Urinary metabolites of some alicyclic nitrosamines

We have studied the urinary metabolites of N-nitrosopiperidine, 3- and 4-hydroxy-N-nitrosopiperidine, N-nitroso-4-piperidone, N-nitrosohexamethyleneimine and N-nitroso-heptamethyleneimine. The N-nitrosopiperidines induce primarily oesophageal tumours in rats; N-nitrosohexamethyleneimine induces oesophageal and liver tumours and N-nitrosoheptamethyleneimine induces oesophageal and lung tumours. The products were identified by gas chromatographic comparison with standards, where possible, and by gas chromatography-mass spectrometry. The percentage of the dose excreted as metabolites in the urine increased with ring size. Hydroxy and ketone derivatives of all three of the N-nitrosoalicyclic amines were found. Pimelic acid was the major metabolite (congruent to 25%) of N-nitrosoheptamethyleneimine; adipic acid was identified as a metabolite of N-nitrosohexamethyleneimine, but not glutaric acid was found from N-nitrosopiperidine.