CANCER

Epidemiologic data do not support a straightforward association between exogenous nitrate or nitrite exposure and human carcinogenesis. A discussion of dose-response relationships between human carcinogenesis and nitrate or nitrite exposure is not appropriate without supporting epidemiologic data and a physiologically based pharmacokinetic model that would permit analysis of the complex relationships between exogenous and endogenously formed nitrate, nitrite, and N-nitrosamines. In addition, because there is no evidence that either nitrate or nitrite alone is carcinogenic in animals, a discussion of dose-response relationships between carcinogenesis in animals and nitrate or nitrite exposure is not possible. The only evidence of a role of nitrite in carcinogenesis comes from studies in which nitrite was administered simultaneously with a nitrosatable amine; in these cases, carcinogenesis can be attributed to the endogenous formation of carcinogenic nitrosamines.

Cancer risk associated with endogenous nitrosamine formation is a function of four variables: the amount of nitrite ingested or formed from nitrate, the amount of nitrosatable substances ingested, the rate of in vivo nitrosation, and the carcinogenic potency of the resulting nitrosamine. Establishing human dose-response relationships for a phenomenon that has so many variables is not straightforward. The carcinogenic potencies of nitrosamines based on rodent bioassays vary by at least a factor of 1,000 (Shephard et al. 1987). Daily dietary intakes of nitrosatable amines, amides, guanidines, and ureas have been estimated to range from less than 1 mg to hundreds or even thousands of milligrams (Shephard et al. 1987). Dietary nitrate intake is estimated to vary from about 75 to 270 mg (NRC 1981), and the extent to which nitrate is reduced to nitrite endogenously depends on gastric acidity and the nature



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