Carcinogenicity of methylated derivatives of N-nitrosodiethylamine and related compounds in Sprague-Dawley rats.

Five nitrosamines, which can be considered alkyl derivatives of N-nitrosodiethylamine, were tested for carcinogenicity by administration to Sprague-Dawley rats in drinking water at approximately equimolar concentrations. N-Nitrosodi-n-propylamine was a potent carcinogen but less so than N-nitrosodiethylamine and gave the same spectrum of tumors. N-Nitrosodiisopropylamine was very much weaker than N-nitrosodiethylamine and induced only tumors of the nasal turbinates in significant incidence. At the doses given, neither N-nitrosodiisobutylamine nor N-nitrosodi-sec-butylamine was significantly carcinogenic. In contrast, the cyclic nitrosamine N-nitrosohexamethyleneimine was equally potent with N-nitrosodiethylamine and gave the same spectrum of tumors in liver, esophagus, and nasal turbinates. The results support the concept that oxidation at the alpha carbon atom of nitrosamines is a significant step in carcinogenesis.