Carcinogenesis bioassay of acetamide, hexanamide, adipamide, urea and P-tolylurea in mice and rats

As a part of the National Cancer Institute's effort to screen environmental and occupational chemicals for chronic toxicity and carcinogenicity, the amides acetamide, hexanamide, adipamide, urea, and p-tolylurea were fed to male and female C57B1/6 mice and Fischer 344 rats from 12 months. Rats received the following concentrations of compounds in their diets: acetamide, 2.36%; hexanamide, 1.5%; adipamide, 2.4% and 5.8%; urea, 0.45%, 0.9%, and 4.5%; and p-tolylurea, 0.2%. Mice received acetamide, 1.18% and 2.36%; hexanamide, 1.0% and 1.5%; adipamide, 1.6% and 2.4%; urea, 0.45%, 0.9%, and 4.5%; and p-tolylurea, 0.2%. In acetamide treated rats, there was a compound-related occurrence of neoplastic nodules (1/47 male, 3/48 female) and hepatocellular carcinomas (41/47 male, 33/48 female). The incidence, speed of onset and frequency of metastases, were greater in males than in females. In male mice treated with acetamide (low dose, 7/50; high dose, 7/46); hexanamide (low dose, 6/35; high dose, 6/39); and p-tolylurea (10/43), there was a compound-related increase in hematopoietic tumors, namely malignant lymphomas. Therefore, under the conditions of these studies, acetamide was an hepatocarcinogen in rats. In male mice, acetamide, hexanamide, and p-tolylurea caused malignant lymphomas. Urea and adipamide were considered to be non-carcinogenic.