International Agency for Research on Cancer (IARC) - Summaries & Evaluations
VOL.: 37 (1985) (p. 209)
CAS No.: 64091-91-4
Chem. Abstr. Name: 1-Butanone, 4-(methylnitrosoamino)-1-(3-pyridinyl)-
5. Summary of Data Reported and Evaluation
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) has been
found in a variety of tobacco products (chewing tobacco, snuff,
cigarettes and cigars), in mainstream and sidestream smoke from cigars
and cigarettes, in saliva of chewers of betel quid with tobacco, and
in saliva of oral-snuff users. Some of the NNK in saliva appears to
be formed endogenously from salivary nitrite and nicotine. Thus, there
is widespread exposure to NNK among users of tobacco products and
those exposed to sidestream smoke.
5.2 Experimental data
NNK was tested for carcinogenicity in several studies by
subcutaneous injection in rats and hamsters and by intraperitoneal
injection in mice. In rats, it induced carcinomas of the nasal
cavity, lung and liver, with a clear dose-response relationship. In
hamsters, it induced benign and malignant tumours of the nasal cavity,
trachea and lung, even after a single administration. In mice, NNK
and its metabolites 4-(methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanone
and 4-(methylnitrosamino)-1-(3-pyridyl)butan-1-ol induced benign and
malignant tumours of the lung.
NNK and its metabolites can cross the placental barrier in mice.
NNK can be metabolically activated by mouse foetal tissues.
Administration of NNK to rats results in abnormal DNA methylation
in liver and lung. NNK is mutagenic to Salmonella typhimurium in the
presence of an exogenous metabolic system. It induces unscheduled DNA
synthesis in primary cultures of rat hepatocytes.
5.3 Human data
No case report or epidemiological study of the carcinogenicity of
NNK to humans was available to the Working Group.
There is sufficient evidence for the carcinogenicity of
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone to experimental
No data on humans were available.
For definition of the italicized terms, see Preamble Evaluation.
Subsequent evaluation: Suppl. 7 (1987) (p. 68: Group 2B)
Last updated: 21 April 1998