Preclinical toxicologic evaluation of dianhydrogalactitol in dogs and monkeys.
Thirty dogs in four different treatment schedules and 14 monkeys in a single multiple-treatment schedule were used to evaluate the toxicity of dianhydrogalactitol. Highest nontoxic, low toxic, high toxic, and lethal doses were established in single injection doses and five daily injections in dogs, and in five daily injections in monkeys. Dose ranges of 20-320 mg/m2 (single injection) and 5-80 mg/m2 (five daily injections) in dogs, and 3-96 mg/m2 (five daily injections) in monkeys were established. The monkeys were more sensitive than dogs to the low toxic dose and more tolerant to the high toxic dose in the repeated daily injections. The dose-response curves for the dogs and monkeys had similar slopes and inflection points. Because of the steep slope between the lethal dose and the highest nontoxic dose in both species, caution should be used in the initial clinical trials.
D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004988:Ethers, Cyclic / Q000633:toxicity; D005260:Female; D004376:Galactitol / Q000031:analogs & derivatives / Q000633:toxicity*; D000882:Haplorhini; D007928:Lethal Dose 50; D008253:Macaca mulatta; D008297:Male; D013402:Sugar Alcohols / Q000633:toxicity*
D004988:Ethers, Cyclic; D013402:Sugar Alcohols; D004376:Galactitol