
Nitrosamines (or more formally ''N''-nitrosamines) are
organic compound
Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...
s produced by industrial processes. The
chemical structure
A chemical structure of a molecule is a spatial arrangement of its atoms and their chemical bonds. Its determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target m ...
is , where R is usually an
alkyl group
In organic chemistry, an alkyl group is an alkane missing one hydrogen.
The term ''alkyl'' is intentionally unspecific to include many possible substitutions.
An acyclic alkyl has the general formula of . A cycloalkyl group is derived from a cy ...
. Nitrosamines have a
nitroso group () that are "probable human carcinogens", bonded to a deprotonated
amine
In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...
. Most nitrosamines are
carcinogen
A carcinogen () is any agent that promotes the development of cancer. Carcinogens can include synthetic chemicals, naturally occurring substances, physical agents such as ionizing and non-ionizing radiation, and biologic agents such as viruse ...
ic 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".
Chemistry

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 () and secondary amines, although other
nitrosyl sources (e.g. , ,
RONO) have the same effect:
:
The nitrous acid usually arises from protonation of a
nitrite
The nitrite polyatomic ion, ion has the chemical formula . Nitrite (mostly sodium nitrite) is widely used throughout chemical and pharmaceutical industries. The nitrite anion is a pervasive intermediate in the nitrogen cycle in nature. The name ...
. This synthesis method is relevant to the generation of nitrosamines under some biological conditions. The nitrosation is also reversible, particularly in acidic solutions of
nucleophile
In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they are ...
s.
Aryl
In organic chemistry, an aryl is any functional group or substituent derived from an aromatic ring, usually an aromatic hydrocarbon, such as phenyl and naphthyl. "Aryl" is used for the sake of abbreviation or generalization, and "Ar" is used ...
nitrosamines rearrange to give a ''para''-nitroso aryl amine in the
Fischer-Hepp rearrangement.
With regards to structure, the core of nitrosamines is planar, as established by
X-ray crystallography
X-ray crystallography is the experimental science of determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to Diffraction, diffract in specific directions. By measuring th ...
. 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 agent Alkylation is a chemical reaction that entails transfer of an alkyl group. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting ...
s 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 tumour
A neoplasm () is a type of abnormal and excessive growth of tissue (biology), tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tiss ...
s in rats. Subsequent studies showed that approximately 90% of the 300 nitrosamines tested were carcinogen
A carcinogen () is any agent that promotes the development of cancer. Carcinogens can include synthetic chemicals, naturally occurring substances, physical agents such as ionizing and non-ionizing radiation, and biologic agents such as viruse ...
ic 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
Snus (, ; ) is a Swedish smokeless tobacco, tobacco product. It is consumed by placing a pouch of powdered tobacco leaves under the lip for nicotine to be absorbed through the Mucous membrane, oral mucosa. Snus, not to be confused with Nicoti ...
(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
Ranitidine, previously sold under the brand name Zantac among others, is a medication used to decrease stomach acid production. It was commonly used in treatment of peptic ulcer disease, gastroesophageal reflux disease, and Zollinger–Ellis ...
, valsartan, duloxetine, and others.
The US Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
published guidance about the control of nitrosamine impurities in medicines. Health Canada
Health Canada (HC; )Health Canada is the applied title under the Federal Identity Program; the legal title is Department of Health (). is the Structure of the Canadian federal government#Departments, with subsidiary units, department of the Gove ...
published guidance about nitrosamine impurities in medications and a list of established acceptable intake limits of nitrosamine impurities in medications.
Examples
See also
* Hydrazines
Hydrazines (R2N−NR2) are a class of chemical compounds with two nitrogen atoms linked via a covalent bond and which carry from one up to four alkyl or aryl substituents. Hydrazines can be considered as derivatives of the inorganic hydrazine ( ...
derived from these nitrosamines, e.g. UDMH
Unsymmetrical dimethylhydrazine (abbreviated as UDMH; also known as 1,1-dimethylhydrazine, heptyl or Geptil) is a chemical compound with the formula H2NN(CH3)2 that is primarily used as a rocket propellant. At room temperature, UDMH is a colorle ...
, are also carcinogenic.
* Possible health hazards of pickled vegetables
* Tobacco-specific nitrosamines
Additional reading
*
*
References
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
{{Authority control
Nitrogen cycle
Functional groups
Garde manger
Carcinogens
IARC Group 1 carcinogens