Drug Dependence Clinical Research Program: New Biomarkers for Tobacco Exposure

描述（由申请人提供）：美国食品药品监督管理局烟草制品中心（CTP）最近公布了一份研究优先事项清单，该清单被认为与其烟草制品监管职责最相关。列出的第一个优先事项是“了解烟草产品的多样性。“虽然关于传统香烟的化学成分和人体暴露于烟草毒物的大量数据，但对新的和新兴的烟草产品（如鼻烟，电子香烟和水烟）的了解要少得多，用户可能认为这些产品比传统香烟危害小。我们资助的PSO，DA 012393，为许多进行烟草行为和毒理学研究的研究人员提供分析化学支持，包括一些与CTP的使命相关的研究人员。我们的PSO还开发了新的暴露生物标志物，并改进了用于评估烟草毒素暴露的分析化学方法。在本修订申请中，我们建议开发新的暴露生物标志物：（1）烟草生物碱尼古丁作为烟草烟雾颗粒物（TPM，“焦油”）的生物标志物，以及（2）假羟尼古丁，烟草特异性致癌物4-（甲基亚硝胺）-1-（S-吡啶基）-1-丁酮（NNK）的化学前体。在开发这些生物标志物的过程中，我们将分析使用新产品的受试者的尿液样本：水烟，鼻烟和电子烟。我们还将分析传统烟草产品使用者的尿液样本：香烟，雪茄和口吸鼻烟。我们还将分析新的和传统的烟草产品的有毒物质及其前体。我们的申请涉及FOA中列出的当前项目的四个FDA研究重点（2-5）。如果获得资助，我们预计我们开发的新生物标志物将有助于FDA评估新的和新兴的烟草产品，增强我们的PSO支持与FDA CTP使命相关的研究的能力，并推进烟草暴露评估领域。我们希望我们的分析化学方法将识别烟草中预测人类毒性的物质，从而代表监管或开发降低危害产品的可能目标。

DESCRIPTION (provided by applicant): The U.S. Food and Drug Administration Centerfor Tobacco Products (CTP) recently published a list of research priorities deemed most relevant to its responsibility for the regulation of tobacco products. The first priority listed is "understandng the diversity of tobacco products." While extensive data are available on the chemical composition and human exposure to tobacco toxicants for conventional cigarettes, much less is known about new and emerging tobacco products such as snus, electronic cigarettes, and hookah, that users may perceive as less harmful than conventional cigarettes. Our funded PSO, DA012393, provides analytical chemistry support to numerous investigators carrying out behavioral and toxicological studies of tobacco, including some relevant to the mission of CTP. Our PSO also develops new biomarkers of exposure, and improved analytical chemistry methods for assessment of exposure to tobacco toxins. In this Revision Application, we are proposing to develop new biomarkers of exposure: (1) the tobacco alkaloid nicotelline as a biomarker for tobacco smoke particulate matter (TPM, "tar"), and (2) pseudooxynicotine, the chemical precursor to the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(S-pyridyl)-1-butanone (NNK). In developing these biomarkers, we will analyze urine samples from subjects using new and emerging products: hookah, snus, and electronic cigarettes. We will also analyze urine samples from users of conventional tobacco products: cigarettes, cigars, and oral snuff. We will also analyze new and conventional tobacco products for toxic substances and their precursors. Our application addresses four FDA research priorities (2-5) listed in the FOA for the present program. If funded, we expect that the new biomarkers that we develop will aid the FDA in evaluation of new and emerging tobacco products, enhance the ability of our PSO to support studies relevant to the FDA CTP's mission, as well as advance the field of tobacco exposure assessment. We expect that our analytical chemistry methods will identify substances in tobacco that predict human toxicity, and thus represent possible targets for regulation or development of reduced harm products.