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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: Harvard Particle Center
Center Director: Koutrakis, Petros
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: Stacey Katz/Gail Robarge,
Project Period: October 1, 2005 through September 30, 2010
RFA: Particulate Matter Research Centers (2004)
Research Category: Particulate Matter
Description:
Objective:Our laboratory has pioneered the development of the ambient particle concentrator as a means to carry out inhalation toxicological assessments of responses to ambient particles. Normal and compromised animal exposures to concentrated air particles (CAPs) in Boston have produced consistent and reproducible findings of biologic importance. The specific objectives of this project are: 1) To differentiate the cardiovascular effects of locally emitted particles from those of transported particles using normal animals; and 2) To determine whether spontaneously hypertensive rats, a genetically susceptible population, have enhanced vascular responses to exposures of different particle sources as compared to normal animals.
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.
Expected Results:This proposal offers the unique application of novel techniques to improve understanding effects of specific sources of particles and mechanisms of health effects. This combination of exposure scenarios and pulmonary and cardiovascular outcomes will provide new data to assess the effect of specific particle sources on specific mechanistic pathways by which ambient air particles produce adverse health effects.
Supplemental Keywords:Air Particulates, Inhalation Exposure, Cardiovascular, Pulmonary Mechanisms, Concentrated Air Particles,
Progress and Final Reports:
2006 Progress Report
2007 Progress Report
2008 Progress Report
Main Center Abstract and Reports:
R832416 Harvard Particle Center
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