Pulmonary toxicological evaluation and chemical interactions of menthol, mint, and tobacco flavored e-cigarette products - PROJECT SUMMARY (See instructions): Menthol, cooling/ice, and tobacco flavors are among the most abundant for Electronic Nicotine Delivery Systems (ENDS) or electronic cigarettes. These flavors are not regulated due to the potential public health benefit cessation of combustible tobacco use. However, the toxicological effects of vaping these products are not entirely understood. Further, increased use of cooling/ice/menthol-like products is correlated with higher e-cig consumption due to their cooling and antitussive properties. However, the modified risk and toxicity of these products are poorly understood. The K99 /R00 proposal aimed at identifying the chemical agents (flavoring chemicals) that cause lung toxicity using cell culture and mouse models. As the K99 phase provided biologically significant data from acute exposures, we will continue the same aims as below with a modified R00 plan mainly focusing on sub-chronic (in vitro) and chronic (in vivo) exposures mentioned in Aims 2 and 3. The R00 phase will focus on validating the toxicants identified in the aerosols and relating them to the biological response and biomarkers. Moreover, these findings will be validating during prolonged exposures to flavored ENDS and chemical agents. This study hypothesizes that menthol/cooling flavors and tobacco flavors contain harmful chemicals that induce adverse cellular and biological responses and chemically interact upon aerosolization, causing augmented toxicity with preexisting respiratory conditions. Aim 1: Identify the chemistry of menthol, menthol-like (cooling), and tobacco flavors, including flavoring chemicals and secondary products formed upon aerosolization. Aim 2: Determine in vitro and in vivo toxicity and health effects of menthol, menthol-like (cooling), and tobaccoflavored ENDS in EpiAirway 3D tissues and mice (C57BL/6J and BALB/C) under normal and pre-existing respiratory conditions. Aim 3: Determine in vitro and in vivo toxicity and health effects of menthol, menthollike (cooling), and tobacco flavoring chemicals in EpiAirway 3D tissues and mice (C57BL/6J and BALB/C) under normal and pre-existing respiratory conditions. In R00 phase, effects in lung after sub chronic and chronic exposure to CS and then switching over to ENDS (menthol, cooling, and tobacco) will also be determined, allowing to assess the benefit or the modified toxicity of switching from CS to ENDS. This will further be studied in normal, asthma, and COPD, 3D tissues (sub chronic) and mice with the same phenotypes. Thus, Dr. Muthumalage, in his R00 proposes to perform a comparative toxicity, and biomarkers of disease under normal and pre-existing respiratory disease conditions providing information necessary for regulation of harmful constituents in these products.
