Comparative Toxicity of Coarse ParticlesEPA 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
The objective of this study is to determine the contribution of coarse particles to the adverse effects associated with exposure to ambient PM. We hypothesize that differences in the toxicity of coarse PM (PM10-2.5) samples are due to the source contributions to the particles, and in testing this hypothesis, we will: 1) measure the differential toxicity of coarse particles both in vitro and in vivo; and 2) identify 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. Our own studies have demonstrated that ambient particles produce toxicity in vitro and the extent of the adverse effects is influenced by particle size as well as the source of the particles. Little research has been published, however, on whether the physico-chemcial properties of coarse particles influence their toxicity in mammalian cells. Thus, while a considerable data base has been established to understand the influence of physico-chemical properties of fine and ultrafine particle toxicity, it will be critical to understand the ability of various coarse particles to produce adverse health effects. In the proposed studies, a group of particle toxicologists will collaborate with a source apportionment epidemiologist/researcher to explore the toxicity of a variety of urban and rural coarse particles in established models of mammalian cell toxicity.
To test the hypothesis that there is a source-, and therefore component-, dependent difference in the toxicity of coarse particles, we will expand our preliminary and ongoing studies which examine the in vitro and in vivo toxicity of a wide range of ambient particles. Our primary approach is to study the toxicity of coarse PM collected from urban and rural sites throughout the U.S. We propose to study coarse particle toxicity in vitro as well as in vivo in a rodent model. The proposed in vitro studies will utilize human pulmonary, vascular, and cardiac primary cells and cell lines and the endpoints will be relevant to epidemiologic evidence of cardiopulmonary morbidity and mortality such as: 1) asthma and 2) vascular cell inflammation. By taking advantage of seasonal and geographical variations in particle makeup, these bioassays will be performed on daily samples of coarse ambient particles in order to evaluate the source contribution of particle components to observed effects. After completion of the in vitro bioassays, a selected subset of coarse particle samples will be used in mouse studies which will utilize aspiration delivery of collected particles (to bypass the filtering function of the nose and upper airways) to assess differential cardiopulmonary toxicity of coarse particles.
As determined in preliminary studies, we expect that coarse particle toxicity will be influenced by a variety of factors including particle components (e.g., crustal material vs. metals vs. biologics), particle concentration, and the differing composition of urban and rural coarse particles. By careful analysis of the several endpoints included in the in vitro and in vivo toxicity experiments, this work will provide key information regarding the toxicity of urban and rural coarse particles and the data obtained in these studies can readily be used for extrapolation to ambient environments. In summary, the results from this proposal address a number of research needs and the proposed work in coarse particle toxicity and exposure assessment will aid decision-making in coarse particle risk assessment.