assessment of In Vitro Toxicity/Genotoxicity of ENDS and Combustible Products

Introduction:
This text provides an overview of an in vitro toxicology study conducted to support a Premarket Tobacco Product application (PMTa) for Electronic Nicotine Delivery Systems (ENDS). The study aimed to assess the genotoxic potential of ENDS e-liquids, aerosols, and U.S. market comparators using bacterial mutagenicity, in vitro micronucleus, and cytotoxicity assays. The study also compares the toxicity levels of ENDS to those of combustible tobacco products.

Key Points:

* The study followed guidelines set by the International Conference on harmonization (ICh) S2(R1) and Organization for Economic Cooperation and Development (OECD) for genotoxicity testing.
* Three different test matrices were used for each flavor variant of a single ENDS product, including e-liquid, total particulate matter (TPM), and gas vapor phase (GVP).
* The ames bacterial reverse mutation assay, the in vitro micronucleus (IVMN) genotoxicity assay, and the Neutral Red Uptake (NRU) cytotoxicity assay were conducted on market combustible and ENDS products.
* The TPM and GVP of the products were generated using an intense puffing regimen and collected and assayed separately.
* The study found that the ENDS e-liquids, TPM, and GVP were either negative or demonstrated limited response at the highest concentrations tested, while the combustible market cigarette comparator was consistently positive in the assays.
* The study highlights the potential of ENDS to reduce harm associated with combustible tobacco product use due to lower comparative toxicant levels.
* The study emphasizes the importance of using a multi-assay approach for in vitro toxicity assessment of tobacco products.

Main Message:
The study underscores the significance of in vitro toxicology testing for ENDS PMTa applications, as recommended by the U.S. Food and Drug administration Center for Tobacco Products. The results demonstrate that ENDS products exhibit lower toxicity and genotoxicity compared to combustible tobacco products, further supporting the potential of ENDS to reduce harm associated with traditional tobacco use. The study emphasizes the importance of a multi-assay approach for in vitro toxicity assessment of tobacco products and provides a valuable example for companies seeking to submit PMTa applications for ENDS.

Jordan, K. et al. "assessment of In Vitro Toxicity/Genotoxicity of ENDS and Combustible Products." RaI Services Company