Carcinogenic dose-related response to nitrosamines.
Dose-response studies were carried out, principally with dimethylnitrosamine and diethylnitrosamine, in rats. The compounds were given in the drinking water at levels of 33-1,690 ppb, each being given at 15 dose levels. This range of dosage corresponds to approximately 2-1,080 microgram/kg b.w./day for male animals and 3-1,470 microgram/kg b.w./day for females. Subsidiary experiments using mice and hamsters, and also in rats, where the dialkyl compounds were first given on weaning and at 20 weeks of age were also carried out. In each of these experiments 15 dose levels were used. Additional experiments with N-nitrosopyrrolidine and N-nitrosopiperidine were undertaken. The problems encountered in the experimental design and in the execution of the studies are discussed, and the necessity for pilot studies is emphasized. A preliminary consideration of the results are presented. Lowest levels at which carcinogenic responses were observed were 132 ppb for dimethyl- and diethylnitrosamine in male rats after median survival times in excess of 900 days. Hyperplastic nodules of the liver occurred with dimethyl nitrosamine at a level of 2 microgram/kg b.w./day.