Toxicologic Studies for Investigational New Drugs

The general purpose of this program was to provide preclinical animal safety data on candidate antiparasitic test materials. The testing provided acute and subacute toxicity data to meet requirements of the Food and Drug Administration and, specifically, to support data requirements for Investigational New Drug Applications for Phase I and early Phase II clinical studies. Nine drugs (WR 6026-2HC1; WR 171,669-HC1; WR 228,258-2HC1; allopurinol riboside; WR 231,010; WR 235,591; Formycin B; cycloguanil pamoate; and WR 180,409) were tested for Walter Reed Army Institute of Research. Each material was evaluated using one or more of the following tests: Salmonella typhimurium/mammalian microsome plate incorporation assay; in vitro chromosomal aberration study in human lymphocytes; mouse lymphoma forward toxicity study in mice; intramuscular irritation study in rabbits; approximate lethal dose/maximum tolerated dose determination study in dogs; oral toxicity study in hamsters; twenty-eight-day subacute toxicity studies in dogs and rats; subchronic studies in rats; fertility, teratology, and dogs. Originator supplied keywords include: Antiparasitic drugs; mutagenicity; clastogenicity.