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Project Description |
Why this study?
In 1997, in the EPA's revised NAAQS for PM, they stated that "Although a variety of responses to constituents of ambient PM have been hypothesized to contribute to the reported health effects, the relevant toxicological and human studies published to date have not identified any accepted mechanism(s) that would explain how such relatively low concentrations of ambient PM might cause the health effects reported in the epidemiological literature". Since then, numerous studies have been conducted, exposing isolated cell cultures in vitro, or laboratory animals or human volunteers in vivo.
Our research into many of the published studies examining the effects of particles and particle-derived products using laboratory animal in vivo studies and rodent and human lung cell in vitro exposures has shown that :
- studies with exposure to both particulate and the co-polluting gases in air are very limited
- only one study has included irradiation to produce photochemical transformations, and that was for a diesel exhaust and sulphurous pollutants mixture using UV lights and dogs
- mostly individual sources of particulate matter were studied, that is, only a few chemical species were tested together; and
- only a few species have been tested.
The toxic effects seen in these mostly individual pollutant systems cannot explain the epidemiological findings that have shown airborne particulate matter and gaseous copollutants to be associated with various health effects. These include increased death and hospitalization rates even after correcting for "harvesting effects".
The Nature of the Problem
Many of the gaseous pollutants interact physically and chemically with particulate matter and aerosols, dependent on temperature, sunlight and humidity . These mixtures are often photochemically active during the day producing products which are often much more toxic than the parent components, and producing many unknown products. These interactions can affect the growth of these aerosols, their chemical characteristics and composition, and consequently their toxicity .
The effects of aerosol and gaseous mixtures are not additive effects of single components . New compound components of particulate aerosols are continually being discovered , and therefore, humans are likely exposed to many as yet undetected species. We believe that only chemically-active, airborne particulate can fully address the effect of complex particulate and gaseous pollutant mixtures. Thus, there is a need to develop new techniques to study and test these environmental mixtures of particulate matter and gaseous co-pollutants, for toxicological effects and risk assessment.
These new studies must use more realistic mixtures, that include both freshly generated emissions, and that have chemically active components created in real sunlight, as would be observed in the atmosphere. In addition, in vitro exposure techniques for particulates are needed that can deliver particulates to lung cells without prior suspension in culture medium, and therefore avoiding potential alteration of the particle characteristics.
What We Propose
We propose to conduct a series of outdoor irradiation chamber experiments and lung cell exposures that include:-
simple systems of one gas with and without re-suspended PM (e.g. NBS diesel exhaust particulate, Arizona road dust);
- dark exposure to freshly injected diesel exhaust;
- sunlight irradiated diesel exhaust with and without urban VOC/NOx;
- aerosolized ROFA, and crustal particulate, with and without realistic urban VOC/NOx mixtures of gaseous pollutants, before and after a day of irradiation leading to photochemical transformations and secondary organic aerosol formation; and
- other selected combinations of VOC composition and PM seeds.
In each of these, we will conduct triplet sets of lung cell exposures in which in one exposure path we remove the co-pollutant gases using a large gas striping denuder but pass the particles; in another exposure path we will use particle filtration to remove the particles, but pass the gases; and in a third exposure path we will pass both the gases and particles.
Each of the gas/PM treated streams will be used to conduct in vitro cell exposures by:- direct deposition of PM and gases on lung cells using electrostatic techniques;
- by solid-phase filtration and extraction (such as filters, SPME fibers, cold traps); and
- by liquid-phase collection and concentration (trapping in liquid with various devices such as bubblers).
In vitro cell exposures to air pollutants are a convenient means of screening a large number of types of aerosols, compounds and mixtures. Although important cell-cell interaction may be lost in an in vitro exposure system, several studies have found that human lung cells (lung epithelial cells and alveolar macrophages) exposed to ozone in vitro, produce similar pro-inflammatory mediators to those found in bronchoalveolar lavage fluid of human volunteers, exposed to ozone in vivo. Exposure of respiratory epithelial cells in vitro allows reproducible and controlled exposure conditions of aerosols and gaseous compounds, and can therefore serve as a convenient model to test potential health effect induced by complex mixtures.
In vitro cell approach can be used to determine dose-response and temporal relationships between exposure and a particular endpoint, with an ultimate goal of creating extrapolation models for risk assessment. Analysis of cellular and molecular changes evoked by exposure to air pollutants in vitro can give valuable mechanistic information on the toxic potential of air pollutants.
In addition, interactions among components of complex particulate mixtures could be analyzed in vitro, by comparing cellular responses induced by exposure to "pure particles" or individual compounds to the responses induced by exposure to complex mixtures. Results from these studies will establish that exposure to controlled generated environmental particulate and gaseous mixtures induces responses in human lung epithelial cells that can be used to model potential adverse health effects in humans exposed to complex chemical mixtures of aerosols and gaseous pollutants in the atmosphere.