Nishiguchi Y, Ishibashi S, Tarui M, Fujimoto S, Tawaratani T, Yoshida M, Uchimoto H, Adachi T, Hamasu Y, Sumi N
Research Laboratories, Nippon Shinyaku Co., Ltd, Kyoto Japan.
J Toxicol Sci. 1994 Nov;19 Suppl 3:305-26. doi: 10.2131/jts.19.supplementiii_305.
Twenty male and 20 female Slc : SD rats were orally given lactitol, a hepatic encephalopathy drug, for 13 weeks at doses of 0, 0.625, 2.5 or 10 g/kg/day. A 5 week recovery test was conducted after the discontinuation of the drug treatment. Soft stool and decreased food consumption were seen in the 2.5 and 10 g/kg groups. In the 10 g/kg group, there were diarrhea, soiled fur, abdominal distention, salivation, piloerection, decreased body weight gain and increased water consumption. Urinalysis showed decreased urine volume and K+ excretion in the 10 g/kg group. In this dose group, biochemical examination showed decreased ALP, total cholesterol, triglyceride, glucose, Ca, Na+, Cl- and total protein. In the pathological examination, the cecum weight was increased in all dose groups. In the 2.5 and 10 g/kg groups, cecum distention with mucosal hyperplasia was observed. The adrenal weight was increased in the 10 g/kg group and hypertrophy of zona fasciculata of adrenal gland were seen in the 2.5 and 10 g/kg groups. The thymic weight was decreased in the 10 g/kg group. Ophthalmoscopic and hematologic examinations failed to reveal any drug induced changes. The increased cecum weight in the 0.625 g/kg group was regarded as toxicologically insignificant because of the failure of the association with any clinical or morphological findings. The above mentioned changes were satisfactorily reversible except for those in the cecum. Based on the results obtained, the NOAEL of this study was suggested to be 0.625 g/kg/day.
选取20只雄性和20只雌性Slc:SD大鼠，口服给予肝性脑病药物乳糖醇，剂量分别为0、0.625、2.5或10 g/kg/天，持续13周。药物治疗停止后进行为期5周的恢复试验。2.5和10 g/kg组出现软便和食物摄入量减少。10 g/kg组出现腹泻、被毛污染、腹胀、流涎、竖毛、体重增加减少和饮水量增加。尿液分析显示10 g/kg组尿量和钾排泄减少。该剂量组的生化检查显示碱性磷酸酶、总胆固醇、甘油三酯、葡萄糖、钙、钠、氯和总蛋白减少。病理检查发现，所有剂量组的盲肠重量均增加。2.5和10 g/kg组观察到盲肠扩张伴黏膜增生。10 g/kg组肾上腺重量增加，2.5和10 g/kg组肾上腺束状带肥大。10 g/kg组胸腺重量减轻。眼底镜和血液学检查未发现任何药物引起的变化。0.625 g/kg组盲肠重量增加被认为在毒理学上无显著意义，因为与任何临床或形态学发现均无关联。除盲肠变化外，上述变化均可满意地逆转。根据所得结果，本研究的无观察到有害作用水平建议为0.625 g/kg/天。
