Toxicologic Evaluation of Intravenously-Administered Piperazinedione (NSC 135758) in BDF1 Mice

摘要

In BDF1 mice administered a single intravenous dose of piperazinedione, calculated estimates of the LD90, LD50, and LD10 were 28.00, 19.97, and 14.24 mg/kg (84.00, 59.91, and 42.72 mg/sq.), respectively, for males and 28.30, 21.65, and 16.56 mg/kg (84.90, 64.95, and 49.68 mg/sq.), respectively, for females. Estimates for mice administered five daily doses of piperazinedione were 10.06, 8.92, and 7.91 mg/kg/day (30.18, 26.76, and 23.73 mg/m./day) in males and 15.69, 10.08, and 6.47 mg/kg/day (47.07, 30.24, and 19.41 mg/m./day) in females. Susceptibility to lethal toxicity was, therefore, similar for male and female mice when piperazinedione was administered as a single intravenous dose and different when administered as five daily intravenous doses. Reversible toxicity to the hematopoietic and lymphoid systems as well as the thymus and the spleen was observed in both male and female mice administered a single dose of piperazinedione. Although lesions to the gastrointestinal tract were not observed upon microscopic examination, there was an initial loss in body weight followed by a return to normal. A slight peripheral anemia, reticulocytopenia, leukopenia (especially lymphopenia) was confirmed microscopically as hematopoietic hypoplasia and lymphoid depletion in tissues taken at the time of necropsy. Alterations in BUN and transaminases were variable, not dose related, and, therefore, were not considered biologically significant.