We examined the toxicity and carcinogenicity in rodents of
methyl-n-amylnitrosamine (MNAN), multiple doses of which are known to induce esophageal and nasal
tumors in rats. A single i.p. injection of 50-70 mg MNAN/kg into adult rats produced a 74% incidence of esophageal
squamous carcinomas (mean latency, 63 weeks). Single doses of 3.0-12.5 mg/kg of MNAN injected into newborn and 3-day-old rats and hamsters were not carcinogenic in rats and only weakly carcinogenic in hamsters. The low doses (used because larger doses produced lethal
interstitial pneumonia) probably explain the low carcinogenicity, despite previous findings of extensive formation of stable hydroxy-MNANs from MNAN by the esophagus of both species at these ages, which may indicate MNAN activation. One i.p. injection of 70-100 mg MNAN/kg into adult Syrian hamsters was weakly carcinogenic for the esophagus and forestomach. Six
injections of 75 mg MNAN/kg into adult hamsters induced lung and nasal cavity
tumors (65 and 43% incidences, respectively), but only a few esophageal
tumors. Three
injections of 15 mg MNAN/kg into adult Swiss mice induced lung
adenomas and esophageal
papillomas in 71 and 32% incidences, respectively. These results partially agreed with previous studies on hydroxy-MNAN formation by the esophagus of these species. Six s.c.
injections of 75 mg 2-oxo-MNAN/kg into adult rats induced
tumors of the nasal cavity, esophagus and soft tissue at the injection site in 68, 63, and 32% incidences, respectively. This does not support the view that 2-oxo-MNAN is an active metabolite of MNAN.