title: Disposition and metabolism of cumene in F344 rats and B6C3F1 mice.
abstract: Cumene is a high-production volume chemical that has been shown to be a central nervous system depressant and has been implicated as a long-term exposure carcinogen in experimental animals. The absorption, distribution, metabolism, and excretion of [(14)C]cumene (isopropylbenzene) was studied in male rats and mice of both sexes after oral or intravenous administration. In both species and sexes, urine accounted for the majority of the excretion (typically ≥ 70%) by oral and intravenous administration. Enterohepatic circulation of cumene and/or its metabolites was indicated because 37% of the total dose was excreted in bile in bile duct-cannulated rats with little excreted in normal rats. The highest tissue (14)C levels in rats were observed in adipose tissue, liver, and kidney with no accumulation observed after repeat dosing up to 7 days. In contrast, mice contained the highest concentrations of (14)C at 24 h after dosing in the liver, kidney, and lung, with repeat dosing accumulation of (14)C observed in these tissues as well as in the blood, brain, heart, muscle, and spleen. The metabolites in the expired air, urine, bile, and microsomes were characterized with 16 metabolites identified. The volatile organics in the expired air comprised mainly cumene and up to 4% α-methylstyrene. The major urinary and biliary metabolite was 2-phenyl-2-propanol glucuronide, which corresponded with the main microsomal metabolite being 2-phenyl-2-propanol.
authors.affiliation: Lovelace Respiratory Research Institute, 2425 Ridgecrest Dr. SE, Albuquerque, NM 87108, USA.
authors.forename: Ling-Jen
authors.initials: LJ
authors.lastname: Chen
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Wegerski
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Kramer
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Thomas
authors.forename: Jacob D
authors.initials: JD
authors.lastname: McDonald
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: Dix
authors.forename: J Michael
authors.initials: JM
authors.lastname: Sanders
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001555:Benzene Derivatives / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D001646:Bile / Q000378:metabolism; D002273:Carcinogens / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D005260:Female; D020719:Glucuronides / Q000378:metabolism; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008861:Microsomes / Q000378:metabolism; D009928:Organ Specificity; D020005:Propanols / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012727:Sex Characteristics; D013045:Species Specificity; D013343:Styrenes / Q000737:chemistry / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D001555:Benzene Derivatives; D002273:Carcinogens; D002492:Central Nervous System Depressants; D020719:Glucuronides; D020005:Propanols; D013343:Styrenes; C017623:2-phenyl-2-propanol; C015763:cumene; C017915:alpha-methylstyrol