The toxicity of trifluoroethanol (TFE) was investigated in mice and dogs. In mice, the acute LD50 was approximately 350 mg/kg by the oral or intraperitoneal routes and 1.6 ml/100 ml after a 10-min inhalation. Various compounds which are known to reduce the lethality of other alcohols by blocking their oxidation to toxic metabolites were tested for their effect on TFE lethality in mice. Disulfiram, allopurinol, and 3-amino-1,2,4-triazole pretreatment were each found to provide a significant protection as the LD50 of TFE nearly doubled in each case. Sodium acetate was ineffective. Ethanol treatment for 48 hours after TFE injection markedly reduced the toxicity of TFE. Ethanol also inhibited conversion of TFE to trifluoroacetate in vivo. TFE was not oxidized by alcohol dehydrogenase and NAD in vitro; however, TFE was a competitive inhibitor of ethanol oxidation. Mice were not killed by doses up to 800 mg/kg of trifluoroacetaldehyde hydrate or up to 5000 mg/kg of sodium trifluoroacetate. Free trifluoroacetic acid was as toxic as hydrochloric acid. No deaths occurred after 100 mg/kg of TFE ip daily for 18 days; however, the mice failed to gain weight during the treatment period. Two dogs died 48 hours after 400 mg/kg of TFE iv without significant changes in blood urea nitrogen, serum glucose, serum lactate, or bromosulfalein retention time. © 1969.
