nitrosamine nitrosamine in organic chemistry, nitrosamines (or more formally n-nitrosamines) are organic compounds with the chemical structure r2n−n=o, where r is usually an alkyl group. they feature a nitroso group (no+) bonded to a deprotonated amine. most nitrosamines are carcinogenic in nonhuman 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". structure of the nitrosamino group chemistry metabolic activation of the nitrosamine ndma, involving its conversion to an alkylating agent the organic chemistry of nitrosamines is well developed with regard to their syntheses, their structures, and their reactions. they usually are produced by the reaction of nitrous acid (hno2) and secondary amines. hono + r 2 nh ⟶ r 2 n − no + h 2 o the nitrous acid usually arises from protonation of a nitrite. this synthesis method is relevant to the generation of nitrosamines under some biological conditions. with regards to structure, the c2n2o 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 alkylating agents that modify bases in dna, inducing mutations. the specific alkylating agents vary with the nitrosamine, but all are proposed to feature alkyldiazonium centers. 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 tumours in rats. subsequent studies showed that approximately 90% of the 300 nitrosamines tested were carcinogenic 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 dip snuff, 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 nitrosamines are produced by the reaction of nitrites and secondary amines. nitrites are used as food preservatives, e.g. cured meats. secondary amines arise by the degradation of proteins (food). nitrite and nitrosamine intake are associated with risk of gastric cancer and oesophageal cancer. adverse reaction with dimethylamine during the 1970s, an elevated frequency of liver cancer was found in norwegian farm animals after the farm animals had been fed on herring meal that was preserved using sodium nitrite. the sodium nitrite had reacted with dimethylamine in the fish and produced dimethylnitrosamine, which was determined to be carcinogenic during the studies of the 1950s. opposing reactions with ascorbic acid endogenous nitrosamine formation can be affected by ascorbic acid, either inhibiting its formation or increasing its formation, depending upon whether ascorbic acid is consumed in conjunction with it as opposed to the effect being reversed by factors related to dietary fat consumed at the same time. in the case of formation of carcinogenic nitrosamines in the stomach from dietary nitrite (used as a processed meat preservative), ascorbic acid markedly decreases nitrosamine formation in the absence of fat in the meal, through inhibition. however, when 10% of the meal is fat, the effect is reversed, such that ascorbic acid then markedly increases nitrosamine formation. a yeast study has shown that n-nitrosamines can perturb amino acid metabolism and mitochondrial function. examples substance name cas number synonyms molecular formula physical appearance carcinogenity category n-nitrosonornicotine 16543-55-8 nnn c9h11n3o light yellow low-melting solid 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone 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