ALKYLDIOL ANTIDOTES TO ETHYLENE-GLYCOL TOXICITY IN MICE

A series of alkyldiols were compared to ethanol or pyrazole as antidotes in ethylene glycol toxicity. Mouse liver alcohol dehydrogenase oxidized ethanol and a series of alkyldiols. The Km values in millimoles per liter determined from the assays were 0.4 with ethanol, 53 with ethylene glycol, 14 with propylene glycol, 5.4 with 1,3-propanediol, 3.8 with 1,2-butanediol, 1.5 with 1,3-butanediol, 0.5 with 1,4-butanediol, 56 with 2,3-butanediol, 0.23 with 1,5-pentanediol, and 0.031 with 1,6-hexanediol. These data indicated that ethanol and the alkyldiols, with the exception of 2,3-butanediol, had higher affinities for mouse liver alcohol dehydrogenase than ethylene glycol. Propylene glycol (27.2 mmol/kg), 1,2-butanediol (11.2 mmol/kg), and 1,3-butanediol (22.3 mmol/kg) were the only alkyldiols found to protect mice. Acute and delayed toxicity and hexobarbital sleeping time studies indicated that the alkyldiols which protected the mice were, in general, the least toxic and least hypnotic of the alkyldiols. Therapeutic ratios found by dividing the 144 hr LD50 of an antidote by the dose which produced the maximum antidotal effect were 3.17 for ethanol, 2.56 for pyrazole, 6.16 for propylene glycol, 4.15 for 1.2-butanediol, and 5.11 for 1,3-butanediol. These data suggest that the alkyldiol antidotes are effective and may be safter than either ethanol or pyrazole. © 1979.