TY - JOUR T1 - Metabolism and Disposition of <em>n</em>-Butyl Glycidyl Ether in F344 Rats and B6C3F1 Mice JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 2218 LP - 2224 DO - 10.1124/dmd.107.016931 VL - 35 IS - 12 AU - L.-J. Chen AU - E. H. Lebetkin AU - E. I. Nwakpuda AU - L. T. Burka Y1 - 2007/12/01 UR - http://dmd.aspetjournals.org/content/35/12/2218.abstract N2 - 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 ER -