Project Summary/Abstract
The Center for Tobacco Products (CTP) toxicity research priorities 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.” CTP regulatory guidance
documents include genotoxicity in the types of toxicity information required for submissions. However, there
are no standardized guidances and regulatory approved methods for the application of traditional genetic
toxicology assays to evaluate and compare toxicities 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, invited expert stakeholders will draw on their collective experiences to discuss and
to develop recommendations that will be published. Although the initial focus will be on the regulatory genetic
toxicology assays (Ames test, in vitro mammalian assays for cytogenetic damage and gene mutation), much of
the information discussed will be applicable to all in vitro assays. These workshops will provide a unique
opportunity for multiple stakeholders to share their expertise in developing recommendations that will serve as
a resource for regulatory agencies, academic laboratories, and industry as they address the public health
issues related to the use of tobacco products. It is envisioned that some of these recommendations would form
the basis for formal guidance documents and/or serve as authoritative publications that can be referenced for
optimal methodologies and data interpretation. The first workshop in this series (November 2018) identified
important issues for using in vitro genetic toxicology assays for evaluating tobacco products. This list provides
the focused high-priority topics for subsequent workshops. Sub-workgroups were established to collect
background information for generating appropriate tobacco test samples, and these reports were presented
and discussed during the second workshop (June 2019). During the third and fourth workshops (scheduled for
February and September 2020) the workgroup will tackle key challenges and develop consensus
recommendations. Topics will include: (1) the relative merits and representativeness, of different types of
samples and the identification of critical factors, pitfalls, and recommendations for using each sample type
(with an emphasis on whole smoke and aerosols) for in vitro testing, (2) reference samples, (3) appropriate
chemical characterization of samples, (4) appropriate Ames test strains, (5) considerations for using different
mammalian cell lines and potential new strategies for exposing suspension cells to whole smoke/aerosol, (6)
recommendations for top sample concentration, and (7) approaches to determining actual target exposure.
