No evidence of carcinogenicity of N-nitrosocimetidine in rats

Cimetidine is a histamine H2-antagonist. Since in vitro formed N-nitrosocimetidine (NC) has been shown to be genotoxic, we investigated it for carcinogenicity. Two groups of 40 Sprague-Dawley rats each received 500 and 50 mg/kg NC, respectively, by gavage twice weekly for one year with subsequent lifetime follow-up. An additional 40 rats were given the structurally related carcinogen methylnitro-nitrosoguanidine (MNNG) orally at weekly doses of 80 mg/kg for 3 months. 100 animals served as untreated controls. MNNG-treated rats died with carcinomas of the forestomach (median induction time: 226 days). No evidently treatment-related tumors were seen in animals receiving NC. The median survival time in both NC-treated groups was reduced (400 and 393 vs. 630 days in the control). No evidence of carcinogenicity of NC was seen in this bioassay. It is concluded that NC is not carcinogenic, or at least significantly less so than MNNG.