Phase 2 Report of Preclinical Single and Five Daily Dose Intravenous Lethality Studies in CD2F1 Mice and Toxicity Studies in Beagle Dogs and Fischer 344 Rats of Benzisoquinolinedione (NSC-308847)

摘要

The antineoplastic drug Benzisoquinolinedione (BIDA, NSC-308847) was given intravenously to mice, dogs and rats as a single dose or five consecutive daily doses. In mice, the combined sex LD90, LD50 and LD10 were 236, 207 and 182 mg/sq m for x1 and 98, 85 and 75 mg/sq m/day for x5. Clinical signs in mice were labored breathing, struggling, loss of locomotor ability, hyperextension of limbs, increased irritability, ataxia, dehydration, decrease in body weight, prostration and death. Doses used in the dog studies were 18.4, 9.2 and 0.92 mg/kg for x1 and 11.4, 3.8 and 0.38 mg/kg/day for x5. Immediate reactions in dogs were struggling against restraint, increased muscle tension, vocalizations, excessive salivation, labored breathing, hyperextension of limbs and muscle tremors, which were followed by continuous barking, defensive appearance and reddish-colored urine. Clinical signs in rats were diarrhea, emaciation, tail lesions, dehydration, hunched posture, abnormal gait, moribundity and death.