Metabolism and disposition of n-butyl glycidyl ether in F344 rats and B6C3F1 mice.
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.
Chen
L-J
LJ
Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. ljferguson@lrri.org
Lebetkin
E H
EH
Nwakpuda
E I
EI
Burka
L T
LT
D000284:Administration, Oral; D000818:Animals; D001711:Biotransformation; D002250:Carbon Radioisotopes; D003641:Deamination; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000378:metabolism* / Q000652:urine; D004853:Epoxy Resins / Q000008:administration & dosage / Q000378:metabolism*; D005243:Feces / Q000737:chemistry; D005260:Female; D020719:Glucuronides / Q000652:urine; D005978:Glutathione / Q000031:analogs & derivatives / Q000652:urine; D008297:Male; D051379:Mice; D010084:Oxidation-Reduction; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D013431:Sulfates / Q000652:urine; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D004852:Epoxy Compounds; D004853:Epoxy Resins; D020719:Glucuronides; D013431:Sulfates; C022794:n-butyl glycidyl ether; D005978:Glutathione