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Nitrosamines (or more formally N-nitrosamines) are produced by industrial processes.California Water Boards, State Water Resources Control Board, "Nitrosamines", 09 December 2024 The chemical structure is , where R is usually an alkyl group. Nitrosamines have a nitroso group () that are "probable human carcinogens",World Health Organization, Medical product alert, Note on Nitrosamine impurities, "Update on Nitrosamine impurities", 20 November 2019 bonded to a deprotonated amine. Most nitrosamines are in animals. A 2006 systematic review supports a "positive association between nitrite and nitrosamine intake and gastric cancer, between meat and processed meat intake and gastric cancer and oesophageal cancer, and between preserved fish, vegetable and smoked food intake and gastric cancer, but is not conclusive".
With regards to structure, the core of nitrosamines is planar, as established by X-ray crystallography. The N-N and N-O distances are 132 and 126 pm, respectively in dimethylnitrosamine, one of the simplest members of a large class of N-nitrosamines.
Nitrosamines are not directly carcinogenic. Metabolic activation is required to convert them to the that modify bases in DNA, inducing mutations. The specific alkylating agents vary with the nitrosamine, but all are proposed to feature alkyldiazonium centers.
The US Food and Drug Administration published guidance about the control of nitrosamine impurities in medicines. Health Canada published guidance about nitrosamine impurities in medications and a list of established acceptable intake limits of nitrosamine impurities in medications.
History and occurrence
In 1956, two British scientists, John Barnes and Peter Magee, reported that a simple member of the large class of N-nitrosamines, dimethylnitrosamine, produced liver in rats. Subsequent studies showed that approximately 90% of the 300 nitrosamines tested were in a wide variety of animals.
Tobacco exposure
A common way ordinary consumers are exposed to nitrosamines is through tobacco use and cigarette smoke. Tobacco-specific nitrosamines also can be found in American Dipping tobacco, Chewing Tobacco, and to a much lesser degree, snus (127.9 ppm for American dip snuff compared to 2.8 ppm in Swedish snuff or snus).
Dietary exposure
Medication impurities
There have been recalls for various medications due to the presence of nitrosamine impurities. There have been recalls for angiotensin II receptor blockers, ranitidine, valsartan, duloxetine, and others.
Examples
N-Nitrosonornicotine 16543-55-8 NNN C9H11N3O Light yellow low-melting solid 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanoneHecht, Steven S.; Borukhova, Anna; Carmella, Steven G. "Tobacco specific nitrosamines" Chapter 7; of "Nicotine safety and toxicity" Society for Research on Nicotine and Tobacco; 1998 - 203 pages 64091-91-4 NNK, 4′-(nitrosomethylamino)-1-(3-pyridyl)-1-butanone C10H15N3O2 Light yellow oil N-Nitrosodimethylamine 62-75-9 Dimethylnitrosamine, N, N-dimethylnitrosamine, NDMA, DMN C2H6N2O Yellow liquid EPA-B2; IARC-2A; OSHA carcinogen; TLV-A3 N-Nitrosodiethylamine 55-18-5 Diethylnitrosamide, diethylnitrosamine, N, N-diethylnitrosamine, N-ethyl- N-nitrosoethanamine, diethylnitrosamine, DANA, DENA, DEN, NDEA C4H10N2O Yellow liquid EPA-B2; IARC-2A 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol 76014-81-8 NNAL N-Nitrosoanabasine 37620-20-5 NAB C10H13N3O Yellow Oil IARC-3 N-Nitrosoanatabine 71267-22-6 NAT C10H11N3O Clear yellow-to-orange oil IARC-3
See also
Additional reading
External links
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