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Health Problems Associated With Nitrites And Nitrosamines


Source: Ambio, Vol. 5, No. 2, pages 67-72, 28 references, 19761976 Abstract:

Lijinsky W

Human health effects from exposure to nitrite and nitrosamine carcinogens are reviewed. Nitrites are poisonous in large doses, whereas nitrates are not. The toxic effect induces methemoglobinemia by interacting with the hematin component of hemoglobin to form nitrosohemoglobin. Hemoglobin in infants appears to be more sensitive to oxidation to methemoglobin than in adults. Nitrite has occasionally been responsible for illness. In animal studies, no long term adverse affects of moderate doses of nitrite have been observed. The best known reaction of nitrites occurs with amines in the presence of acid to form a variety of products. Nitroso compounds are potent hepatotoxins in humans and animals. Nitroso compounds are formed from secondary amino compounds and nitrite over a wide pH range. The optimal pH appears to be about 3. Comparatively few samples of foods prepared with nitrite have contained detectable nitrosamines. Formation of nitrosamines has been demonstrated in-vivo in animals and humans. Safe doses for a carcinogen are difficult to establish from animal studies, because at low doses the incidence of tumors may only be significant in very large populations. The effects of carcinogens are cumulative, whereby any amount may result in tumor development at some stage. Feeding various amines together with nitrite to rats induces tumors in a variety of organs, including liver, lung, esophagus, stomach, and nervous system. A large number of secondary and tertiary amines fed to rats together with nitrite have failed to induce significant incidence of tumors. There may be insufficient nitrosation of amines in animal feed to form tumors during an animal's lifetime. Oral administration has been most effective in eliciting tumors by nitroso compounds. Restrictions imposed on the amount of residual nitrite allowed in commerically cured meats and fish reduce human exposure to carcinogens containing nitroso compounds.

Nitrite sources and nitrosamine formation in vitro and in vivo.



Author Address: Br. Food Manuf. Ind. Res. Assoc., Leatherhead, Surrey, Engl., UK. Source: FOOD COSMET TOXICOL; 17 (5). 1979. 473-480. Abstract:


HEEP COPYRIGHT: BIOL ABS. The ingestion by normal adults of a meal including vegetables rich in nitrate led to a rapid increase in the salivary nitrite concentration. This was followed by a fall towards the fasting nitrite levels, although the concentration in the saliva remained elevated for as long as 21 h. Using foods as sources of nitrosatable amines, studies were made both in vitro and in vivo on the formation of N-nitroso compounds under the conditions encountered in the human stomach, with special reference to the different thiocyanate concentrations in smokers and non-smokers. The nitrite level and pH of gastric contents increased markedly following the consumption of a meal containing nitrite, reaching maxima within about 45 min and then returning towards fasting levels. N-Nitrosopiperidine (NPIP) and Nnitrosopyrrolidine were the major volatile nitrosamines produced when foods were incubated with nitrite under acid conditions in vitro. At the nitrite concentrations likely to occur in the stomach, nitrosamine formation was reduced and was significantly lower in the absence of thiocyanate than in its presence at levels of 0.2-3 mM. Trace amounts of NPIP were detected occasionally in the gastric contents of volunteers after ingestion of homogenized foods containing nitrite. Both volatile and non-volatile N-nitroso compounds were obtained from a tobaccosmoke condensate following incubations in vitro simulating those likely to occur within the human stomach. Under the same conditions, Nnitrosation occurred in incubations containing the antidepressant nortriptyline, but this was greatly reduced in the presence of ascorbic acid. Levels of nitrite and the amine as low as 5 ppm were reported carcinogenic in rats. Genotoxicity

Source: Scandinavian Journal of Work, Environment and Health, Vol. 19, Supplement 2, pages 50-56, 64 references, 1993

Victorin K


The genotoxicity of nitrogen oxides was discussed. Indirect effects result from the fact that nitric-oxide (10102439) and nitrogen-dioxide (10102440) form nitrous-acid (7782776) and nitric-acid (7697372) in aqueous solution which are in equilibrium with nitrite and nitrate ions. Undissociated nitrous-acid reacts directly with amino acids in DNA and nitrosates amines to form nitrosamines which in themselves are alkylating agents. Nitrogen-dioxide and, to a lesser extent, nitric-oxide induce mutagenicity in bacterial and mammalian and plant cell assay systems. The few in-vivo studies have provided negative results, except one study in which male Sprague-Dawley-rats were exposed to nitrogendioxide and nitric-oxide, both of which induced chromosome aberrations and mutations in lung cells recovered from the animals. No definitive evidence of carcinogenicity has been obtained, although inhalation of nitrogen-dioxide caused a small statistically significant increase in the incidence of lung adenomas in A-mice, a strain susceptible to pulmonary adenoma induction. A long term study in mice exposed to nitrogendioxide or ozone (10028156) plus nitrogen-dioxide found that both gases promoted the development of lung tumors initiated by bis(2hydroxypropyl)nitrosamine. The genotoxic potential of nitrate and nitrite ions was considered. Nitrite has demonstrated genotoxicity, including carcinogenicity, in both in-vitro and in-vivo studies. Nitrate has shown little genotoxic activity. Many nitrosamines and polycyclic aromatic hydrocarbons (nitroPAHs) have demonstrated genotoxic activity, including carcinogenicity. Nitrosamines can be formed in-vivo after inhalation of nitrogen-dioxide; however, the relative importance of inhaled nitrogen-dioxide as a source of nitrosamines is considered unimportant when compared with ingestion of nitrosamines or nitrites plus amines.