REPRODUCTIVE AND DEVELOPMENTAL TOXICITY STUDIES OF LANDIOLOL HYDROCHLORIDE (ONO-1101) (3) TERATOGENICITY STUDY IN RABBITS

• Published in: Journal of toxicological sciences 1997/12/12, Vol.22(SupplementIII), pp.527-536
• Main Authors: NISHIMURA, Tatsuya, CHIHARA, Noboru, SAKAMOTO, Takahiko, NAKAGAWA, Yutaka, AZE, Yoshiya, TANAKA, Masaharu, SHIMOUCHI, Koji, OZEKI, Yoshikazu, FUJITA, Tsuneo
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Antagonists - administration & dosage; Adrenergic beta-Antagonists - toxicity; Animals; Body Weight - drug effects; Dose-Response Relationship, Drug; Eating - drug effects; Embryonic and Fetal Development - drug effects; Female; Fetus - drug effects; Injections, Intravenous; Maternal-Fetal Exchange; Morpholines - administration & dosage; Morpholines - toxicity; Organ Size - drug effects; Pregnancy; Pregnancy, Animal - drug effects; Rabbits; Rabbits (i.v.); Urea - administration & dosage; Urea - analogs & derivatives; Urea - toxicity
• ISSN: 0388-1350; 1880-3989
• DOI: 10.2131/jts.22.SupplementIII_527

A teratogenicity study oflandiolol hydrochloride (ONO-1101), a novel ultra short acting β-blocker, was conducted in KAR:NZW rabbits. ONO-1101 was administered intravenously at a dose level of 0 (control), 25, 50 or 100 mg/kg/day to pregnant rabbit from day 6 to 18 of gestation to examine the effects on dams and fetuses. Death occurred on 3 animals in the 100mg/kg/day group and one animal in the 50 mg/kg/day group during the treatment period. Hypoactivity, bradypnea/apnea and clonic convulsion after administration was observed in animal dosed 100 mg/kg/day. No maternal effects were seen on body weight, food consumption, necropsy findings or organ weights. External, skeletal and visceral findings revealed no adverse effects of ONO-1101 on fetuses. From the above results, it is estimated that the no-toxic dose level of ONO-1101 under these experimental conditions is 25 mg/kg/day for dams and 100 mg/kg for fetuses.