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“暴露于以下物质的毒性评估 末端气溶胶、水管烟雾、雪茄烟雾中与烟草相关成分的复杂混合物，以及 无烟烟草使用毒理学测试，如体内，硅胶，以及体外模型，更 在生理上与人类相关。尽管CTP监管指南文件包括遗传毒性和 其他体外试验中要求提交毒性资料的类型，目前尚无标准化规定 各种烟草产品的评价指南或经监管部门批准的方法，包括END。 因此，501(C)(3)非营利性组织体外科学研究所(IIVS)组织了一次 确定、讨论和提出最佳科学/技术建议的系列研讨会 产生和解释用于比较烟草内部和跨烟草毒性的体外测试数据的方法 产品类别。作为真正的工作会议，专家利益相关者将讨论和制定 随后将公布的建议。该系列(2018-2022年)的最初重点一直是使用 调节性遗传毒理学试验(Ames试验、哺乳动物细胞遗传损伤体外试验和 基因突变)与各种类型的烟草和尼古丁产品有关。展望未来，我们将最终敲定 建议使用遗传毒理学分析和过渡到侧重于人体体外试验 潜在靶组织的模型，其中一些可以用作疾病模型。这些研讨会提供了 为多个利益相关者提供分享其专业知识的独特机会，并将提供发布的资源 监管机构、学术实验室和工业可能会在解决公共卫生问题时使用 与烟草产品的使用有关。研讨会的一些报告可以作为权威出版物， 可作为最佳方法和数据解释的参考。到目前为止，讲习班(1-7)已经 确定了使用体外分析来评价烟草产品的重要问题，并集中于 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信息 信息，在讲习班之间举行讨论，并提出讨论的建议 在研讨会期间。这些讲习班产生了多套建议。三 手稿已经出版，一份正在印刷，七份正在准备中。最终建议 使用Ames检测来比较不同烟草和尼古丁产品内部和之间的差异将是 在研讨会8(2023年2月)上发言。研讨会9(2023年6月)将集中讨论：1)口服烟草和尼古丁 产品(化学和体外方法)，以及2)评估一般毒性和疾病的方法- 利用人体3-D组织模型研究烟草产品的潜力。

Project Summary/Abstract Research priorities for the Center for Tobacco Products (CTP) include “Evaluation of toxicity from exposures to complex mixtures of tobacco-related constituents in ENDS aerosol, waterpipe smoke, cigar smoke, and smokeless tobacco using toxicological assays such as in vivo, in silico, as well as in vitro models that are more physiologically relevant to humans.” 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 (2018 – 2022) has been on the use of the regulatory genetic toxicology assays (Ames test, in vitro mammalian assays for cytogenetic damage and gene mutation) with various types of tobacco and nicotine products. Going forward we will finalize recommendations for the use of the genetic toxicology assays and transition to an emphasis on human in vitro models of potential target tissue, some of which can be utilized as 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 (1-7) 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, and to develop recommendations that are discussed during the workshops. Multiple sets of recommendations have resulted from these workshops. Three manuscripts have been published, one is in press, and seven are in preparation. Final recommendations for using the Ames assay to compare within and between various tobacco and nicotine containing products will be addressed in Workshop 8 (February 2023). Workshop 9 (June 2023) will focus on: 1) oral tobacco and nicotine products (chemistry and in vitro methods), and 2) approaches for evaluating both general toxicity and disease- causing potential of tobacco products using human 3-D tissue models.