Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Drug Metabolism & Disposition
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Drug Metabolism & Disposition

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

Disposition and Metabolism of Cumene in F344 Rats and B6C3F1 Mice

Ling-Jen Chen, Christopher J. Wegerski, Daniel J. Kramer, Leslie A. Thomas, Jacob D. McDonald, Kelly J. Dix and J. Michael Sanders
Drug Metabolism and Disposition March 2011, 39 (3) 498-509; DOI: https://doi.org/10.1124/dmd.110.034769
Ling-Jen Chen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christopher J. Wegerski
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daniel J. Kramer
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Leslie A. Thomas
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jacob D. McDonald
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kelly J. Dix
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J. Michael Sanders
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF
Loading

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 [14C]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 14C 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 14C at 24 h after dosing in the liver, kidney, and lung, with repeat dosing accumulation of 14C 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.

Footnotes

  • This project was conducted for the National Toxicology Program, National Institutes of Health National Institute of Environmental Health Sciences [Contract N01-ES-75562, HHSN291200775562C].

  • This article may be the work product of an employee or group of employees of the National Institutes of Health (NIH) National Institute of Environmental Health Sciences (NIEHS); however, the statements, opinions, or conclusions contained therein do not necessarily represent the statements, opinions or conclusions of NIH, NIEHS, or the U.S. government.

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

    doi:10.1124/dmd.110.034769.

  • ↵Embedded Image The online version of this article (available at http://dmd.aspetjournals.org) contains supplemental material.

  • ABBREVIATIONS:

    AMS
    α-methylstyrene
    HPLC
    high-performance liquid chromatography
    ESI
    electrospray ionization
    MS
    mass spectrometry
    MS/MS
    tandem mass spectrometry
    BDC
    bile duct-cannulated
    LSC
    liquid scintillation counter
    VOC
    volatile organic compound.

  • Received June 17, 2010.
  • Accepted November 22, 2010.
  • U.S. Government work not protected by U.S. copyright
View Full Text

 

DMD articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Drug Metabolism and Disposition: 39 (3)
Drug Metabolism and Disposition
Vol. 39, Issue 3
1 Mar 2011
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Drug Metabolism & Disposition article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Disposition and Metabolism of Cumene in F344 Rats and B6C3F1 Mice
(Your Name) has forwarded a page to you from Drug Metabolism & Disposition
(Your Name) thought you would be interested in this article in Drug Metabolism & Disposition.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Disposition and Metabolism of Cumene in F344 Rats and B6C3F1 Mice

Ling-Jen Chen, Christopher J. Wegerski, Daniel J. Kramer, Leslie A. Thomas, Jacob D. McDonald, Kelly J. Dix and J. Michael Sanders
Drug Metabolism and Disposition March 1, 2011, 39 (3) 498-509; DOI: https://doi.org/10.1124/dmd.110.034769

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

Disposition and Metabolism of Cumene in F344 Rats and B6C3F1 Mice

Ling-Jen Chen, Christopher J. Wegerski, Daniel J. Kramer, Leslie A. Thomas, Jacob D. McDonald, Kelly J. Dix and J. Michael Sanders
Drug Metabolism and Disposition March 1, 2011, 39 (3) 498-509; DOI: https://doi.org/10.1124/dmd.110.034769
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Authorship Contributions
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Metabolic enzymes in nintedanib metabolism
  • Mechanism of AO Inactivation by Hydralazine
  • Warfarin PBPK modeling with target binding
Show more Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About DMD
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-009X (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics