O’Neil HC, Vincent MJ, Han AA, Brown SE, Hazell AM, Krieder ML, Madl AM. Hazard and risk banding framework for prioritization and bridging of e-liquids for toxicity testing. Poster presented at Society of Toxicology Annual Meeting, virtual event, March 2021.
The number of e-liquids available on the market have dramatically multiplied with the increasing use of electronic nicotine delivery systems (ENDS) as a reduced-risk nicotine alternative to combustible cigarettes or other tobacco products. E-liquids are available across a broad range of flavors (from fruity or dessert flavors to more traditional tobacco and mint flavors), nicotine strengths, and nicotine forms (freebase or nicotine salt). E-liquid flavorant ingredients may vary widely in concentration and in number of constituents. Due to the complexity and increasing number of e-liquid formulations, not all products are tested for health hazards using robust toxicity testing. In order to prioritize formulations for toxicity testing, a read-across or bridging framework, that accounts for ingredient homology across formulations and hazard banding, can be applied. Characteristic ingredients of the various flavor categories including mint, tobacco, dessert/candy, fruit, coffee/tea, and alcoholic beverages were identified and thereafter categorized by hazard. Ingredients predictive for carcinogenesis, mutagenicity/genotoxicity, reproductive/developmental toxicity, and skin or respiratory sensitization potential were identified in flavor categories by computational modeling and review of established toxicological databases. For the flavor ingredients with the highest hazard categories, screening risk assessments were performed utilizing health guidance values or thresholds of toxicological concern. Based on this hazard banding and risk assessment, a subset of e-liquid products were identified as candidates for in vitro toxicity testing, from which the results are generalizable to a broader group of e-liquid products with comparable hazard profiles. The hazard and risk banding framework illustrated in this analysis demonstrates how specific e-liquid formulations can be evaluated from a toxicological perspective to inform on the hazard and risk of a broader group of e-liquid products. These tools are also useful in directing new product development and in determining implications for public health