Synthetic Cooling Agents in US-marketed E-cigarette Refill Liquids and Disposable E-cigarettes: Chemical Analysis and Risk Assessment.

Abstract Background Menthol, through its cooling sensory effects, facilitates smoking and tobacco product initiation, which is reflected by the high popularity of mint/menthol-flavored E-cigarettes. More recently, E-cigarette vendors started marketing synthetic cooling agents as additives that impart a cooling effect but lack a characteristic minty odor. Knowledge about content of synthetic coolants in US-marketed E-cigarette products and associated health risks is limited. Methods E-liquid vendor sites were searched with the terms “koolada”, “kool/cool”, “ice”, or WS-3/WS-23, denoting individual cooling agents, and relevant refill E-liquids were purchased. “Ice” flavor varieties of Puffbar, the popular disposable E-cigarette brand, were compared with non-“Ice” varieties. E-liquids were characterized, and synthetic coolants quantified using GC/MS. Margin of exposure (MOE), a risk assessment parameter, was calculated to assess the risk associated with synthetic coolant exposure from E-cigarette use. Results WS-3 was detected in 24/25 of the identified refill E-liquids (24/25), while almost all Puffbar disposables flavor varieties contained WS-23 (13/14), with 5/14 also containing WS-3, in both “Ice”- and non-“Ice” flavors. Modeling consumption of WS-3 from vaped E-liquids resulted in MOEs below the safe margin of 100 for most daily use scenarios (3-mL:14/25 E-liquids; 5-mL:18/25; 10-mL:20/25). MOEs for WS-23 from 11/13 Puffbar products were ≤100 in all use scenarios. Conclusions Synthetic cooling agents (WS-3, WS-23) were present in US-marketed E-cigarettes, at levels that may result in consumer exposures exceeding safety thresholds set by regulatory agencies. Synthetic cooling agents are not only found in mint-or menthol-flavored products, but also in fruit- and candy-flavored products, including popular disposable E-cigarette products such as Puffbar. Implications Synthetic cooling agents are widely used in “kool/cool”- and “ice”-flavored E-liquids and in E-liquids without these labels, both as a replacement for menthol or to add cooling ‘notes’ to non-menthol flavors. These agents may be used to bypass regulatory limits on menthol content in tobacco products. Since synthetic cooling agents are odorless, they may not fall under the category of “characterizing flavor”, potentially circumventing regulatory measures based on this concept. Regulators need to consider the additional health risks associated with exposure to synthetic cooling agents.