REPRODUCTIVE AND DEVELOPMENTAL TOXICITY STUDIES OF LANDIOLOL HYDROCHLORIDE (ONO-1101)(4) PERINATAL AND POSTNATAL STUDY IN RATS

• Published in: Journal of toxicological sciences 1997/12/12, Vol.22(SupplementIII), pp.537-558
• Main Authors: NISHIMURA, Tatsuya, CHIHARA, Noboru, SHIRAKAWA, Ryugen, SUGAI, Satoshi, SAKAMOTO, Takahiko, NAKAGAWA, Yutaka, AZE, Yoshiya, SHIMOUCHI, Koji, OZEKI, Yoshikazu, FUJITA, Tsuneo
• Format: Article
• Language: eng ; jpn
• Subjects: Adrenergic beta-Antagonists - administration & dosage; Adrenergic beta-Antagonists - toxicity; Animals; Body Weight - drug effects; Eating - drug effects; Female; Fertility - drug effects; Injections, Intravenous; Lactation - drug effects; Male; Maternal-Fetal Exchange; Morpholines - administration & dosage; Morpholines - toxicity; Organ Size - drug effects; Pregnancy; Pregnancy, Animal - drug effects; Prenatal Exposure Delayed Effects; Rats; Rats (i.v.); Rats, Sprague-Dawley; Urea - administration & dosage; Urea - analogs & derivatives; Urea - toxicity
• ISSN: 0388-1350; 1880-3989
• DOI: 10.2131/jts.22.SupplementIII_537

A perinatal and postnatal study of landiolol hydrochloride (ONO-1101), a novel ultra short acting β-blocker, was conducted in Sprague-Dawley (SD) rats. ONO-1101 was administered intravenously at a dose level of 0 (control), 25, 50 or 100 mg/kg/day from day 17 of gestation to day 20 after parturitation to examine the effects on pregnancy, delivery, lactation and the effects on postnatal growth and development of offspring. In the 100 mg/kg/day group, hypoactivity, reddish lacrimation, clonic convulsion and bradypnea/apnea were observed after administration and 5 animals died in the treatment period, and body weight on day 21 and food consumption on days 14-21 of dam at weaning were lower than control group. In the 50 mg/kg/day group, reddish lacrimation was occasionally seen in some animals. ONO-1101 had no effects on pregnancy, delivery, lactation and necropsy findings or organ weights of dams. In the 100 mg/kg/day group, viability of offspring on day 4 after birth decreased and body weight gain of the suckling suppressed, but those changes recovered after weaning. On the skeletal examination of offspring culled on day 4 after birth, decrease in the mean number of osiffied phalanges of hindpaw and increase in the incidence of unossified talus bone were seen in the 100 mg/kg/day group, however, no delay of ossification was found form the weanling. There were no influence of ONO-1101 on external differentiation, functional, behavioral or learning abilities or reproductive performance in offspring. From the above results, it is estimated that the no-toxic dose level of ONO-1101 under these experimental conditions is 50 mg/kg/day for dam and offspring.