Skip Navigation



ToxSci Advance Access published online on January 19, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi091
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
85/1/460    most recent
kfi091v1
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 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 Hinderliter, P. M.
Right arrow Articles by Bogdanffy, M. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hinderliter, P. M.
Right arrow Articles by Bogdanffy, M. S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Toxicological Sciences © Society of Toxicology 2005; all rights reserved.
Received October 13, 2004
Accepted November 17, 2005

Biotransformation and Toxicokinetics

Validation of Human Physiologically-Based Pharmacokinetic Model for Vinyl Acetate Against Human Nasal Dosimetry Data

P. M. Hinderliter 1*, K. D. Thrall 2, R. A. Corley 2, L. J. Bloemen 3, and M. S. Bogdanffy 1

1 Haskell Laboratory for Health and Environmental Sciences, E. I. du Pont de Nemours and Co., P. O. Box 50, Newark, DE 19714
2 Battelle Pacific Northwest Laboratories, Biological Sciences Division, 902 Battelle Blvd, P. O. Box 999 MS P7-59, Richland, WA 99352
3 Dow Benelux NV, Epidemiology, Health Services, P.O. Box 48, 4560AA Terneuzen, The Netherlands

* To whom correspondence should be addressed.
P. M. Hinderliter, E-mail: paul.m.hinderliter{at}usa.dupont.com


  Abstract

Vinyl acetate has been shown to induce nasal lesions in rodents in inhalation bioassays. A physiologically-based pharmacokinetic (PBPK) model for vinyl acetate has been used in human risk assessment but previous in vivo validation was only conducted in rats. Controlled human exposures to vinyl acetate were conducted to provide validation data for the application of the model in humans. Five volunteers were exposed to 1, 5 and 10 ppm 13C1, 13C2 vinyl acetate via inhalation. A probe inserted into the nasopharyngeal region sampled both 13C1, 13C2 vinyl acetate and the major metabolite 13C1, 13C2 acetaldehyde during resting and light exercise. Nasopharyngeal air concentrations were analyzed in real time utilizing ion trap mass spectrometry (MS/MS). Experimental concentrations of both vinyl acetate and acetaldehyde were then compared to predicted concentrations calculated from the previously published human model. Model predictions of vinyl acetate nasal extraction compared favorably with measured values of vinyl acetate as did predictions of nasopharyngeal acetaldehyde when compared to measured acetaldehyde. The results showed that the current PBPK model structure and parameterization are appropriate for vinyl acetate. These analyses were conducted from 1 to 10 ppm vinyl acetate, a range relevant to workplace exposure standards but which would not be expected to saturate vinyl acetate metabolism. Risk assessment based on this model further concluded that 24 hours per day exposures up to 1 ppm do not present concern on cancer or non-cancer toxicity. Validation of the vinyl acetate human PBPK model provides support to these conclusions.

Keywords: vinyl acetate; nasal dosimetry; PBPK modeling; human.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Toxicol SciHome page
J. B. Morris and A. R. Buckpitt
Upper Respiratory Tract Uptake of Naphthalene
Toxicol. Sci., October 1, 2009; 111(2): 383 - 391.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
J. B. Morris and A. F. Hubbs
Inhalation Dosimetry of Diacetyl and Butyric Acid, Two Components of Butter Flavoring Vapors
Toxicol. Sci., March 1, 2009; 108(1): 173 - 183.
[Abstract] [Full Text] [PDF]


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.