Table 1.

Summary of repeated dose toxicity studies in rats and monkeys

SpeciesCrl:CD(SD) ratsCynomolgus monkeys
Doses0, 20, 60 and 197 mg/kg0, 10, 30 and 78.8 mg/kg
RegimensIntravenous, every 3 weeksIntravenous, every 3 weeks
Days 1, 22, 43 (3 times in total)Days 1, 22, 43 (3 times in total)
No. of animals10/sex/group (Main): all dose groups3/sex/group (Main): all dose groups
5/sex/group (Recovery): 60 and 197 mg/kg groups2/sex/group (Recovery): 30 and 78.8 mg/kg groups
Lethal dose>197 mg/kg78.8 mg/kg (1 female died)
Body weight≤60 mg/kg: normal≤30 mg/kg: normal
197 mg/kg: low body weight gain78.8 mg/kg: decreased in 1 male and 1 female
Hematology20 mg/kg: normal≤30 mg/kg: normal
≥60 mg/kg: decreased RBC and WBC parameters78.8 mg/kg: decreased RBC parameters
Target organs and tissues≥20 mg/kg: intestines, testis≥10 mg/kg: intestines
≥60 mg/kg: bone marrow, thymus, lymph node, skin, kidney, incisor≥30 mg/kg: lung, skin, testis
78.8 mg/kg: bone marrow, kidney
STD10/HNSTDSTD10: >197 mg/kgHNSTD: 30 mg/kg
  • Abbreviations: RBC, red blood cell; WBC, white blood cell.