Biological and chemical studies involving methyl-t-butylnitrosamine, a non-carcinogenic nitrosamine

Methyl-t-butylnitrosamine (MtBN) was tested for carcinogenicity by s.c. injection in the Syrian golden hamster. No tumors were observed at 160, 80 or 40 mg/kg/week, in accord with Druckrey's report that ethyl-t-butylnitrosamine (EtBN), the homolog of MtBN, was not carcinogenic in the rat. Acetoxymethyl-t-butylnitrosamine, an activated form of MtBN, was also chronically tested by s.c. injection and found to be non-carcinogenic. It was demonstrated that 2-methylpropane diazotic acid, the proposed "ultimate" reactive metabolite of MtBN, afforded the carbenium ion product t-butyl alcohol in 63% yield. These results are consistent with the hypothesis that MtBN and EtBN are not carcinogenic because the proposed "ultimate" metabolite in their metabolic activation cannot interact with the critical cellular site due to steric reasons.