Synthetic nicotine has arrived

Abstract

The introduction of a new product line of the popular disposable electronic cigarette brand Puffbar, advertised as containing synthetic nicotine, has drawn attention to the increasing use of synthetic nicotine in marketed products and its uncertain regulatory status. A search of the Truth Tobacco Industry Documents revealed that the industry considered using synthetic nicotine already in the 1960s, efforts that were abandoned due to high costs and insufficient purity. Recent patents revealed renewed efforts to develop more efficient strategies for the synthesis of nicotine. Nicotine exists as two stereoisomers, S-nicotine and R-nicotine. While S-nicotine is the prevalent (>99%) form of nicotine in tobacco, a market-leading form of synthetic nicotine contains both stereoisomers at equal amounts, raising concerns about inaccurate labelling and the poorly understood health effects of R-nicotine. Other manufacturers, including a leading vendor of pharmaceutical grade nicotine, developed stereospecific strategies to synthesise pure S-nicotine, now added to electronic cigarette products marketed in the USA and UK. While S-nicotine and R-nicotine can be differentiated by enantioselective High Performance Liquid Chromatography (HPLC), differentiation of synthetic (fossil-derived) from tobacco-derived S-nicotine will require development of methods to measure carbon isotope (14C or 13C) content. Vendors claim that the FDA has no authority to regulate synthetic nicotine as a tobacco product, allowing them to circumvent the premarket tobacco product application process. However, legal analysis suggests that FDA may have the authority to regulate synthetic nicotine as a drug. Alternatively, Congress needs to include nicotine from any source within the legal definition of tobacco products.

Differences in Acellular Reactive Oxygen Species (ROS) Generation by E-Cigarettes Containing Synthetic Nicotine and Tobacco-Derived Nicotine

“…Additionally, amongst the drink/beverage-flavored vape-products analyzed, the synthetic nicotine-containing vape product generated significantly less ROS than its tobacco-derived nicotine-containing counterpart. Synthetic nicotine lacks the impurities contained within tobacco-derived nicotine [ 11 , 17 ]. Vape products using synthetic nicotine lack tobacco specific nitrosamines (TSNAs), a carcinogen found in tobacco and tobacco-derived nicotine [ 11 , 17 , 18 ].…”

“…Synthetic nicotine lacks the impurities contained within tobacco-derived nicotine [ 11 , 17 ]. Vape products using synthetic nicotine lack tobacco specific nitrosamines (TSNAs), a carcinogen found in tobacco and tobacco-derived nicotine [ 11 , 17 , 18 ]. In our study, the differences in exogenous ROS between aerosols generated by TFN and tobacco-derived nicotine-containing vape-products with Pink Lemonade, Spearmint, and Banana-Ice flavoring may be due to the differences in impurities within each type of nicotine salt (tobacco-derived or synthetic) used.…”

“…Moreover, since May 2016, the FDA has required all e-cigarette manufacturers and retailers to file premarket tobacco market applications (PMTAs) to gain permission from the agency to market their products [ 9 ]. The Center for Tobacco Products (CTP) oversees all products containing tobacco-derived nicotine; however, the FDA has not decided how to regulate synthetic nicotine-containing vape products; these products continue to remain unregulated [ 2 , 10 , 11 ]. In recent years, a more significant number of e-cigarette manufacturers have been using synthetic nicotine instead of tobacco-derived nicotine when producing e-cigarettes and e-liquids, all to bypass/evade FDA regulations [ 10 ].…”

“…No studies to date have been conducted involving comparative analyses in exogenous ROS levels between aerosols generated by synthetic-nicotine-containing e-cigarettes and those by e-cigarettes containing tobacco-derived nicotine. With the substantial rise in youth usage of e-cigarettes and a more significant number of e-cigarette manufacturers producing TFN e-cigarettes, more studies examining differences in ROS levels between aerosols generated by tobacco-based nicotine and synthetic nicotine-containing e-cigarettes are needed [ 11 ]. Unlike previous studies which have analyzed the ROS concentration levels within aerosols generated by tobacco-derived nicotine-containing e-cigarettes, our study includes analyses of the acellular ROS levels generated by TFN e-cigarettes [ 4 , 5 , 6 ].…”

Moving targets: how the rapidly changing tobacco and nicotine landscape creates advertising and promotion policy challenges

“…105 Little is known about the R-nicotine enantiomer because previously human exposure to and intake of R-nicotine was minimal 105 ; the substantial presence of R-nicotine in synthetic nicotine products has unknown health impact. 9 FDA has not made a decision about how it may regulate synthetic nicotine products, 101 exemplifying how a regulatory agency may lag behind the commercial market, constrained by outdated and narrow legislation. News reports in 2021 stated the Japanese health ministry will regulate tobacco-free nicotine pouches as pharmaceutical products.…”