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Lung Injury from Inhaled Ultrafine Particles in Compromised Rats of Old Age: Influence of Priming and Adaptation

EPA Grant Number: R826784
Title: Lung Injury from Inhaled Ultrafine Particles in Compromised Rats of Old Age: Influence of Priming and Adaptation
Investigators: Oberdörster, Günter , Finkelstein, Jacob N.
Current Investigators: Oberdörster, Günter , Elder, Alison C.P. , Finkelstein, Jacob N.
Institution: University of Rochester
EPA Project Officer: Katz, Stacey
Project Period: September 1, 1998 through September 20, 2001 (Extended to September 20, 2002)
Project Amount: $606,545
RFA: Health Effects of Particulate Matter and Associated Air Pollutants (1998)
Research Category: Particulate Matter , Health Effects

Description:

Epidemiological studies found that ambient particles at low concentrations are associated with mortality and serious morbidity in susceptible parts of the population, e.g., the elderly with cardiorespiratory conditions. Based on results of our previous and preliminary studies we hypothesize that the ultrafine particles as part of the ambient fine mode particles cause oxidative stress in the compromised aged organism which escalates into a significant pulmonary inflammation in the primed (endotoxin-sensitized) organism. Priming of humans can occur following exposures to a variety of agents, including endogenous (intestinal) as well as exogenous (airborne) exposure to endotoxin. Experimental studies have shown that depending on the timing of a second stimulus after priming either a state of sensitization with heightened response or a state of tolerance with lowered response can occur. We focus on ultrafine particles (~20-30 nm) because (i) at low mass concentrations they have a high number concentration and large surface area which is of toxicological significance; (ii) they have a higher deposition efficiency in the alveolar region than any other particle size; (iii) they penetrate rapidly across the pulmonary epithelium and reach interstitial sites; and (iv) they are generally more biologically reactive than larger particles.

Approach:

We will test our hypothesis by establishing exposure response relationships for environmentally-relevant particles of ultrafine carbon and iron oxide in emphysematous and healthy 26-month old rats, with and without prior short-term endotoxin inhalation. Exposure will be for 6 hrs. at concentrations of 30, 60, and 120 ?g/m3. We will evaluate parameters of pulmonary and systemic mediators of inflammation, cell activation and tissue damage related to oxidative stress. Comparison will be made to larger particles of carbon and iron oxide resembling accumulation mode particles. We will also investigate the role of alveolar macrophages and epithelial type II cells in the ultrafine particle-induced events using an AM-depleted rat model and a novel in vitro system to expose AM and type II cells to airborne ultrafine particles.

Expected Results:

We expect that low inhaled mass concentrations of ultrafine carbon and iron oxide particles will induce effects in old rats with emphysema (as a model of COPD) and that a significantly increased inflammatory response with systemic effects occurs with endotoxin priming characterized by increased activation of inflammatory cells, greater release of inflammatory mediators and greater release of oxidants causing tissue damage.

Improvement in Risk Assessment/Risk Management: First results of our studies will become available in time to be considered for the next Air Quality Criteria Document of EPA. If our results demonstrate that the aged organism under certain conditions (compromised; sensitized) is significantly affected by short-term exposure to low mass concentrations of ultrafine particles, this will have serious consequences for public health and regulatory standards for particulate matter. Not only will the new PM2.5 standard have to be reconsidered, but a drastic change to a standard defined by particle number has to be made. Furthermore, respective sources for ultrafine particles have to be targeted to be controlled.

Publications and Presentations:

Publications have been submitted on this project: View all 24 publications for this project

Journal Articles:

Journal Articles have been submitted on this project: View all 8 journal articles for this project

Supplemental Keywords:

Urban air, exposure, risk, human health, sensitive population, animal, elderly, susceptibility, particulates, metals, , Air, Scientific Discipline, Health, RFA, Susceptibility/Sensitive Population/Genetic Susceptibility, Toxicology, Disease & Cumulative Effects, genetic susceptability, Atmospheric Sciences, Environmental Engineering, particulate matter, Environmental Chemistry, exposure assessment, ultrafine particles, environmental hazard exposures, Acute health effects, elderly, health effects, mortality, respiratory problems, air contaminant exposure, air quality, sensitive subgroups, tissue damage, emphysema, highrisk groups, lung inflammation, toxics, air pollutants, air toxics, chronic health effects, human health effects, particulates, respiratory, sensitive populations, air pollution, airway disease, effects assessment, inhalability, metals, tolerance, lung dysfunction, oxidant stress, human susceptibility, health risks, laboratory animals, morbidity

Progress and Final Reports:
2000 Progress Report
Final Report

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.

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