Health Effects: Known animal and suspected human carcinogen (liver, esophagus, lung) (HE2); Suspect teratogen (HE5)
Affected Organs: Liver, esophagus, stomach (in animals)
N-Nitrosodiethylamine is an OSHA Select Carcinogen without a PEL.
In human esophageal mucosa, the de-ethylation of N-nitrosodiethylamine to form acetaldehyde appears to be catalyzed by the cytochrome P450, CYP2A6, but not by CYP2E1. It is also catalyzed by human CYP2A13.
In addition to causing single-strand chromosome breaks, ethyl-DNA adducts are formed in cells containing CYP2E1 and other P450 enzymes that act on N-nitroso-diethylamine to lead to the formation of the reactive ethyl diazonium ion. The persistence of these adducts is related to tumor induction.
Single doses of N-nitrosodiethylamine in rodents have been used to initiate liver cancer for research on tumor promoters. Researchers may be subject to inhalational exposure to this chemical in animal rooms where animals injected with it are kept.
N-Nitrosodiethylamine constituted 5% of all airborne nitrosamines found in one study of the vulcanized rubber industry.
In 2004, the California Department of Health Services established a notification level for N-nitrosodiethylamine of 10 nanograms per liter of drinking water, due to its potential presence in association with drinking water treatment.
Godoy, W., et al.: CYP2A6/2A7 and CYP2E1 expression in human oesophageal mucosa: regional and inter-individual variation in expression and relevance to nitrosamine metabolism. Carcinogenesis23(4): 611-616, 2002.
Ito, N., Tamano, S. and Shirai, T.: A medium-term rat liver bioassay for rapid in vivo detection of carcinogenic potential of chemicals. Cancer Sci. 94(1): 3-8, 2003.
Moennikes, O., et al.: A constitutively active dioxin/aryl hydrocarbon receptor promotes hepatocarcinogenesis in mice. Cancer Res. 64(14): 4707-4710, 2004.
No Author: N-Nitrosodiethylamine (CAS No. 55-18-5) (PDF). Report on Carcinogens (latest edition); U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program.
Oury, B., Limasset, J.C. and Protois, J.C.: Assessment of exposure to carcinogenic N-nitrosamines in the rubber industry. Int. Arch. Occup. Environ. Health70(4): 261-271, 1997.
Pohanish, R.P. (editor): N-Nitrosodiethylamine. In, Sittig's Handbook of Toxic and Hazardous Chemicals and Carcinogens, Fourth Ed., Vol. 2. Norwich, NY: Noyes Publications, William Andrew Publishing, 2002, pp. 1730-1731.
Sansone, E.B. and Keimig, S.D.: Potential occupational exposure associated with parenteral administration of N-nitrosodiethylamine to Macaca mulatta: evidence of post-injection release to the atmosphere. IARC Sci. Publ. 105: 226-229, 1991.
Su, T., Bao, Z., Zhang, Q.-Y., Smith, T.J., Hong, J.-Y. and Ding, X.: Human cytochrome P450 CYP2A13: predominant expression in the respiratory tract and its high efficiency metabolic activation of a tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Cancer Res. 60(18): 5074-5079, 2000.
Verna, L., Whysner, J. and Williams, G.M.: N-nitrosodiethylamine mechanistic data and risk assessment: bioactivation, DNA-adduct formation, mutagenicity, and tumor initiation. Pharmacol. Ther. 71(1-2): 57-81, 1996.
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