In a study published in JAMA, Yale scientists found that tobacco companies have begun to market products which contain nicotine analogs that mimic highly addictive nicotine.
Nicotine analogs are compounds that are not nicotine but closely related to it in structure. According to the scientists, the inhalation toxicity and addictive properties of these chemicals in humans, like 6-methyl nicotine (6MN) and nicotinamide, are not known. Importantly, the U.S. Food and Drug Administration's (FDA) mandate to regulate tobacco products covers nicotine and it appears that the e-cigarette manufacturers are attempting to exploit this mandate by suggesting their products are “not subject to FDA tobacco requirements.”
The researchers tested two marketed product lines and found significant discrepancies between the nicotine analog contents listed on the labels and what the products actually contained, raising concerns about the potential risks and unclear health effects related to the use of these products. In addition, the researchers also found artificial sweeteners and synthetic cooling agents in some products, which may increase appeal of these products to those who haven’t vaped before, and the health impacts of vaping these substances remain unknown.
“Taken together, it is really problematic that companies are introducing nicotine analogs with unknown health and addiction risks into novel products. They are essentially attempting to avoid regulation,” said Hanno Erythropel, PhD, a research scientist at the Yale School of Medicine and the study’s lead author. “Action needs to be taken as soon as possible to avoid potential harm from use of these products.”
For this study, the scientists analyzed two lines of commercially available e-cigarette and e-liquid products that were marketed as containing nicotine analogs. They observed significant inconsistencies between the information on the product labels and the product contents.
For example, Spree Bar disposable e-cigarette products were marketed as containing 50 mg/g of the nicotine analog 6MN, but only contained about 6 mg/g of 6MN, meaning that labels are off by almost 90 percent.
Another type of e-cigarette refill liquid product said on its label that it contained the nicotine analog compound nicotinamide, yet the researchers found that these products also contained low levels of 6MN, which is not indicated at all on the product label.
Animal experiments have demonstrated that 6MN might be more potent at activating nicotinic receptors, but nicotinamide’s activity on nicotinic receptors is not yet known.
In addition, the researchers also detected the sweetener neotame, a sugar substitute that is 7,000 to 13,000 times sweeter than table sugar according to the FDA, in Spree Bar products. Neotame has not previously been detected in vaping products. WS-23, a coolant found in other vaping products, was also detected here. Both neotame and WS-23 may increase appeal of these products to those who haven’t vaped before, and the health impacts of vaping these substances remain unknown.
The researchers argue that nicotine analog-containing products should be regulated and also highlight the critical need for more scientific evidence to understand the health effects of nicotine analogs.
Yale authors include Erythropel; Suchitra Krishnan-Sarin, PhD; Julie Zimmerman, PhD; and Paul Anastas, PhD. Co-authors from Duke University who are affiliated with Yale’s Tobacco Centers of Regulatory Science (TCORS) are Sven Jordt, PhD, and Sairam Jabba, DVM, PhD.
TCORS formed at Yale in 2013 to research the influence of flavors, including menthol, on tobacco and nicotine addiction. The work at Yale and other federally funded Tobacco Centers of Regulatory Science provides science-based knowledge to the FDA to inform regulation of tobacco- and nicotine-containing products.
Funding for the study was provided by the Yale TCORS, grant U54DA036151, from the National Institute on Drug Abuse (NIDA) of the National Institutes of Health (NIH) and the Center for Tobacco Products of the FDA. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the FDA.