Dose response studies of carcinogenesis in rats by nitrosodiethylamine.

A dose-response study was conducted in Fischer rats with nitrosodiethylamine, which was administered in regulated amounts as a solution in drinking water. Groups of 20 female rats each received a different treatment, one group consisted of 12 animals; one of the groups was untreated. The concentrations of the solutions fed ranged from 113 to 0.45 mg/liter at six successive concentrations differing from a factor of 2.5. The treatment times were 17 weeks at the highest concentration; 22 weeks with 45 mg/liter; and 30 weeks with 18, 7, 2.8, 1.1 and 0.45 mg/liter. The two lowest dose levels were also given for 60 weeks, and the 0.45-mg/liter dose was given for 104 weeks. Animals were allowed to die naturally with tumors, and the time to death with tumors was an index of the potency of treatment. In the top four treatment groups, the potency measured in this way was proportional to the total dose of carcinogen administered. At all other doses, survival time was much less dependent on the dose administered, whether or not tumors were induced by the treatment. The principal tumors found were in the upper gastrointestinal tract, mainly the esophagus, at all doses. In the two highest dose groups, there was a high incidence of liver tumors also. There were few liver tumors in the lower dose groups, but there was a dose-related incidence of tumors of the upper gastrointestinal tract. It was remarkable that a nitrosodiethylamine concentration of 0.45 mg/liter (0.45 ppm) administered for 104 weeks induced tumors of the upper gastrointestinal tract in 70% of the treated rats.