# NIH grant: Assessing the Respiratory Effects of Inhaling Synthetic Coolants Used as Flavor Ingredients in ENDS (1R01HL184945-01) — retained record

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NIH grant 1R01HL184945-01: Assessing the Respiratory Effects of Inhaling Synthetic Coolants Used as Flavor Ingredients in ENDS
Institute: {'code': 'HL', 'abbreviation': 'NHLBI', 'name': 'National Heart Lung and Blood Institute', 'admin_org_id': '12500068', 'admin_funding_url': ''}. PI: Maciej Lukasz Goniewicz. Award: $830722.
Start: 2026-08-15T00:00:00.
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.
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