ToxSci Advance Access published online on July 13, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl059
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina, Chapel Hill, North Carolina 27599 U.S.A.; Environmental Media Assessment Group, National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711 U.S.A.
* To whom correspondence should be addressed. A plethora of epidemiological studies have shown that exposure to elevated levels of ambient particulate matter (PM) can lead to adverse health outcomes, including cardiopulmonary-related mortality. Subsequent animal toxicological studies have attempted to mimic these cardiovascular and respiratory responses, in order to better understand underlying mechanisms. However, it is difficult to quantitate the amount of PM deposited in rodent lungs following inhalation exposure, thus making fundamental dose-to-effect assessment and linkages to human responses problematic. To address this need, Spontaneously Hypertensive rats were exposed to an oil combustion-derived PM (HP12) via inhalation while maintained in whole-body plethysmograph chambers. Rats were exposed 6 h/day to 13 mg/m3 of HP12 for one or four days. Immediately following the last exposure, rats were sacrificed and their tracheas and lung lobes harvested and separated for neutron activation analysis. Total lower respiratory tract deposition ranged from 20-60 µg to 89-139 µg for 1- and 4-day exposures, respectively. Deposition data were compared to default and rat-specific estimates provided by the Multiple Path Particle Deposition (MPPD) model, yielding model predictions that were <33% of the measured dose. This study suggests that HP12 exposure decreased particle clearance, as the mass of HP12 in the lungs following a 4-day protocol was nearly four times that observed after a 1-day exposure. This work should improve the ability of risk assessors to extrapolate rat-to-human exposure concentrations on the basis of lung burdens, and thus better relate inhaled doses and resultant toxicological effects. This paper has been reviewed by the National Health and Environmental Effects Research Laboratory and the National Center for Environmental Assessment, U.S. Environmental Protection Agency, and approved for publication. Mention of trade names or commercial products does not constitute endorsement or recommendation for use.
Received April 20, 2006
Accepted July 9, 2006
Respiratory Toxicology
Particle Deposition in Spontaneously Hypertensive Rats Exposed Via Whole-Body Inhalation: Measured and Estimated Dose
Lindsay B. Wichers 1 *,
William H. Rowan III 2,
Julianne P. Nolan 2,
Allen D. Ledbetter 2,
John K. McGee 2,
Daniel L. Costa 3,
and
William P. Watkinson 2
2 Pulmonary Toxicology Branch, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711 U.S.A.
3 Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711 U.S.A.
Lindsay B. Wichers, E-mail: wichers.lindsay{at}epa.gov
Abstract
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. K. Saxena, M. I. Gilmour, M. C. Schladweiler, M. McClure, M. Hays, and U. P. Kodavanti Differential Pulmonary Retention of Diesel Exhaust Particles in Wistar Kyoto and Spontaneously Hypertensive Rats Toxicol. Sci., October 1, 2009; 111(2): 392 - 401. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Wallenborn, J. K. McGee, M. C. Schladweiler, A. D. Ledbetter, and U. P. Kodavanti Systemic Translocation of Particulate Matter-Associated Metals Following a Single Intratracheal Instillation in Rats Toxicol. Sci., July 1, 2007; 98(1): 231 - 239. [Abstract] [Full Text] [PDF]
|
|