Ethylene glycol and glycolate kinetics in rats and dogs.
Ethylene glycol (EG) toxicity results from its metabolism to glycolic acid and other toxic metabolites. The accumulation of glycolate and the elimination kinetics of EG and its metabolites are not well understood, so studies with male Sprague-Dawley rats and mixed breed dogs have been carried out. EG was administered by gavage to rats and dogs, which were placed in metabolic cages for urine and blood sample collection at timed intervals. The peak plasma level of EG occurred at 2 hr after dosing and that of glycolate between 4-6 hr. The rate of EG elimination was somewhat faster in rats with a half-life of 1.7 hr compared to 3.4 hr in dogs. The maximum plasma level of glycolate was greater in rats, although the pattern of accumulation was similar to that in dogs. Glycolate disappeared from the plasma at the same time as EG, suggesting a slower rate of elimination of the metabolite than that of EG. Renal excretion of EG was an important route for its elimination, accounting for 20-30% of the dose. Renal excretion of glycolate represented about 5% of the dose. EG induced an immediate, but short-lived diuresis compared to that in control rats. Minimal clinical effects (mild acidosis with no sedation) were noted at these doses of EG (1-2 g/kg) in both rats and dogs. The results indicate that the toxicokinetics of EG and glycolate were similar in both species.
Hewlett
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Department of Pharmacology and Therapeutics, Louisiana State University Medical Center, Shreveport 71130-3932.
Jacobsen
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Collins
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McMartin
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D000818:Animals; D004285:Dogs; D019855:Ethylene Glycol; D005026:Ethylene Glycols / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005260:Female; D006016:Glycolates / Q000097:blood / Q000493:pharmacokinetics; D006207:Half-Life; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D005026:Ethylene Glycols; D006016:Glycolates; C031149:glycolic acid; D019855:Ethylene Glycol