NorNicotine constitution

Precursors and Formation. Tobaccos used for commercial products in the U.S.A, contain between 0,5 and 2,7% alkaloids. Nicotine constitutes 85-95% of the total alkaloids (14,26,27). Important minor alkaloids are nornicotine, anatabine, anabasine, cotinine and N -formylnornicotine (Figure 6), Several of these alkaloids are secondary and tertiary amines and, as such, amenable to N-nitrosation. The N-nitrosated alkaloids identified to date in tobacco and tobacco smoke include N -nitrosonornico-tine (NNN), 4-(methylnitrosamino)-l-(3-pyridyl)-l-butanone (NNK) and N -nitrosoanatabine (NAT Figure 7). In model experiments, nitrosation of nicotine also yielded 4-(methylnitrosamino)-4-(3-pyridyl)butanal (NNA 28). 

In a study for precursor determination, we stem-fed individual Burley leaves with nicotine-2 - C or nornicotine-2 - C (29). Subsequently, the leaves were air cured, dried and analyzed for NNN and NNN- C. Recovery of the p-activity in the form of NNN- C amounted to 0.009% and 0.007%, respectively of the stem-fed label. This demonstrates that both alkaloids give rise to NNN. More importantly, it points to the fact that the tertiary amine, nicotine, which constitutes 0.5-2.6% of commercial tobaccos (26,27), is the major precursor for the carcinogenic tobacco-specific NNN, while the secondary amine, nornicotine is of lesser importance because it amounts to only 0.005-0.06% in tobacco (Figure 8). 

In tobacco samples examined so far, the levels of NAB were significantly less than those of NNN. In fact, NAB has not yet been detected with certainty in unburned tobacco (15). These findings are in line with the major role of nicotine rather than nornicotine as a precursor to NNN since kinetic studies showed that nornicotine and anabasine were nitrosated at similar rates (25). These rates are relatively high, which suggests that the formation of NNN and NAB could be favored in vivo. When chewing tobacco was incubated with human saliva for 3 hours at 37 and the mixture analyzed for NNN, the concentrations of NNN increased by 44% over that in the chewing tobacco, presumably as a result of further nitrosation (15). Thus, in vivo formation of NNN and NAB could constitute an additional exposure of smokers or chewers to these tobacco specific nitrosamines. 

Alkaloids constitute approximately 2-4% by weight of fresh cigarette tobaccos (Kuhn 1965), with nicotine constituting roughly 95% of the total alkaloid fraction. The predominant secondary alkaloids, along with approximate percentages by weight of the alkaloid fraction, include anatabine (2-3%), nornicotine (1%), anabasine (0.5%), and myosmine (0.1%) (Kuhn 1965 Leete 1983). 

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