Toxicity of benzyl alcohol in adult and neonatal mice.
Benzyl alcohol, a bacteriostatic agent found in many parenteral preparations, has been implicated as the agent responsible for precipitating "the gasping syndrome" in premature neonates. To investigate this toxicity, benzyl alcohol was administered intraperitoneally to adult (23-28 g) and neonatal (2-7 g) CD-1 male mice. Gross behavioral changes were monitored. Low doses (less than 800 mg/kg) produced minimal toxic effects within an initial 4-h observation period. At the end of this time, the LD50 was determined to be 1000 mg/kg for both age groups. When mortality in the adult group was observed after 7 d following a single treatment with benzyl alcohol, the LD50 on day 7 was determined to be 650 mg/kg. Rapid absorption and conversion of benzyl alcohol to its primary metabolite, benzaldehyde, occurred within both experimental groups; the plasma levels of each were comparable in both neonatal and mature animals when determined by GC. In an attempt to alter the toxicity of benzyl alcohol, pyrazole and disulfiram were used to inhibit the activities of alcohol dehydrogenase and aldehyde dehydrogenase, respectively. Treatment with pyrazole, before benzyl alcohol exposure, resulted in an increase in benzyl alcohol levels to 203% of control values and a marked increase in toxicity. Although pretreatment with disulfiram led to benzaldehyde levels which were 368% of control values, toxicity was unchanged. These data imply that the acute toxicity of benzyl alcohol, which includes sedation, dyspnea, and loss of motor function, is due to the alcohol itself and not to its metabolite, benzaldehyde.
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001547:Benzaldehydes / Q000633:toxicity; D019905:Benzyl Alcohol; D001592:Benzyl Alcohols / Q000633:toxicity*; D001593:Benzyl Compounds / Q000633:toxicity*; D004221:Disulfiram / Q000494:pharmacology; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D011720:Pyrazoles / Q000494:pharmacology
D001547:Benzaldehydes; D001592:Benzyl Alcohols; D001593:Benzyl Compounds; D011720:Pyrazoles; C031280:pyrazole; D019905:Benzyl Alcohol; C032175:benzaldehyde; D004221:Disulfiram