Workshop series to identify, discuss, and develop recommendations for the optimal generation and use of in vitro assay data for tobacco product regulation.

项目概要/摘要 烟草制品中心（CTP）的研究重点包括“毒理学测定（体内和体内）”。 体外），以比较同一类别内不同类型烟草产品的毒性，包括电子 尼古丁输送系统（ENDS）、雪茄、水烟和无烟烟草。虽然CTP监管 指南文件包括遗传毒性和其他体外试验中所需的毒性信息类型 对于提交，没有标准化指南或监管批准的方法来评估 各种烟草制品，包括ENDS。因此，体外科学研究所（IIVS），501（c）（3） 非营利组织，组织了一个研讨会系列，以确定，讨论和发展的建议， 用于生成和解释体外试验数据以进行比较的最佳科学/技术方法 烟草产品类别内和类别间的毒性。设计为真正的工作会议，专家利益相关者 将讨论并提出建议，然后公布。该系列的最初重点是 调节性遗传毒理学试验（艾姆斯试验，体外哺乳动物细胞遗传学损伤试验 基因突变）。展望未来，将越来越重视人类疾病模型。这些 讲习班为多个利益攸关方提供了分享其专门知识的独特机会， 管理机构、学术实验室和工业界在解决以下问题时可能使用的已发布资源： 与使用烟草制品有关的公共卫生问题。部分研讨会报告可作为 权威出版物，可作为最佳方法和数据解释的参考。目前为止 讲习班确定了使用体外分析评估烟草制品的重要问题， 重点关注CTP的几个高优先级主题。成立了多个工作组， 提供背景资料，在讲习班之间举行讨论，起草草稿， 在讲习班期间提出和讨论的建议。共识声明有 这些研讨会的成果。两份手稿已经出版，两份正在编写中。为 即将举行的研讨会工作组正在编写更多背景文件。方法 产生用于体外细胞暴露的气溶胶和比较毒性效力的定量方法将是 2021年4月虚拟研讨会的重点。现计划于2021年10月及2022年4月举办工作坊。 各工作组正在讨论和编写背景文件，重点是ENDS产品， 此外，（1）剂量测定方法，（2）艾姆斯试验的建议，以及（3） 小鼠淋巴瘤基因突变测定。还将包括评估一般毒性和 和烟草制品的致病潜力，使用三维呼吸模型，

Project Summary/Abstract Research priorities for the Center for Tobacco Products (CTP) 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.” Although CTP regulatory guidance documents include genotoxicity and other in vitro assays in the types of toxicity information required for submissions, there is no standardized guidance or regulatory approved methods for the evaluation 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, expert stakeholders will discuss and develop recommendations that will then be published. The initial focus of the series has been on the regulatory genetic toxicology assays (Ames test, in vitro mammalian assays for cytogenetic damage and gene mutation). Going forward there will be an increasing emphasis on human disease models. These workshops provide a unique opportunity for multiple stakeholders to share their expertise and will provide published resources that regulatory agencies, academic laboratories, and industry may use as they address the public health issues related to the use of tobacco products. Some of workshop reports may serve as authoritative publications that can be referenced for optimal methodologies and data interpretation. So far, the workshops have identified important issues for using in vitro assays for evaluating tobacco products, and have focused on several of CTP’s high-priority topics. Multiple working groups have been established to collect background information, to hold discussions between workshops, to draft manuscripts, and to develop recommendations that are presented and discussed during the workshops. Consensus statements have resulted from these workshops. Two manuscripts have been published and two are in preparation. For upcoming workshops additional background documents are in preparation by working groups. Methods for generating aerosols for in vitro cell exposure and quantitative approaches to comparing toxicity potency will be the focus of a virtual workshop in April 2021. Workshops for October 2021 and April 2022 are now planned. Working groups are discussing and preparing background manuscripts with a focus on ENDS products and, in addition, (1) methods for dosimetry, (2) recommendations for the Ames test, and (3) recommendations for the mouse lymphoma gene mutation assay. Also included will be approaches for evaluating both general toxicity and disease-causing potential of tobacco products using 3-D respiratory models,