90-Day toxicity study of dichloroacetate in dogs.
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. 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 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 this study.
Cicmanec
J L
JL
Toxicology and Microbiology Division, Health Effects Research Laboratory, Cincinnati, Ohio 45268.
Condie
L W
LW
Olson
G R
GR
Wang
S R
SR
D000818:Animals; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D002493:Central Nervous System Diseases / Q000139:chemically induced / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology; D003231:Conjunctivitis / Q000139:chemically induced / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D003999:Dichloroacetic Acid / Q000633:toxicity*; D004285:Dogs; D004417:Dyspnea / Q000139:chemically induced; D004798:Enzymes / Q000097:blood; D004906:Erythrocyte Count; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010291:Paresis / Q000139:chemically induced; D013733:Testicular Diseases / Q000139:chemically induced / Q000473:pathology
D004798:Enzymes; D006454:Hemoglobins; D003999:Dichloroacetic Acid