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

研讨会系列旨在识别、讨论和制定烟草产品监管体外检测数据的最佳生成和使用建议

• 批准号: 10038732
• 负责人: Rodger D Curren
• 金额: $ 5万
• 依托单位: INSTITUTE FOR IN VITRO SCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10038732
• 关键词: Workshop; Series; Identify; Discuss; Develop

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.

项目概要/摘要 烟草制品中心 (CTP) 毒性研究重点包括“毒理学测定（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 (ENDS)、雪茄、水烟和无烟烟草监管指南。” 然而，文件中需要提交的毒性信息类型中包括遗传毒性。 对于传统遗传技术的应用，没有标准化的指导和监管批准的方法 毒理学测定来评估和比较各种烟草产品（包括 ENDS）的毒性。 501(c)(3) 非营利组织体外科学研究所 (IIVS) 组织了一系列研讨会 确定、讨论和制定最佳科学/技术方法的建议 解释体外测定数据，以比较烟草产品类别内和不同类别的毒性。 作为真正的工作会议，受邀专家利益攸关方将利用他们的集体经验进行讨论和 制定将要发表的建议，尽管最初的重点将是监管遗传。 毒理学测定（艾姆斯试验、体外哺乳动物细胞遗传学损伤和基因突变测定），大部分 讨论的信息将适用于所有体外测定，这些研讨会将提供独特的信息。 多个利益相关者有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、学术实验室和工业界解决公共卫生问题提供资源 预计将形成其中一些建议。 正式指导文件的基础和/或作为可供参考的权威出版物 该系列的第一个研讨会（2018 年 11 月）确定了最佳方法和数据解释。 该列表提供了使用体外遗传毒理学测定评估烟草产品的重要问题。 成立了后续研讨会的重点主题以收集信息。 生成适当烟草测试样品的背景信息，并提出了这些报告 并在第二次研讨会（2019 年 6 月）第三次和第四次研讨会（计划于 2019 年 6 月）期间进行了讨论。 2020年2月和9月）工作组将应对关键挑战并达成共识 建议的主题将包括：（1）不同类型的相对优点和代表性。 样本以及关键因素、陷阱的识别以及使用每种样本类型的建议 （重点是整个烟雾和气溶胶）用于体外测试，(2) 参考样品，(3) 适当的 样品的化学特性，(4) 适当的艾姆斯测试菌株，(5) 使用不同菌株的注意事项 哺乳动物细胞系和将悬浮细胞暴露于全烟雾/气溶胶的潜在新策略，(6) 最高样品浓度的建议，以及 (7) 确定实际目标暴露的方法。