N-
Nitrosocimetidine, a nitroso derivative of the
drug cimetidine, was given to groups of 20 male and 20 female rats in
drinking water at a concentration of 0.5 mM for more than 2 years. The life span of the rats was not decreased compared with untreated control animals, and there was no significant increase in incidence of any
tumor that could be attributed to the treatment. In comparison, 45% or more of 20 male rats treated with the analogous nitrosoguanidine, N-nitroso-
N-methyl-N'-nitroguanidine, at an equimolar concentration in
drinking water developed
neoplasms of the glandular stomach. There was some shortening of life span in these animals. An additional group of 20 male rats was given an identical treatment with N-nitroso-
N-methyl-N'-nitroguanidine in water, but prepared fresh on alternate days, rather than once a week, to minimize decomposition. These animals died more rapidly than did the previous group and had a higher incidence of
neoplasms of the glandular stomach. The
neoplasms seen in this organ were usually
adenomas or
adenocarcinomas, but there were a few
hemangiosarcomas and neurosarcomas. There is a possibility that
nitrosocimetidine could be formed by interaction of
cimetidine with
nitrite in the stomach, but the carcinogenic risk arising would be very small based on the negative result of this study.