||90-Day Toxicity Study of Dichloroacetate in Dogs.
Cicmanec, J. L. ;
Condie, L. W. ;
Olson, G. R. ;
Wang, S. R. ;
||Health Effects Research Lab., Research Triangle Park, NC. Environmental Toxicology Div. ;Pathology Associates, Inc., West Chester, OH. ;Computer Sciences Corp., Cincinnati, OH.
Water pollution effects(Animals) ;
Lactate dehydrogenase ;
Giant cells ;
Toxic hepatitis ;
Body weight ;
Organ weight ;
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Male and female juvenile beagle dogs were dosed daily for 90 days with dichloroacetate (DCA). The compound was administered orally via gelatin capsules at doses of 0, 12.5, 39.5, and 72 mg/kg/day. Each dose group consisted of five males and five females. The dogs were observed clinically and blood samples were taken at 15-day intervals for hematologic and serum chemistry values. Decreased total erythrocyte count and hemoglobin levels were observed in mid- and high-dose dogs beginning at Day 30. Serum concentrations of LDH were elevated at Days 30 and 45 in females and at Day 75 in males treated with DCA at 72 mg/kg/day. Degeneration of testicular germinal epithelium and syncytial giant cell formation was noted in males of all dose groups. Hepatic vacuolar change and chronic hepatitis appeared only in DCA-treated dogs. In addition, suppurative bronchopneumonia and chronic pancreatitis were noted in many high-dose and some middose subjects. A no-adverse-effect level was not determined in the study.