International Agency for Research on Cancer (IARC) - Summaries & Evaluations


VOL.: 37 (1985) (p. 241)

CAS Nos: 80508-23-2; 16543-55-8; 84237-38-7
Chem. Abstr. Name: Pyridine, 3-(1-nitroso-2-pyrrolidinyl)-; pyridine, 3-(1-nitroso-2-pyrrolidinyl)-,(S)-; pyridine,3-(1-nitroso-2-pyrrolidinyl)-, (+,-)-

5. Summary of Data Reported and Evaluation

5.1 Exposures

N'-Nitrosonornicotine (NNN) 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 NNN in saliva appears to be formed endogenously from nitrite in saliva and tobacco alkaloids. Thus, there is widespread exposure to NNN among users of tobacco products and those exposed to sidestream smoke.

5.2 Experimental data

NNN was tested for carcinogenicity in rats, mice and hamsters by different routes of administration in multiple experiments. Following its oral administration, NNN produced carcinomas of the upper digestive tract, mainly the oesophagus, and of the nasal cavity in rats and nasal-cavity tumours in hamsters. Following its subcutaneous administration, NNN produced primarily tumours of the nasal cavity in rats and tumours of the trachea in hamsters. Intraperitoneal injection produced lung tumours in mice and tumours of the nasal cavity and trachea in hamsters. There was evidence of a dose-response relationship after subcutaneous administration of NNN to rats.

Several metabolites of NNN were tested in mice by intraperitoneal injection, producing lung tumours. NNN-1-N-oxide was also tested in rats and hamsters by oral administration; it produced nasal-cavity and oesophageal tumours in rats.

NNN 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 NNN was available to the Working Group.

5.4 Evaluation

There is sufficient evidence for the carcinogenicity of N'-nitrosonornicotine to experimental animals.

No data on humans were available.

For definition of the italicized terms, see Preamble Evaluation.

Previous evaluation: Vol. 17 (1978)

Subsequent evaluation: Suppl. 7 (1987) (p. 68: Group 2B)


Last updated: 21 April 1998

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