Grantee Research Project Results
2002 Progress Report: Effects of Exposure to Fine and Ultrafine Concentrated Ambient Particles near a Heavily Trafficked Freeway in Geriatric Rats (Pilot Project)
EPA Grant Number: R827352C005Subproject: this is subproject number 005 , established and managed by the Center Director under grant R827352
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Southern California Children's Environmental Health Center
Center Director: McConnell, Rob Scot
Title: Effects of Exposure to Fine and Ultrafine Concentrated Ambient Particles near a Heavily Trafficked Freeway in Geriatric Rats (Pilot Project)
Investigators: Kleinman, Michael T. , Cho, Arthur K. , Froines, John R. , Sioutas, Constantinos
Current Investigators: Kleinman, Michael T.
Institution: University of California - Los Angeles , University of Southern California , Michigan State University , University of California - Irvine
Current Institution: University of California - Irvine
EPA Project Officer: Chung, Serena
Project Period: June 1, 1999 through May 31, 2005 (Extended to May 31, 2006)
Project Period Covered by this Report: June 1, 2001 through May 31, 2002
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text | Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air
Objective:
The objective of this research project is to focus on the central hypothesis of the Southern California Particle Center and Supersite, which is that organic constituents associated with particulate matter (PM)—including quinones, other organic compounds (polycyclic aromatic hydrocarbons [PAHs]), nitro-PAHs, and aldehydes/ketones), and metals—are capable of generating reactive oxygen species and acting as electrophilic agents. They have a central role in allergic airway disease such as asthma and cardiovascular effects through their ability to generate oxidative stress, inflammation, and immunomodulating effects in the lungs and airways.
This research project examines the hypothesis that free radicals produced by reactive organic and inorganic constituents of motor vehicle exhaust particles will induce injury to lung epithelium and changes in heart rate and blood pressure in aged rats exposed to ultrafine and fine particles near a freeway. This research project may result in a new animal model to be used in our ongoing freeway studies.
Progress Summary:
Aged rats (22 to 24 months) were exposed to a concentration of fine and ultrafine particles for 4 hours per day over a 3-day period. There were eight control and eight exposed rats. These rats were euthanized 24 hours post exposure. The lung was lavaged and the tissue fixed for immunohistochemical and morphometric analyses. Bronchoalveolar lavage (BAL) fluid was analyzed for inflammatory cytokines (TNFα, IL-2, IL-8). Macrophages were isolated, and functional assays were run to analyze free radical (superoxide) production and phagocytic activity. In addition, four additional rats were implanted with a pressure transducer and transponder so that blood pressure and heart rate could be measured during and after exposure.
The data showed an increase in blood pressure and heart rate for animals exposed to the concentrated ambient particles (CAPs), as well as a trend towards an increase in cytokine and superoxed production. There were no significant differences in the total number of cells recovered or in the number of viable cells recovered between the groups exposed to purified air or to fine + ultrafine (F + UF) CAPs. The background production of superoxide by macrophages isolated from the BAL were not significantly different; however, the phorbol myristate acetate-stimulated superoxide production was increased approximately twofold in the macrophages from CAP-exposed rats compared to those from the rats exposed to purified air. Although there were no significant differences, it was notable that CAP-exposed animals had approximately twofold increases in both inflammatory and antiinflammatory cytokines. In the four animals implanted with cardiac monitors and telemetry transmitters, heart rate and blood pressure were monitored before and after exposures in a repeated measures design. Each animal received a purified air exposure, followed by 2 repeated days of F + UF CAPs. Two weeks after the last CAP exposure, the rats were exposed to purified air for 3 consecutive days.
Future Activities:
We will conduct a second study with aged rats because the results of the pilot project were encouraging. We will use eight instrumented and eight noninstrumented rats (18-20 months), exposing them for 6 hours per day for 3 consecutive days to F + UF CAPs at a site approximately 50 m downwind of a freeway. Control rats (eight instrumented and eight noninstrumented) will be exposed to purified air.
Eight noninstrumented rats per group will be euthanized for biochemical, cytological, and histological assays. The right cardiac lobe will be ligated, removed, and snap frozen for cytokine and mediator expression analysis. The remainder of the lung will be lavaged, and the tissue will be fixed for morphometric analyses. Cell counts and cell differentials will be determined. BAL fluid will be analyzed for inflammatory cytokines (TNFα, IL-2, IL-6) and a proinflammatory arachidonic acid metabolite (LTB4). In addition, two acute phase proteins (C-reactive protein and serum amyloid A) will be measured in blood serum. These proteins are associated with changes in cardiac rhythm, rate, and pressure.
Journal Articles:
No journal articles submitted with this report: View all 3 publications for this subprojectSupplemental Keywords:
Particulate matter, quinones, PAHs, aldehydes, ketones, metals, allergic airway disease, human health risk, free radicals, cardiovascular effects, oxidative stress, freeway study, California, motor vehicle emissions, mobile sources, concentrated ambient particles (CAPs),, RFA, Scientific Discipline, Air, Geographic Area, HUMAN HEALTH, particulate matter, Environmental Chemistry, Health Risk Assessment, Air Pollutants, State, mobile sources, Health Effects, Environmental Monitoring, engine exhaust, ambient aerosol, asthma, motor vehicle emissions, epidemiology, human health effects, automotive emissions, particulate emissions, automotive exhaust, air pollution, children, PAH, human exposure, PM characteristics, California (CA), indoor air quality, aerosols, atmospheric chemistryRelevant Websites:
Progress and Final Reports:
Original AbstractMain Center Abstract and Reports:
R827352 Southern California Children's Environmental Health Center Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R827352C001 The Chemical Toxicology of Particulate Matter
R827352C002 Pro-inflammatory and the Pro-oxidative Effects of Diesel Exhaust Particulate in Vivo and in Vitro
R827352C003 Measurement of the “Effective” Surface Area of Ultrafine and Accumulation Mode PM (Pilot Project)
R827352C004 Effect of Exposure to Freeways with Heavy Diesel Traffic and Gasoline Traffic on Asthma Mouse Model
R827352C005 Effects of Exposure to Fine and Ultrafine Concentrated Ambient Particles near a Heavily Trafficked Freeway in Geriatric Rats (Pilot Project)
R827352C006 Relationship Between Ultrafine Particle Size Distribution and Distance From Highways
R827352C007 Exposure to Vehicular Pollutants and Respiratory Health
R827352C008 Traffic Density and Human Reproductive Health
R827352C009 The Role of Quinones, Aldehydes, Polycyclic Aromatic Hydrocarbons, and other Atmospheric Transformation Products on Chronic Health Effects in Children
R827352C010 Novel Method for Measurement of Acrolein in Aerosols
R827352C011 Off-Line Sampling of Exhaled Nitric Oxide in Respiratory Health Surveys
R827352C012 Controlled Human Exposure Studies with Concentrated PM
R827352C013 Particle Size Distributions of Polycyclic Aromatic Hydrocarbons in the LAB
R827352C014 Physical and Chemical Characteristics of PM in the LAB (Source Receptor Study)
R827352C015 Exposure Assessment and Airshed Modeling Applications in Support of SCPC and CHS Projects
R827352C016 Particle Dosimetry
R827352C017 Conduct Research and Monitoring That Contributes to a Better Understanding of the Measurement, Sources, Size Distribution, Chemical Composition, Physical State, Spatial and Temporal Variability, and Health Effects of Suspended PM in the Los Angeles Basin (LAB)
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.