Disposition of three glycol ethers administered in drinking water to male F344/N rats.
The glycol ethers 2-methoxyethanol (ME), 2-ethoxyethanol (EE), and 2-butoxyethanol (BE) are widely used solvents in industrial and consumer applications. The reproductive, teratogenic, and hematotoxic effects of the glycol ethers are due to the alkoxyacetic acid metabolites of these compounds. The effect of alkyl group length on disposition of these three glycol ethers was studied in male F344/N rats allowed access for 24 hr to 2-butoxy[U-14C]ethanol, 2-ethoxy[U-14C]ethanol, or 2-methoxy[U-14C]ethanol in drinking water at three doses (180 to 2590 ppm), resulting in absorbed doses ranging from 100 to 1450 mumols/kg body wt. Elimination of radioactivity was monitored for 72 hr. The majority of the 14C was excreted in urine or exhaled as CO2. Less than 5% of the dose was exhaled as unmetabolized glycol ether. Distinct differences in the metabolism of the glycol ethers as a function of alkyl chain length were noted. For BE 50-60% of the dose was eliminated in the urine as butoxyacetic acid and 8-10% as CO2; for EE 25-40% was eliminated as ethoxyacetic acid and 20% as CO2; for ME 34% was eliminated as methoxyacetic acid and 10-30% as CO2. Ethylene glycol, a previously unreported metabolite of these glycol ethers, was excreted in urine, representing approximately 10, 18, and 21% of the dose for BE, EE, and ME, respectively. Thus, for longer alkyl chain lengths, a smaller fraction of the administered glycol ether was metabolized to ethylene glycol and CO2. Formation of ethylene glycol suggests that dealkylation of the glycol ethers occurs prior to oxidation to alkoxyacetic acid and, as such, represents an alternate pathway in the metabolism of these compounds that does not involve formation of the toxic acid metabolite.
Medinsky
M A
MA
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico 87185.
Singh
G
G
Bechtold
W E
WE
Bond
J A
JA
Sabourin
P J
PJ
Birnbaum
L S
LS
Henderson
R F
RF
D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005026:Ethylene Glycols / Q000493:pharmacokinetics* / Q000633:toxicity; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D011916:Rats, Inbred F344
D005026:Ethylene Glycols; D002245:Carbon Dioxide; D000426:Alcohol Dehydrogenase; C005219:methyl cellosolve; C017096:n-butoxyethanol; C021296:2-ethoxyethanol