Project 1: Toxicity testing of New & Manipulated Tobacco Products p139-181

为了履行其规范烟草制品和保护公众健康的使命，FDA烟草制品中心 烟草制品（CTP）致力于了解人们如何使用各种各样的烟草 产品的可用性和由此产生的接触毒素和成瘾性化学品。作为有力的第一步， 为了指导研究工作，FDA CTP根据同行评审的毒理学发现， 可能被吸入、摄入或吸收的对健康有害和潜在有害的成分（HPHC） 由于烟草产品的使用。HPHC包括致癌物质，呼吸道，心血管， 生殖和发育有毒物质：所有这些化学物质都是烟草的已知成分 产品.从2013年开始，FDA规定的烟草制品中HPHC含量报告将 烟草行业的要求。虽然烟草产品的排放和含量很重要， 产品总体毒性的组成部分、用户行为和由此产生的人体接触对于 了解多种烟草产品类型和品牌之间的危害差异。这 该项目旨在告知FDA CTP正在进行的量化实际人体暴露的努力，并确定 并测量直接导致烟草使用相关疾病风险的毒素。科学的力量 传统生物标志物监测数据的可靠性取决于假设所有研究对象都忠实地 长期单独使用试验产品。我们知道大多数烟草使用者， 所有消费者的品牌忠诚度，往往不符合这一要求。人类的行为和 为支持该项目而收集的暴露数据旨在增强传统的生物标志物 在收集这些数据时，通过提供不受试者不依从性混淆的数据主体 在直接使用烟草制品之前和之后立即。利用人类交叉 试验和一个既定的加强方法范例，从新的和 将对经处理的烟草产品进行测量。这些可辩护的客观数据将得到 强大的质量保证/质量控制计划，并将迅速提供给FDA CTP和其他 合作中心通过一个安全的、基于电子邮件的互联网为烟草监管提供信息 数据库

In keeping with its mission to regulate tobacco products and protect the public health, the FDA Center for Tobacco Products (CTP) is committed to understanding how people use the myriad of diverse tobacco products available and the resulting exposure to toxins and addictive chemicals. As a strong first step to guide research efforts, the FDA CTP has established, based on peer-reviewed toxicological findings, a list of harmful and potentially harmful constituents to health (HPHCs) that may be inhaled, ingested, or absorbed as a result of tobacco product use. The HPHCs include carcinogens, respiratory, cardiovascular, reproductive, and developmental toxicants: all of these chemicals are known components of tobacco products. Starting in 2013, FDA-mandated reporting of the quantities of HPHCs in tobacco products will be required of the tobacco industry. Although tobacco product emissions and content are important components of a product's overall toxicity, user behavior and resulting human exposures are critical to understanding the difference in harm among the many tobacco product types and brands available. This project is designed to inform the FDA CTP's ongoing efforts to quantify actual human exposures, and identify and measure toxins that directly contribute to the risk of tobacco use-related disease. The scientific potency of traditional biomarker monitoring data hinges on the assumption that all of the study subjects faithfully and solely use the test product for prolonged periods. We know that most tobacco users, having the highest brand loyalty of all consumers, often do not comply with this requirement. The human behavior and exposure data that will be collected in support of this project are designed to enhance traditional biomarkers by providing a body of data that is not confounded by subject non-compliance, as these data are collected before and immediately after direct use of the tobacco products. Using a combination of human crossover trials and an established boost method paradigm, the relative exposures to HPHCs from new and manipulated tobacco products will be measured. These defensible objective data will be supported by a robust Quality Assurance/Quality Control program, and will be made available rapidly to FDA CTP and other collaborating Centers to inform tobacco regulation via a secure, privilege-based internet accessible database.