Carcinogenicity of N-nitrosodiethanolamine in rats at five different dose levels

N-nitrosodiethanolamine, an N-nitroso compound of environmental significance, has been tested for carcinogenicity in male Sprague-Dawley rats at five different dose levels. Administration p.o. in the drinking water of 1.5, 6, 25, 100, or 400 mg N-nitrosodiethanolamine per kg per day was tolerated well. Median total doses administered were between 0.86 g/kg body weight at the highest and 100.3 g/kg body weight at the lowest dose level. Treatment-related tumors were observed in the liver and the nasal cavity. The induction of hepatocellular carcinomas was clearly dose related, low doses also inducing benign lesions. Other liver tumors were of mesenchymal and ductal origin and nasal cavity neoplasms were diagnosed as squamous-cell carcinomas and neuroepitheliomas of the olfactory epithelium. Statistical evaluation of the 1.5-mg/kg dose regimen clearly indicates that even such low doses are carcinogenic. This potent carcinogenic activity is surprising since a high percentage (60 to 90%) of an administered dose of N-nitrosodiethanolamine is excreted unchanged in the urine. Thus, we propose that an as yet unidentified metabolite may possess high carcinogenic potential.