RT Journal Article SR Electronic T1 Metabolism and Disposition of n-Butyl Glycidyl Ether in F344 Rats and B6C3F1 Mice JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 2218 OP 2224 DO 10.1124/dmd.107.016931 VO 35 IS 12 A1 L.-J. Chen A1 E. H. Lebetkin A1 E. I. Nwakpuda A1 L. T. Burka YR 2007 UL http://dmd.aspetjournals.org/content/35/12/2218.abstract AB The disposition of [14C]-labeled n-butyl glycidyl ether (BGE, 3-butoxy-1,2-epoxypropane) was studied in rats and mice. The majority of a single p.o. dose (2–200 mg/kg) was excreted in urine (rats, 84–92%; mice, 64–73%) within 24 h. The rest of the dose was excreted in feces (rats, 2.6–7.7%; mice, 5.3–12%) and in expired air as 14CO2 (rats, 1.5%; mice, 10–18%), or remained in the tissues (rats, 2.7–4.4%; mice, 1.5–1.7%). No parent BGE was detected in rat or mouse urine. Fifteen urinary metabolites were identified, including 3-butoxy-2-hydroxy-1-propanol and its monosulfate or monoglucuronide conjugates, 3-butoxy-2-hydroxypropionic acid, O-butyl-N-acetylserine, butoxyacetic acid, 2-butoxyethanol, and 3-butoxy-1-(N-acetylcystein-S-yl)-2-propanol, the mercapturic acid metabolite derived from conjugation of glutathione (GSH) with BGE at the C-1 position. Some of these metabolites underwent further ω-1 oxidation to form a 3′-hydroxybutoxy substitution. One urinary metabolite was from ω-oxidation of 3-butoxy-1-(N-acetylcystein-S-yl)-2-propanol to yield the corresponding carboxylic acid. Oxidative deamination of 3-butoxy-1-(cystein-S-yl)-2-propanol gave the corresponding α-keto acid and α-hydroxy acid metabolites that were present in mouse urine but not in rat urine. An in vitro incubation of BGE with GSH showed that the conjugation occurred only at the C-1 position with or without the addition of GSH S-transferase. The American Society for Pharmacology and Experimental Therapeutics