Nitrosamine

Not to be confused with nitroamine.

Structure of the nitrosamino group

Nitrosamines are chemical compounds of the chemical structure R¹N(-R²)-N=O, that is, a nitroso group bonded to an amine. Most nitrosamines are carcinogenic.

Uses

Nitrosamines are used in the manufacture of some cosmetics, pesticides, and in most rubber products.

Occurrence

Nitrosamines occur in latex products such as balloons, and in many foods and other consumables. Nitrosamines from condoms are not expected to be of toxicological significance.

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).

Under acidic conditions the nitrite forms nitrous acid (HNO₂), which is protonated and splits into the nitrosonium cation N≡O⁺ and water: H₂NO₂⁺ = H₂O + NO⁺. The nitrosonium cation then reacts with an amine to produce nitrosamine.

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 pickling salt. 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 also be found in E-cigarette vapour, though this is reported to be trace amounts, possibly from the propylene glycol and/or vegetable glycerine used in manufacture.

Biology

Cancer

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 nitrosamine compounds were deemed to be carcinogenic.

In the 1970s, there was an increased frequency of liver cancer 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 gastric cancer (GC) and oesophageal cancer (OC), and between preserved fish, vegetable and smoked food intake and GC, but is not conclusive.

Hydrazines derived from these nitrosamines, e.g. UDMH, are also carcinogenic.

Inhibition

Endogenous nitrosamine formation can be inhibited by ascorbic acid.

Examples

Substance Name	CAS #	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
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

• Tobacco-specific nitrosamines

External links

• Oregon State University, Linus Pauling Institute article on Nitrosamines and cancer, including info on history of meat laws
• Risk factors in Pancreatic Cancer