Crampton R F
Oncology. 1980;37(4):251-4. doi: 10.1159/000225446.
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.
主要使用二甲基亚硝胺和二乙基亚硝胺在大鼠身上进行了剂量反应研究。这些化合物以33 - 1690 ppb的浓度添加到饮用水中，每个浓度设置15个剂量水平。这个剂量范围相当于雄性动物约2 - 1080微克/千克体重/天，雌性动物约3 - 1470微克/千克体重/天。还进行了辅助实验，使用小鼠和仓鼠，以及在大鼠中，在断奶时和20周龄时首次给予二烷基化合物。在每个实验中都使用了15个剂量水平。还开展了关于N - 亚硝基吡咯烷和N - 亚硝基哌啶的额外实验。讨论了实验设计和研究实施过程中遇到的问题，并强调了预实验的必要性。给出了对结果的初步考量。在雄性大鼠中，二甲基亚硝胺和二乙基亚硝胺在中位存活时间超过900天后观察到致癌反应的最低水平为132 ppb。二甲基亚硝胺在2微克/千克体重/天的水平时出现肝脏增生性结节。
