2002 Progress Report: Health Effects of Airborne Particulate Matter and GassesEPA Grant Number: R829215
Title: Health Effects of Airborne Particulate Matter and Gasses
Investigators: Pinkerton, Kent E. , Aust, Ann , Buckpitt, Alan , Kennedy, Ian M. , Lighty, JoAnn S , Veranth, John
Current Investigators: Pinkerton, Kent E. , Aust, Ann , Kennedy, Ian M. , Leppert, Valerie , Veranth, John
Institution: University of California - Davis , University of Utah , Utah State University
Current Institution: University of California - Davis , University of California - Merced , University of Utah , Utah State University
EPA Project Officer: Chung, Serena
Project Period: October 1, 2001 through September 30, 2004 (Extended to September 30, 2005)
Project Period Covered by this Report: October 1, 2001 through September 30, 2002
Project Amount: $833,481
RFA: Health Effects of Particulate Matter (2001) RFA Text | Recipients Lists
Research Category: Air Quality and Air Toxics , Nanotechnology , Health Effects , Particulate Matter , Air
The objective of this research project is to examine the mechanisms of particulate toxicity in the lungs of neonatal rats following short- (1-3 day) and long-term (28 day) exposures to iron/soot or coal fly ash particles in the presence or absence of ozone. This project specifically examines the effects that directly impact epithelial cells of the neonatal airways, centriacinar regions, and alveoli. Epithelial cells are the first cells in the respiratory tract to come into contact with inhaled particles. In our investigation, we hypothesize the following: (1) damage to epithelial cells can serve as a direct and highly sensitive measure of particle toxicity; (2) epithelial cells lining the transitional zone between the airways and gas exchange regions of the lungs (i.e., the central acinus) are particularly sensitive and play a key role in the initiation and progression of particle-induced pulmonary injury; (3) epithelial-particle interactions initiate a cascade of events that underlie the adverse effects associated with inhaled particles; and (4) particle toxicity (in the presence of a transition metal such as iron) begins with the depletion of cellular glutathione levels in epithelial cells, thus accentuating cytotoxic events leading to cell death. In turn, cell death begins the process of cellular proliferation. Each of these events negatively impacts on the ability of the lungs to translocate and clear particles, thus leading to further irritation and injury. Each of these hypotheses will be tested using novel approaches to examine epithelial cell structure and function throughout the airways and alveoli.
During the current project period, we have been able to examine in detail the characteristics of iron and soot particles generated under experimental conditions for inhalation studies. This characterization has been instrumental in describing the generation of combustion particles under controlled conditions. We have been able to maintain constant levels of soot while varying the concentrations of iron particles under controlled conditions. We have been successful in generating ultrafine particles at consistent and constant concentrations, with our target being 250 µg/m3. Under these conditions, we can regulate the concentration of iron oxide particles generated within the range of 40 to 100 µg/m3 to look at the effects of increasing concentrations of this transition metal on potential health effects to the respiratory system. We have been able, through the use of electron microscopy and chemical analyses, to demonstrate that the particles generated within the soot fraction consist of both elemental and organic carbon. For the iron oxide particles generated, we have been able to confirm that the majority of these particles are Fe2O3 (maghemite). The mixing of iron and soot particles does not in any way change the chemical composition of the iron oxide particles. We have further demonstrated in studies completed during this project period that laboratory-generated particles used to examine iron and its interaction with soot in the respiratory tract of rats show significant synergistic interactions with soot that lead to bioavailable iron responsible for the induction of ferritin, oxidative stress, elevation of IL-1, and NFB activation in the lungs of healthy adult rats. These findings provide significant evidence to support the hypothesis that transition metals interacting with other components may underlie particulate matter-associated respiratory effects.
Our plans during the next year are to conduct new experiments to examine the health effects of sustained particle exposure in both neonatal animals, as well as young adult animals to airborne iron and soot particles.