14-Day Toxicity of 1-Methylethyl 2-Chloro-5-(((1-Methylethoxy)Thiomethyl)Amino) Benzoate (NSC-D629243) in Beagle Dogs.

摘要

The purpose of the study was to determine potential target organ toxicity and its reversibility in dogs that were treated orally, twice daily, for 14 consecutive days with NSC-D629243. Beagle dogs (2/sex with 2 extra males in the 0 mg/kg/dose group) were treated by gavage with NSC-D629243 in sesame oil at doses of 0, 87.5, 175, 350, and 700 mg/kg/dose. The findings in the study suggest that the toxic effects of NSC-D629243 were associated with severe gastrointestinal disease. The cause of death (other than aspiration of dosing solutions or gavage error) in dogs which were found dead or were moribund sacrificed and the chief toxic syndrome found in drug-treated animals in the study was functional intestinal absorptive failure. Evidence for the conclusion was not based exclusively on gross and histopathological findings, which were not of high-grade severity and were not present in all animals that were affected in other ways by the treatment. Rather, in-life clinical changes (i.e. vomiting, diarrhea, decreased food consumption) and clinical pathology changes (electrolyte imbalance) provided more definitive evidence of NSC-D629243-induced toxicity. NSC-D629243 given orally twice daily for 14 consecutive days at a dose of 87.5 mg/kg/dose was considered non-toxic.