Smoke Chemistry, In vitro Cytotoxicity, and Genotoxicity Demonstrates Enhanced Toxicity of Cigarillos Compared to Cigarettes.

There has been limited toxicity testing of cigarillos, including comparison to cigarettes. The present study compared the smoke chemistry and the cytotoxic and genotoxic potential of ten conventional cigarettes and ten cigarillos based on the greatest market share. Whole smoke and total particulate matter (TPM) were generated using the Canadian Intense (CI) and International Organization for Standardization (ISO) puffing protocols. Tobacco specific nitrosamines (TSNAs), carbonyls, and polycyclic aromatic hydrocarbons (PAHs) were measured using GC-MS. TPM smoke extracts were used for the in vitro assays. Cytotoxicity was assessed in HBEC4 cells using the neutral red uptake assay. Genotoxic potential was assessed using the micronucleus (MN; A549 cells), Ames, and thymidine kinase (TK) assays. TPM from all cigarillos tested was more cytotoxic than cigarettes. MN formation was significantly greater for cigarillos compared to cigarettes at the highest dose of TPM, with or without rat liver S9 fraction. In the Ames test +S9, both tobacco products exhibited significant dose-dependent increases in mutation frequency (MF), indicating metabolic activation is required for genotoxicity. In the TK assay +S9, cigarillos showed a significantly enhanced MF although both tobacco products were positive. The levels of all measured PAHs, TSNAs, and carbonyls (except acrolein) were significantly greater in cigarillos than cigarettes. The CI puffing protocol demonstrated increased smoke constituent levels compared to ISO. Even though the gas vapor phase was not tested, the results of this study showed that under the tested conditions the investigated cigarillos showed greater toxicity than comparator cigarettes. This study found that there is significantly greater toxicity in the tested US marketed cigarillos than cigarettes for tobacco constituent levels, cytotoxicity, and genotoxicity. These findings are important for understanding the human health toxicity from the use of cigarillos relative to cigarettes and for building upon knowledge regarding harm from cigarillos to inform risk mitigation strategies.