Final Report: Comparative Toxicity of Coarse Particles

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

Objective:

The objective of this study was to determine the contribution of coarse particles (PM10-2.5) to the adverse health effects associated with exposure to ambient PM. The aims and objectives were not changed from the original submission. We hypothesized that differences in the toxicity of coarse PM samples are due to the source contributions to the particles, and in testing this hypothesis, we: (1) measured the differential toxicity of coarse particles both in vitro and in vivo; and (2) identified whether coarse particles from urban and rural sources differ in toxicity. A number of investigators have clearly demonstrated that PM 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 collaborated 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.

Summary/Accomplishments (Outputs/Outcomes):

Sampling: Sampling for coarse and fine PM was completed at the rural and urban sites in the New York City metropolitan area and the San Joaquin Valley in central California during Years 1 and 2, respectively.  In general, as shown in Table 1, PM2.5 (fine PM) made up the largest portion of ambient PM at the NYC urban and rural sampling sites. At one urban and one rural site in both New York and California, PM greater than 10 µm (i.e., super coarse PM) was collected. While these data are limited, super coarse PM (PM>10) made up significant portions of total ambient PM. By mass concentration, 22% of the total PM at the rural farm site in Walkill was super coarse PM. Unexpectedly, a larger fraction of total PM (30%) was comprised of super coarse PM for the urban residential sampling site in the Bronx. Consistent season-dependent differences in the ambient concentrations of coarse and fine PM were observed for the New York sampling sites. In general, Winter fine PM concentrations were higher than summer values for all 5 New York sites.

Only one ‘season’ was studied in the San Joaquin Valley in central California, but similar to the New York sites, fine PM made up a greater proportion of the ambient PM for 4 of the 5 sites (Figure 1). The mean mass was greater for coarse PM at the coastline sampling site (Trinidad) and was likely a result of aerosols generated by the ocean waves. Interestingly, the maximum amount collected over any of the 2-3 day periods was generally twice the mean value except for the super coarse PM fraction collected at the rural Tranquility site.  During this sampling period, tilling of farm fields and high winds were recorded. Thus, a novel observation of this study was the magnitude of the relative mass concentration of super coarse PM, a size fraction that has received little to no attention in any previous investigations, at both urban and rural sites.

New York Bio-Assay Results:

Summary: Significant size and site-dependent toxic effects were observed in the in vitro studies with 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) or site (urban vs. rural) do not influence the toxicity of the New York coarse PM samples.

In vitro: 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. Fine PM produced greater amounts of ROS than did coarse (i.e., PM10-2.5) collected at the urban sites (Manhattan and Bronx), and this size-dependent effect was strongest in the endothelial cells and not observed with rural PM (Figure 1).

Figure 1. The effect of season on ROS production by coarse (A) and fine (B) PM samples. Vascular endothelial cells were exposed to 50 mg/mL PM (in triplicate) for 5 hours. Data represent the mean relative fluorescence unit ± SEM. * p-value < 0.05, *** p-value < 0.005.

In vivo response in mice vs. in vitro ROS response: In addition to using cell models to assess PM toxicity, a mouse model was used to assess the effect of coarse and fine PM on % PMNs and total protein in lavage fluid. The animal toxicity data were generated on a subset of PM samples. As noted above, the greatest ROS responses were observed in the urban locations for the fine PM fraction. In comparison, however, the largest degree of inflammation in the mouse lungs, represented by the % PMNs in lavage fluid, occurred with the coarse PM fraction. At all locations, the coarse PM samples produced significantly greater inflammation than the corresponding fine PM samples. In terms of locale, coarse and fine PM from both urban and rural locales produced significant increases in % PMNs compared to controls, although coarse PM responses were also significantly greater than the corresponding fine PM responses

Importantly, the predictability of in vivo effects from the in vitro ROS findings was very low. Whereas fine PM produced greater ROS for the New York urban sites, in mice, coarse PM produced significantly greater lung inflammation than did fine PM at both the urban and rural sites. These contrasting in vitro and in vivo results with New York PM 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 coarse PM (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 New York. These findings need to be confirmed at additional rural and urban sites before application to the protection of the environment and human health.

The toxicity of super coarse PM was dependent on the bioassay and collection site. For ROS activity, the in vitro response to super coarse PM was significantly less than that of the coarse and fine PM collected in the Bronx, while little to no size-dependent effect on ROS was found for the rural Walkill site. However, for the in vivo bioassay, the findings were completely different. The observation of a highly significant size-dependent difference in % PMNs in mice treated with fine or coarse PM was extended to the response to super coarse PM and, in fact, the inflammatory response (% PMNs) was significantly greater in mice treated with super coarse PM compared to mice treated by aspiration with the other 2 size fractions.

California Bio-Assay Results:

Summary: 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, resuspended, and microwave digested but are awaiting chemical analyses by ICP-MS. In vitro and in vivo bioassays have been completed.

In vitro: Significant size and site-dependent toxic effects were observed in the ROS studies for the Central California (San Joaquin Valley) PM samples. As observed with the New York PM samples, the urban PM samples collected in Central California (Clovis/Fresno, Bakersfield, and Davis) elicited the greatest ROS response in endothelial cells (Figure 2). Surprisingly, the coarse PM samples produced significantly greater ROS activity than the fine PM samples. As observed with the New York PM samples, coarse PM elicited significantly greater PMNs in the lavage fluid of mice treated with PM by oropharyngeal aspiration. The super coarse PM from the urban (Bakersfield) and rural (Tranquility) sites produced even greater lung inflammation and, importantly, the level of lung inflammation paralleled the amount of endotoxin measured in the extracted PM samples (i.e., super coarse > coarse > fine) (data not shown).

Figure 2. Comparison of the effect of urban and rural PM collected in Central CA on ROS activity in vascular endothelial cells (mean ± SE).


Journal Articles on this Report : 4 Displayed | Download in RIS Format

Other project views: All 12 publications 4 publications in selected types All 4 journal articles
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Journal Article Bleck B, Tse DB, Gordon T, Ahsan MR, Reibman J. Diesel exhaust particle-treated human bronchial epithelial cells upregulate Jagged-1 and OX40 ligand in myeloid dendritic cells via thymic stromal lymphopoietin. The Journal of Immunology 2010;185(11):6636-6645. R833742 (Final)
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  • Journal Article Bleck B, Grunig G, Chiu A, Liu M, Gordon T, Kazeros A, Reibman J. MicroRNA-375 regulation of thymic stromal lymphopoietin by diesel exhaust particles and ambient particulate matter in human bronchial epithelial cells. The Journal of Immunology 2013;190(7):3757-3763. R833742 (Final)
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  • Journal Article Mirowsky JE, Jin L, Thurston G, Lighthall D, Tyner T, Horton L, Galdanes K, Chillrud S, Ross J, Pinkerton KE, Chen LC, Lippmann M, Gordon T. In vitro and in vivo toxicity of urban and rural particulate matter from California. Atmospheric Environment 2015;103:256-262. R833742 (Final)
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  • Journal Article Mirowsky J, Hickey C, Horton L, Blaustein M, Galdanes K, Peltier RE, Chillrud S, Chen LC, Ross J, Nadas A, Lippmann M, Gordon T. The effect of particle size, location and season on the toxicity of urban and rural particulate matter. Inhalation Toxicology 2013;25(13):747-757. R833742 (Final)
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  • Supplemental Keywords:

    toxicology, lung, air pollution;, RFA, Scientific Discipline, Air, particulate matter, Health Risk Assessment, Biology, atmospheric particulate matter, sensitive populations, atmospheric particles, cardiopulmonary responses, human health effects, bioavailability, cardiovascular vulnerability, sensitive subgroups, cardiotoxicity, exposure assessment

    Progress and Final Reports:

    Original Abstract
  • 2008 Progress Report
  • 2009 Progress Report
  • 2010 Progress Report