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PARTICLE DEPOSITION IN SPONTANEOUSLY HYPERTENSIVE (SH) RATS EXPOSED VIA WHOLE-BODY INHALATION: MEASURED VS. ESTIMATED DOSE.
Citation:
WICHERS, L., W. ROWAN, J. P. NOLAN, A. D. LEDBETTER, J. K. MCGEE, D. L. COSTA, AND W. P. WATKINSON. PARTICLE DEPOSITION IN SPONTANEOUSLY HYPERTENSIVE (SH) RATS EXPOSED VIA WHOLE-BODY INHALATION: MEASURED VS. ESTIMATED DOSE. . Presented at 45th Annual Society of Toxicology Meeting 2006, San Diego, CA, March 05 - 09, 2006.
Description:
It has been well documented by epidemiological studies that exposure to elevated levels of ambient particulate matter (PM) can lead to adverse health outcomes, including cardiopulmonary-related morbidity and mortality. As a result of these findings, many animal toxicological studies have been undertaken to attempt to mimic these cardiovascular and respiratory responses. However, it is difficult to assess the quantity of PM reaching the lungs of rodents following inhalation exposures, thus making dose-to-effect linkages problematic. To address this need, SH rats were exposed to an oil combustion-derived PM (HP12) via inhalation while maintained in whole-body plethysmograph chambers, such that pulmonary function data were collected during exposure. Rats (n=16) were exposed for 6 hr/d to air (n=2/group) or 13 mg/m3 HP12 (n=6/group) for 1 or 4 days; immediately following the last exposure, rats were sacrificed and their tracheas and lung lobes were harvested for neutron activation analysis. Total deposition ranged from 20?60 ?g to 89?139 ?g 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; correlations between measured and estimated lung lobe depositions ranged from 0.715?0.902, with rat-specific inputs providing approximations closest to those measured (R2=0.81). The results of this study provide actual deposition data for whole-body inhalation exposure to PM, allowing comparisons of estimated and measured particle doses and patterns as a way of validating the MPPD model. This work should improve the ability of risk assessors to extrapolate rat-to-human exposure concentrations following known lung burdens, thus elucidating the associations between inhaled doses and toxicological effects. (Abstract does not represent EPA policy. This research was supported by EPA CT826513.)