Novel e-cigarette products include less nicotine analog than labeled

Key takeaways:

• E-cigarette products containing nicotine analogs 6-methylnicotine and nicotinamide are marketed as nicotine replacements.
• Product label amounts did not match measured amounts.

The measured amount of 6-methylnicotine, a nicotine analog, was 87% to 88% less than the amount on the label for all nine flavors of the Spree Bar e-cigarette, according to a research letter published in JAMA.

Further, in Nixotine e-cigarette liquids labeled to contain the nicotine analog nicotinamide, the measured amount was lower than the labeled amount, according to researchers.

“Huge discrepancies between product label and actual contents may lead to uncertainty in chemical exposures in the people who use these products,” Sairam V. Jabba, DVM, PhD, senior research scientist at Duke University School of Medicine, told Healio. “It is largely unknown about the acute (immediate or short-term) and chronic (long-term) health effects from inhalation of these nicotine analogs.”

Jabba noted that there are no clinical studies of the addiction potential for these nicotine analogues in humans.

“All these uncertainties regarding these analogs makes it very challenging for clinicians to assess the hazard and health risks associated with the use of these products,” Jabba said.

In this study, Jabba and colleagues analyzed nine flavors of the Spree Bar e-cigarette and two flavors of Nixotine e-cigarette liquid — all marketed as nicotine replacements and exempt from FDA regulations — to find out the chemical constituents of these products using untargeted or targeted gas chromatography-mass spectroscopy analysis. Further, to evaluate product consistency, the researchers determined if what is written on their labels about the nicotine alternative content matches the measured contents.

Spree Bar flavors are labeled to contain 5% 6-methylnicotine (6MN), whereas Nixotine products are labeled to contain 0 mg/mL, 12 mg/mL, 24 mg/mL or 36 mg/mL of nicotinamide.

As labeled, all nine Spree Bar flavors had 6MN; however, the amount listed on the label was well above what was measured in every flavor.

The advertised amount of 6MN in each flavor was 50 mg/g (5%), but the highest amount found was 6.27 mg/g in blood orange peach, which is 87% less than labeled. The lowest amount of 6MN was observed in the blue razz ice Spree Bar at 5.82 mg/g, or 88% less than labeled.

In the six Nixotine products labeled to contain nicotinamide, researchers found nicotinamide, but the amount was lower than what was listed in all cases.

The unflavored Nixotine e-cigarette liquid labeled to contain 12 mg/mL nicotinamide only contained 9.74 mg/g (7% less), the 24 mg/mL labeled product only contained 14.44 mg/g (31% less) and the 36 mg/mL labeled product only contained 16.63 mg/g (46% less).

Similarly, the cherry flavored Nixotine e-cigarette liquid labeled to contain 12 mg/mL nicotinamide only contained 8.32 mg/g (18% less), the 24 mg/mL labeled product only contained 12.95 mg/g (35% less) and the 36 mg/mL labeled product only contained 16.47 mg/g (46% less).

Notably, 6MN was also found in these six products, and this was not written on the label. The highest amount of 6MN in the assessed unflavored e-liquids was 0.17 mg/g, and the lowest amount was 0.09 mg/g. In the cherry e-liquids, the highest 6MN amount was 0.11 mg/g, and the lowest amount was 0.06 mg/g.

In the two e-cigarette liquids labeled to contain 0 mg/mL nicotinamide, no nicotinamide or 6MN was detected.

In the chemical analysis, researchers also identified the addition of neotame, an artificial sweetener, and WS-23 (2-isopropyl-N-2,3-trimethylbutyramide), the popular synthetic coolant, in Spree Bars.

Neotame was found in all nine Spree Bar flavors but not in any Nixotine products. The highest amount was 0.86 mg/g in blue razz ice, and the lowest amount was 0.2 mg/g in strawberry apple melon.

“The Spree Bar products contained neotame, a high intensity artificial sweetener that is heat stable and 7,000 to 13,000 times sweeter than table sugar,” Jabba told Healio. “To the best of our knowledge, this is the first report demonstrating the addition of neotame to vape products. The sweetener is potentially added to mask the aversive taste of nicotine analog 6MN.”

In addition to neotame, researchers found WS-23 in all nine Spree Bar flavors. The blue razz ice flavor had the highest amount at 16.39 mg/g, whereas the rainbow fruit flavor had the lowest amount at 4.34 mg/g.

WS-23 was not detected in any of the Nixotine products.

“With e-cigarettes being increasingly considered by clinicians for smoking cessation, the arrival of these nicotine analog-containing products with unknown health risk should raise significant concern among clinicians from advising e-cigarettes for cessation,” Jabba told Healio.

More research on nicotine analog-containing products is needed to gain a better understanding of how they impact the user, Jabba said.

“Future studies will include in vitro (petri dish) and in vivo (animal) studies to understand the toxicological effects, inhalation effects and addiction potential of these nicotine analogues,” Jabba told Healio. “Human studies will include understanding the appeal and abuse potential of 6MN and 6MN containing products.

“It will be critical going forward how FDA will regulate nicotine analogs and nicotine analog-containing products to protect public health,” he added.

Reference:

• Some e-cigarette chemicals mimic nicotine, possibly bypassing regulation. https://corporate.dukehealth.org/news/some-e-cigarette-chemicals-mimic-nicotine-possibly-bypassing-regulation. Published Aug. 7, 2024. Accessed Aug. 7, 2024.