Individual tailpipe emissions
Transport and fate in the environment
Prevention and control of exposure
Absorption, Metabolism and Molecular Mechanisms of Action
Organ Sites of Toxicity
Absorption and Metabolic Effects of Acute and Chronic Ozone Exposures
Much of the current understanding of the molecular targets of ozone comes from extrapolating animal exposure models to potential human exposures. Ozone reacts with polyunsaturated fatty acids and sulfhydryl, amino and some electron-rich compounds, and these elements are shared across species. Several types of reactions between ozone and these elements are thought to occur and free radicals may be produced in the process. Based on this information, it is believed that the O3 molecule is unlikely to cross the liquid lining of the respiratory tract and reach tissue.
Acute and short-term exposure studies have demonstrated ozones effects on lung lipids which include an increase in acachidonic acid, which when metabolized produces a number of biologically active mediators that have both localized and systemic effects.
Studies have demonstrated an increase in collagen, a structural protein involved in fibrosis, following prolonged ozone exposure. This increase in tissue may affect the exchange of gases to the blood and inhibit certain metabolic functions. Furthermore, both short- and long-term exposure to ozone appears to increase the metabolism of xenobiotics within the lung, the adverse effect of which will depend on the xenobiotic involved.
Both acute and chronic exposures to ozone can negatively impact the barrier function of the lung, and these exposures can initiate an inflammatory response from the immune system. This immune response involves the release of biologically active mediators that can have adverse effects on the lung tissue itself. Some effects may include the thickening of the air-blood barrier in the lungs, thus reducing the diffusion of oxygen into the blood.
Exposure to elevated concentrations of ozone results in deficiencies in the immune response of the respiratory tract, including alveolobronchiolar clearance, biochemical functionality of the alveolar macrophage, and immunologic competence. These changes in host defense have been associated with increased susceptibility to bacterial respiratory infections. However, the incidence of viral respiratory infections has not been exclusively associated with exposure to increased concentrations of ozone.
Elevated concentrations of ozone cause consistent types of alterations in lung structure among the animal models studied. In the lungs, the most affected cells are the ciliated epithelial cells of the airways and Type 1 epithelial cells of the gas-exchange region. Even relatively short-term exposures to low levels of ozone demonstrate significant effects on a hosts cellular defenses, as shown in Figure 1.
The chemical reactivities of ozone make it a potentially genotoxic agent. Results of in vitro studies are difficult to interpret due to the very high concentration of ozone used, but generally these studies demonstrate that ozone; can cause DNA strand breaks, is sometimes weakly mutagenic, and causes cellular transformation and chromosome breakage.
Figure 1. Microscopic views of human lung tissue (epithelium, or lining) show damage resulting from exposure to relatively low levels of ozone. In the control image (upper) from the lung of a person exposed only to air, the tiny cilia that clear the lungs of mucus appear along the top of the image in a neat and regular row. In the lung exposed to 20 ppb of ozone added to the air for four hours during moderate exercise, many cilia appear missing and others appear misshapen. Arrows point to tiny bodies called neutrophils in the ozone-exposed subject. The presence of neutrophils indicates inflammation. Magnification: x400. (American Review of Respiratory Diseases, Vol. 148, 1993, Robert Aris et al., pp. 1368-1369.)
Absorption and Metabolic Effects of Acute and Chronic Particulate Matter (PM) Exposures
Mechanisms of Action
Exposures to ambient PM have been demonstrated to cause changes in heart rate, heart rate variability, and affects the autonomic control of the heart and the cardiovascular system. The inhalation of particulate matter affects the heart by uptake of particles into the circulation or the subsequent release of soluble substances into circulation.
Lung injury from PM exposure was clearly demonstrated in study that examined human exposures before, during, and after the temporary closure of a steel mill in Utah. Intertracheal instillation of filter extract materials in human volunteers provoked greater lung inflammatory responses for material obtained before and after the temporary closing versus that collected during the plant closure. Analysis of the extract materials revealed notably greater quantities of metals for when the plant was open, suggesting that such metals may be important contributors to the pulmonary toxicity of PM exposures in Utah Valley residents.
PM exposures have been associated with increased susceptibility to respiratory infections. Studies in rats have shown increased rates of L. monocytogenes infections in populations exposed to residual-oil-fly-ash (ROFA) compared to populations that were not exposed. Acute exposures to ROFA appeared to slow pulmonary clearance of L. monocytogenes and to alter alveolar macrophage function.
Lung injury from PM exposure can have substantial secondary effects. Lung inflammation can cause the impairment of oxygenation and thereby adversely affect the heart. Furthermore this inflammation can cause adverse systemic hemodynamic effects and can cause increased blood coagulability that can increase the risk of heart attacks and strokes.
The toxicology of PM have not been studied as fully as ozone and current exposure limits are based on the Environmental Protection Agencys 1996 report on Air Quality Criteria for Particulate Matter (http://www.epa.gov/ncea/partmatt.htm).
Health effects of PM have been studied using both human and animal models, but much of the current information has been derived from controlled animal exposures. These studies have examined the effects of particle-associated soluble metals, ROFA, combustion particles, diesel exhaust particles, ultrafine particles, concentrated ambient particles (CAPS), and bioaerosols.
In vitro and in vivo studies have shown that exposures to high concentrations of ROFA or soluble transition metals can result in cellular injury and produce inflammatory changes. Exposure to high concentrations of soluble metals in PM can cause mortality in compromised animals, but some studies suggest that metals are not the only toxic component of ambient PM, rather there may be many different toxic agents that contribute to ambient PM health effects.
There is increasing toxicological evidence that diesel exhaust particles increase the allergic response to inhaled antigens and diesel exhaust has been linked to eosinophil degranulation and induction of cytokine production. These findings indicate that constituents of diesel PM affect and hinder some aspects of the immune response.
Ultrafine PM (less than 0.1 micrometers aerodynamic diameter) trigger a significantly greater inflammatory response when compared with fine particles of the same chemical composition at similar mass doses. Studies have shown that these ultrafine particles can generate greater oxidative stress in animal models, and these effects may be due to the higher surface area of ultrafine particles.
Studies of human and animal exposures have shown that acute or short-term exposures to concentrated ambient particles (CAPS) are capable of inducing a mild inflammation in the lower respiratory tract, as well as increased concentration of blood fibrinogen.