A screening approach for the evaluation of tobacco-free 'modern oral' nicotine products using Real Time Cell Analysis

Introduction:
This text describes a study that explores the use of Real Time Cell Analysis (RTCA) as a screening tool for Modern Oral Products (MOPs), also known as tobacco-free nicotine pouches. The study includes an evaluation of multiple parameters, such as cell types, extract nicotine concentration, osmolarity, and cytotoxicity acceptance criteria, to optimize the approach for assessing MOPs.

Key Points:

* The RTCA platform was chosen for its real-time and semi-automated nature compared to classical cytotoxicity assays.
* Nicotine extract concentration was determined to characterize and quality control the extracts generated in this study.
* HGFs were chosen as a physiologically relevant route of exposure for MOPs, but H292s were used for the majority of the testing due to their ease of culture and growth.
* Flavor (Table 3) and nicotine strength (4-11 mg) do not increase the overall toxicity of MOPs in a short-term assay.
* The study demonstrates that flavored nicotine products have a key role to play in providing alternatives for smokers and that electonic cigarettes have played an important role in reducing smoking rates in the UK.
* The next phase of the assessment framework will be to consider any genotoxicological effects and to conduct repeated dose studies in a more physiologically relevant 3D tissue system.

Main Message:
The main message of this text is that RTCA is a reliable and efficient screening technique for MOPs and can be used to quickly identify variants that may pose risks and require further in vitro investigation with repeated use. The study also highlights the potential for MOPs, with nicotine levels comparable to levels found in Swedish-style snus, to have similar or greater harm reduction potential compared to smoking. However, it is important to continue to evaluate tobacco free-MOPs and their risk profile through a robust pre-clinical assessment framework.

East, N., Bishop, E., Breheny, D., Gaca, M., & Thorne, D. (2021). A screening approach for the evaluation of tobacco-free “modern oral” nicotine products using Real Time Cell Analysis. Toxicology Reports, 8, 481–488. https://doi.org/10.1016/j.toxrep.2021.02.014