Does the Level of NNK in Tobacco and Tobacco Products Depend on the Level of Pseudooxynicotine or of Nicotine-1′-N-Oxide?

Summary 4-(N’-methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potentially carcinogenic tobacco specific nitrosamine (TSNA) and an important compound in the Harmful and Potentially Harmful Constituents (HPHCs) list of U.S. Food and Drug Administration (FDA). For this reason, significant effort is being made for an understanding of the formation of this compound and for the reduction of its level in tobacco products. Formation of NNK is assumed to be the result of nitrosation of 4-(methylamino)-1-(3-pyridyl)-1-butanone (pseudooxynicotine or PON). Present study evaluated the correlation between the levels of NNK and those of PON in a variety of tobaccos and tobacco products. Since nicotine-1′-N-oxide can be involved in the formation of PON, the correlation of the levels of this compound with the levels of NNK was also evaluated. Two original methods were developed for the quantitation of PON in tobacco and tobacco products and a well-established method has been used for the analysis of NNK. The correlation between the levels of NNK with that of PON was proven to be very poor. The same result was obtained for the correlation between NNK levels and nicotine-1′-N-oxide. This indicated that a higher level of PON or of nicotine-1′-N-oxide in tobacco or tobacco products does not lead to a higher level of NNK. The study does not prove that NNK in tobacco or tobacco products is not generated via PON, but it demonstrated that the limiting factor in the formation of NNK in tobacco and tobacco products is not the level of PON or that of nicotine-1′-N-oxide, and other factors are responsible for the effectiveness of NNK formation.