Research Projects

Project at a Glance

Title: Mechanism of Particulate Toxicity: Effects on the Respiratory System

Principal Investigator / Author(s): Pinkerton, Kent

Contractor: UC Davis

Contract Number: 96-310


Research Program Area: Health & Exposure

Topic Areas: Health Effects of Air Pollution, Toxic Air Contaminants


Abstract:

Ambient exposure to particulate matter (PM) has been associated with a variety of adverse health effects primarily involving the cardiopulmonary system. However, the biological mechanisms to explain how exposure to PM exacerbates or directly causes adverse cardiopulmonary effects are unknown. This study was designed to determine if exposure to ammonium nitrate (NH4N03) and carbon (C), two common components found in California PM, could be used to measure adverse biological changes in the respiratory tract of rats. Three different concentrations of NH4N03 (300, 150 and 75 g/m3) and C (200, 100 and 50 g/m3) were used. Simultaneous exposure to NH4N03 and C was done in the presence or absence of 0.2 ppm ozone for all experiments. Initial studies used a single six-hour exposure period. Subsequent studies used a repeated exposure of six hours per day for three consecutive days. Adult male (9-weeks old), senescent male (22 to 24-months old) and young male and female (1 to 3-weeks old) Fischer 344 (F344) rats were used to determine PM exposure effects on cell permeability, glutathione levels and cell proliferation rates within the respiratory tract. Bronchoalveolar lavage (BAL) and fluorescent micro spheres were also used to defme particle effects and patterns of particle deposition in the lungs respectively. Adult male Sprague Dawley (SD) rats were also used in limited studies to determine potential strain differences as well as site-specific responses of the respiratory tract to particle exposure. F344 rats demonstrated a significant increase in cell proliferation of airway interstitial cells at the intermediate concentration of NH4N03 and C in adult following a single day of exposure, but no changes in cellular permeability or glutathione levels. Repeated exposure to particles for three consecutive days in adult F344 rats did not demonstrate significant effects in any biological parameter measured in the respiratory tract. In contrast, male SD rats exposed to particles for three days demonstrated a significant increase in the number of cells recovered by BAL. In addition, the cell proliferation rates in SD rats for both epithelial and interstitial cells at airway bifurcations were significantly increased following three days of exposure to NH4N03 and C. Significant particle and ozone effects were also noted for the cell proliferation rates within the proximal alveolar regions of these same adult male SD rats. These differences between rats could be strain dependent or due to differences in the target particle concentrations achieved in these experiments. Further studies in senescent F344 rats using a three-day exposure regimen demonstrated a significant an increase in BAL cell number recovered from the lungs, but no other significant changes in the respiratory tract. In young male and female F344 rats exposed to all three concentrations of particles, only the highest concentration of NH4N03 and C in was associated with significant elevations in the rate epithelial and interstitial cell proliferation within the terminal bronchioles following combined exposure to particles and 0.20 ppm ozone. These studies provide evidence for limited, but significant PM effects in the respiratory tract of healthy rats of all ages following short-term exposure to NH4N03 and C. These fmdings further support the need for future studies to defme the precise mechanisms of PM-induced lung injury and its potential interaction with ozone, even in healthy individuals.


 

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