Identification and analysis of a new tobacco-specific N-nitrosamine, 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanol

A new tobacco-specific N-nitrosamine, 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanol (iso-NNAL) was isolated from snuff tobacco. Structural characterization of this N-nitrosamine was confirmed by mass spectral analysis. Five popular US brands of moist snuff and three popular US brands of dry snuff tobacco were analyzed for moisture, nicotine and tobacco-specific N-nitrosamines. The moisture content varied from 20 to 53% in moist snuff and from 4.7 to 5.6% in dry snuff. The nicotine levels in these samples varied from 0.6 to 3.2%. The newly identified iso-NNAL was present in concentrations ranging from 0.07 to 2.5 p.p.m. whereas other tobacco-specific N-nitrosamines, N-nitrosonornicotine, N-nitrosoanatabine, N-nitrosoanabasine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone were found to range from 0.1 to 178 p.p.m. Iso-NNAL was not detected in mainstream and sidestream smoke of cigarettes. Iso-NNAL is genotoxic in primary rat hepatocytes; its tumorigenic properties are currently being tested in mice and rats.