Grantee Research Project Results
2006 Progress Report: Assessing Toxicity of Local and Transported Particles Using Animal Models Exposed to CAPs
EPA Grant Number: R832416C003Subproject: 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, 2005 through September 30, 2006
RFA: Particulate Matter Research Centers (2004) RFA Text | Recipients Lists
Research Category: Human Health , Air
Objective:
The Project is intended to differentiate the toxicological effects of locally emitted and transported particles. To do so, 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 predominantly from local sources. We expect that exposures starting at 11am will be relatively more enriched in transported particles. Specific biologic outcomes will include: breathing patterns, 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. 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.
Progress Summary:
We had not previously done studies assessing lung and heart in vivo oxidant responses in the compromised model that we plan to use, i.e. spontaneously hypertensive rats and their strain matched controls, Wistar Kyoto rats. These studies were done in the first year of this grant and show increased responses for both the heart and lungs in the compromised population. Lung data are illustrated in Figure 1 below.
Figure 1. In Vivo Oxidant Responses With Spontaneously Hypertensive Rats
Table 1 shows the target number of studies for each outcome in the exposure plan for these studies. Because limited numbers of animals can be used in each outcome at a time, multiple repetitions of these experiments will be needed.
Table 1. Target Numbers of Outcomes Per Group of Rats in Each 4 hr-Exposure Experiment
Tables 2 and 3 list the number of studies completed and the number of animals studied to date for breathing pattern and chemiluminescence outcomes, respectively. Note that we performed six morning and six afternoon exposures during Year One of the Center.
Table 2. Actual Number of Animals Assessed to Date: Breathing Pattern Data
Table 3. Number of Animals Assessed to Date: Chemiluminescence Data
Data analyses are not complete. However, it is clear that there are no AM/PM differences in sham controls. Therefore, within the time frame of these experiments, diurnal variations do not appear to be of concern for any outcomes measured.
Future Activities:
We expect to complete these exposure sets by December 2006, and have much of the exposure data analyzed. In the coming year we expect to complete analyses of all the outcomes. This project is scheduled to be finished within the first two and a half years of the grant.
Journal Articles:
No journal articles submitted with this report: View all 14 publications for this subprojectSupplemental Keywords:
concentrated air particles, acute cardiovascular effects, coarse particles, fine particles, vascular dysfunction,, RFA, Health, Scientific Discipline, Air, particulate matter, Environmental Chemistry, Health Risk Assessment, Risk Assessments, ambient air quality, atmospheric particulate matter, human health effects, chemical characteristics, automobile exhaust, airborne particulate matter, cardiovascular vulnerability, chemical composition, biological mechanism , biological mechanisms, ambient particle health effects, mobile sources, human exposure, autonomic dysfunction, oxidative stressRelevant Websites:
http://www.hsph.harvard.edu/epacenter Exit
Progress and Final Reports:
Original AbstractMain 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
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.