Carcinogenesis in rats by nitrosodimethylamine and other nitrosomethylalkylamines at low doses

Four nitrosomethylalkylamines were given to F344 rats in drinking water at concentrations of 0.22 mM or less. The total doses delivered to each animal were 0.5 and 0.2 mmol of nitrosodimethylamine (NDMA), 0.6 mmol of nitrosomethyl-2-oxopropylamine (NMOP) and nitrosomethyl-2-hydroxy-propylamine (NMHP) and 0.9 mmol of nitrosomethyl-2,3-dihydroxypropylamine (NMDHP). NDMA induced liver neoplasms in most of the animals, including 35% with hemangiosarcomas as well as hepatocellular tumors at the higher dose, but only hepatocellular tumors at the lower dose and the latter group of rats survived longer. NMOP induced a high incidence of esophageal tumors and NMHP induced a high incidence of both esophageal and nasal cavity tumors. NMDHP was the least potent of the 4 carcinogens, and induced lung tumors, neoplastic nodules in the liver, a few esophageal tumors and a few nasal cavity tumors, but after a long induction time.