Genda Y, Yamamura H, Takahashi Y, Ishijima N, Furuhama K, Kakihata K, Ohno H, Nomura M
Drug Safety Research Center, Developmental Research Laboratories, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
J Toxicol Sci. 1995 Oct;20 Suppl 1:47-66. doi: 10.2131/jts.20.supplementi_47.
The single-dose intravenous toxicities of iodixanol, a new nonionic iso-osmolar contrast medium, were investigated in mice, rats and monkeys. The LD50 values were estimated to be 17.9 gI/kg for male mice and 16.2 gI/kg for female mice, 18.8 gI/kg for male rats and 22.0 gI/kg for female rats, and more than 10.0 gI/kg for monkeys. There was no marked sex difference in mice or rats, nor any significant difference observed between these two rodent species. Decrease in spontaneous locomotor activity, ptosis, respiratory depression and abdominal posture were observed in many mice and rats. These signs disappeared mostly by 8 days after dosing in surviving animals. Death occurred between immediately and 4 days after dosing in mice, and between immediately and 14 days after dosing in rats. Transient depression of body weight gain was observed in the surviving mice and rats by 7 days after dosing. Histological examinations revealed congestion or hemorrhage in the renal medulla, vacuolation or necrosis of the renal proximal tubular epithelium in mice and rats that died and vacuolation of the renal proximal tubular epithelium in surviving rats. There were no significant treatment-related changes in the laboratory and pathological examinations in monkeys.
研究了新型非离子等渗造影剂碘克沙醇的单剂量静脉毒性，实验对象为小鼠、大鼠和猴子。雄性小鼠的半数致死量（LD50）估计为17.9 gI/kg，雌性小鼠为16.2 gI/kg；雄性大鼠为18.8 gI/kg，雌性大鼠为22.0 gI/kg；猴子的LD50超过10.0 gI/kg。小鼠和大鼠中均未观察到明显的性别差异，这两种啮齿动物之间也未观察到显著差异。许多小鼠和大鼠出现自发运动活动减少、眼睑下垂、呼吸抑制和腹部姿势改变。在存活的动物中，这些症状大多在给药后8天内消失。小鼠在给药后立即至4天内死亡，大鼠在给药后立即至14天内死亡。给药后7天，存活的小鼠和大鼠出现体重增加的短暂抑制。组织学检查显示，死亡的小鼠和大鼠肾髓质充血或出血，肾近端小管上皮细胞空泡化或坏死，存活大鼠肾近端小管上皮细胞空泡化。猴子的实验室检查和病理检查未发现与治疗相关的显著变化。
