Genotoxicity evaluation of tobacco and nicotine delivery products: Part One. Mouse lymphoma assay.

Introduction:
This article describes a study that evaluates the suitability of the Mouse Lymphoma assay (MLa) for genotoxicity testing of a variety of tobacco and nicotine products. The study compares the genotoxicity of total particulate matter (TPM) from a 3R4F cigarette, a commercial electronic cigarette liquid (e-liquid), electronic cigarette (e-cigarette) aerosol matter captured from the same e-liquid, and TPM from a commercial ThP. The study was conducted under different treatment conditions, including 3-hour exposures with and without metabolic activation and a longer 24-hour exposure without metabolic activation.

Key Points:

* The 3R4F cigarette produced a clear positive response in inducing mutation under all treatment conditions.
* The e-liquid, e-cigarette aerosol, and ThP did not show a marked induction of mutation under any treatment condition.
* Data were presented as a function of nicotine equivalents for comparisons between these different tobacco products and test matrices.
* The study used the MLa assay according to OECD Test Guideline 490 and ICh S2(R1) guidance.
* The test articles included TPM from a 3R4F cigarette, ThP, e-cigarette, and e-liquid from the same e-cigarette.
* The study used a RM200 smoking machine to generate TPM from cigarettes and e-cigarettes and a RM200a smoking machine for ThP.
* The e-liquid was diluted and prepared in DMSO prior to use.
* Partner and quality control pads were analyzed for nicotine, water, and glycerol content using gas chromatography techniques.

Main Message:
The study concludes that the MLa assay is suitable for genotoxicity testing of tobacco and nicotine products. The results show that the 3R4F cigarette produced a positive response in inducing mutation, while the e-liquid, e-cigarette aerosol, and ThP did not show a marked induction of mutation under any treatment condition. The study also demonstrates that data can be presented as a function of nicotine equivalents to compare different tobacco products and test matrices. Overall, the study provides valuable information for regulators and manufacturers of tobacco and nicotine products regarding the genotoxicity of these products.

Thorne D, Leverette R, Breheny D, et al. Genotoxicity evaluation of tobacco and nicotine delivery products: Part One. Mouse lymphoma assay. Food and chemical toxicology : an international journal published for the British Industrial Biological Research association. 2019;132:110584. doi:10.1016/j.fct.2019.110584