的成瘾性。因此，糖 可能是导致吸烟相关发病率的最多种多样的关键因素 死亡率。然而，关于烟草含糖量之间的关系缺乏强有力的量化数据。 和相关毒物在美国商业香烟中的产生量，以及相关的使用者暴露、行为和 香烟的吸引力。在这项研究中，我们将利用我们在烟草化学、流行病学、 以及评估生物标记物以及行为和主观措施的人体试验，以解决这些关键问题 知识鸿沟。在目标1中，我们将使用稳定同位素标记的糖添加到商业香烟中，这是 并将分析相应标记的热解产物的剂量依赖性形成。 这种香烟冒出的烟。表征美国卷烟填充物中的糖对相关 香烟烟雾的化学特征。我们还将分析糖含量对尼古丁水平的影响 以及烟雾中烟草特有的亚硝胺(TSNA)。在目标2中，我们将分析美国商业中的糖 并使用PATH生物标志物数据来调查卷烟烟草中糖分含量对 美国吸烟者的有毒物质和致癌物质摄入量。在目标3中，我们将调查糖含量对 香烟烟草对香烟滥用的责任和吸引力，通过进行实验室研究，吸烟者将 在实验室环境中评估不同糖分水平的研究香烟。这项提案的总体目标是 为FDA提供科学依据，以确定是否应将糖添加到HPHC列表中，并 它们在烟草产品中的含量是否应该受到监管。

PROJECT SUMMARY Sugars, which are present naturally in some tobacco types and are also added to cigarette tobacco filler as additives, are not included in the FDA list of harmful and potentially harmful constituents (HPHC). Existing research data suggests that sugars in tobacco filler may contribute to the harmful properties of cigarettes in three critical ways: by enhancing smoke palatability and appeal and, as precursors to aldehydes and furans in the smoke, by increasing smoke toxicity and carcinogenicity and potentially addictiveness. Therefore, sugars are potentially the most versatile key constituents contributing to the smoking-associated morbidity and mortality. However, there is lack of robust quantitative data on the relationship between tobacco sugar content and relevant toxicant yields in U.S. commercial cigarettes, and the associated user exposures, behaviors, and cigarette appeal. In this study, we will leverage our combined expertise in tobacco chemistry, epidemiology, and human trials assessing biomarkers and behavioral and subjective measures, to address these key knowledge gaps. In Aim 1, we will use stable isotope-labeled sugars added to a commercial cigarette that is low in sugars and will analyze the dose-dependent formation of correspondingly labeled pyrolysis products in the smoke of this cigarette. to characterize the impact of sugars in the filler of U.S. cigarettes on the relevant chemical profile of cigarette smoke. We will also analyze the impact of sugar content on the levels of nicotine and tobacco-specific nitrosamines (TSNA) in the smoke. In Aim 2, we will analyze sugars in U.S. commercial cigarettes and use PATH biomarker data to investigate the impact of sugar content in cigarette tobacco on toxicant and carcinogen intake in U.S. smokers. In Aim 3, we will investigate the impact of sugar content in cigarette tobacco on cigarette abuse liability and appeal by conducting a laboratory study in which smokers will assess study cigarettes with differing levels of sugars in a laboratory setting. The overall goal of this proposal is to provide the FDA with the scientific basis to determine whether sugars should be added to HPHC list and whether their levels in tobacco products should be regulated.