RT Journal Article
SR Electronic
T1 Metabolism and Disposition of α-Methylstyrene in Rats
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 166
OP 171
VO 29
IS 2
A1 Kristi S. De Costa
A1 Sherry R. Black
A1 Brian F. Thomas
A1 Jason P. Burgess
A1 James M. Mathews
YR 2001
UL http://dmd.aspetjournals.org/content/29/2/166.abstract
AB α-Methylstyrene (AMS) is a volatile hydrocarbon used primarily in the production of specialty polymers and resins. In the present study, the tissue distribution, metabolism, and excretion of [14C]AMS was investigated in male rats after i.v. administration (11 mg/kg). Over 90% of AMS administered intravenously to rats was excreted in 72 h. Urinary excretion accounted for 86% of the administered dose, volatile breath and feces accounted for 2.2 and 1.9%, respectively, and elimination as carbon dioxide was negligible. Metabolites were isolated from rat urine following a high oral dose of AMS (1000 mg/kg) and characterized using gas chromatography/mass spectrometry and NMR spectrometry. The metabolites were 2-phenyl-1,2-propanediol (3% of urinary radioactivity) and its glucuronide (50%), atrolactic acid (27%),S-(2-hydroxy-2-phenylpropyl)-N-acetylcysteine (13%), and 2-phenylpropionic acid (1%); the glucuronides and mercapturates were each conjugated on the methylene carbon beta to the ring. The presence of both of the diastereomeric isomers of the mercapturates and of the glucuronides suggested that the initial epoxidation of AMS was not stereoselective and proceeded with addition of active oxygen to yield enantiomeric epoxides. Incubation of AMS with human liver slices produced the same metabolites as those excreted in rat urine, with 2-phenyl-1,2-propanediol present as the predominant metabolite after 5 h of incubation. The American Society for Pharmacology and Experimental Therapeutics