DOSE-RESPONSE STUDIES OF CARCINOGENESIS IN RATS BY NITROSODIETHYLAMINE

  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (12) , 4997-5003
Abstract
A dose-response study was conducted in Fischer rats with nitrosodiethylamine administered in regulated amounts as a solution in drinking water. The concentrations of the solutions fed ranged from 113-0.45 mg/l at 6 successive concentrations differing by a factor of 2.5. The treatment times were 17 wk at the highest concentration; 22 wk with 45 mg/l and 30 wk with 18, 7, 2.8, 1.1 and 0.45 mg/l. The 2 lowest dose levels were given for 60 wk and the 0.45-mg/l dose 104 wk. The time to natural death with tumors was an index of the potency of treatment. In the top 4 treatment groups the potency 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 2 highest dose groups there was a high incidence of liver tumors. 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/l (0.45 ppm) administered for 104 wk induced tumors of the upper gastrointestinal tract in 70% of the treated rats.