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

项目总结 最近，合成冷却剂WS-3(N-乙基-对-薄荷烷-3-甲酰胺)和WS-23(2-异丙基-N，2，3 三甲基丁酰胺)，只给人一种凉爽的感觉，没有薄荷味道，在e- 香烟(ECs)，在市场上以“冰”作为味道名称的一部分(例如，“西瓜冰”)。与薄荷醇不同， 合成冷却剂可以以非常高的浓度(重量5%)添加到电子液体中，从而允许用户 为了在蒸发过程中获得极端的冷却/麻醉特性，而不会出现薄荷醇的不良特性(例如，眼睛- 浇水、严酷)。合成冷却剂有可能增加对EC的间接和直接危害 用户。这项拟议的研究将是第一次系统地研究合成冷却剂对 蒸发的吸引力、吞吐行为和毒性。我们将使用单盲随机交叉试验 青少年尿布(N=120，年龄21-29岁)，精确操纵电子液体，特征良好 商用EC设备，有效的心理行为测量，以及一种新的喷雾回放方法来估计 使用和不使用合成冷却剂蒸发电子液体对HPHCs和其他毒物的人体暴露 (即WS-3和WS-23)。具体来说，我们的目标是确定电子液体与(芒果冰、烟草冰)的影响 以及没有(芒果、烟草)存在的合成冷却剂对滥用的责任(上诉、感官 影响、需求)、EC吞吐行为(即EC地形)和毒物暴露(有害的和潜在的 有害成分)。此外，为所有参与者收集的每种条件下的地形数据被蒸发 将平均产生四种人类衍生的吞噬养生法。将对以下每个人进行机器蒸发 四种电子液体使用相关的人类衍生膨化方案来确定HPHC和 主流EC蒸气中的其他有毒物质。调查结果将立即通知所需的证据库 FDA制定关于在EC产品中使用合成冷却剂添加剂的规则。

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.