IDEAS home Printed from https://ideas.repec.org/a/wly/riskan/v15y1995i3p335-342.html
   My bibliography  Save this article

Physiologically‐Based Pharmacokinetic Modeling of a Mixture of Toluene and Xylene in Humans

Author

Listed:
  • Robert Tardif
  • Sylvain Laparé
  • Ginette Charest‐Tardif
  • Jules Brodeur
  • Kannan Krishnan

Abstract

A physiologically‐based pharmacokinetic (PBPK) model for a mixture of toluene (TOL) and xylene (XYL), developed and validated in the rat, was used to predict the uptake and disposition kinetics of TOL/XYL mixture in humans. This was accomplished by substituting the rat physiological parameters and the blood:air partition coefficient with those of humans, scaling the maximal velocity for hepatic metabolism on the basis of body weight0.75, and keeping all other model parameters species‐invariant. The human TOL/XYL mixture PBPK model, developed based on the quantitative biochemical mechanism of interaction elucidated in the rat (i.e., competitive metabolic inhibition), simulated adequately the kinetics of TOL and XYL during combined exposures in humans. The simulations with this PBPK model indicate that an eight hour co‐exposure to concentrations that remain within the current threshold limit values of TOL (50 ppm) and XYL (100 ppm) would not result in significant pharmacokinetic interferences, thus implying that data on biological monitoring of worker exposure to these solvents would be unaffected during co‐exposures.

Suggested Citation

  • Robert Tardif & Sylvain Laparé & Ginette Charest‐Tardif & Jules Brodeur & Kannan Krishnan, 1995. "Physiologically‐Based Pharmacokinetic Modeling of a Mixture of Toluene and Xylene in Humans," Risk Analysis, John Wiley & Sons, vol. 15(3), pages 335-342, June.
    • Handle: RePEc:wly:riskan:v:15:y:1995:i:3:p:335-342
    DOI: 10.1111/j.1539-6924.1995.tb00326.x
    as

    Download full text from publisher

    File URL: https://doi.org/10.1111/j.1539-6924.1995.tb00326.x
    Download Restriction: no
    File URL: https://libkey.io/10.1111/j.1539-6924.1995.tb00326.x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:wly:riskan:v:15:y:1995:i:3:p:335-342. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Wiley Content Delivery (email available below). General contact details of provider: https://doi.org/10.1111/(ISSN)1539-6924 .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.