Grantee Research Project Results
2004 Progress Report: Health Effects of Airborne Particulate Matter and Gasses
EPA Grant Number: R829215Title: Health Effects of Airborne Particulate Matter and Gasses
Investigators: Pinkerton, Kent E. , Kennedy, Ian M. , Aust, Ann , Veranth, John , Leppert, Valerie
Institution: University of California - Davis , Utah State University , University of California - Merced , University of Utah
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, 2003 through September 30, 2004
Project Amount: $833,481
RFA: Health Effects of Particulate Matter (2001) RFA Text | Recipients Lists
Research Category: Air Quality and Air Toxics , Nanotechnology , Human Health , Particulate Matter , Air
Objective:
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) exposure to iron/soot or coal fly ash particles in the presence or absence of ozone. We will examine effects that directly impact on the airways, centriacinar regions, and alveoli of the lungs. Because epithelial cells are the first cells in the respiratory tract to come into contact with inhaled particles, we hypothesize that damage to these cells can serve as a direct and highly sensitive measure of particle toxicity. We hypothesize that 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. We further hypothesize that epithelial-particle interactions initiate a cascade of events that underlie the adverse effects associated with inhaled particles. We hypothesize that particle toxicity (in the presence of a transition metal, 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 impact negatively on the ability of the lungs to translocate and clear particles, thus leading to further irritation and injury. We will test each of these hypotheses using novel approaches to examine epithelial cell structure and function throughout the airways and alveoli.
Progress Summary:
Particulate matter (PM) has been associated with a variety of negative health outcomes involving the respiratory and cardiovascular systems. Children appear to be particularly vulnerable to the effects of particle pollution to the respiratory system. The precise mechanisms to explain how exposure to airborne particles may cause adverse effects in children, however, are unknown. To study their influence on early postnatal development, a simple, laminar diffusion flame was used to generate an aerosol of soot and iron particles in the size range of 10 to 50 nm. Exposure of 10-day old rat pups to particles of soot and iron was for 6 hours/day for 3 days. The lungs were examined following a single injection of bromodeoxyuridine (BrdU) 2 hours prior to necropsy. Neonatal rats exposed to these particles demonstrated a significant reduction in the rate of cell proliferation in those gas exchange regions arising immediately beyond the terminal bronchioles (defined as the proximal alveolar region). These findings strongly suggest exposure to airborne particles during early neonatal life has significant direct effects on lung growth by altering cell division within critical sites of the respiratory tract during periods of rapid postnatal development. Such effects may have lasting consequences in life which alter of the lungs in early life. These findings were published in the journal Inhalation Toxicology in 2004.
In collaboration with engineers at the University of California (UC) at Davis and UC–Merced, new studies were done to examine the importance of the oxidation state of iron oxide nanoparticles cogenerated with soot during combustion using electron energy-loss spectroscopy. These novel studies have determined differences in oxidation states of the iron when comparing the core of the particle to the surface of the particle. Their experimental findings indicate that the core of each particle is composed of γ-Fe2O3, which is reduced to FeO at their surfaces. Such findings provide further potential mechanisms to contribute to the toxicity of transition metals in the presence of soot in particulate matter. These findings suggest that a synergistic interaction between soot and iron particles could account for those biological responses found in earlier studies that were absent with exposure to iron alone or soot alone.
During this period, a dry powder aerosol generator was designed capable of producing well-dispersed dust suspensions using only a small quantity of PM2.5-enriched powders. This system was developed to allow for dust resuspension for inhalation experiments with limited amounts of coal flyash materials collected and size-fractionated from source sampling. With premixing of the test powder with large diameter glass beads (100 µm), the device is able to deliver concentrations from 100 - 1000 µg/m3 to a test chamber using only a few milligrams of the test powder per hour. Scanning electron microscope examination of filter samples show the aerosol contains well-dispersed particles resuspended from the test powder with no evidence of glass bead fragments. This system for aerosolizing small quantities of archived materials has been published in the journal Aerosol Science and Technology.
Future Activities:
Our plans are to complete experiments to examine the health effects of prolonged particle exposure in animals to airborne iron and soot particles. Our studies with young adult animals is designed to examine not only local measures of oxidative stress within the lungs but also systemic markers of oxidative stress that may prove useful in better monitoring PM effects using noninvasive approaches to measure these effects.
Journal Articles on this Report : 4 Displayed | Download in RIS Format
Other project views: | All 23 publications | 15 publications in selected types | All 15 journal articles |
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Pinkerton KE, Zhou Y-M, Teague SV, Peake JL, Walther RC, Kennedy IM, Leppert VJ, Aust AE. Reduced lung cell proliferation following short-term exposure to ultrafine soot and iron particles in neonatal rats: key to impaired lung growth? Inhalation Toxicology 2004;16(Suppl 1):73-81. |
R829215 (2003) R829215 (2004) R829215 (Final) R827995 (Final) |
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Teague SV, Veranth JM, Aust AE, Pinkerton KE. Dust generator for inhalation studies with limited amounts of archived particulate matter. Aerosol Science and Technology 2005;39(2):85-91. |
R829215 (2004) R829215 (Final) R831714 (2005) |
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Zhou Y-M, Zhong C-Y, Kennedy IM, Pinkerton KE. Pulmonary responses of acute exposure to ultrafine iron particles in healthy adult rats. Environmental Toxicology 2003;18(4):227-235. |
R829215 (2003) R829215 (2004) R829215 (Final) R826246 (Final) R827995 (Final) |
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Zhou Y-M, Zhong C-Y, Kennedy IM, Leppert VJ, Pinkerton KE. Oxidative stress and NFκB activation in the lungs of rats: a synergistic interaction between soot and iron particles. Toxicology and Applied Pharmacology 2003;190(2):157-169. |
R829215 (2003) R829215 (2004) R829215 (Final) R827995 (Final) |
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Supplemental Keywords:
childrens’ health, airborne particles, pulmonary system, lungs,, RFA, Health, PHYSICAL ASPECTS, Scientific Discipline, Air, Waste, Ecosystem Protection/Environmental Exposure & Risk, Bioavailability, particulate matter, Health Risk Assessment, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Physical Processes, Disease & Cumulative Effects, Environmental Monitoring, Children's Health, tropospheric ozone, genetic susceptability, Incineration/Combustion, Immunology, health effects, particulates, ambient air quality, urban air, PM10, sensitive populations, coal fly ash particles, neonates, PM 2.5, air pollutants, effects assessment, neonatal rats, lead, ozone, exposure, ambient measurement methods, ambient air, alveolar cells, airway disease, pulmonary disease, epithelial cells, children, particles, human exposure, clinical studies, animal models, sensitive subgroups, ecological risk, urban soot, ambient particulates, Acute health effects, allergic response, measurement methods , iron/soot, animal studies, coal fly ash, combustion gases, soot profiles, exposure assessment, human health riskRelevant Websites:
http://www.envtox.ucdavis.edu/cehs/ Exit
http://agcenter.ucdavis.edu/agcenter/ Exit
Progress and Final Reports:
Original AbstractThe 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.