Impact of sugars on tobacco product toxicity and abuse liability

项目摘要 糖，天然存在于某些烟草类型中，也被添加到卷烟烟草填料中， 添加剂，不包括在有害和潜在有害成分（HPHC）的FDA清单。现有 研究数据显示，烟草填充物中的糖可能会导致香烟的有害特性， 三个关键途径：通过提高烟雾的适口性和吸引力，以及作为醛和呋喃的前体， 通过增加烟的毒性和致癌性以及潜在的成瘾性，因此，糖 可能是导致吸烟相关疾病的最通用的关键成分， mortality.然而，烟草糖含量之间的关系缺乏可靠的定量数据， 和相关的有毒物质产量，以及相关的用户暴露，行为， 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， 以及评估生物标志物、行为和主观指标的人体试验，以解决这些关键问题。 知识差距。在目标1中，我们将使用稳定的同位素标记糖添加到商业香烟中， 低糖，并将分析相应标记的热解产物的剂量依赖性形成， 这支香烟的烟雾。描述美国香烟填充物中的糖对相关 香烟烟雾的化学成分我们还将分析糖含量对尼古丁水平的影响 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 烟草中的糖含量，并使用PATH生物标志物数据来研究烟草中糖含量对 美国吸烟者的有毒和致癌物质摄入量。在目标3中，我们将研究糖含量对 通过进行实验室研究，吸烟者将 在实验室环境中评估具有不同糖水平的研究香烟。本提案的总体目标是 为FDA提供科学依据，以确定是否应将糖添加到HPHC列表中， 是否应管制烟草制品中的汞含量。

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.