Toxic Properties Of Dialkylnitrosamines and Some Related Compounds

Abstract

The title compounds, which have some commercial applications, are described, and their toxic action is reviewed. Most results refer to rats. Their main acute effect is hepatic centrilobular necrosis, though lung lesions may appear. The compounds also induce tumours in liver, lung, and kidney. One, dimethylnitrosamine, has been shown to cause kidney tumours after a single dose. The necrotic and carcinogenic doses of the compounds are closely related. The relation between structure and toxicity is discussed. Analogous formamides are much less toxic (the LD 50 9s in rats by intraperitoneal injection of dimethyl- and diethyl-formamides are 3,800 mg./kg. and 1,740 mg./kg.) and they do not cause centrilobular necrosis or tumours. Nitrosamines are oxidized in vivo and by liver preparations in vitro . Their toxic action is due to the release of powerful alkylating agents in the liver. They also inhibit protein synthesis and alkylate liver protein and ribonucleic acid. In all cases the effective agent appears to be a metabolite. The possible hazard to man in the uses of these compounds is emphasized.