Abstract
Dichloroacetate (DCA) was administered daily for three consecutive months to rats by gavage at 125, 500, and 2000 mg/kg and to dogs in gelatine capsules at 50, 75, and 100 mg/kg. Rats of both sexes at 2000 mg/kg experienced 13.3% mortality rates. Among dogs one of three females at 75 mg/kg and one of four males at 100 mg/kg died. Compound-related effects experienced by both species included suppressed food consumption and body weight gain, hind limb weakness and/or paralysis (high dose groups), depressed erythroid hemograms, reduced blood levels of glucose, lactate, and pyruvate, vacuolation of myelinated white tracts in the cerebrum and to a lesser extent cerebellum, and degeneration of testicular germinal epithelium with syncytial giant cell formation. Species differences in reactions to DCA were also noted. High dose male rats frequently exhibited aspermatogenesis while DCA-treated dogs experienced prostate glandular atrophy, cystic mucosal hyperplasia in the gall bladder, hemosiderin-ladened Kupffer cells, and ocular lesions. The ocular lesions in dogs characteristically consisted of three components: (1) bilateral lenticular opacities; (2) injected bulbar conjunctivae and superficial corneal vascularization; and (3) tendency for keratoconjunctivitis sicca. In both species, a 1-month recovery period produced a general normalization trend. However, the lenticular opacities (dogs), gall bladder anomaly (dogs), brain lesions (both species), loss of testicular germinal epithelium (rats), and aspermatogenesis (rats) persisted or showed minimal improvement.
Published Version
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