Benzyl alcohol adverse effects in the rat: implications for toxicity as a preservative in parentral injectable solutions.
1. Short-term intake of a 2% benzyl alcohol in the rat drinking fluid resulted in sex-dependent inhibition of hepatic alcohol dehydrogenase. 2. Benzyl alcohol intake also inhibited female but not male mitochondrial aldehyde dehydrogenase isoenzymes with the apparent low and high Km. 3. The benzyl alcohol inhibition kinetics were found non-competitive with the major differences in Vmax being confined to the cytoplasmic enzymes. 4. The velocity of the enzymatic reaction was greater for the substrate benzaldehyde than benzyl alcohol. 5. The results suggest sex-dependent hepatic alcohol dehydrogenase-substrate competition between benzyl alcohol and ethanol which may precipitate adverse metabolic interaction particularly in the susceptible female subject. 6. Modulation of the activity of this enzyme by benzyl alcohol may contribute to its toxicity as preservative in parentral injectable solutions.
Texas Tech University Health Sciences Center School of Medicine, Lubbock 79430.
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Messiha
D000079:Acetaldehyde / Q000378:metabolism; D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors; D000818:Animals; D019905:Benzyl Alcohol; D001592:Benzyl Alcohols / Q000009:adverse effects* / Q000633:toxicity; D003593:Cytoplasm / Q000201:enzymology; D000431:Ethanol / Q000378:metabolism; D005260:Female; D007263:Infusions, Parenteral; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D012727:Sex Characteristics; D012996:Solutions
D001592:Benzyl Alcohols; D012996:Solutions; D000431:Ethanol; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde; D019905:Benzyl Alcohol