The toxicokinetics of 1,3-butylene glycol versus ethanol in the treatment of ethylene glycol poisoning.
Ethylene glycol (EG) is a toxic chemical found in antifreeze and heat exchangers. Standard therapy for EG intoxication in administration of ethanol (ETOH) to inhibit its metabolism by alcohol dehydrogenase (ADH). Studies indicate 1,3-butylene glycol (BG) binds to ADH more efficiently than EG and is orally less toxic than EG or ETOH. Male rats were divided into 5 groups of 6 animals. Groups received by oral intubation a single dose of EG (32 mmole/kg), BG (39 mmole/kg) initially and every 6 h up to 72 h, ETOH (39 mmole/kg) initially and every 6 h up to 72 h, or EG initially and then either BG or ETOH every 6 h up to 72 h. Administration of ETOH produced hepatotoxicity and pulmonary pathology as indicated by changes in clinical chemistry, urinalysis, and histopathology, while BG did not. Neither ETOH nor BG produced any apparent nephrotoxicity. ETOH produced ataxia, lethargy and central nervous system depression while BG did not. BG produced a higher concentration of urinary EG indicating a better inhibition of ADH metabolism of EG. Ethanol produced a higher EG blood concentration than BG. Ethanol's higher EG blood concentration may be partially attributed to dehydration and a decreased urine output as well as inhibition of ADH metabolism. Ethanol produced mortality in all animals prior to 72 h. The EG/ETOH combination produced mortality more quickly due to additive toxicity of the combination. Lack of any significant toxicity produced by BG and the production of significant toxicities by ETOH indicates that BG is potentially a better antidote than ETOH.
Cox
S K
SK
Section of Toxicology, James H Quillen College of Medicine, Johnson City, TN 37614.
Ferslew
K E
KE
Boelen
L J
LJ
D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors; D000818:Animals; D002072:Butylene Glycols / Q000493:pharmacokinetics / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury; D004326:Drinking; D004435:Eating; D000431:Ethanol / Q000493:pharmacokinetics / Q000633:toxicity*; D019855:Ethylene Glycol; D005026:Ethylene Glycols / Q000378:metabolism / Q000633:toxicity*; D007441:Intubation, Gastrointestinal; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D002072:Butylene Glycols; D005026:Ethylene Glycols; D000431:Ethanol; C028491:1,3-butylene glycol; D000426:Alcohol Dehydrogenase; D019855:Ethylene Glycol