Dose-response study with N-nitrosodiethanolamine in F344 rats.

A dose-response study of the carcinogenicity of N-nitrosodiethanolamine was conducted in F344 rats. The nitrosamine was administered in drinking-water at a controlled rate (20 ml/rat/day, 5 days/wk) to groups of 16 or 20 rats of each sex. The doses administered were as follows: 2500 mg/litre drinking-water for 45-wk, 1000 mg/litre for 50 wk, 400 mg/litre for 50 wk and 400 mg/litre for 75 wk. Almost all of the treated animals died with hepatocellular carcinomas, of which 20-45% metastasized in each group. The females in each treatment group tended to die earlier, because they received a higher dose per unit body weight, but for each sex there was a dose-related decrease in survival as the carcinogen dose increased. There was a considerable incidence of tumours of the nasal cavity. The incidence of these tumours tended to be higher in males than in females and might be sex- or lifespan-related. A number of rats had cholangiocarcinomas in the liver and there were a few kidney tumours and tumours of the oesophagus in animals given the higher doses. None of these tumours was seen in the untreated controls of either sex, almost all of which outlived the treated animals. It is concluded that N-nitrosodiethanolamine is a carcinogen of considerable potency in rats.