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