2006 Progress Report: Project 1 -- Pulmonary Metabolic ResponseEPA Grant Number: R832414C001
Subproject: this is subproject number 001 , established and managed by the Center Director under grant R832414
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: San Joaquin Valley Aerosol Health Effects Research Center (SAHERC)
Center Director: Wexler, Anthony S.
Title: Project 1 -- Pulmonary Metabolic Response
Investigators: Fanucchi, Michelle V. , Buckpitt, Alan , Plopper, Charles
Current Investigators: Fanucchi, Michelle V. , Winkle, Laura Van , Buckpitt, Alan , Plopper, Charles
Institution: University of California - Davis
EPA Project Officer: Chung, Serena
Project Period: October 1, 2005 through September 30, 2010 (Extended to September 30, 2011)
Project Period Covered by this Report: October 1, 2005 through September 30, 2006
RFA: Particulate Matter Research Centers (2004) RFA Text | Recipients Lists
Research Category: Health Effects , Air
The objective is to determine whether the increased pulmonary vulnerability to polycyclic aromatic hydrocarbons (PAHs) in neonates is exacerbated when the PAH is adsorbed to particulate matter. By compromising detoxification mechanisms, particles of mixed composition, such as graphitic carbon and a PAH, graphitic carbon and a transition metal, or graphitic carbon with both a transitional metal and a PAH, will result in more injury than particles composed of only one component.
Validation of Particle Delivery Method
In order to evaluate the acute effects of particulate exposure in rats, we must deliver a known quantity of sub-micron particles quickly to assess the time course of injury and clearance. We first validated the use of a dry powder insufflator (Model DP-4, PennCentury, Philadelphia, PA) for acute, intrapulmonary delivery of particulates. The DP-4 consistently delivered 1 to 5 mg of particles evenly throughout the airways.
Validation of a Strategy to Systematically Define the Impact That Individual Components of Particulate Matter Have on the Cytotoxicity of Airway Epithelium
We evaluated the early response (2-hr post insufflation) and clearance (24-hr post-insufflation) to a single intratracheal insufflation of 2.5 mg submicron carbon particles coated with 0-20% 1-nitronaphthalene (an atmospherically formed nitro-PAH) in adult rats. To maintain the local position of the particles within the airways, the lungs were inflation-fixed with formalin vapor generated by flowing air through an air stone immersed in 37 percent formaldehyde at low pressure.
The lungs were then evaluated by high resolution histopathology. We found that carbon particles not coated with 1-nitronaphthalene did not cause any appreciable cellular injury to airway epithelium and that the majority of the particles were cleared from the airways within 2 hours.
However, particles coated with 1-nitronaphthalene caused focal areas of exfoliation and cellular injuries in all airways evaluated (proximal, mid-level and distal airways) and were not completely cleared from the airways.
The initial experiments described above did not indicate a strong dose-response relationship between the amount of 1-nitronaphthalene coated on the particles and the amount of injury present in the airways. This suggests that we are above the linear portion of a dose-response curve and need to reduce the amount of 1-nitronapthalene per particle. Also, we will be investigating whether it is the concentration of the PAH on individual particles or the total PAH concentration administered that is important in particle toxicity. We will also be investigating whether the type of core particle affects the toxicity. The current studies have used sub-micron carbon black (free of contaminates) and future studies will also utilize flame-generated soot doped with 1-nitronaphthalene. The flame generated soot will be provided by Dr. Ian Kennedy of the Particle Generation, Modification and Characterization Core.
In addition, ambient particles from urban and rural sites in the San Joaquin Valley will be assessed for their cytotoxicity. The samples with the greatest cytotoxicity will be analyzed for PAH concentrations. The laboratory generated particles will then be adjusted to use PAH’s relevant to those found in San Joaquin Valley samples.
Journal Articles:No journal articles submitted with this report: View all 43 publications for this subproject
Supplemental Keywords:RFA, Health, Scientific Discipline, Air, particulate matter, Environmental Chemistry, Health Risk Assessment, Epidemiology, Risk Assessments, ambient aerosol, lung injury, air toxics, toxicology, long term exposure, lung disease, airway disease, airborne particulate matter, particle exposure, endothelial function, pariculate matter, human exposure, ambient particle health effects, ultrafine particulate matter, epidemiological studies, PM, human health risk
Progress and Final Reports:Original Abstract
Main Center Abstract and Reports:R832414 San Joaquin Valley Aerosol Health Effects Research Center (SAHERC)
Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R832414C001 Project 1 -- Pulmonary Metabolic Response
R832414C002 Endothelial Cell Responses to PM—In Vitro and In Vivo
R832414C003 Project 3 -- Inhalation Exposure Assessment of San Joaquin Valley Aerosol
R832414C004 Project 4 -- Transport and Fate Particles
R832414C005 Project 5 -- Architecture Development and Particle Deposition