Suplatast tosilate (IPD-1151T)のラット経口投与による52週間反復投与毒性試験および5週間回復試験

DOI Web Site

書誌事項

タイトル別名
  • A FIFTY-TWO WEEK ORAL CHRONIC TOXICITY STUDY OF SUPLATAST TOSILATE (IPD-1151T) IN RATS

この論文をさがす

抄録

A 52-week oral repeated dose toxicity study of suplatast tosilate (IPD-1151T), a new anti-allergic agent, as well as a 5-week recovery study were carried out at dose levels of 0 (control), 50, 300 and 1800 mg/kg/day using male and female fats. The results were as follows: 1. In general conditions, transient salivation after each administration and excretions with peculiar smells were noted in both sexes given 1800 mg/kg/day. Since one male and six female rats given 1800 mg/kg/day showed bradypnea, clonic/tonic convulsions, lying on the belly and/or side, subnormal temperature, abnormal gait, paralysis of extremities, they were sacrificed in moribund. 2. The body weight was lowered from the early stage of administration period in both sexes given 1800 mg/kg/day. 3. There were no remarkable changes in food consumption, urinalysis, fecal examination, hematology and ophthalmology. 4. Biochemical examination revealed a decrease in triglyceride in males given 300 mg/kg/day or more. 5. In pathological examination, the animals sacrificed in moribund showed necrosis and degeneration of neurons and/or sponge-like change of neuropile in nucleus caudatus of the cerebrum, necrosis and partial disappearance of granular cells and Purkinje's cells, and swelling of Bergmann's cells in the cerebellum. In survived animals, the relative organ weight in the liver increased in males given 300 mg/kg/day or more and females given 1800 mg/kg/day, and histopathological examination revealed slight vacuolization, hypertrophy of centrilobular hepatocytes in males given 1800 mg/kg/day. Furthermore, in some females, similar changes of the cerebrum and the cerebellum, as mentioned above, were slightly observed. In electron microscopic examination, slight proliferation of smooth endoplasmic reticulum in hepatocytic cytoplasm was observed in males given 1800 mg/kg/day. The necrobiotic changes, such as condensation of nuclear chromatin, increased electron density of cytoplasm and nuclei, mitochondrial accumulation and vacuolization, in the cells possibly derived from small granular cells in the cerebellum were observed in females given 1800 mg/kg/day. The mitochondrial swelling, decreased and dilated rough endoplasmic reticulum, and increased electron density of cytoplasm and nuclei with formation of cytoplasmic vacuole and membranous degenerated structure in neurons of cerebral temporal lobe cortex were observed in females given 1800 mg/kg/day. 6. In a recovery study, electron microscopic examination revealed a slight degeneration of myelinated nerve fibers in the cerebellum in males given 1800 mg/kg/day. On the contrary, there were no remarkable changes in general condition, body weight and various clinical parameters. It was noted that these changes induced by IPD-1151T seemed to be reversible changes. 7. From the above results, the non-effective dose levels were estimated to be 50 mg/kg/day in males and 300 mg/kg/day in females.

収録刊行物

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ