Assessment of a novel heated non-tobacco product versus the 1R6F reference cigarette: A comparative study

Abstract

Heated tobacco products (HTPs) have emerged as a new option for smokers seeking alternatives to cigarettes. Tobacco Heating System (THS) 3.0 consists of an induction heating device that heats specially designed tobacco sticks (i.e., HTPs) or heated non-tobacco products (HnTPs), without triggering combustion. HnTPs are tobacco-free and consist of a cellulose-based substrate with nicotine salt, aerosol former, and flavors. This study assessed the chemical composition, physical properties, cytotoxicity, genotoxicity, and mutagenicity of HnTP aerosol in comparison with cigarette smoke. The absence of tobacco and combustion results in substantially reduced amount of harmful and potentially harmful constituents (HPHCs) in the HnTP aerosol compared to cigarette smoke. Characterization of the aerosol demonstrated that HPHCs are reduced on average by at least 99% compared to cigarette smoke, and the aerosol is liquid-based, further distinguishing it from combustion-derived particulate matter. Non-targeted differential screening analysis did not identify any new compounds of toxicological concern compared to cigarette smoke. In vitro studies with a battery of tests, including neutral red uptake, micronucleus, and Ames assay, demonstrated that aerosol fractions of HnTP, when used together with THS 3.0 device, induced substantially less cytotoxicity, mutagenicity, and genotoxicity responses than cigarette smoke. Collectively, the evidence demonstrates that HnTP used as part of the induction heating system does not involve combustion and results in substantially fewer and lower levels of HPHCs, leading to reduced in vitro toxicity compared to cigarette smoke.