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 industrial solvents to which certain groups of workers are exposed. Pharmacological and metabolic interactions between these solvents and ethanol were explored in male CD-1 mice. The effects of these solvents on the duration of ethanol-induced loss of righting reflex and on ethanol elimination in mice were studied. The solvents were dissolved in corn oil and injected intraperitoneally 30 min before ethanol 4 g/kg ip. The four solvents prolonged significantly the duration of ethanol-induced loss of righting reflex when given in the following doses (mmol/kg): MnBK, 3.75 and 5; MIBK, 5; MEK, 5 and 10, acetone, 20 and 40. This prolongation was dose related and increased as the dose of the solvent was increased. The concentrations of ethanol in blood or brain on return of the righting reflex were similar in solvent-treated and control animals, with the exception of the group of mice treated with 40 mmol/kg acetone in which the ethanol concentrations were significantly lower than in control animals. The mean elimination rate of ethanol was markedly reduced in mice treated with MnBK 5 mmol/kg, MEK 15 mmol/kg, and acetone 40 mmol/kg. All four solvents reduced the activity of mouse liver alcohol dehydrogenase in vitro. It is concluded that enhancement of the ethanol-induced loss of righting reflex by these solvents in mice is well correlated to reduced elimination rate of ethanol.
Département de pharmacologie, Faculté de médecine, Université de Montréal, Québec, Canada.
J
J
Cunningham
M
M
Sharkawi
G L
GL
Plaa
D000096:Acetone / Q000378:metabolism / Q000633:toxicity; D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000818:Animals; D002074:Butanones / Q000378:metabolism / Q000633:toxicity; D000431:Ethanol / Q000378:metabolism / Q000633:toxicity*; D007659:Ketones / Q000378:metabolism / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008742:Methyl n-Butyl Ketone / Q000378:metabolism / Q000633:toxicity; D051379:Mice; D004856:Postural Balance / Q000187:drug effects; D012018:Reflex / Q000187:drug effects
D002074:Butanones; D007659:Ketones; D000096:Acetone; D000431:Ethanol; C005222:methylethyl ketone; D008742:Methyl n-Butyl Ketone; D000426:Alcohol Dehydrogenase; C005458:methyl isobutyl ketone