Effects of route of administration and dose on the carcinogenicity of N-nitrosodiethanolamine in the Syrian golden hamster.

N-Nitrosodiethanolamine was assayed for carcinogenicity in Syrian golden hamsters by s.c. injection, topical application, and oral cavity swabbing. Three groups of 30 hamsters each received 27 weekly s.c. injections of either 500, 170, or 58 mg of N-nitrosodiethanolamine per kg in 0.9% NaCl solution. In the group treated with 500 mg/kg, 19 of 30 animals developed nasal cavity tumors, 7 of 30 had tracheal tumors, and 2 of 30 had tumors of the larynx. Among the animals treated with 170 mg/kg, 7 of 29 presented with nasal cavity tumors and 4 of 29 presented with tracheal tumors. In the group treated with 58 mg/kg, only two tracheal tumors were observed. Acetone solutions of N-nitrosodiethanolamine were applied to the shaved backs of three groups of 30 hamsters, each three times weekly for 36 weeks, at doses of 25, 8, or 2.5 mg; the total doses were the same as in the groups treated by s.c. injection. At the 25-mg dose level, 5 of 30 animals developed nasal cavity tumors and 4 of 30 animals had tumors of the trachea. No skin tumors were observed. The incidence of respiratory tract tumors in the groups treated with 8 or 2.5 mg was not significant compared to controls. The oral cavities of 40 hamsters were swabbed three times weekly for 45 weeks with 20 mg of N-nitrosodiethanolamine; the total dose was the same as the highest doses given by s.c. or topical administration. Seventeen of 38 hamsters had nasal cavity tumors, 6 of 38 developed tracheal tumors, and 1 of 38 presented with a tumor of the larynx. No tumors were observed in the oral cavity. The results of this study demonstrate that N-nitrosodiethanolamine is organospecific for the Syrian golden hamster nasal cavity and trachea and that it induces tumors in these sites at doses lower than previously reported.