STUDY ON THE DEVELOPMENTAL TOXICITY OF ORALLY-ADMINISTERED ISOBUTYLIDENEDIUREA IN RATS

Developmental toxicity of isobutylidenediurea (IBDU) was determined by oral administration to Wistar rats. The substance was administered as an aqueous suspension to 22-24 pregnant rats per group by gavage in d aily doses of 100, 400 and 1000 mg/kg body weight from day 6 post-coit um (p.c.) to day 15 p.c. The control group received the vehicle only ( 0.5% aqueous carboxymethyl cellulose solution). There were no substanc e-related effects in the dams concerning food consumption, body weight , body weight gain, uterine weights and clinical or autopsy observatio ns even at the highest dose of 1000 mg/kg body weight/day. The reprodu ction data revealed no biologically relevant differences between the c ontrol and treated groups. The incidence and type of the foetal extern al, soft tissue and skeletal findings, which were classified as malfor mations, variations and/or retardations observed in the treated foetus es were similar to the concurrent and/or historical control data. Thus , under the conditions of this study, no signs of maternal toxicity or embryo/foetotoxicity were induced by IBDU and the no-observable-adver se-effect level on the maternal and developing organism was 1000 mg/kg body weight/day. (C) 1997 Elsevier Science Ltd.