Preclinical toxicologic evaluation of chromomycin A3 (NSC-58 514) in mice, dogs and monkeys

The toxicity of chromomycin A3, a potent antitumor antibiotic derived from Streptomyces griseus, was assessed in mice, dogs and monkeys. In mice, the LD50 after 5 daily iv doses was 603 μg/kg. In dogs and monkeys, the single-dose iv minimal lethal dose was 200 and 330 μg/kg, respectively, while this value after 5 daily iv doses was 100 μg/kg for both species. The principal clinicopathologic findings in dogs and monkeys that became moribund or died included emesis, hemorrhagic diarrhea, fever, dehydration, and necrosis of intestinal and lymphoid tissues with occasional necrosis in other organs. Laboratory findings were consistent with clinical signs. Dogs and monkeys that survived treatment exhibited mild, reversible toxic alterations.