Chemical Properties
Nitrosonornicotine is prepared by reacting nornicotine with
nitrous acid or by reacting nicotine with excess nitrite at
approximately pH 4. It is a yellowoil. NNN is somewhat soluble in water and very
soluble in slightly acidified water and in organic solvents.
Like other nitrosamines, it can be oxidized and reduced and
has additional reactions due to the pyridine ring, such as
formation of the N-oxide.
Definition
ChEBI: N'-Nitrosonornicotine is a member of pyrrolidines and a member of pyridines.
Production Methods
There is no evidence that NNN has been manufactured
commercially but it is used as a research chemical. NNN belongs in the category of so-called tobacco-specific nitrosamines
because it has been found only associated with
tobacco or with tobacco smoking. There is substantial exposure
to NNN of humans who smoke tobacco or use snuff or
chewing tobacco. NNN was not present in freshly harvested
tobacco but was present in snuff (12–29 mg/kg), in cigars (up
to 11 mg/kg), in chewing tobacco (as much as 90 mg/kg), and
in other tobacco products. NNN can be formed in the
mouth by interaction of nicotine eluted from the tobacco with
nitrite in the saliva; the nicotine may also be swallowed
and react with nitrite in the stomach. NNN has also been
identified in tobacco smoke (140 ng per cigarette up to 10
times that). An extensive survey of the amount of nitrosamines,
including NNN, in the mainstream and in the sidestream
smoke of cigarettes and cigars showed large
variations from 0.1 μg/cigarette to 3.7 μg and more
in cigar smoke. Evidence from one comparative study of
tobacco-specific nitrosamines in cigarettes suggests that
levels of NNN (measured as a sum of all tobacco-specific
nitrosamines) are higher in non-Moldovan cigarette tobacco
and Moldovan blended cigarettes, suggesting that current
tobacco production and manufacturing technologies may
create conditions that favor N-nitrosation of alkaloids and
other tobacco constituents.
Carcinogenicity
NNN is classified as reasonably anticipated to be a human
carcinogen by NTP and carcinogenic to humans (Group 1)
by IARC. In several strains of rat, oral administration
of NNN induced tumors of the esophagus and nasal
cavity or nasal cavity tumors only (drinking water
treatment). In mice by i.p. injection, there were lung
tumors, and in hamsters subcutaneous injection led to tumors
of the trachea and nasal cavity, while similar exposures
via subcutaneous injection induced nasal cavity tumors in
rats.
