Mechanisms of Particulate Matter Toxicity in Neonatal and Young Adult Rat Lungs

EPA Grant Number: R832347C135
Subproject: this is subproject number 135 , established and managed by the Center Director under grant R832347
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Health Effects Institute (2005 — 2010)
Center Director: Greenbaum, Daniel S.
Title: Mechanisms of Particulate Matter Toxicity in Neonatal and Young Adult Rat Lungs
Investigators: Pinkerton, Kent E.
Institution: Health Effects Institute , Desert Research Institue , Michigan State University , University of California–Davis , University of Medicine and Dentistry of New Jersey
EPA Project Officer: Hunt, Sherri
Project Period: April 1, 2005 through March 31, 2010
RFA: Health Effects Institute (2010) RFA Text |  Recipients Lists
Research Category: Health Effects , Air

Objective:

Ambient particulate matter (PM) is a complex mixture of solid and liquid particles suspended in air. Depending on the source of pollution, PM varies in size, chemical composition, and other physical and biologic properties. On the basis of epidemiologic findings and supporting results of toxicologic studies, many governmental agencies have set regulatory standards or guidelines for concentrations of ambient PM. Particles # 10 μm in aerodynamic diameter (PM10) are of most concern because these particles are considered to be respirable by humans. To protect the general population and groups considered most vulnerable to adverse effects from PM in the United States, the U.S. Environmental Protection Agency monitors PM10 levels and has promulgated National Ambient Air Quality Standards for particles # 2.5 μm in aerodynamic diameter (PM2.5 or fine particles). Some scientists believe that ultrafine particles (# 100 nm in diameter) may be particularly toxic.

Much work has focused on understanding the effects of particles derived from combustion sources: these particles are in the fine and ultrafine range and generally are composed of an elemental carbon core that binds metals (such as iron, vanadium, nickel, copper, and platinum), organic carbon compounds, and sulfates. Critical questions in PM research involve understanding the mechanisms by which particles may cause effects and the key characteristics of particles, both physical and chemical, that are associated with toxicity. To address these questions, HEI issued RFA 96-1, Mechanisms of Particle Toxicity: Fate and Bioreactivity of Particle-Associated Compounds, in 1996.

Approach:

In response, Dr. Kent Pinkerton and colleagues from the University of California–Davis, will conducte a study to evaluate the effects of short-term exposure on the airways of rats using laboratorygenerated ultrafine metal particles, either alone or in combination with soot. The rationale for the study will be that combinations of metal and soot should provide an understanding of the interaction between components of combustion sourcederived particles found in ambient air.

The major objective of this study is to determine if the biologic response to inhaled ultrafine particles depended on particle composition. The investigators will focuse on oxidative stress and inflammatory responses in rat lungs and airways after exposure to three different particle compositions: iron, soot, or a combination of iron and soot.

To accomplish these objectives, the investigators will constructe a flame combustion system connected to an animal exposure inhalation unit and generated particles of iron, soot, and combinations of iron and soot. The investigators will characterize the particles physically and chemically. Young adult male rats will be exposed for six hours per day on three consecutive days to: iron particles alone (57 or 90 μg/m3/day); soot particles alone (250 μg/m3/day); a combination of iron and soot particles (250 μg/m3/day total, with an iron concentration of 45 μg/m3); or a filtered air control. Male and female neonatal rats will be exposed for six hours per day for three consecutive days at age 10–12 days and again at age 23–25 days, but only to the combination of iron and soot particles. In one experiment the concentration of iron will be 30 μg/m3 and in the other it was 100 μg/m3; the total concentration of the combination of iron and soot particles was 250 μg/m3/day.

Dr. Pinkerton and coworkers will obtaine bronchoalveolar lavage fluid 2 hours and lung tissue 24 hours after the end of the third day’s exposure, respectively. They will measure several oxidative stress, inflammatory response, and lung injury endpoints.


Main Center Abstract and Reports:

R832347    Health Effects Institute (2005 — 2010)

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R832347C135 Mechanisms of Particulate Matter Toxicity in Neonatal and Young Adult Rat Lungs
R832347C136 Uptake and Inflammatory Effects of Nanoparticles in a Human Vascular Endothelial Cell Line
R832347C138 Health Effects of Real-World Exposure to Diesel Exhaust in Persons with Asthma
R832347C140 Extended Follow-Up and Spatial Analysis of the American Cancer Society Study Linking Particulate Air Pollution and Mortality
R832347C141 Air Pollution Effects on Ventricular Repolarization
R832347C143 Measurement and Modeling of Exposure to Selected Air Toxics for Health Effects Studies and Verification by Biomarkers
R832347C144 Genotoxicity of 1,3-Butadiene and Its Epoxy Intermediates
R832347C145 Effects of Concentrated Ambient Particles and Diesel Emissions on Rat Airways
R832347C147 Atmospheric Transformation of Diesel Emissions