Metabolism of isomeric N-methyl-N-nitroso-(methylphenyl)-methylamines

Isomeric N-methyl-N-nitroso-(2-, 3-, and 4-methylphenyl)-methylamines (2a, 2b and 2c, Fig. 1.) were metabolized in rats to the corresponding 2-, 3- and 4-(N-methyl-N-nitroso-aminomethyl)-benzoic acids (4-MNAB) (3a, 3b and 3c). The structures of 3b and 2c were established by synthesis and confirmed by spectroscopic evidence. Metabolic formation of 3a, 3b and 3c was determined by HPLC analysis and the time-course of 3c excretion was established. Oral intubation of the acid 3c resulted in almost quantitative excretion of this metabolite in 24 h urine thus indicating rapid detoxication. Toxicity and carcinogenicity of the isomeric 2a, 2b and 2c were compared with those of the parent N-methyl-N-nitroso-benzylamine (MNBA).