[Four-week repeated dose oral toxicity study of BMY-28100 in juvenile beagle dogs]

Three groups, each consisting of 3 male and 3 female juvenile beagle dogs, were orally given BMY-28100 for 4 weeks at dose levels of 50, 160 and 500 mg/kg/day, respectively. Additionally, one male and one female dogs were added to each of the control and high dose groups in order to examine the recovery, and observed for 4 weeks after withdrawal of BMY-28100. The results obtained are summarized as follows: 1. BMY-28100 provoked an increased incidence of emesis in the 500 mg/kg group during the treatment period. 2. BMY-28100 sporadically brought distention of the cecum containing considerable amounts of contents in dogs sacrificed after the 4-week administration period. However, no macroscopic or microscopic changes were observed in the cecum itself after removal of the contents. In the 500 mg/kg group, hypocellularity in the sternum bone marrow was observed in a male and a female, and thymic atrophy in a male. 3. No changes ascribed to BMY-28100 treatment were detected after the 4-week recovery period. Based upon these results, the no-effect dose level of BMY-28100 was estimated to be 160 mg/kg/day, except for effects on the cecum.