Assessing the respiratory effects of inhaling synthetic coolants used as flavor ingredients in ends

The National Institutes of Health awarded Health Research, Inc. (Roswell Park Division) $830,722 on August 15, 2026, under the Family Smoking Prevention and Tobacco Control Act Regulatory Research program (CFDA 93.077) to assess the respiratory effects of inhaling synthetic coolants used as flavor ingredients in electronic nicotine delivery systems.

The project will evaluate pulmonary function and inflammatory effects resulting from inhalation of the synthetic coolants WS-3 and WS-23, which are increasingly used in "ice"-flavored ENDS products in response to regulatory restrictions on menthol. Although these compounds are recognized as safe for ingestion, their safety has not been evaluated for inhalation, the primary exposure route for ENDS. The research uses an established animal model of chronic inhalation across two specific aims: the first assesses respiratory impact in individuals naive to tobacco products initiating vaping with ENDS containing synthetic coolants compared to the same products without coolants or with menthol, including dose-response effects; the second simulates scenarios in which menthol cigarette smokers switch to vaping ENDS with synthetic coolants, determining changes in pulmonary function and inflammation.

The award runs through July 31, 2031. Work is performed in Buffalo, New York. The assistance type is a Project Grant.

Abstract

In recent years, the industry has introduced synthetic coolants as flavors in response to emerging regulations restricting menthol use in various tobacco products. These coolants are commonly found in electronic nicotine delivery systems (ENDS) with "ICE" flavors. "ICE"-flavored ENDS are increasingly popular, including FDA- unauthorized brands (e.g., puff bar, elfbar, lost mary) with flavor descriptors that connote both characterizing and cooling features (e.g., "tobacco ICE," "tobacco cool," and "tobacco chill"). The two most used synthetic coolants in ENDS products are WS-3 and WS-23 compounds. Although synthetic coolants WS-3 and WS-23 are recognized as safe for ingestion, their safety has not been evaluated for inhalation, a primary exposure route for ENDS. There is a GAP in knowledge of the respiratory effects resulting from the inhalation of these two synthetic coolants used in ENDS. The overall goal of this project is to assess the potential respiratory impact of vaping ENDS containing synthetic coolants WS-3 or WS-23 using an established animal model of chronic inhalation. The project has two specific aims reflecting different real-life behaviors of individuals using tobacco products. The first set of experiments is designed to be relevant to individuals who are naïve to tobacco products but would initiate vaping with ENDS containing synthetic coolants. Thus, specific aim 1 will assess the pulmonary function and inflammatory effects of ENDS with synthetic coolants and compare their impact to the same product without the coolants or with menthol. In this specific aim, we will also study the dose-response effect of each synthetic coolant in ENDS. In specific aim 2, we will simulate scenarios under which a smoker of menthol cigarettes 'switches' to vaping ENDS with synthetic coolants. Thus, we will determine the changes in pulmonary function and inflammatory damage in animals pre-exposed to cigarette smoke with menthol, followed by switching to ENDS with or without synthetic coolants or with menthol. A comprehensive set of biomarkers has been selected to evaluate study outcomes, including measurement of functional respiratory parameters, histological measurement of inflammation, damage markers in lung tissue and BAL, immune cell infiltration in the lung, cytokine profile in BAL, and oxidative stress markers. The results of this project will provide new insights into the health risks of ENDS with synthetic coolants and the possible unintended consequences of replacing menthol with synthetic coolants by ENDS manufacturers. The findings will inform the FDA of actions to regulate synthetic coolants in ENDS by potentially including these emerging chemicals in the product standards.