Disposition and metabolism of cumene in F344 rats and B6C3F1 mice.

Drug metabolism and disposition: the biological fate of chemicals (2010-11-26)
Ling-Jen Chen, Christopher J Wegerski, Daniel J Kramer, Leslie A Thomas, Jacob D McDonald, Kelly J Dix, J Michael Sanders
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
α-Methylstyrene, 99%, contains 15 ppm p-tert-butylcatechol as inhibitor
Sigma-Aldrich
Cumene, 98%
Sigma-Aldrich
2-Phenyl-2-propanol, 97%
Supelco
α-Methylstyrene monomer, analytical standard
Supelco
Cumene, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Cumene, PESTANAL®
Supelco
Cumene solution, certified reference material, 5000 μg/mL in methanol