Model risk analysis of nitrosatable compounds in the diet as precursors of potential endogenous carcinogens.
The potential health risk posed by the endogenous formation of N-nitroso compounds (NOC) from nitrosation of dietary ureas, guanidines, amides, amino acids and amines (primary, secondary and aromatic) was estimated according to the model: Risk = [daily intake of precursor] X [gastric concentration of nitrite]n X [nitrosatability rate constant] X [carcinogenicity of derivative]. The daily intakes of these compound classes span five orders of magnitude (100 g/day amides, top; 1-10 mg/day secondary amines, ureas, bottom); the nitrosation rate constants span seven orders of magnitude (aryl amines, ureas, top; amides, secondary amines, bottom); and the carcinogenicity estimates span a 10,000-fold range from 'very strong' to 'virtually noncarcinogenic'. The resulting risk estimates likewise span an enormous range (nine orders of magnitude): dietary ureas and aromatic amines combined with high nitrite concentration could pose as great a risk as the intake of preformed N-nitrosodimethylamine in the diet. In contrast, the risk posed by the in-vivo nitrosation of primary and secondary amines is probably negligible. The risk contributed by amides (including protein), guanidines and primary amino acids is intermediate between these two extremes.
Shephard
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SE
Institute of Toxicology, Swiss Federal Institute of Technology, Schwerzenbach.
Schlatter
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C
Lutz
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WK
D000588:Amines / Q000493:pharmacokinetics; D000596:Amino Acids / Q000493:pharmacokinetics; D001711:Biotransformation; D002273:Carcinogens / Q000096:biosynthesis*; D004032:Diet; D004044:Dietary Proteins / Q000493:pharmacokinetics*; D004128:Dimethylnitrosamine / Q000493:pharmacokinetics; D019791:Guanidine; D006146:Guanidines / Q000493:pharmacokinetics; D006801:Humans; D007700:Kinetics; D015233:Models, Statistical; D009603:Nitroso Compounds / Q000096:biosynthesis*; D012306:Risk; D014508:Urea / Q000493:pharmacokinetics
D000588:Amines; D000596:Amino Acids; D002273:Carcinogens; D004044:Dietary Proteins; D006146:Guanidines; D009603:Nitroso Compounds; D014508:Urea; D019791:Guanidine; D004128:Dimethylnitrosamine