Abstract
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.
Footnotes
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This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences.
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Current address: Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive SE, Albuquerque, NM 87108 (L.-J.C.).
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Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
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doi:10.1124/dmd.107.016931.
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ABBREVIATIONS: BGE, n-butyl glycidyl ether; NTP, National Toxicology Program; GSH, glutathione; GST, glutathione S-transferase; HPLC, high-performance liquid chromatography; ESI, electrospray ionization; MS, mass spectrometry; MS/MS, tandem mass spectrometry; LC/MS, liquid chromatography/mass spectrometry.
- Received May 29, 2007.
- Accepted September 12, 2007.
- The American Society for Pharmacology and Experimental Therapeutics
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