Workshop Series to Identify, Discuss and Develop Recommendations for the Optimal Generation and Use of In Vitro Assay Data for Tobacco Product Regulation

项目摘要/摘要 烟草制品中心(CTP)的毒性研究重点包括“毒理学分析(体内和体内)” 体外)比较同一类别内不同类型烟草产品的毒性，包括电子烟 尼古丁输送系统(完)、雪茄、水烟和无烟烟草。CTP监管指南 文件包括提交所需毒性信息类型中的遗传毒性。然而，在那里 对于传统基因的应用，没有标准化的指导和监管批准的方法 毒理学测试是评估和比较各种烟草产品的毒性，包括END。因此， 501(C)(3)非营利性组织体外科学研究所组织了一系列讲习班 确定、讨论和制定最佳科学/技术方法的建议 以及解释用于比较烟草产品类别内和跨烟草产品类别的毒性的体外测试数据。设计 作为真正的工作会议，受邀的专家利益攸关方将利用他们的集体经验来讨论和 制定将公布的建议。尽管最初的重点将是监管基因 毒理学检测(Ames试验，哺乳动物细胞遗传损伤和基因突变的体外检测)，大部分 所讨论的信息将适用于所有的体外分析。这些研讨会将提供一个独特的 为多个利益相关者提供机会，分享他们在制定建议方面的专业知识，这些建议将作为 为监管机构、学术实验室和行业提供的资源，用于解决公共卫生问题 与使用烟草产品有关的问题。据设想，其中一些建议将形成 正式指导文件的基础和/或作为可供参考的权威出版物 最佳方法和数据解释。本系列的第一个讲习班(2018年11月)确定了 使用体外遗传毒理学方法评价烟草制品的重要问题。此列表提供了 为随后的讲习班重点讨论的高优先专题。成立了子工作组，以收集 生成适当的烟草测试样本的背景信息，并介绍了这些报告 并在第二次研讨会(2019年6月)上进行了讨论。在第三和第四期讲习班期间(计划于 2020年2月和9月)工作组将解决关键挑战并达成共识 建议。主题将包括：(1)不同类型的 样品和关键因素的识别、陷阱和使用每种样品类型的建议 (重点是全烟和气溶胶)用于体外试验，(2)参考样品，(3)适当 样品的化学特性，(4)适当的Ames试验菌株，(5)使用不同 哺乳动物细胞系和悬浮细胞暴露在全烟/气溶胶中的潜在新策略，(6) 关于最高样品浓度的建议，以及(7)确定实际目标暴露的方法。

Project Summary/Abstract The Center for Tobacco Products (CTP) toxicity research priorities include “toxicological assays (in vivo and in vitro) to compare toxicity across different types of tobacco products within the same class, including electronic nicotine delivery systems (ENDS), cigars, waterpipes, and smokeless tobacco.” CTP regulatory guidance documents include genotoxicity in the types of toxicity information required for submissions. However, there are no standardized guidances and regulatory approved methods for the application of traditional genetic toxicology assays to evaluate and compare toxicities of various tobacco products, including ENDS. Therefore, the Institute for In Vitro Sciences (IIVS), a 501(c)(3) nonprofit organization, has organized a Workshop Series to identify, discuss and develop recommendations for the best scientific/technical approaches for generating and interpreting in vitro assay data for comparing toxicity within and across tobacco product classes. Designed as true working meetings, invited expert stakeholders will draw on their collective experiences to discuss and to develop recommendations that will be published. Although the initial focus will be on the regulatory genetic toxicology assays (Ames test, in vitro mammalian assays for cytogenetic damage and gene mutation), much of the information discussed will be applicable to all in vitro assays. These workshops will provide a unique opportunity for multiple stakeholders to share their expertise in developing recommendations that will serve as a resource for regulatory agencies, academic laboratories, and industry as they address the public health issues related to the use of tobacco products. It is envisioned that some of these recommendations would form the basis for formal guidance documents and/or serve as authoritative publications that can be referenced for optimal methodologies and data interpretation. The first workshop in this series (November 2018) identified important issues for using in vitro genetic toxicology assays for evaluating tobacco products. This list provides the focused high-priority topics for subsequent workshops. Sub-workgroups were established to collect background information for generating appropriate tobacco test samples, and these reports were presented and discussed during the second workshop (June 2019). During the third and fourth workshops (scheduled for February and September 2020) the workgroup will tackle key challenges and develop consensus recommendations. Topics will include: (1) the relative merits and representativeness, of different types of samples and the identification of critical factors, pitfalls, and recommendations for using each sample type (with an emphasis on whole smoke and aerosols) for in vitro testing, (2) reference samples, (3) appropriate chemical characterization of samples, (4) appropriate Ames test strains, (5) considerations for using different mammalian cell lines and potential new strategies for exposing suspension cells to whole smoke/aerosol, (6) recommendations for top sample concentration, and (7) approaches to determining actual target exposure.