In foods, nitrosamines are produced from nitrites and secondary amines, which often occur in the form of proteins. Their formation can occur only under certain conditions, including strongly acidic conditions such as that of the human stomach. High temperatures, as in frying, can also enhance the formation of nitrosamines. The presence of nitrosamines may be identified by the Liebermann nitroso reaction (not to be confused with the Liebermann reagent which reacts red or blue in the presence of phenols).
2 → H2O + NO+.
These processes lead to significant levels of nitrosamines in many foodstuffs, especially beer, fish, and fish byproducts, and also in meat and cheese products preserved with nitrite compounds. The U.S. government established limits on the amount of nitrites used in meat products in order to decrease cancer risk in the population. There are also rules about adding ascorbic acid or related compounds to meat, as the compounds inhibit formation of nitrosamines.
Tobacco-specific nitrosamines can also be found in tobacco smoke, 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).
Nitrosamines can be formed from nitrates (usually agricultural runoff) in drinking water upon ingestion. The EPA standard is 10 ppm but is considered by the National Academy of Sciences as lacking margin of safety for sensitive individuals.
In 1956, two British scientists, John Barnes and Peter Magee, reported that dimethylnitrosamine produced liver tumours in rats. Research was undertaken and approximately 90% of the 300 nitrosamine compounds tested were deemed to be carcinogenic in a wide variety of experimental animals.
In the 1970s, an elevated frequency of liver cancer was found in Norwegian farm animals. The farm animals had been fed on herring meal, which was preserved using sodium nitrite. The sodium nitrite had reacted with dimethylamine in the fish and produced dimethylnitrosamine. Nitrosamines can cause cancers in a wide variety of animal species, a feature that suggests that they may also be carcinogenic in humans. At present, available epidemiological evidence from case-control studies on nitrite and nitrosamine intake supports a positive association with gastric cancer risk. Regarding oesophageal cancer, available evidence supports a positive association between nitrite and nitrosamine intake and gastric cancer (GC), between meat and processed meat intake and GC and oesophageal cancer, and between preserved fish, vegetable and smoked food intake and GC, but is not conclusive.
Endogenous nitrosamine formation can be inhibited by ascorbic acid. In the case of formation of carcinogenic nitrosamines in the stomach from dietary nitrite (used as processed meat preservative), ascorbic acid markedly decreases nitrosamine formation in the absence of fat in the meal; but when 10% fat is present, this reverses the effect such that ascorbic acid then markedly increases nitrosamine formation.
|Substance name||CAS number||Synonyms||Molecular formula||Physical appearance||Carcinogenicity 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|
|N-Nitrosoanatabine||71267-22-6||NAT||C10H11N3O||Clear yellow-to-orange oil||IARC-3|
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Evidence now exists that ascorbic acid is a limiting factor in nitrosation reactions in people.
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