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.
