Chemical composition and carcinogenicity of smokeless tobacco

In the United States, smokeless tobacco (ST) is marketed as chewing tobacco and as oral snuff. During the past 15 years, consumption of chewing tobacco has declined by 30.6%, whereas snuff use has significantly increased, namely, by 51.8%. This increase is primarily due to the growing popularity of oral snuff use among teenage and young adolescent males. Chewing of tobacco is associated with an increased risk for oral cancer. Snuff dipping is causally and specifically associated with cancer of the cheek, gum, and pharynx. In laboratory animals, snuff induces cancer of the mouth. Several carcinogens have been identified in ST, the tobacco-specific N-nitrosamine (TSNA), N'-nitrosonornicotine (NNN), and 4(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) being the most important. NNN and NNK are formed from nicotine during curing, aging, and especially during fermentation of tobacco. Oral swabbing of a low concentration of a mixture of NNN plus NNK in water induces oral tumors in rats. The concentration of the strongly carcinogenic TSNA is higher in snuff than in other ST products. According to our analytical studies, the three leading snuff brands in the US (92% of the market) contain far higher concentrations of nicotine, unprotonated nicotine, and TSNA than the less popular brands. Thus, the leading US snuff brands are the strongest inducers of nicotine dependence and also have the highest carcinogenic potential.