NTP chronic bioassay studies in rats and male mice did not show carcinogenicity where nitrate was administered alone in drinking water or diet (three studies in mice and four studies in rats) or was coadministered with nitrosatable compounds, and when nitrite was given alone in the diet by gavage or in the drinking water to rats and mice. It has been shown to lower the incidence of tumors in animal experiments, and reduce the risk for cancer that is associated with ingested nitrite in epidemiological studies. Ascorbic acid is an inhibitor of nitrosation reactions. Nitrosamines need to be activated metabolically by cytochrome P450 enzymes to electrophilic intermediates to exert a carcinogenic effect, while nitrosamides are direct-acting carcinogens. Nitrosating agents (e.g., nitrous acid and nitrous anhydride) that arise from nitrite under acidic gastric conditions can react with amines or amides to form nitrosamines or nitrosamides, and the induction of tumors in animals via endogenous synthesis of N-nitroso compounds has been demonstrated. Nitrosating agents can react under certain conditions with nitrosatable compounds to form N-nitrosamines and N-nitrosamides, some of which are animal carcinogens. Nitrosating agents can be ingested from food and drinking water, and synthesized from ingested nitrate and nitrite. Sodium and potassium nitrate have been tested for potential carcinogenicity, alone and in combination with nitrosatable compounds. Fan, in Encyclopedia of Toxicology (Third Edition), 2014 Carcinogenicity
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