N-nitrosamines: environmental occurrence, in vivo formation and metabolism

A number of amines and quaternary ammonium salts can be nitrosated to N-nitrosamines under environmental conditions as well as in vivo. Of the N-nitrosamines which have been bioassayed to date, more than 250 are proven animal carcinogens. In the absence of data which document that N-nitrosamines can be carcinogenic to man, we concur with the International Agency for Research on Cancer that those nitrosamines that were proven carcinogens in at least 2 animal species "should be regarded for practical purposes as if they were carcinogenic to humans" (1). Such evaluation pertains also to N-nitrosodiethanolamine (NDELA), N-nitrosomorpholine (NMOR) and the tobacco-specific N-nitrosamines (TSNA). This presentation discusses the environmental occurrence, analysis, reduction, bioassay data for carcinogenicity and metabolism of these 3 types of nitrosamines. The data at hand make it prudent to encourage reduction of the occurrence of N-nitrosamines in the workplace, in the environment and in food, tobacco and other personal use products. Emphasis should also be placed on research efforts to inhibit the in vivo formation of N-nitrosamines and their metabolic activation to reactive carcinogenic species. The latter efforts require increased knowledge as to the activation of nitrosamines and their reaction with cellular macromolecules including DNA.