Toxicologic Evaluation of Intravenously-Administered Vincristine (NSC 67574) in BDF1 Mice

摘要

In BDF1 mice administered a single intravenous dose of vincristine, calculated estimates of the LD(90), LD(50), and LD(10) were 4.60, 3.99, and 3.46 mg/kg (13.80, 11.87, and 10.38 mg/sq m) respectively for males and 4.98, 4.52, and 4.11 mg/kg (14.94, 13.56, and 12.33 mg/sq m) respectively for females. Estimates in BDF1 mice administered five daily intravenous doses of vincristine were 1.16, 0.98, and 0.82 mg/kg/day (3.48, 2.94, and 2.46 mg/sq m/day) in males and 1.23, 1.10, and 0.99 mg.kg/day (3.69, 3.30, and 2.97 mg/sq m/day) in females. Susceptibility to lethal toxicity was, therefore, similar for male and female mice when administered either as a single or five daily intravenous doses. Qualitative toxicity was similar in both sexes in both the single dose and five daily dose schedules. Reversible toxicity to the thymus, urogenital, and gastrointestinal systems was observed in the single dose schedule; whereas reversible toxicity to the gastrointestinal tract only was observed in the five daily dose schedule. Histopathologically confirmed gastrointestinal toxicosis was confirmed by an initial loss of body weight. Reticulocytopenia and leukopenia (particularly lymphopenia) were not confirmed microscopically as myeloid suppression indicating the marrow sparing effect of vincristine. No significant alterations of clinical chemistry were observed in either schedule.