ToxSci Advance Access published online on April 5, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfj182
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Community and Environmental Medicine, School of Medicine, University of California, Irvine, CA 92697-1825, U.S.A.; Members of the University of California, Los Angeles Southern California Particle Center and Supersite
* To whom correspondence should be addressed. The purpose of this paper is to present a method for estimating particle doses that may be used to reconcile particle deposition doses used in in-vitro toxicology studies with in-vivo exposure levels. The focus is on the tracheobronchial tree of heavily-exposed individuals. A review of the factors that influence inhaled particle deposition doses in environmental exposures leads to the identification of cases in which greater than average tracheobronchial tree doses are received. Exercising individuals and those with chronic obstructive pulmonary disease not only inhale increased volumes of air, but they also may have uneven ventilation that leads to greater than average particle deposition doses per unit of tracheobronchial tree surface area. In addition, deposition hot spots, as occur at airway bifurcations, will greatly increase the particle exposures of target cells in the tracheobronchial tree. Three particle exposure scenarios are proposed, and the average and local doses to the tracheobronchial epithelium are calculated. When various factors that enhance particle doses (enhancement factors, or EFs) in-vivo are considered, substantial particle doses may be justified for in-vitro tissue culture studies that use tracheobronchial target cells, such as epithelial cell cultures. The use of such EFs is intended to improve in-vitro dosing with particles. Although the exposure of cells in-vitro cannot fully replicate the complexity of in-vivo exposures, it is possible to calculate toxicologically relevant doses that may define adverse health effects in potentially sensitive human populations. Local groups of tracheobronchial cells in high-dose individuals are predicted to receive particle doses that are 3,000 to 25,000 times higher than the doses averaged over the entire tracheobronchial region.
Received January 10, 2006
Accepted March 12, 2006
In Vitro Toxicology
Tracheobronchial Particle Dose Considerations for In-Vitro Toxicology Studies
Robert F. Phalen 1 *,
Michael J. Oldham 1,
and
Andre E. Nel 2
2 Medicine/Immunology and Allergy, University of California, Los Angeles, CA 90095; Members of the University of California, Los Angeles Southern California Particle Center and Supersite
Robert F. Phalen, E-mail: rfphalen{at}uci.edu
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  T. L. Watterson, B. Hamilton, R. Martin, and R. A. Coulombe Jr Urban Particulate Matter Causes ER Stress and the Unfolded Protein Response in Human Lung Cells Toxicol. Sci., November 1, 2009; 112(1): 111 - 122. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Ghelfi, C. R. Rhoden, G. A. Wellenius, J. Lawrence, and B. Gonzalez-Flecha Cardiac Oxidative Stress and Electrophysiological Changes in Rats Exposed to Concentrated Ambient Particles are Mediated by TRP-Dependent Pulmonary Reflexes Toxicol. Sci., April 1, 2008; 102(2): 328 - 336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Oberdorster and J. N. Finkelstein TO THE EDITOR Toxicol. Sci., December 1, 2006; 94(2): 439 - 439. [Full Text] [PDF]
|
|
|
|
|
|
R. F. Phalen, M. J. Oldham, and A. E. Nel TO THE EDITOR Toxicol. Sci., December 1, 2006; 94(2): 440 - 440. [Full Text] [PDF]
|
|