Final Report: Effects of Exposure to Fine and Ultrafine Concentrated Ambient Particles near a Heavily Trafficked Freeway in Geriatric Rats (Pilot Project)

EPA Grant Number: R827352C005
Subproject: 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 Particle Center
Center Director: Froines, John R.
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.
Institution: University of California - Irvine , University of California - Irvine
EPA Project Officer: Chung, Serena
Project Period: June 1, 1999 through May 31, 2005 (Extended to May 31, 2006)
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text |  Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air


Topic A: Studies Emphasizing Investigation of the Biological Mechanisms of Particulate Matter (PM) Effects in Relation to PM Physical and Chemical Characteristics

A geriatric rat model was used to test 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 animals exposed to ultrafine particles (UF) and fine particles (F) near a freeway.

Summary/Accomplishments (Outputs/Outcomes):

This study was carried out in two phases. In Phase 1, twelve rats aged 22 to 24 months were exposed 6 hours per day for two consecutive days to F and UF concentrated ambient particles (CAPs) at a site approximately 50 m downwind of a heavily trafficked freeway. The average exposure concentration was about 300 μg/m3. Control rats (n=10) were exposed to purified air. Four rats from the CAPs-exposure group were implanted with pressure transducers and transponders and their blood pressures and heart rates were measured. Measurements were made before and after each exposure. One of the implanted rats was euthanized because of a tumorous growth. Two weeks after the last CAPs exposure, the remaining implanted rats were exposed to purified air on 3 consecutive days, and blood pressure and heart rate were again measured before and after exposure.

Eight rats per group were euthanized 24 hours after their last exposure. Biochemical, cytological and histological assays were performed on blood, plasma, bronchoalveolar lavage, and heart and lung tissues. The endpoints included cell counts and cell differentials, inflammatory cytokines (TNFα, IL-1α, IL-1β, IFNγ) and anti-inflammatory cytokines (IL-4, IL-6, IL-10) in BAL. BAL from CAPs exposed animals had approximately 2 fold increases in some inflammatory and anti-inflammatory cytokines, relative to unexposed controls. IL-1α, IL-1β, IL-6 and IL-10 were increased in lung lavage fluid from exposed animals.

Heart rate and blood pressure were measured in the three surviving rats that had been implanted with cardiac monitors and telemetry transmitters. Average blood pressure and heart rate were both elevated when pre- and post-exposure measures were compared. The elevation in blood pressure after exposure was statistically significant, although the sample size is very small.

The surgical preparation of geriatric rats was difficult, and if scaled up, the protocol would benefit from implanting transmitters into rats at a younger age, before the exposure experiment was to commence. Notably, at a relatively low exposure concentration of F over just two days, we were able to detect post-exposure cardiovascular changes in three aged rats compared to controls and found some elevated cytokines in lavage fluid in a group of eight exposed animals.

A second exposure study was carried out in Phase 2. Thirty-four 22-month-old rats were exposed to filtered air (n=17) or PM2.5 CAPs (n=17) at a site in Boyle Heights, CA with high levels of particulate pollution dominated by motor vehicle exhaust from freeway sources. Control group animals received filtered air. Blood pressure was obtained via tail cuff from all rats in the experiment. Electrocardiograph (ECG) parameters (heart rate [HR], heart rate variability [HRV]) and temperature were obtained from 5 animals in each group. Rats were monitored telemetrically for twenty minutes at the lab immediately before transport to the exposure site and twenty minutes at the lab immediately after the end of the exposure. Within 18–24 hours after the exposure ended, animals were euthanized by a lethal intraperitoneal injection of sodium pentobarbital (Nembutal, 65 mg/kg). Lung tissue samples were analyzed for malonaldehyde and glutathione as markers for oxidative stress, for IL-1β, TNFα, and IL-6, and for C-reactive protein. Western blots were analyzed for MAP kinases ERK1, ERK2, pERK2, JNK1, JNK2, p38 and pp38.

The concentration of CAPs ranged from 540–943 μg/m3 (mean: 655 μg/m3) at a site in Boyle Heights, CA, with high levels of ambient particulate matter dominated by motor vehicle exhaust. With respect to cardiovascular responses, increased trends in the root mean square of successive differences in normal beat intervals (RMSSD) of HRV, a parameter highly correlated with vagal activity in the heart, were observed on the second and third days of exposure. No significant exposure-related changes in blood pressure or heart rate were observed. The cytokine concentrations were not significantly different between control and exposed rats. All of the MAPK’s were lower in the exposed rats than in the control rats. The decreases were significant (p≤0.05) for ERK1 and pJNK. These MAPK’s are involved in protection of cells from apoptosis and further study of these parameters is warranted in future studies.

Journal Articles on this Report : 3 Displayed | Download in RIS Format

Other subproject views: All 3 publications 3 publications in selected types All 3 journal articles
Other center views: All 150 publications 149 publications in selected types All 149 journal articles
Type Citation Sub Project Document Sources
Journal Article Campbell A, Oldham M, Becaria A, Bondy SC, Meacher D, Sioutas C, Misra C, Mendez LB, Kleinman M. Particulate matter in polluted air may increase biomarkers of inflammation in mouse brain. NeuroToxicology 2005;26(1):133-140. R827352 (2004)
R827352 (Final)
R827352C005 (Final)
R827352C014 (Final)
  • Abstract from PubMed
  • Full-text: ScienceDirect-Full Text PDF
  • Abstract: ScienceDirect-Abstract & Full Text HTML
  • Other: University of California-Full Text PDF
  • Journal Article Kleinman MT, Hamade A, Meacher D, Oldham M, Sioutas C, Chakrabarti B, Stram D, Froines JR, Cho AK. Inhalation of concentrated ambient particulate matter near a heavily trafficked road stimulates antigen-induced airway responses in mice. Journal of the Air & Waste Management Association 2005;55(9):1277-1288. R827352 (2004)
    R827352 (Final)
    R827352C001 (Final)
    R827352C005 (Final)
    R827352C014 (Final)
    R832413C003 (2010)
  • Abstract from PubMed
  • Full-text: Taylor & Francis-Full Text PDF
  • Abstract: Taylor & Francis-Abstract
  • Journal Article Oldham MJ, Phalen RF, Robinson RJ, Kleinman MT. Performance of a portable whole-body mouse exposure system. Inhalation Toxicology 2004;16(9):657-662. R827352 (2004)
    R827352 (Final)
    R827352C005 (Final)
    R827352C016 (Final)
  • Abstract from PubMed
  • Full-text: UC Irvine-Full Text PDF
  • Abstract: Taylor and Francis-Abstract
  • Supplemental Keywords:

    RFA, Scientific Discipline, Air, Geographic Area, HUMAN HEALTH, particulate matter, Environmental Chemistry, Health Risk Assessment, Air Pollutants, State, mobile sources, Environmental Monitoring, Health Effects, ambient aerosol, asthma, engine exhaust, epidemiology, human health effects, motor vehicle emissions, particulate emissions, automotive emissions, air pollution, automotive exhaust, children, PAH, human exposure, indoor air quality, California (CA), PM characteristics, aerosols, atmospheric chemistry

    Relevant Websites: Exit

    Progress and Final Reports:

    Original Abstract
  • 1999
  • 2000
  • 2001
  • 2002 Progress Report
  • 2003
  • 2004

  • Main Center Abstract and Reports:

    R827352    Southern California Particle 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)