title: Metabolism of citral, an alpha,beta-unsaturated aldehyde, in male F344 rats.
abstract: Citral is a naturally occurring aliphatic aldehyde of the terpene series and is an isomeric mixture of geranial and neral. It is the main component (approximately 80%) of lemongrass oil, which is found in all citrus fruits and used extensively in the food, cosmetic, and detergent industries. In this study, urinary metabolites of citral in male F344 rats were characterized and identified by comparison with synthetic standards of known stereochemistry. Stereospecific oxidation of citral at the C-8 methyl was investigated, as was the hydrolytic sensitivity of biliary and urinary metabolites. For metabolite identification, urine was collected over dry ice for 24 hr after a single po 500 mg/kg dose of [14C]citral. Elimination in urine was rapid, with approximately 50% of the dose excreted within 24 hr. The urine was fractionated by reverse-phase HPLC, monitoring both radioactivity and UV. Synthetic standards were prepared; a comparison of their spectra with the isolated metabolites was used for identification. Citral was rapidly metabolized and excreted as metabolites, including several acids and a biliary glucuronide. Seven urinary metabolites were isolated and identified: 3-hydroxy-3,7-dimethyl-6-octenedioic acid; 3,8-dihydroxy-3,7-dimethyl-6-octenoic acid; 3,9-dihydroxy-3,7-dimethyl-6-octenoic acid; E- and Z-3,7-dimethyl-2,6-octadienedioic acid; 3,7-dimethyl-6-octenedioic acid; and E-3,7-dimethyl-2,6-octadienoic acid. Although citral is an alpha,beta-unsaturated aldehyde and has the potential of being reactive, the urinary metabolites of citral appear to arise from metabolic pathways other than nucleophilic addition to the double bond.
authors.affiliation: Systemic Toxicology Branch, Division of Toxicology and Research Testing, National Institute of Environmental Health Sciences.
authors.forename: J J
authors.initials: JJ
authors.lastname: Diliberto
authors.forename: P
authors.initials: P
authors.lastname: Srinivas
authors.forename: D
authors.initials: D
authors.lastname: Overstreet
authors.forename: G
authors.initials: G
authors.lastname: Usha
authors.forename: L T
authors.initials: LT
authors.lastname: Burka
authors.forename: L S
authors.initials: LS
authors.lastname: Birnbaum
mesh_terms: D000080462:Acyclic Monoterpenes; D000818:Animals; D001646:Bile / Q000378:metabolism; D001711:Biotransformation; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D006868:Hydrolysis; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D039821:Monoterpenes; D010084:Oxidation-Reduction; D051381:Rats; D011916:Rats, Inbred F344; D013237:Stereoisomerism; D013729:Terpenes / Q000378:metabolism*
chemical_list: D000080462:Acyclic Monoterpenes; D039821:Monoterpenes; D013729:Terpenes; C007076:citral