Methyl CCNU (NSC-95 441):Toxicity of 1single iv Infusion in Rhesus Monkeys. Vehicle : Emulphor EL-620 - 5%,Ethanol - %,and Saline - 90%.

摘要

Methyl CCNU (Urea, 1-(2-chloroethyl)-3-(4-methyl cyclohexyl)-1-nitroso), a compound with marked antitumor activity and formulated 2.5mg/ml in 5% Emulphor EL-620, 5% ethanol,and 90% saline,was submitted to a preclinical pharmacological evaluation. Groups of 2monkeys were infused within a 1hour period with a single dose of 45, 30, 15, 7.5, 3.75,or 1.87mg/kg. The 2monkeys treated with 45mg/kg developed severe toxicity. One was necropsied on day 8in poor general condition with metaplasia of the esophageal and intestinal epithelium, hypocellularity of the bone marrow,lymphoid tissues,and degeneration of germinal epithelium in the testes. The other died from chronic toxicity on day 75. Lesions included glomerulonephritis, dysplasia of the renal tubules,uremia,and uremic pneumonitis. Chronic interstitial nephritis occurred in one half monkeys treated with 30mg/kg. The other monkeys survived and exhibited reversible dose related neutropenia and lymphopenia,occasional elevation of the transaminases without histopathological changes. A single dose of 1.87mg/kg was non toxic.