Pharmacological and Metabolic Interactions between Ethanol and Methyl n-Butyl Ketone, Methyl Isobutyl Ketone, Methyl Ethyl Ketone, or Acetone in Mice

Methyl n-butyl ketone (MnBK), methyl isobutyl ketone (MIBK),methyl ethyl ketone (MEK), and acetone are widely used industrialsolvents to which certain groups of workers are exposed. Pharmacologicaland metabolic interactions between these solvents and ethanolwere explored in male CD-1 mice. The effects of these solventson the duration of ethanol-induced loss of righting reflex andon ethanol elimination in mice were studied. The solvents weredissolved in corn oil and injected intraperitoneally 30 mm beforeethanol 4 g/kg ip. The four solvents prolonged significantlythe duration of ethanol-induced loss of righting reflex whengiven in the following doses (m mol/kg): MnBK, 3.75 and 5; MIBK,5; MEK, 5 and 10, acetone, 20 and 40. This prolongation wasdose related and increased as the dose of the solvent was increased.The concentrations of ethanol in blood or brain on return ofthe righting reflex were similar in solvent-treated and controlanimals, with the exception of the group of mice treated with40 mmol/kg acetone in which the ethanol concentrations weresignificantly lower than in control animals. The mean eliminationrate of ethanol was markedly reduced in mice treated with MnBK5 mmol/kg, MEK 15 mmol/ kg, and acetone 40 mmol/kg. All foursolvents reduced the activity of mouse liver alcohol dehy-drogenasein vitro. It is concluded that enhancement of the ethanol-inducedloss of righting reflex by these solvents in mice is well correlatedto reduced elimination rate of ethanol.