[Intravenous single dose toxicity of iodixanol, a new nonionic iso-osmolar contrast medium, in mice, rats and monkeys].

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.