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TISSUE REMODELING IN THE HUMAN LUNG IN RELATION TO PARTICLE CONCENTRATION AND METAL CONTENT
Citation:
Gallagher, J, J Inmon, A. Levine, Rogers, T., NC State, J. W. Scott, M. B. Schenker, Schlaegle, S. RJ Lee, F. Green, AND K. Pinkerton. TISSUE REMODELING IN THE HUMAN LUNG IN RELATION TO PARTICLE CONCENTRATION AND METAL CONTENT. Presented at Society of Toxicology Annual Meeting, Nashville, TN, March 17-22, 2002.
Description:
TISSUE REMODELING IN THE HUMAN LUNG IN RELATION TO PARTICLE CONCENTRATION AND METAL CONTENT. J Gallagher1, J Inmon1, S Schlaegle2, A Levine2, T Rogers3, J Scott1, F Green4, M Schenker5, K Pinkerton5 1NHEERL, US-EPA, RTP, NC, USA; 2RJ Lee Group Inc, Monroeville, Pa, USA; 3State U of NC, Raleigh, NC, USA; 4Dept. of Pathology and Laboratory Medicine, U of Calgary, Alberta, Canada; 5Dept of Epidemiology and Preventative Medicine, U of Ca, Davis, Ca, USA.
We have little information about retained particle/metal burden in human lung and associated health effects. We have previously shown that anatomical remodeling of the terminal and respiratory bronchioles occur at sites of carbonaceous and mineral dust deposition. We extend the value of these findings by providing information on lung particle and metal content in relation to indicators of effect as classified by standard diagnostic criteria for 1) chronic bronchitis 2) asthma 3) mineral dust disease and 4) smoking-related disease. Lung autopsies were examined from 40 male Hispanics from the Central Valley of California who had died from non-respiratory related causes. Computer-controlled scanning electron microscopy was used to determine particle concentration (No.particles/cm2 sample area/mg ashed tissue) and inductively coupled plasma emission spectrometry for metal analysis. Lung samples with and without indicators of effect were compared. Significant (p <0.05) fold increases in no. of particles was observed for indicators of mineral dust disease (4.0X); lymph node fibrosis (2.0X) smoking related disease (2.2X). In contrast, no. of particles were (1.6X) lower in samples with indicators of an asthma effect. For all samples,. irrespective of disease state, >90 % of the 24,000 particles analyzed were < 2.5 m in diameter, 70 % < 1 m and 42 % <0.5 m. Significant inter-individual variability in metal concentrations was observed. Ti, V and Mn concentrations were significantly (p <.05) elevated in mineral dust disease and lymph node fibrosis. Consistent with tobacco contaminants, significant fold increases were shown for Ni (2.9X), Cr (3.6X), and Cd (4.6X) respectively, in samples with indicators of smoking related disease. Elevated metal concentrations were not observed in asthmatic lung tissue. Determining the fate/dose of particulates in humans is essential for predicting health effects and elucidating the mechanisms by which particles cause these effects. Our data support the association between particulate exposure and increased risk of lung disease. Microdisection, histology and evaluation of tissue changes coupled with characterization and measurement of internal particle/metal burden provide a means toward establishing dose levels and anatomical sites in human lung required to produce adverse health outcomes. This abstract does not represent EPA policy.