The abuse liability, topography and toxicology of ice flavors and non-menthol synthetic cooling agents in e-cigarette products

PROJECT SUMMARY Recently, synthetic cooling agents, WS-3 (N-ethyl-p-menthane-3-carboxamide) and WS-23 (2-isopropyl-N,2,3 trimethylbutyramide), that solely impart a cooling sensation without a mint flavor, have been detected in e-

cigarettes (ECs) and are marketed with “ice” as part of the flavor name (e.g., “watermelon ice”). Unlike menthol, synthetic cooling agents can be added at very high concentrations (>5% by weight) to e-liquids allowing users to get extreme cooling/anesthetic properties during vaping, without menthol’s unappealing properties (e.g., eye-

watering, harshness). Synthetic cooling agents have the potential to increase indirect and direct harm to EC users. The proposed study will be the first to systematically investigate the effects of synthetic cooling agents on the appeal, puffing behavior, and toxicity of vaping. We will use a single-blind randomized crossover trial with

young adult vapers (N = 120, aged 21-29-years), precisely manipulated e-liquids, a well-characterized commercial EC device, validated psycho-behavioral measures, and a novel puff-playback method to estimate human exposures to HPHCs and other toxicants from vaping e-liquids with and without synthetic cooling agents

(i.e., WS-3 and WS-23). Specifically, we aim to determine the impact of e-liquids with (mango ice, tobacco ice) and without (mango, tobacco) the presence of synthetic cooling agents on abuse liability (appeal, sensory effects, demand), EC puffing behavior (i.e., EC topography), and toxicant exposure (harmful and potential

harmful constituents). Additionally, topography data collected for all participants for each of the conditions vaped will be averaged to produce four human-derived puffing regimens. Machine vaping will be conducted for each of the four e-liquids using the associated human-derived puffing regimens to determine the range of HPHCs and

other toxicants in mainstream EC vapor. Findings would immediately inform the evidence base needed to inform FDA rulemaking surrounding the use of synthetic cooling agent additives in EC products.