Carcinogens N-nitroso compounds

In 1976, Ross al. first reported that the powerful carcinogens, N-nitrosodimethylamine (NOMA) and N-nitrosodi-n-propyl-amine (NDPA) were found at parts per million (ppm) concentrations in certain commercial herbicide formulations (1., ). Since then, scientists have learned that carcinogenic N-nitroso compounds can be formed in a wide variety of media of interest to those who manufacture, use, or study pesticide products. Some of these nitrosation-supporting media are listed in Table I. 

Safe" secondary amines resulting in non-carcinogenic N-nitroso compounds after nitrosation (German Patent Application No P 3029 318 6)... 

The most direct way of testing the possibility that reaction of an ingested amine with nitrite can give rise to sufficient of a carcinogenic N-nitroso compound to induce tumors has been to feed the amine and nitrite simultaneously to animals for most of their lifespan. The first successful experiment of this type was that of Sander and BUrkle ( ), using the amine methyl benzyl amine, which when fed to rats with nitrite induced esophageal tumors, the same tumor induced in rats by feeding nitrosomethyl benzyl amine. Similar experiments were carried out in mice with piperazine (24), and in rats with heptamethyleneimine (25). 

Nitrite ion has been shown to be toxic in the human body and animals, since diazotization of amines present in the body can lead to carcinogenic N-nitroso compounds. Furthermore, nitrite oxidizes hemoglobin to methemoglobin which is incapable of binding oxygen. In contrast, nitrate itself is not toxic but is easily reduced to nitrite by microorganisms. 

Montesano, R., and Bartsch, H., Mutagenic and carcinogenic N-nitroso compounds. Possible environmental hazards. Mutation Res., 1976, 2 ., 179... 

Calmels et al. [66] isolated an CTizyme catalyzing nitrosamine formation in Pseudomonas aeruginosa and Neisseria mucosae at neutral pH. Their results suggest that carcinogenic N-nitroso compounds may be formed endogenously with nitrosating enzymes that are provided by some bacteria. 

Loogna, G. O., Kann, Y. M. Safety measures in handling N-nitroso compounds, in proce ings of the Second Symposium on Carcinogenic N-Nitroso Compounds Action, Synthesis, Detection, p. 122, Tallin, 1975... 

Chou, J.T., and Jurs, P.C. 1979. Computer-assisted structure-activity studies of chemical carcinogens. N-nitroso compounds. J. Med. Chem. 2 762-797. 

The condition of gastritis, caused by any of several possible environmental factors, leads to elevation of the pH of the stomach and, concomitantly, to the establishment of a microbial flora capable of nitrate reduction. This process, in turn, leads to a steady formation of carcinogenic N-nitroso compounds over a long time period, vjhich leads ultimately to gastric cancer."... 

Mirvish, S. S., L. Wallcave, M. Eagen, and P. Shubik. 1972. Ascorbate-nitrite reaction Possible means of blocking the formation of carcinogenic N-nitroso compounds. Science 7 65-68. 

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