US EPA

2772704 

Journal Article 

[Reproductive and developmental toxicity studies of tiropramide hydrochloride (II) -- teratological study in rats by oral administration] 

Shimazu, H; Katsumata, Y; Shiota, Y; Fujioka, M; Suzuki, K; Ogawa, J; Yasuda, E; Ohta, M; Ito, S 

1992 

0 

Yakuri to Chiryo / Japanese Pharmacology and Therapeutics
ISSN: 0386-3603 

DART/TER/93001573 

20 

8 

Japanese 

A teratological study of tiropramide hydrochloride was conducted in Sprague-Dawley female rats treated orally at daily dose of 25, 50 or 100 mg/kg/day from day 7 to day 17 of gestation. Then, effect on pregnancy, delivery and lactation of dams, and on fetal development and post-natal development of pups to maturity were examined. In F0 dams, salivation were observed during the dosing period in the 50 and 100 mg/kg groups. On the body weight changes and food consumption during the dosing period, dosing effects were observed in the 100 mg/kg group, but, no effects were observed in any of the treatment groups during the lactation period. The maintenance of pregnancy, length of pregnancy, delivery and lactation performance were not affected in any of the treatment groups. In the F1 fetuses, no marked changes were observed in the external and skeletal examinations. But, in the visceral examination, number of fetuses with thymic remnant in neck was significantly increased in the 50 and 100 mg/kg groups. No abnormalities were observed in the post-natal development of the F1 pups. Further, no adverse effects were observed in the functional test, behavior test or reproductive ability test of the F1 pups. Based on the above results, it was concluded that the no-effect dose of tiropramide hydrochloride for general toxicity of dams was 50 mg/kg, for reproductive ability was 100 mg/kg and for F1 generation was 25 mg/kg.