Long-term experiment of maximal non-carcinogenic dose of dimethylnitrosamine for carcinogenesis in rats

Studies were made on the maximal non-carcinogenic dose of dimethylnitrosamine (DMN) in rats. Groups of Wistar strain rats of both sexes, 6 weeks old, were given standard diet without DMN (group 1), or containing 0.1 ppm DMN (group 2), 1.0 ppm DMN (group 3), or 10 ppm DMN (group 4) for 96 weeks and then sacrificed for hematological, serum-biochemical, and histopathological examinations. After 96 weeks, the weights of the body and main organs in the different groups were not significantly different. The leucocyte count and blood urea-nitrogen (BUN) in group 4 were slightly increased, but other serum findings were not significantly different in different groups. Hepatocellular carcinomas were found in group 3 (1 male and 3 females), but not in group 2. Hemangioendotheliomas of the liver, adrenal adenomas, pituitary adenomas, interstitial cell tumors of the testis, ovarian tumors, and leukemia were also found. Pyelonephritis was found in both experimental and control animals, but no kidney tumors developed with these dose levels of DMN. These results show that on long-term oral administration to rats, 1.0 ppm DMN is the minimum carcinogenic dose, while a level of about 0.1 ppm DMN is non-carcinogenic.