120-Hour Continuous Intravenous Infusion Range-Finding Study of 70 Percent DMSOin Fischer 344 Rats

摘要

The purpose of the study was to determine an appropriate infusion rate of 70percent DMSO to be used as a vehicle in a future study. The study consisted of four groups of rate, 2/sex/group. Groups 1 through 4 were administered 70 percent DMSO at a rates of 0.1, 0.5, 1.0, or 2.0 mL/kg/hr, respectively. All rats were infused for 120 continuous hours. On Study Day 8, all surviving animals were sacrificed. Clinical signs of toxicity were observed in all groups throughout the study. All male animals infused with DMSO at rates of 1.0 mL/kg/hr and 2.0 mL/kg/hr were either found dead or were sacrificed moribund by Study Day 2. By Study Day 4, all females in these groups were also dead. Clinical pathology data showed toxicologically significant decreases in hematocrit, erythrocyte count and blood hemoglobin concentration, as well as large increases in the percentage of reticulocytes and nucleated erythrocytes. Urine output in treated animals was consistently elevated, in a dose-dependent fashion with, slight increases in specific gravity and evidence of hemoglobinuria. The kidneys of some DMSO-exposed rats had treatment-induced nephrosis, which consisted of minimal tubular epithelial vacuolar degeneration, formation of bright eosinophilic proteinaceous luminal casts (interpreted as hemoglobin casts) and an increase in the number of intracytoplasmic eosinophilic granules in renal tubular epithelial cells.