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A-TRAC Administrative Supplement Grant

Research Project: Administrative Supplements for Tobacco Regulatory Research on Tobacco Flavors and Flavorings


Daniel Conklin, Ph.D.
Daniel Conklin, Ph.D.
University of Louisville

  1. Identify and quantify the chemical products generated due to thermal degradation when tobacco product flavorings and additives are heated or burned; For this, we will heat or burn major classes of commonly used flavor chemicals currently used in tobacco products (alcohols, phenols, aldehydes, esters, ethers, hydrocarbons, ketones, lactones, organic acids, pyrazines, pyridines, and pyrones) at temperatures achieved by conventional pyrolysis and non-conventional heating methods used in aerosol formation, determine the extent of degradation of parent compounds, identify structures of the products and estimate the relative concentration of products generated during such thermal degradation; and
  2. Compare the relative toxicity of different flavorings commonly used in tobacco products with those flavorings after burning or heating. In in vitro assays we will measure the EC50 of each of the major classes of commonly used flavor chemicals (listed in Aim 1) in affecting platelet adhesion, endothelial activation and myocardial excitability, particularly Q-T prolongation and compare the sensitivity of these assays vis-à-vis assays for pulmonary and immune cell toxicity.  To avoid cross-species extrapolation, we will use human platelets and human epithelial and endothelial cells in culture.  In select assays, we will use freshly isolated human endothelial cells from venous biopsies. For measuring changes in cardiac excitability, we will examine changes in the inward rectifying potassium current (IKur) from induced pluripotent human fibroblasts differentiated into cardiac myocytes.  We will compare the results from these assays to determine which in vitro assay is capable of comparative toxicological assessments that can examine the harm potential between different flavorings currently used in tobacco products.

This study will provide valuable information about the chemicals generated from the thermal degradation of tobacco product flavorings, help establish their concentrations at different temperatures and determine which in vitro assays can effectively compare the cardiovascular toxicity of different flavorings used in cigarettes, cigars and e-cigarettes. Such information could prove critical to the FDA when determining the need and nature of potential regulation of these flavors and their derivatives.