Potent carcinogenicity of nitrosodiethanolamine in rats

Nitrosodiethanolamine is found in synthetic cutting oils and in many cosmetic preparations and is probably the N-nitroso compound to which human exposure is greatest. It is formed by reaction of the commonly used amines diethanolamine and triethanolamine with nitrosating agents. An assessment of the possible risk in human exposure to nitrosodiethanolamine must be based on sound chronic toxicity data. A previously published chronic test of this compound in rats has shown it to induce liver tumours after very high oral doses, and tumours of the nasal cavity after administration of high repeated doses to Syrian hamsters by subcutaneous injection. To improve our understanding of the carcinogenic potency of nitrosodiethanolamine, we undertook a more extensive study, in which the compound was administered at concentrations ranging from 3,900 to 31,250 parts per million (p.p.m.) in drinking water, to groups of rats for about 6 months. We report here that when the animals were killed, all bore hepatocellular carcinomas, many of which metastasized at the higher doses, indicating that nitrosodiethanolamine is a carcinogen of considerable potency in the rat. However, it is inactive or very weakly active in short-term tests, such as the Salmonella mutagenesis test developed by Ames.