A comparative assessment of HPHC yields and <i>in vitro</i> toxicity for 1R6F reference cigarette smoke versus aerosol generated by Tobacco Heating System 3.0

Heated tobacco products (HTPs) have emerged as an alternative to cigarettes in the last 10 years. HTPs heat rather than burn tobacco to produce a nicotine-containing aerosol. Avoiding combustion reduces the amount of harmful and potentially harmful constituents (HPHCs) in HTP aerosol compared to cigarette smoke. As heating technologies evolve, it is important to thoroughly assess new iterations to confirm that the aerosol they produce contains fewer and lower levels of HPHCs than cigarette smoke. Tobacco Heating System (THS) 3.0 is an induction heating device used with specially designed tobacco sticks. This paper describes the chemical composition, physical properties, cytotoxicity, genotoxicity, and mutagenicity of the aerosols produced by THS 3.0 using the International Organization for Standardization (ISO) intense puffing regimen for regular and menthol tobacco sticks. Targeted chemical testing and physics evaluations confirmed that &gt;95% of the aerosol droplets are respirable with substantial HPHC yield reductions compared to cigarette smoke. A standard battery of <i>in vitro</i> toxicology tests was performed to assess the aerosols’ cellular effects. Results from the neutral red uptake, micronucleus, and Ames assays showed that THS 3.0 aerosol fractions induced substantially less cytotoxicity and have substantially lower genotoxic and mutagenic potentials than cigarette smoke fractions. Collectively, the evidence demonstrates that inductively heated tobacco sticks used with THS 3.0 produce aerosol emissions and substantially lower levels of HPHCs similar to those with THS 2.2—a previous version of HTP with resistive heating—leading to reduced <i>in vitro</i> cytotoxicity and genotoxicity compared to cigarette smoke.