4,5-Dihydroxy-2-hexanone: a new metabolite of N-hexane and of 2,5-hexanedione in rat urine.
Male Wistar rats were exposed to 2000 ppm n-hexane or were treated with a single dose of 2,5-hexanedione (200 mg kg-1). Analysis of the urine collected after both treatments revealed the formation of 4,5-dihydroxy-2-hexanone via 5-hydroxy-2-hexanone or 2,5-hexanedione, respectively. Identification of this new n-hexane metabolite included enzymatic hydrolysis of the excreted glucuronide, derivatization of the keto group with O-methylhydroxylamine, and subsequent GC-MS analysis. The chemical structure derived from the mass spectra obtained was confirmed by further analysis of the methoxime-TMS derivatives and of deuterated 4,5-dihydroxy-2-hexanone excreted after treating rats with 2,5-[2H10]-hexanedione. 4,5-Dihydroxy-2-hexanone is proposed to be identical with a urinary constituent that is excreted by rats after n-hexane exposure and is converted to 2,5-dimethylfuran or 2,5-hexanedione, respectively, depending on the conditions of urine treatment prior to GC-MS analysis.
D000085:Acetates / Q000032:analysis; D000280:Administration, Inhalation; D000818:Animals; D002849:Chromatography, Gas; D005965:Glucuronates / Q000378:metabolism; D006586:Hexanes / Q000652:urine*; D006588:Hexanones / Q000652:urine*; D006868:Hydrolysis; D006898:Hydroxylamines; D007274:Injections, Intraperitoneal; D007659:Ketones / Q000652:urine*; D008297:Male; D009498:Neurotoxins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014297:Trimethylsilyl Compounds
D000085:Acetates; D005965:Glucuronates; D006586:Hexanes; D006588:Hexanones; D006898:Hydroxylamines; D007659:Ketones; D009498:Neurotoxins; D014297:Trimethylsilyl Compounds; C054726:4,5-dihydroxy-2-hexanone; C026385:n-hexane; C005214:methoxyamine; C011269:2,5-hexanedione