Risk Analysis for the Carcinogen Pulegone in Mint- and Menthol-Flavored e-Cigarettes and Smokeless Tobacco Products

摘要

Pulegone, a constituent of oil extracts prepared from mint plants, including peppermint, spearmint and pennyroyal, is a carcinogen that causes hepatic carcinomas, pulmonary metaplasia, and other neoplasms on oral administration in rodents. In 2018, the US Food and Drug Administration (FDA) banned synthetic pulegone as a food additive. Studies by the Centers for Disease Control and Prevention (CDC) detected substantial amounts of pulegone in mint- and menthol-flavored e-cigarette liquids and smokeless tobacco products marketed in the United States. The tobacco industry has minimized pulegone levels in cigarette flavorings because of toxicity concerns. Mint- and menthol-flavored e-cigarettes may be exempt from proposed federal regulations; therefore, the health risk associated with pulegone in these products should be considered. Methods | To assess the risk associated with pulegone, we calculated the margin of exposure (MOE) by dividing the FDA-provided no-observed adverse effect level (NOAEL) of pulegone at which no treatment-related tumors were reported in animal studies (13.39 mg/kg of body weight/d) by the mean human exposure from mint- and menthol-flavored e-cigarette or smokeless tobacco products analyzed in the CDC studies.