[Twenty-six-week intravenous toxicity study of montirelin hydrate (NS-3) in rats followed by 9-week recovery test].

A repeated dose toxicity study of montirelin hydrate (NS-3), a new drug for the treatment of disturbance of consciousness, was conducted in Sprague-Dawley rats. Male and female rats were given the drug intravenously for 26 weeks at doses of 0 (control), 0.0004, 0.02, 1 and 50 mg/kg. After discontinuation of the treatment, a 9-week recovery test was also conducted in the 0, 1 and 50 mg/kg groups. No deaths related to the treatment were observed. Tremor and polyuria were seen in the 50 mg/kg group. There were decrease in body weight gain, and increase in water consumption in the 1 and 50 mg/kg groups. In those dose groups of males, decrease in food consumption was observed. Ophthalmoscopic examination failed to show any abnormalities attributable to the treatment. Blood chemical examination disclosed decrease in total cholesterol in the 50 mg/kg group. There were also decreases in phospholipid in the 50 mg/kg group of females, and in triglyceride in the 1 and 50 mg/kg groups of males. Urinalysis and hematologic examination failed to show any abnormalities attributable to the treatment. In pathological examination, serous cell hypertrophy and increase in organ weight of the submandibular gland were observed in the 1 and 50 mg/kg groups, and increase in organ weight of thyroid was revealed in the 0.02 mg/kg group and over. The changes mentioned above were satisfactorily reversible except for the decrease in food consumption in the 50 mg/kg group of males. Increased thyroid weight in the 0.02 mg/kg group was considered to be of no toxicological significance. These results show that the NOAEL of montirelin hydrate is 0.02 mg/kg for 26-week repeated dose toxicity in rats.