Metabolism and disposition of diethylene glycol in rat and dog.
The disposition of carbon-14-labeled diethylene glycol (DEG) was determined in rats after oral, iv, and dermal administration, and in dogs after oral administration. Oral administration of DEG to rats was by gavage of 50 or 5000 mg/kg doses, or by provision of 0.3 1.0, and 3.0% in drinking water. Oral doses were well absorbed and excreted primarily (approximately 80%) in urine within 24 hr of administration. Greater than half of the dose was excreted unchanged, with 10-30% of the dose appearing as a single metabolite. The metabolite was isolated and characterized by 13C-NMR to be 2-(hydroxy) ethoxyacetic acid (HEAA). Confirmation of identity was provided by synthesis of HEAA and comparison of its NMR spectra and chromatographic behavior with those of the metabolite. Intravenous doses (50 mg/kg) were eliminated by the same routes and at the same rates as those administered orally and exhibited the same metabolic profile. The fate of oral doses of DEG administered to dogs (500 mg/kg) was similar to that of DEG in rats, with about 30% of the administered dose being excreted in urine as HEAA. DEG slowly penetrated the skin of rats after application of 50 mg to a 12-cm2 area. Only about 10% of the dose was absorbed in 72 hr of exposure, and the absorbed dose appeared to have the same fate as doses administered iv or orally. In all studies with rats, excretion of radiolabel in feces and persistence in tissues were low. The highest percentage of conversion to 14CO2 was 7%, found for doses of 0.3% DEG in drinking water.
Mathews
J M
JM
Center for Bioorganic Chemistry, Research Triangle Institute, Research Triangle Park, NC 27709-2194.
Parker
M K
MK
Matthews
H B
HB
D000085:Acetates / Q000652:urine; D000284:Administration, Oral; D000818:Animals; D002247:Carbon Isotopes; D002250:Carbon Radioisotopes; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005026:Ethylene Glycols / Q000378:metabolism* / Q000493:pharmacokinetics; D005260:Female; D007275:Injections, Intravenous; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D000085:Acetates; D002247:Carbon Isotopes; D002250:Carbon Radioisotopes; D005026:Ethylene Glycols; C018968:beta-hydroxyethoxyacetic acid; C013484:diethylene glycol