Nitrosamine
Encyclopedia
Nitrosamines are chemical compound
s of the chemical structure
R1N(-R2)-N=O, some of which are carcinogenic
.
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 nitrite
s and secondary amine
s, which often occur in the form of protein
s. Their formation can occur only under certain conditions, including strongly acid
ic 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's reaction.
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, in order to inhibit nitrosamine formation.
Nitrosamines can also be found in tobacco
smoke, American dip snuff
and to a much lesser degree, snus
. (127.9 PPM
for American dip snuff compared to 2.8 PPM in Swedish snuff or snus.)
ic.
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 cancer
s 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. The evidence in relation with oesophageal cancer
is insufficient."
Hydrazines derived from these nitrosamines, e.g. UDMH
, are also carcinogenic.
Chemical compound
A chemical compound is a pure chemical substance consisting of two or more different chemical elements that can be separated into simpler substances by chemical reactions. Chemical compounds have a unique and defined chemical structure; they consist of a fixed ratio of atoms that are held together...
s of the chemical structure
Chemical structure
A chemical structure includes molecular geometry, electronic structure and crystal structure of molecules. Molecular geometry refers to the spatial arrangement of atoms in a molecule and the chemical bonds that hold the atoms together. Molecular geometry can range from the very simple, such as...
R1N(-R2)-N=O, some of which are carcinogenic
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
.
Usages
Nitrosamines are used in manufacture of some cosmetics, pesticides, and in most rubber products.Occurrences
Nitrosamine occurs in latexLatex
Latex is the stable dispersion of polymer microparticles in an aqueous medium. Latexes may be natural or synthetic.Latex as found in nature is a milky fluid found in 10% of all flowering plants . It is a complex emulsion consisting of proteins, alkaloids, starches, sugars, oils, tannins, resins,...
products such as balloons, and in many foods and other consumables. Nitrosamines from condoms are not expected to be of toxicological
Toxicology
Toxicology is a branch of biology, chemistry, and medicine concerned with the study of the adverse effects of chemicals on living organisms...
significance.
In foods, nitrosamines are produced from nitrite
Nitrite
The nitrite ion has the chemical formula NO2−. The anion is symmetric with equal N-O bond lengths and a O-N-O bond angle of ca. 120°. On protonation the unstable weak acid nitrous acid is produced. Nitrite can be oxidised or reduced, with product somewhat dependent on the oxidizing/reducing agent...
s and secondary amine
Amine
Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...
s, which often occur in the form of protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s. Their formation can occur only under certain conditions, including strongly acid
Acid
An acid is a substance which reacts with a base. Commonly, acids can be identified as tasting sour, reacting with metals such as calcium, and bases like sodium carbonate. Aqueous acids have a pH of less than 7, where an acid of lower pH is typically stronger, and turn blue litmus paper red...
ic conditions such as that of the human stomach
Stomach
The stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...
. High temperatures, as in frying, can also enhance the formation of nitrosamines. The presence of nitrosamines may be identified by the Liebermann's reaction.
Under acidic conditions the nitrite forms nitrous acid
Nitrous acid
Nitrous acid is a weak and monobasic acid known only in solution and in the form of nitrite salts.Nitrous acid is used to make diazides from amines; this occurs by nucleophilic attack of the amine onto the nitrite, reprotonation by the surrounding solvent, and double-elimination of water...
(HNO2), which is protonated and splits into the nitrosonium
Nitrosonium
The nitrosonium ion is NO+, in which the nitrogen atom is bonded to an oxygen atom with a bond order of 3, and the overall diatomic species bears a positive charge. This ion is usually obtained as the following salts: NOClO4, NOSO4H , and NOBF4. The ClO and BF salts are slightly soluble in CH3CN...
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
Beer
Beer is the world's most widely consumed andprobably oldest alcoholic beverage; it is the third most popular drink overall, after water and tea. It is produced by the brewing and fermentation of sugars, mainly derived from malted cereal grains, most commonly malted barley and malted wheat...
, fish
Fish
Fish are a paraphyletic group of organisms that consist of all gill-bearing aquatic vertebrate animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish, as well as various extinct related groups...
, and fish byproducts, and also in meat
Meat
Meat is animal flesh that is used as food. Most often, this means the skeletal muscle and associated fat and other tissues, but it may also describe other edible tissues such as organs and offal...
and cheese
Cheese
Cheese is a generic term for a diverse group of milk-based food products. Cheese is produced throughout the world in wide-ranging flavors, textures, and forms....
products preserved with nitrite pickling
Pickling
Pickling, also known as brining or corning is the process of preserving food by anaerobic fermentation in brine to produce lactic acid, or marinating and storing it in an acid solution, usually vinegar . The resulting food is called a pickle. This procedure gives the food a salty or sour taste...
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
Ascorbic acid
Ascorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
or related compounds to meat, in order to inhibit nitrosamine formation.
Nitrosamines can also be found in tobacco
Tobacco
Tobacco is an agricultural product processed from the leaves of plants in the genus Nicotiana. It can be consumed, used as a pesticide and, in the form of nicotine tartrate, used in some medicines...
smoke, American dip snuff
Dipping tobacco
Dipping tobacco, traditionally referred to as moist snuff, is a type of finely ground or shredded, moistened smokeless tobacco product. It is commonly and idiomatically known by various terms – most often as dip and sometimes rub or chew...
and to a much lesser degree, snus
Snus
Snus , or Swedish snuff, is a moist powder tobacco product originated from a variant of dry snuff in the early 19th century in Sweden, consumed by placing it under the lip for extended periods of time. The precursor of snus, the dry form of snuff inhaled through the nose, was introduced in Europe...
. (127.9 PPM
Parts-per notation
In science and engineering, the parts-per notation is a set of pseudo units to describe small values of miscellaneous dimensionless quantities, e.g. mole fraction or mass fraction. Since these fractions are quantity-per-quantity measures, they are pure numbers with no associated units of measurement...
for American dip snuff compared to 2.8 PPM in Swedish snuff or snus.)
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 carcinogenCarcinogen
A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...
ic.
In the 1970s, there was an increased frequency of liver cancer found in Norwegian
Norway
Norway , officially the Kingdom of Norway, is a Nordic unitary constitutional monarchy whose territory comprises the western portion of the Scandinavian Peninsula, Jan Mayen, and the Arctic archipelago of Svalbard and Bouvet Island. Norway has a total area of and a population of about 4.9 million...
farm animals. The farm animals had been fed on herring meal, which was preserved using sodium nitrite
Sodium nitrite
Sodium nitrite is the inorganic compound with the chemical formula NaNO2. It is a white to slight yellowish crystalline powder that is very soluble in water and is hygroscopic...
. The sodium nitrite had reacted with dimethylamine
Dimethylamine
Dimethylamine is an organic compound with the formula 2NH. This secondary amine is a colorless, flammable liquified gas with an ammonia-like odor. Dimethylamine is generally encountered as a solution in water at concentrations up to around 40%...
in the fish and produced dimethylnitrosamine.
Nitrosamines can cause cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
s 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
Stomach cancer
Gastric cancer, commonly referred to as stomach cancer, can develop in any part of the stomach and may spread throughout the stomach and to other organs; particularly the esophagus, lungs, lymph nodes, and the liver...
risk. The evidence in relation with oesophageal cancer
Esophageal cancer
Esophageal cancer is malignancy of the esophagus. There are various subtypes, primarily squamous cell cancer and adenocarcinoma . Squamous cell cancer arises from the cells that line the upper part of the esophagus...
is insufficient."
Hydrazines derived from these nitrosamines, e.g. UDMH
UDMH
Unsymmetrical dimethylhydrazine is a toxic volatile hygroscopic clear liquid, with a sharp, fishy, ammoniacal smell typical for organic amines. It turns yellowish on exposure to air and absorbs oxygen and carbon dioxide. It mixes completely with water, ethanol, and kerosene. In concentration...
, are also carcinogenic.
Examples of nitrosamines
| Substance Name | CAS # | Synonyms | Molecular Formula | Physical Appearance | Carcinogenicity Category |
|---|---|---|---|---|---|
| N-Nitrosonornicotine N-Nitrosonornicotine N-Nitrosonornicotine is a nitrosamine found in tobacco that has been classified by the IARC as a Group 1 carcinogen.Although no adequate studies of the relationship between exposure to NNN and human cancer have been reported, there is sufficient evidence that NNN causes cancer in experimental... |
16543-55-8 | NNN | C9H11N3O | Oily yellow liquid | |
| 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone | 64091-91-4 | NNK, 4'-(nitrosomethylamino)-1-(3-pyridyl)-1-butanone | C10H13N3O2 | ||
| N-Nitrosodimethylamine N-Nitrosodimethylamine N-Nitrosodimethylamine , also known as dimethylnitrosamine , is a semi-volatile organic chemical that is highly toxic and is a suspected human carcinogen. The US Environmental Protection Agency has determined that the maximum admissible concentration of NDMA in drinking water is 7 ng L−1... |
62-75-9 | Dimethylnitrosamine, N,N-Dimethylnitrosamine, NDMA, DMN | C2H6N2O | Yellow liquid | EPA-B2; IARC-2A; OSHA Occupational Safety and Health Administration The United States Occupational Safety and Health Administration is an agency of the United States Department of Labor. It was created by Congress of the United States under the Occupational Safety and Health Act, signed by President Richard M. Nixon, on December 29, 1970... Carcinogen; TLV Threshold Limit Value The threshold limit value of a chemical substance is a level to which it is believed a worker can be exposed day after day for a working lifetime without adverse health effects. Strictly speaking, TLV is a reserved term of the American Conference of Governmental Industrial Hygienists... -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 | IARC International Agency for Research on Cancer The International Agency for Research on Cancer is an intergovernmental agency forming part of the World Health Organisation of the United Nations.... -3 |
||
| N-Nitrosoanatabine | 71267-22-6 | IARC-3 |
See also
- NitroamineNitroamineNitroamines are organic compounds that contain the nitroamino functional group, R2N-NO2. The R's are the continuation of the ring structure, see RDX. Examples of nitroamines are the explosives HMX, cyclotrimethylene trinitramine, Hexanitrohexaazaisowurtzitane and tetryl...
(without the 's'), compounds of the formula R2N-NO2. - NitrosoNitrosoNitroso refers to a functional group in organic chemistry which has the general formula RNO. Nitroso compounds are a class of organic compounds containing the nitroso functional group, R−N=O....
, compounds of the formula R-NO