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。尽管CTP监管 指导文件包括所要求的毒性信息类型中的遗传毒性和其他体外试验。 对于提交的文件，没有标准化的指南或监管部门批准的方法来评估 各种烟草产品，包括烟头。因此，体外科学研究所(IIVS)，a 501(C)(3) 非营利组织，组织了一系列研讨会，以确定、讨论和制定以下建议 生成和解释用于比较的体外分析数据的最佳科学/技术方法 烟草产品类别内部和之间的毒性。设计为真正的工作会议、专家利益相关者 将讨论并制定建议，然后发布这些建议。该系列最初的重点是 关于调节性遗传毒理学试验(Ames试验、体外哺乳动物细胞遗传学损伤试验 和基因突变)。展望未来，人类疾病模型将受到越来越多的重视。这些 研讨会为多个利益相关者提供了一个独特的机会来分享他们的专业知识，并将提供 发布的资源，监管机构、学术实验室和行业可能会在解决这些问题时使用 与使用烟草产品有关的公共卫生问题。研讨会的一些报告可以作为 可供参考的权威出版物，用于最佳方法和数据解释。到目前为止， 研讨会已经确定了使用体外分析来评价烟草产品的重要问题，并已 专注于CTP的几个高优先级主题。已经建立了多个工作组来收集 背景资料，在讲习班之间举行讨论，起草手稿，并制定 研讨会期间提出和讨论的建议。共识声明有 这些讲习班的成果。已经出版了两份手稿，两份正在准备中。为 工作组正在编写即将举行的讲习班和其他背景文件。方法： 产生用于体外细胞暴露的气雾剂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。现已计划在2021年10月和2022年4月举办讲习班。 工作组正在讨论和编写背景手稿，重点放在最终产品和，在 此外，(1)剂量学方法，(2)Ames试验的建议，以及(3) 小鼠淋巴瘤基因突变试验。还将包括评估两种一般毒性的方法 利用3-D呼吸模型研究烟草产品的致病潜力，

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,