Metabolic fate of asymmetric N,N-dialkylnitrosamines having butyl group in the rat.

The metabolic fate of N-alkyl-N-butylnitrosamines (alkyl=ethyl, propyl, and pentyl), which induce tumors in the liver and esophagus but do not induce bladder tumors, was investigated in the rat, in order to elucidate any possible correlation between metabolism and the noncarcinogenicity to the urinary bladder of these N-nitrosamines. They were extensively metabolized in the rat, no unchanged compounds being found in the urine. The metabolic pattern of these N-nitrosamines having a butyl chain was essentially similar to that of N,N-dibutyl-nitrosamine, which induces tumors in the bladder as well as in the liver and esophagus. They were mainly metabolized via omega-oxidation followed by beta-oxidation and/or (omega-1)-oxidation of either of the two alkyl chains. Thus the N-alkyl-N-(3-carboxypropyl)nitrosamine and/or the N-alkyl-N-(2-carboxyethyl)nitrosamine were identified as the principal urinary metabolites. Possible important factors concerned with the induction of bladder tumors by N,N-dialkylnitrosamines are discussed from the metabolic point of view.