The toxicology of nitrate, nitrite and n‐nitroso compounds

Nitrate is essentially non‐toxic to mammals but it can be reduced to nitrite either in improperly stored food, in the rumen of cattle, in the gastrointestinal tract of the human infant, and by the microflora of the human mouth. The nitrite from these and other sources, including that purposely added to food, presents a toxic hazard both because of the direct toxicity of nitrite, and by the formation of carcinogenic N‐nitroso compound by reaction with amino compounds. Administration of toxic amounts of nitrite induces methaemoglobinaemia. The nature of this disease, its importance in human medicine and the reason for the particular sensitivity of the infant, are briefly discussed. The carcinogenic properties of N‐nitroso compounds are described. These compounds have been found in the environment and may be formed in the stomach from amines and nitrite. Our knowledge of the amount of N‐nitroso compounds to which man is exposed, is continually increasing but with the lack of epidemiologic evidence, the assessment of the significance to man of these traces of N‐nitroso compounds depends upon the interpretation of animal experiments and their extrapolation to man. This extrapolation would be more certain if there were a more clear understanding of the factors determining tissue selectivity by carcinogens and tissue sensitivity, and of the mechanism of cumulation of carcinogenic doses and of synergism between carcinogens. Recent experiments suggest that there may soon be a significant breakthrough in the understanding of this. These experiments are briefly discussed.