Matsushima Y, Onodera H, Ogasawara H, Kitaura K, Mitsumori K, Maekawa A, Takahashi M
Eisei Shikenjo Hokoku. 1991(109):61-6.
A 13-week subchronic oral toxicity study of cyanoguanidine was performed in male and female F344 rats by feeding of CRF1 powder diets containing 0, 1.25, 2.5, 5 and 10% cyanoguanidine to determine appropriate dose levels for a subsequent 2-year carcinogenicity study. The rats were randomly allocated to 5 groups, each consisting of 10 males and 10 females. No animals died during the administration period. Inhibition of body weight gain was more marked in both sexes of the 10% group and in females of the 5% group as compared with the control group. Mean food intake in males of the groups treated with 5% or 10% and in females of the 10% group was significantly higher than that in the control group. Serum biochemical investigation revealed a higher level of serum BUN in both sexes of the 10% group. On histopathological examination, toxic changes characterized by the occurrence of intranuclear eosinophilic inclusion bodies in the proximal tubular epithelium of the kidney were observed in both sexes of the 10% group. Similar inclusion bodies were also seen in 2 out of 10 males of the 5% group. From these results, it was concluded that a level of 10% of cyanoguanidine in the diet is unequivocally toxic. A dose level, 5% cyanoguanidine, in the diet might be appropriate as a high dose for a carcinogenicity study.
通过给雄性和雌性F344大鼠喂食含0%、1.25%、2.5%、5%和10%氰基胍的CRF1粉末饲料，进行了一项为期13周的氰基胍亚慢性经口毒性研究，以确定后续两年致癌性研究的合适剂量水平。大鼠被随机分为5组，每组由10只雄性和10只雌性组成。给药期间无动物死亡。与对照组相比，10%组的雌雄两性以及5%组的雌性体重增加抑制更为明显。5%或10%处理组的雄性以及10%组的雌性平均食物摄入量显著高于对照组。血清生化检查显示，10%组的雌雄两性血清尿素氮水平较高。组织病理学检查发现，10%组的雌雄两性均出现以肾近端小管上皮细胞核内嗜酸性包涵体为特征的毒性变化。5%组的10只雄性中有2只也观察到类似的包涵体。从这些结果得出结论，饮食中10%的氰基胍水平具有明确的毒性。饮食中5%的氰基胍剂量水平可能适合作为致癌性研究的高剂量。
