Grantee Research Project Results

2010 Progress Report: Comparative Toxicity of Coarse Particles

EPA Grant Number: R833742
Title: Comparative Toxicity of Coarse Particles
Investigators: Gordon, Terry , Lippmann, Morton , Chen, Lung Chi , Ito, Kazuhiko
Institution: New York University School of Medicine
EPA Project Officer: Chung, Serena
Project Period: March 1, 2008 through February 28, 2012
Project Period Covered by this Report: March 1, 2010 through February 28,2011
Project Amount: $1,199,927
RFA: Sources, Composition, and Health Effects of Coarse Particulate Matter (2006) RFA Text |  Recipients Lists
Research Category: Particulate Matter , Air Quality and Air Toxics , Air

Objective:

The objective of this study is to determine the contribution of coarse particles to the adverse health effects associated with exposure to ambient PM.  We hypothesized that differences in the toxicity of coarse PM (PM_10-2.5) samples are due to the source contributions to the particles, and in testing this hypothesis, we are: 1) measuring the differential toxicity of coarse particles both in vitro and in vivo; and 2) identifying whether coarse particles from urban and rural sources differ in toxicity.  A number of investigators have clearly demonstrated that toxicity in the mammalian lung is governed, in part, by particle size, but little research has been published on whether the physicochemical properties of coarse particles influence their toxicity in mammalian cells.  In the proposed studies, a group of particle toxicologists are collaborating with a source apportionment epidemiologist to explore the toxicity of a variety of urban and rural coarse particles in established models of mammalian cell toxicity.

Progress Summary:

The work on the project aims has proceeded smoothly but at a slower pace than anticipated.  The delays have primarily been due to delays in the digestion of PM samples and the trace element analyses of PM samples.  A microwave digestion system was purchased and a protocol developed to more rapidly address the preparation of hundreds of PM samples for ICP-MS analyses of trace elements.  This system has been very efficient and the speciation data will be available in time for source analyses by the study termination in 2012.  Since Year 2, the in vivo bioassays have been completed for the urban and rural NY samples and the in vitro testing of CA Central Valley samples will be completed by late 2011.

As described in the Preliminary Results section (5) below, significant size and site-dependent toxic effects were observed in the in vitro studies for New York PM, but, interestingly, the in vitro results did not predict the in vivo observations in which coarse particles produced significantly greater lung inflammation in mice.  In addition, the in vivo results suggested that the collection season (winter vs. summer) and site (urban vs. rural) do not influence the toxicity of the NY coarse PM samples.

Figure 1. Relative flourenscence intensity increase
over control values for coarse (10-2.5 µm), and
fine (<2.5 µm) PM (50 µg/ml) for 2 urban and 3 
rural sampling sites. Column and bars represent 
mean and SEM for the ROS response in 
vascular endothelial cells. 

Figure 2. Relative fluorenscence intensity (ROS) of coarse
PM (50 µg/ml) from rural and suburban sites collected in
summer and winter. Column and bars represent mean
and SEM for the ROS response in vascular endothelial
cells. 

Figure 3. Relative fluoresence intensity (ROS) of fine PM
(50 µg/ml) from rural and urban sites collected in summer 
and winter. Column and bars represent mean and SEM 
for the ROS response in vascular endothelial cells. 
 

Figure 4. % PMNs (neutrophils) in lung lavage fluid of
mice treated by oropharyngeal aspiration with 50 µg of
fine and coarse PM (50 µg/ml) from 2 rural and 2 suburban
sites collected in winter. Column and bars represent mean  
and SEM. 

Figure 5. % PMNs (neutrophils) in lung lavage fluid of
mice treated by oropharyngeal aspiration with 50 µg of
fine and coarse PM (50 µg/ml) from 2 rural and 2 suburban
sites collected in winter. Column and bars represent mean  
and SEM.  

Future Activities:

As previously reported for the in vitro studies, the proposed in vivo bioassays demonstrated important toxicity differences in the NY samples and that toxicity is dependent on PM size and sampling region (i.e., rural vs. urban) (Figures 1-3).

As reported in Year 2, the in vitro studies showed that the urban PM samples resulted in greater production of reactive oxygen species (ROS, an index of oxidative stress) in lung and microvasculature cells than did rural PM (Figure 1).  PM2.5 produced greater amounts of ROS than did PM10-2.5 collected at the urban sites (Manhattan and Bronx), and this size-dependent effect was strongest in the endothelial cells and was not observed with rural PM (Figure 2).  Seasonal effects on ROS were present in the in vitro studies, but dependent on the collection site (Figures 2 and 3).

Importantly, the predictability of in vivo effects from the in vitro ROS findings was low.  In mice, PM10-2.5 produced significantly greater lung inflammation than did PM2.5 (Figures 4 and 5).  This was observed at both rural and urban sites and was independent of season.  These contrasting in vitro and in vivo results suggest that further bioassays comparing the adverse cardiopulmonary effects of coarse and fine PM collected at rural and urban sites should focus on studies in test animals.  In regards to the relative toxicity of rural vs. urban PM10-2.5 (a major goal of this study), we observed little to no difference in the in vivo toxicity of coarse PM collected at rural vs. urban sites in NY.  These findings need to be confirmed at additional rural and urban sites before application to the protection of the environment and human health.

Sampling for coarse and fine PM was completed at the rural and urban sites in the San Joaquin Valley in central California during Year 2.  These central California samples have been extracted and resuspended are currently being tested in vitro and in vivo and are undergoing microwave digestion for the chemical analyses by ICP-MS.

Journal Articles:

No journal articles submitted with this report: View all 12 publications for this project

Supplemental Keywords:

ambient particulate matter, RFA, Air, Scientific Discipline, Health Risk Assessment, particulate matter, Biology, bioavailability, sensitive populations, sensitive subgroups, atmospheric particles, cardiopulmonary responses, cardiovascular vulnerability, cardiotoxicity, atmospheric particulate matter, chemical speciation sampling, human health effects

Progress and Final Reports:

Original Abstract

2008 Progress Report

2009 Progress Report

Final Report