Skip Navigation


ToxSci Advance Access originally published online on March 19, 2007
Toxicological Sciences 2007 97(2):265-278; doi:10.1093/toxsci/kfm061
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
97/2/265    most recent
kfm061v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Leavens, T. L.
Right arrow Articles by Dorman, D. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Leavens, T. L.
Right arrow Articles by Dorman, D. C.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Evaluating Transport of Manganese from Olfactory Mucosa to Striatum by Pharmacokinetic Modeling

Teresa L. Leavens*,1, Deepa Rao{dagger}, Melvin E. Andersen* and David C. Dorman*

* CIIT Centers for Health Research, Research Triangle Park, North Carolina 27709 {dagger} The Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisonsin 53706

1 To whom correspondence should be addressed. Fax: (919) 558-1300. E-mail: tleavens{at}ciit.org.

Received December 28, 2006; accepted March 8, 2007


  Abstract

Increased brain manganese (Mn) following inhalation can result from direct transport via olfactory neurons and blood delivery. Human health risk assessments for Mn should consider the relative importance of these pathways. The objective of this study was to develop a pharmacokinetic model describing the olfactory transport and blood delivery of Mn in rats following acute MnCl2 or MnHPO4 inhalation. Model compartments included the olfactory mucosa (OM), olfactory bulb, olfactory tract and tubercle, and striatum. Intercompartmental transport of Mn was described as ipsilateral, anterograde movement to deeper brain regions. Each compartment contained free and bound Mn and included blood influx and efflux. First-order rate constants were used to describe transport. Model parameters were estimated by comparing the model with published experimental data in rats exposed by inhalation to 54MnCl2 or 54MnHPO4 with both nostrils patent or one nostril occluded. The model-derived elimination rate constant from the OM was higher for the chloride salt (0.022 per hour) compared with the phosphate salt (0.011 per hour), consistent with their relative solubilities. Rate constants for Mn transport among the other compartments were similar for both Mn forms. Our results indicate that direct olfactory transport provided the majority of Mn tracer in the olfactory regions during the 21 days following exposure to 54MnHPO4 and 8 days following exposure to 54MnCl2. Only a small fraction of Mn tracer from the tract and tubercle was predicted to be delivered to the striatum, 3 and 0.1% following 54MnHPO4 or 54MnCl2 exposure, respectively.

Key Words: manganese; olfactory transport; pharmacokinetic model.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.