Final Report: Health Effects of Airborne Particulate Matter and Gasses

EPA Grant Number: R829215
Title: Health Effects of Airborne Particulate Matter and Gasses
Investigators: Pinkerton, Kent E. , Aust, Ann , Kennedy, Ian M. , Leppert, Valerie , Veranth, John
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 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

Objective:

The objective of this research project was to examine the mechanisms of particulate toxicity in the lungs of rats following short-term (3 day) and long-term (4 week) exposure to iron/soot or coal fly ash particles. We have examined those effects that directly impact on epithelial cells of the airways, centriacinar regions, and alveoli. Because epithelial cells are the first cells in the respiratory tract to come into contact with inhaled particles, we hypothesized that damage to these cells might serve as a direct and highly sensitive measure of particle toxicity. We further hypothesized 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 could play a key role in the initiation and progression of particle-induced pulmonary injury. We further hypothesized epithelial-particle interactions initiate a cascade of events that underlie the adverse effects associated with inhaled particles. We hypothesized that particle toxicity (in the presence of a transition metal such as iron) could begin 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 impacts negatively on the ability of the lungs to translocate and clear particles, thus leading to further irritation and injury. We have tested each of these hypotheses using novel approaches to examine both pulmonary and systemic effects of exposure to combined iron and soot particles as well as the effects of exposure to iron alone or soot alone. These studies were completed further in young adult and neonatal rats to examine the impact of particle inhalation on the airways and alveoli of the lungs.

Summary/Accomplishments (Outputs/Outcomes):

The significance of our findings is considerable in view of the fact that airborne particles represent a highly complex mixture of compounds. Through these studies, we demonstrated that a diffusion-flame system can be used to combust and generate simple particles containing soot and iron, resulting in a synergistic effect in particles of mixed chemical composition. When these identical particles are found singly, no biological effect is observed. These findings present a number of important factors for regulatory policy:  (1) exposure to ultrafine particles over a short-term basis can lead to significant oxidative stress to the pulmonary system in both adult animals as well as newborn animals; (2) the chemical composition of particles, particularly from mixed particulate sources, are an important consideration in the potential overall toxicity that can be found; (3) transition metals may play an important role in particulate matter (PM) toxicity; (4) airborne particles appear to produce toxicity to the respiratory system through pathways involving oxidative stress; and (5) airborne particles have unique impacts on the rapidly developing lung during the postnatal period to significantly impair cell proliferation in critical sites of the lungs.

The identification of characteristics of iron and soot particles generated under experimental conditions for inhalation studies has been evaluated throughout the course of the grant. This characterization has been instrumental in describing the generation of combustion particles under controlled conditions. These findings were published in the journal Aerosol Science and Technology in 2001. In collaboration with engineers at the University of California (UC)–Davis and UC–Merced, new studies were conducted 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. These findings were published in the journal Sensors and Actuators B in 2005.

A series of particle inhalation studies was conducted to determine the effects of short-term repeated (3 day) exposure of young healthy adult rats to ultrafine iron particles. Such exposures were found to be associated with pulmonary oxidative stress and a proinflammatory response that was dose-dependent on the concentration of iron. These findings were published in the journal Environmental Toxicology in 2003. Further studies were completed to address the potential for synergism between iron and soot particles following short-term repeated (3 day) exposure. These inhalation experiments demonstrated in young adult rats a strong synergistic interaction between soot and iron particles to drive oxidative stress, pulmonary ferretin induction, and the elevation of proinflammatory pulmonary cytokines not found with exposure to iron alone or to soot alone. These findings were published in the journal Toxicology and Applied Pharmacology in 2003. Further studies to examine subacute, repeated (5 days/week x 4 weeks) exposure to iron/soot particles demonstrated a sustained and elevated adverse response in the lungs that also was found to be passed systemically to the vascular blood elements with increased cell death, decreased macrophage function, and increased gene expression for proinflammatory cytokines (IL-1β, TNF α) and the adhesion molecule ICAM-1.

Exposure to ultrafine particles during early postnatal development also may be associated with adverse pulmonary health effects. Neonatal rats exposed to this mixture of iron and soot particles during early postnatal development (10-12 days postnatal age) was associated with a significant reduction in lung cell proliferation during a critical window of intense alveolar growth. Such an effect may result in altered growth in the respiratory system that may be associated with lifelong consequences. These findings were published in the journal Inhalation Toxicology in 2004.

As part of this Science To Achieve Results (STAR) grant, a dry powder aerosol generator that is capable of producing well-dispersed dust suspensions using only a small quantity of PM2.5-enriched powders was designed. This system was developed to allow for dust resuspension for inhalation experiments with limited amounts of coal fly ash 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 shows that 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 was published in the journal Aerosol Science and Technology in 2005.

Conclusions:

Particles of complex mixtures and chemical composition are likely to behave in an equally complex manner to produce health effects. Synergism of the components found in airborne particles is a highly plausible mechanism for observed pulmonary health effects observed in the human population. Our inhalation studies performed in laboratory rodents show a clear synergism with the interaction of iron and soot particles that is not observed with exposure to soot alone or to iron alone. The effects of ultrafine particles are further emphasized in acute short-term exposure to these particles during postnatal development to significantly reduce lung cell proliferation that may have lasting consequences during life.


Journal Articles on this Report : 15 Displayed | Download in RIS Format

Other project views: All 23 publications 15 publications in selected types All 15 journal articles
Type Citation Project Document Sources
Journal Article Donaldson K, Borm PJA, Oberdorster G, Pinkerton KE, Stone V, Tran CL. Concordance between in vitro and in vivo dosimetry in the proinflammatory effects of low-toxicity, low-solubility particles: the key role of the proximal alveolar region. Inhalation Toxicology 2008;20(1):53-62. R829215 (Final)
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  • Journal Article Jasinski J, Pinkerton KE, Kennedy IM, Leppert VJ. Surface oxidation state of combustion-synthesized γ-Fe2O3 nanoparticles determined by electron energy loss spectroscopy in the transmission electron microscope. Sensors and Actuators B: Chemical 2005;109(1):19-23. R829215 (Final)
  • Abstract: Science Direct Abstract
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  • Journal Article Last JA, Ward R, Temple L, Pinkerton KE, Kenyon NJ. Ovalbumin-induced airway inflammation and fibrosis in mice also exposed to ultrafine particles. Inhalation Toxicology 2004;16(2):93-102. R829215 (Final)
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  • Journal Article Madl AK, Pinkerton KE. Health effects of inhaled engineered and incidental nanoparticles. Critical Reviews in Toxicology 2009;39(8):629-658. R829215 (Final)
    R831714 (2005)
    R832414 (2010)
    R832414C003 (2009)
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  • Journal Article Madl AK, Teague SV, Qu Y, Masiel D, Evans JE, Guo T, Pinkerton KE. Aerosolization system for experimental inhalation studies of carbon-based nanomaterials. Aerosol Science and Technology 2012;46(1):94-107. R829215 (Final)
    R832414C003 (Final)
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  • Journal Article 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)
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  • Journal Article Pinkerton KE, Joad JP. Influence of air pollution on respiratory health during perinatal development. Clinical and Experimental Pharmacology and Physiology 2006;33(3):269-272. R829215 (Final)
    R832414 (2009)
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  • Journal Article Plummer LE, Smiley-Jewell S, Pinkerton KE. Impact of air pollution on lung inflammation and the role of Toll-like receptors. International Journal of Interferon, Cytokine and Mediator Research 2012;4:43-57. R829215 (Final)
    R832414 (Final)
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  • Journal Article Smith KR, Kim S, Recendez JJ, Teague SV, Menache MG, Grubbs DE, Sioutas C, Pinkerton KE. Airborne particles of the California Central Valley alter the lungs of healthy adult rats. Environmental Health Perspectives 2003;111(7):902-908 (discussion A408-409). R829215 (Final)
    R826246 (Final)
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  • Journal Article Smith KR, Veranth JM, Kodavanti UP, Aust AE, Pinkerton KE. Acute pulmonary and systemic effects of inhaled coal fly ash in rats: comparison to ambient environmental particles. Toxicological Sciences 2006;93(2):390-399. R829215 (Final)
    R832414 (Final)
    R832414C003 (2006)
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  • Journal Article 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)
  • Full-text: Taylor and Francis-Full Text HTML
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  • Journal Article Wang L, Green FHY, Smiley-Jewell SM, Pinkerton KE. Susceptibility of the aging lung to environmental injury. Seminars in Respiratory and Critical Care Medicine 2010;31(5):539-553. R829215 (Final)
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  • Journal Article Zhong C-Y, Zhou Y-M, Smith KR, Kennedy IM, Chen C-Y, Aust AE, Pinkerton KE. Oxidative injury in the lungs of neonatal rats following short-term exposure to ultrafine iron and soot particles. Journal of Toxicology and Environmental Health, Part A-Current Issues 2010;73(12):837-847. R829215 (Final)
    R832414 (2010)
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  • Journal Article 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)
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  • Journal Article 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)
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  • Supplemental Keywords:

    children’s health, airborne particles, pulmonary system, lungs, RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, Air, Waste, Ecosystem Protection/Environmental Exposure & Risk, Bioavailability, particulate matter, Health Risk Assessment, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Disease & Cumulative Effects, Environmental Monitoring, Physical Processes, Children's Health, genetic susceptability, tropospheric ozone, Incineration/Combustion, Immunology, ambient air quality, health effects, neonates, particulates, PM10, sensitive populations, urban air, coal fly ash particles, air pollutants, effects assessment, PM 2.5, neonatal rats, airway disease, ambient air, ambient measurement methods, epithelial cells, exposure, lead, ozone, pulmonary disease, alveolar cells, children, particles, animal models, human exposure, clinical studies, Acute health effects, ecological risk, sensitive subgroups, urban soot, ambient particulates, measurement methods , allergic response, animal studies, iron/soot, exposure assessment, human health risk, soot profiles, cardiopulmonery responses, combustion gases

    Relevant Websites:

    http://www.envtox.ucdavis.edu/cehs Exit
    http://agcenter.ucdavis.edu/agcenter Exit

    Progress and Final Reports:

    Original Abstract
  • 2002 Progress Report
  • 2003 Progress Report
  • 2004 Progress Report