[A thirteen-week oral repeated dose toxicity study of suplatast tosilate (IPD-1151T) in dogs].
A 13-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, 150, 450 and 1350 mg/kg/day using male and female beagle dogs. The results were as follows: 1. In general conditions, soft feces and diarrhea with specific smell were dose-dependently observed in males and females given 450 mg/kg/day or more. Both sexes given 1350 mg/kg/day, revealed reeling with dropped head, abnormal gait, dysstasia, lying at lateral or prone position, sedation, and tremor, and one male and one female in this group died after showing respiratory depression, collapse and cyanosis. 2. There were no significant or remarkable changes in body weight, food consumption, water consumption, ophthalmology, electrocardiogram, urinalysis, hematology, biochemistry, fecal occult blood test, and absolute and relative organ weights. 3. Pathological examination in dead animals revealed hemorrhagic change in the heart and slight vacuolar changes in hepatocytes. In survived animals, there were no pathological changes attributable to the IPD-1151T. 4. In electron microscopic examination, there were no abnormalities in the liver and kidney attributable to the IPD-1151T. 5. After 5-week recovery period, above-mentioned changes disappeared. 6. From the above results, the non-effective dose level and the toxic dose level were estimated to be 150 mg/kg/day and 1350 mg/kg/day, respectively, and no sex differences were found.
Yamashita
K
K
Drug Safety Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
Yada
H
H
Hayashi
T
T
Irimura
K
K
Hirota
T
T
Morita
K
K
D000284:Administration, Oral; D000818:Animals; D001190:Arylsulfonates / Q000008:administration & dosage / Q000633:toxicity*; D004285:Dogs; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D005260:Female; D006633:Histamine Antagonists / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D013452:Sulfonium Compounds / Q000008:administration & dosage / Q000633:toxicity*
D001190:Arylsulfonates; D006633:Histamine Antagonists; D013452:Sulfonium Compounds; C073028:suplatast tosilate