The carcinogenicity of
N-nitrosomethyl-n-propylamine and five of its derivatives, including N-
nitrosomethyl-n-butylamine, was compared by
oral administration of the compounds to inbred F344 rats. N-Nitromethyl-n-propylamine and N-
nitrosomethyl-n-butylamine given in
drinking water induced
tumors of the upper gastrointestinal tract, mainly
carcinomas of the esophagus, and appeared to be of comparable potency. N-Nitrosomethyl(2-hydroxypropyl)amine also mainly induced esophageal
carcinomas (100% incidence) and lung
tumors, whereas N-nitrosomethyl(2,3-dihydroxypropyl)amine mainly induced nasal cavity
tumors and gave rise to a high incidence of esophageal
tumors; however, it appeared to be less potent than the monohydroxy compound. N-Nitrosomethyl(2-oxopropyl)amine, the
ketone corresponding to N-nitrosomethyl(2-hydroxypropyl)amine, was a more potent
carcinogen than the latter at comparable doses in
drinking water and gave rise to a high incidence of esophageal
tumors and
tumors of the trachea; female rats had a high incidence (15/20) of
angiosarcomas of the liver, but only 2 male rats died with this
tumor. When N-nitrosomethyl(2-oxopropyl)amine was administered at a lower dose in
drinking water or at the same dose given by gavage, the incidence of esophageal
tumors was lower and there were fewer
carcinomas. After administration of large doses in
drinking water to male and female rats, N-nitrosomethyl(3-carboxypropyl)amine, a urinary metabolite of several N-nitrosomethyl-n-alkylamines that induce
tumors of the urinary bladder in rats, gave rise to a high incidence of
transitional cell carcinomas of the bladder. The time to death of animals with these
tumors was long, and there were few other
tumors.