e-Cigarette Tobacco Flavors, Public Health, and Toxicity: Narrative Review.

BACKGROUND: Recently, the US Food and Drug Administration implemented enforcement priorities against all flavored, cartridge-based e-cigarettes other than menthol and tobacco flavors. This ban undermined the products' appeal to vapers, so e-cigarette manufacturers added flavorants of other attractive flavors into tobacco-flavored e-cigarettes and reestablished appeal. OBJECTIVE: This review aims to analyze the impact of the addition of other flavorants in tobacco-flavored e-cigarettes on both human and public health issues and to propose further research as well as potential interventions. METHODS: Searches for relevant literature published between 2018 and 2023 were performed. Cited articles about the toxicity of e-cigarette chemicals included those published before 2018, and governmental websites and documents were also included for crucial information. RESULTS: Both the sales of e-cigarettes and posts on social media suggested that the manufacturers' strategy was successful. The reestablished appeal causes not only a public health issue but also threats to the health of individual vapers. Research has shown an increase in toxicity associated with the flavorants commonly used in flavored e-cigarettes, which are likely added to tobacco-flavored e-cigarettes based on tobacco-derived and synthetic tobacco-free nicotine, and these other flavors are associated with higher clinical symptoms not often induced solely by natural, traditional tobacco flavors. CONCLUSIONS: The additional health risks posed by the flavorants are pronounced even without considering the toxicological interactions of the different tobacco flavorants, and more research should be done to understand the health risks thoroughly and to take proper actions accordingly for the regulation of these emerging products.

Vaping: Public Health, Social Media, and Toxicity.

This viewpoint aims to provide a comprehensive understanding of vaping from various perspectives that contribute to the invention, development, spread, and consequences of e-cigarette products and vaping. Our analysis showed that the specific characteristics of e-cigarette products as well as marketing strategies, especially social media marketing, fostered the spread of vaping and the subsequent effects on human health and toxicity. We analyzed the components of e-cigarette devices and e-liquids, including the latest variants whose impacts were often overlooked. The different forms of nicotine, including salts and freebase nicotine, tobacco-derived nicotine, tobacco-free nicotine, and cooling agents (WS3 and WS23), have brought more choices for vapers along with more ways for e-cigarette manufacturers to advertise false understandings and present a greater threat to vapers' health. Our work emphasized the products of brands that have gained significant influence recently, which are contributing to severe public health issues. On the other hand, we also discussed in detail the toxicity of e-liquid components and proposed a toxicity mechanism. We also noticed that nicotine and other chemicals in e-liquids promote each other's negative effects through the oxidative stress and inflammatory nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, a mechanism leading to pulmonary symptoms and addiction. The impact of government regulations on the products themselves, including flavor bans or regulations, has been limited. Therefore, we proposed further interventions or harm reduction strategies from a public health perspective.

Tobacco Nitrate and Free Radical Levels in the Mainstream Smoke of US Cigarette Brands.

Tobacco nitrate levels have been known to impact the levels of toxicants such as polyaromatic hydrocarbons and tobacco-specific nitrosamines (TSNAs) produced during smoking. Recent work in our group showed that the intrinsic nitrate levels in individual tobacco varieties also have a large influence on the formation of gas-phase (GP) free radicals in the mainstream smoke of cigarettes produced with a single tobacco variety. As tobacco nitrate content is a potential target for future regulatory policies, we investigated whether the levels of GP free radicals in the smoke from commercially available cigarettes is also dependent on the nitrate content in the corresponding tobacco blends. GP and particulate-phase (PP) free radical yields in mainstream smoke produced from 25 popular US cigarette brands were measured by electron paramagnetic resonance (EPR) spectroscopy. For each brand, we also measured levels of the TSNAs NNN (N'-nitrosonornicotine) and NNK (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone) via HPLC-MS and the nicotine content via GC-FID. Our results show that the intrinsic nitrate levels varied >15-fold and GP radicals varied 4-fold among the 25 brands tested. The GP radicals were correlated with intrinsic nitrate levels (r = 0.87, p < 0.001). NNK and NNN levels varied >8-fold and 12-fold, respectively. We found that NNK was moderately correlated to nitrate content (r = 0.42, p = 0.03) while the NNN was strongly correlated to the nitrate content (r = 0.65, p < 0.001). Nicotine levels varied the least (<3-fold) but showed a moderate negative correlation to nitrate content (r = -0.47, p = 0.02). No statistically significant correlation was observed between nicotine and TSNA levels in mainstream smoke. Overall, this demonstrates that the nitrate content of tobacco blends used in US cigarette brands impacts toxicant output in the mainstream smoke, although other proprietary variables (total ventilation, additives, filter type, etc.) may also modulate these results.