© 1991 Oxford University Press
research-article |
90-Day Toxicity Study of Dichloroacetate in Dogs1
*Toxicolgy and Microbiology Division, Health Effects Research Laboratory Cincinnati, Ohio 45268
Pathology Associates, Inc. 6217 Centre Park Drive, Westchester, Ohio 45069
Computer Sciences Corporation Cincinnati, Ohio 45268
Received September 25, 1990; accepted April 18, 1991
90-Day Toxicity Study of Dichloroacetate in Dogs. CICMANEC, J. L., CONDIE, L W., OLSON, G. R., AND WANG, S. R. (1991). Fundam. Appl. Toxrcol. 17,376–389. Male and female juvenile beagle dogs were dosed daily for 90 days with dichloroacetate (DCA). The compound was administered orally was 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 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. One female of the high-dose group died at Day 50 and two high-dose males died at Days 51 and 74. Hindlimb partial paralysis was observed in many high-dose dogs Vacuolization of myelinated white tracts of cerebrum, cerebellum, and/or spinal cord was observed in many high-dose dogs as well as some mid- and low-dose subjects 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 ddition, suppurative bronchopneumonia and chronic pancreatitis were noted in many high-dose and some middose subjacts. A "no-adverse-effect level" was not determined In this study.