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Grantee Research Project Results

2008 Progress Report: Assessing Toxicity of Local and Transported Particles Using Animal Models Exposed to CAPs

EPA Grant Number: R832416C003
Subproject: this is subproject number 003 , established and managed by the Center Director under grant R832416
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Health Effects Institute (2015 - 2020)
Center Director: Greenbaum, Daniel S.
Title: Assessing Toxicity of Local and Transported Particles Using Animal Models Exposed to CAPs
Investigators: Godleski, John J. , Koutrakis, Petros
Institution: Harvard University
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, 2007 through September 30,2008
RFA: Particulate Matter Research Centers (2004) RFA Text |  Recipients Lists
Research Category: Human Health , Air

Objective:

The objective of this project is to differentiate the toxicological effects of locally emitted and transported particles.  To do so, short-term 5 hr animal exposures to concentrated ambient fine particles (CAPs) were conducted during the time periods of 5-10 am and 10:30 am-3:30 pm.  Starting inhalation exposures at 5 am, before significant vertical mixing takes place, captures particles predominantly from local sources, while, exposures starting about 10:30 am are relatively more enriched in transported particles.  Specific biologic outcomes included: breathing patterns, indicators of pulmonary and systemic inflammation, blood pressure, in vivo oxidant responses in the heart and lung, and quantitative morphology of lung and cardiac vessels. To control for circadian variations all outcomes were assessed during both time periods, in relation to those of filtered air (sham) exposures.  Animal exposures were characterized using continuous measurements of particle mass, size, number, and black carbon, as well as integrated measurements of particle mass, sulfate, elements, and organics. Strains of rats used include Sprague Dawley (SD), which we have used extensively in previous CAPs studies, Spontaneously Hypertensive Rats (SHR), a sensitive model in many studies, and Wistar Kyoto (WKY) the strain control for SHR rats.  Studies of cardiopulmonary mechanisms in relationship to in vivo oxidant responses in the heart and lung were also carried out using CAPs.

Approach:

To differentiate the toxicological effects of locally emitted and transported particles on important cardiovascular outcomes, short term animal exposures to CAPs will be conducted during the time periods of 6-10am and 11am-3pm. Starting inhalation exposures at 6am before significant vertical mixing takes place will allow us to capture particles mostly from local sources. In contrast, exposures starting at 11am will be relatively more enriched in transported particles. All outcomes will be assessed in relation to those of filtered air (sham) exposures as well as those of positive controls using particles of known toxicity at both time periods to control for circadian variations. Animal exposures will be characterized using continuous measurements of particle mass, size, number, and black carbon, as well as integrated measurements of particle mass, sulfate, elements and organics. Specific outcome measurements will include: indicators of pulmonary and systemic inflammation, blood pressure, endothelin-1, endothelial nitric oxide synthase, atrial naturetic peptide, in vivo oxidant responses in the heart and lung, and quantitative morphology of lung and cardiac vessels. Statistical analyses will use multi-way ANOVA to assess differences among exposure groups and interactions of exposure and potential effect modifiers. Regression techniques will be used to examine dose-response relationships between measured biological outcomes and particle source contributions as reflected by particle composition. Multiple linear regression using tracer elements will be used to assess the independent effects of multiple pollution sources.

Progress Summary:

Early-late experiments. Exposure data from all the experiments are shown in Table 1. CAPs mass concentrations (Early - 505.8 ± 75.8 µg/m3 and Late 407.2 ± 45.7 µg/m3) were slightly higher than previous published studies from our laboratory, and not significantly different from each other using a paired two-tailed t-test.  There are significant differences in black carbon and elemental carbon between the early and late exposure, supporting the premise that the early exposure would be more influenced by local (primarily traffic sources) whereas the exposures later in the same day were more likely to contain transported particles.  Since these experiments were not done in the summer (when diurnal variation in sulfate production from oxidation of SO2 is greater than in other seasons), there is no significant difference in sulfur between the morning and afternoon.  In these studies, in addition to greater black and elemental carbon in the morning, iron, nickel, and copper levels were also significantly higher in the morning. When these data were analyzed using the ratio of a specific component to the total fine mass (or fraction of the component) essentially the same findings were observed with more robust p-values. Thus, elemental carbon, copper, and nickel were significantly higher in the morning. In addition, several components were found to be significantly higher in the afternoon. These include sodium, potassium, magnesium, manganese, and silicon. The sulfur fraction was higher in the afternoon than the morning, but this difference was not significant. Even though statistically significant differences were found between AM and PM exposures, the differences were modest.
 
Table 1.  CAPs mass and component concentrations during the early and late exposure periods
                 (concentrations are expressed in µg/m3  and fractions in %)
Early mean±SE
Late mean±SE
p =
CAPs Mass
505.8 ± 75.8
407.2 ± 45.7
0.083
*Black Carbon Mass
10.5 ± 0.9
7.3 ± 1.1
0.002
*Elemental Carbon
22.5 ± 2.6
16.5 ± 2.8
0.032
Organic Carbon
72.2 ± 6.9
67.3 ± 6.9
0.505
Total Carbon
94.9 ± 9.0
83.8 ± 9.5
0.261
Sodium
8.9 ± 2.6
10.4 ± 2.9
0.181
Chlorine
9.7 ± 3.6
13.8 ± 6.2
0.174
Silicon
9.5 ± 1.6
8.8 ± 1.1
0.448
Aluminum
3.4 ± 0.6
3.1 ± 0.4
0.437
Sulfur
37.0 ± 5.9
35.7 ± 5.3
0.832
Calcium
6.3 ± 0.9
6.1 ± 0.8
0.761
Titanium
0.33 ± 0.05
0.26 ± 0.04
0.108
Potassium
2.8 ± 0.3
2.7 ± 0.3
0.465
*Iron
13.3 ± 1.9
9.7 ± 1.0
0.035
Zinc
1.0 ± 0.1
1.1 ± 0.1
0.857
*Nickel
0.07 ± 0.015
0.04 ± .007
0.033
Vanadium
0.03 ± 0.01
0.01 ± .009
0.144
Magnesium
1.2 ± 0.3
1.4 ± 0.3
0.293
*Copper
0.4 ± 0.06
0.2 ± 0.03
0.019
Manganese
0.2 ± 0.03
0.3 ± 0.04
0.349
*EC Percent of Mass
5.3 ± 0.5
3.9 ± 0.4
0.007
OC Percent of Mass
17.8 ± 1.7
18.7 ± 1.5
0.586
TC Percent of Mass
23.1 ± 2.1
22.5 ± 1.8
0.753
*Sodium Percent of Mass
2.3 ± 0.7
2.7 ± 0.7
0.026
Chlorine Percent of Mass
2.3 ± 0.9
3.1 ± 1.3
0.180
*Silicon Percent of Mass
2.5 ± 0.4
2.9 ± 0.5
0.040
Aluminum Percent of Mass
0.89 ± 0.17
1.03 ± 0.19
0.107
Sulfur Percent of Mass
7.5 ± 0.7
8.6 ± 0.8
0.123
Calcium Percent of Mass
1.6 ±0.3
2.0 ± 0.4
0.056
Titanium Percent of Mass
0.09 ± 0.01
0.09 ± 0.02
0.814
*Potassium Percent of Mass
0.68 ± 0.07
View all 14 publications for this subproject

Supplemental Keywords:

Air Particulates, Inhalation Exposure, Cardiovascular, Pulmonary Mechanisms, concentrated air particles, acute cardiovascular effects, coarse particles, fine particles, vascular dysfunction, RFA, Health, Air, Scientific Discipline, Health Risk Assessment, Risk Assessments, particulate matter, Environmental Chemistry, chemical characteristics, biological mechanisms, biological mechanism , autonomic dysfunction, human exposure, airborne particulate matter, cardiovascular vulnerability, chemical composition, mobile sources, oxidative stress, ambient particle health effects, automobile exhaust, atmospheric particulate matter, ambient air quality, human health effects

Relevant Websites:

http://www.hsph.harvard.edu/epacenter

Progress and Final Reports:

Original Abstract
  • 2006 Progress Report
  • 2007 Progress Report
  • 2009 Progress Report
  • 2010
  • Final Report


    • Main Center Abstract and Reports:

    R832416    Health Effects Institute (2015 - 2020)

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R832416C001 Cardiovascular Responses in the Normative Aging Study: Exploring the Pathways of Particle Toxicity
    R832416C002 Cardiovascular Toxicity of Concentrated Ambient Fine, Ultrafine and Coarse Particles in Controlled Human Exposures
    R832416C003 Assessing Toxicity of Local and Transported Particles Using Animal Models Exposed to CAPs
    R832416C004 Cardiovascular Effects of Mobile Source Exposures: Effects of Particles and Gaseous Co-pollutants
    R832416C005 Toxicological Evaluation of Realistic Emission Source Aerosol (TERESA): Investigation of Vehicular Emissions

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    Project Research Results

    14 publications for this subproject
    12 journal articles for this subproject
    Main Center: R832416
     206 publications for this center
    199 journal articles for this center

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