N‐Nitrosamines

Abstract

N ‐Nitrosodialkylamines (nitrosamines) are a large group of substances containing the NNO group and various substituents on the amine nitrogen. They can be synthesized by reaction of the corresponding amines with nitrosating agents such as acidic nitrite, N 2 O 3 , N 2 O 4 , or inorganic nitrosyl compounds. They can be analyzed by gas or liquid chromatography with detection generally based on measurement of nitric oxide that is released from the nitrosamines by pyrolysis, photolysis, or acid hydrolysis. Many of the nitrosamines are agents which damage the liver in animals and humans. Most nitrosamines are known animal carcinogens, and some are suspected human carcinogens. Nitrosamines are metabolized by several enzyme systems, the most important being the cytochrome P450 family. Metabolic conversion to active electrophiles that react with DNA appears to be the initiating event in nitrosamine carcinogenesis. Humans may be exposed to nitrosamines by several routes including diet, commercial or industrial preparations such as cutting fluids, cosmetics, or sunscreens, tobacco products, and synthesis inside the body. Nitrosamines have not been unequivocally shown to be human carcinogens, but evidence relating oral cancer to the use of smokeless tobacco is increasingly persuasive.