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

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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.