Metabolism and disposition of n-butyl glycidyl ether in F344 rats and B6C3F1 mice. 2007

L-J Chen, and E H Lebetkin, and E I Nwakpuda, and L T Burka
Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. ljferguson@lrri.org

The disposition of [(14)C]-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 (14)CO(2) (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 omega-1 oxidation to form a 3'-hydroxybutoxy substitution. One urinary metabolite was from omega-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 alpha-keto acid and alpha-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.

UI MeSH Term Description Entries
D008297 Male Males
D010084 Oxidation-Reduction A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). Redox,Oxidation Reduction
D011916 Rats, Inbred F344 An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes. Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D002250 Carbon Radioisotopes Unstable isotopes of carbon that decay or disintegrate emitting radiation. C atoms with atomic weights 10, 11, and 14-16 are radioactive carbon isotopes. Radioisotopes, Carbon
D003641 Deamination The removal of an amino group (NH2) from a chemical compound. Deaminations
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004852 Epoxy Compounds Organic compounds that include a cyclic ether with three ring atoms in their structure. They are commonly used as precursors for POLYMERS such as EPOXY RESINS. Epoxide,Epoxides,Epoxy Compound,Oxiranes,Compound, Epoxy,Compounds, Epoxy
D004853 Epoxy Resins Polymeric resins derived from OXIRANES and characterized by strength and thermosetting properties. Epoxy resins are often used as dental materials. Epoxy Resin,Resin, Epoxy,Resins, Epoxy
D005243 Feces Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.
D005260 Female Females

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