Exposure to air contaminants is significantly associated with both short-term and long-term health effects. However, the precise mechanisms that derive such effects are not always understood. While an extensive background database from in vivo toxicological studies have been developed, most toxicity data is from oral and dermal chemical exposures rather than inhalation exposure. There is a need to explore new alternative approaches to provide toxicity information particularly on this technically demanding area. This research explores the potential of in vitro methods for toxicity assessment of workplace air contaminants. A tiered approach for in vitro toxicity testing of workplace contaminants was designed in which appropriate air sampling and exposure techniques were developed. A diversified battery of in vitro assays including the MTS (tetrazolium salt, Promega), NRU (neutral red uptake, Sigma) and ATP (adenosine triphosphate, Promega) and a multiple human cell system including: A549- lung derived cells; HepG2-liver derived cells, and skin fibroblasts were used. Primarily the application and merits of in vitro methods for prediction of toxicity of selected workplace contaminants including Ammonium hydroxide, Cadmium chloride, Cobalt chloride, Formaldehyde, Glutaraldehyde, Manganese chloride, Mercuric chloride, Sodium dichromate, Sulphureous acid and Zinc chloride was confirmed. To study the toxicity of airborne contaminants an indirect exposure method was established using air sampling techniques followed by static and dynamic direct exposure methods by culturing cells on porous membranes to reveal representative data relating to human airborne exposures. The static method enabled the measurement of an airborne IC50 (50% inhibitory concentration) value for selected volatile organic compounds (VOCs) including: Xylene (IC50 = 5,350-8,200 ppm) and Toluene (IC50 = 10,500- 16,600 ppm) after 1 hr exposure. By implementing the dynamic method, airborne IC50 values were calculated for gaseous contaminants including: NO2 (IC50 = 11 ?? 3.54 ppm; NRU), SO2 (IC50 = 48 ?? 2.83 ppm; ATP) and NH3 (IC50 = 199 ?? 1.41 ppm; MTS). A higher sensitivity of in vitro methods was observed compared to in vivo published data. A range of in vitro bioassays in conjunction with exposure techniques developed in this thesis may provide an advanced technology for a comprehensive risk assessment of workplace air contaminants.

Some suburbs within North West (NW) metropolitan Adelaide have lung cancer mortality up to twice that expected from state averages. Previous international research investigating high lung cancer rates in similar shared industrial and residential areas have had inconsistent results. This case control study was conducted to determine whether residential exposure to industry is a risk factor for lung cancer in NW Adelaide. Contemporary ambient air monitoring was undertaken as an indicator of future respiratory health risk. 142 lung cancer patients and 415 age, gender matched population controls were interviewed utilising an event history calendar. Lifetime exposure indices were calculated for cigarette smoking, passive smoking, occupation, air pollution (residential proximity to industry) and hobbies. Data was analysed utilising chi- quared and conditional logistic regression. Ambient carcinogens and fine particulates with potential industrial sources in the region were monitored in five locations. In the final multivariate model leaving school early, pack- years of cigarettes and not living in close proximity to the power station or light industrial area were statistically significant risk factors for lung cancer. A composite score of residential exposure to all industries was not significant. However cautious interpretation is required as it was noted participating controls resided significantly closer to industry than non-participants. Average concentrations of ambient carcinogens were within guidelines; however diesel exhaust particulate and Polycyclic Aromatic Hydrocarbons were elevated at sites in proximity to heavy vehicle traffic. Diurnal variations in PM[subscript 2.5] included weather and traffic-related short term peaks, and other peaks potentially related to industrial activity. Cigarette smoking is likely to be the primary cause of elevated lung cancer mortality in suburbs of NW Adelaide. The negative effect of residential exposure to two industries may be due to participation bias. Whilst having more thorough exposure assessment than previous research, this study may have been limited by low participation rates in cases and controls. Air monitoring data suggests there is not a significant public health risk at present; however these results are unlikely to be indicative of historical exposures. Future public health initiatives to curb high lung cancer mortality in the NW should focus on smoking prevention and reduction strategies. / Thesis (Ph.D.)--Department of Medicine and Department of Public Health, 2004.

<p>Emissions from Particles and Volatile Organic Compounds (VOC) in Falun.-How is the emission divided between particles and VOC?</p><p>This study investigates the air quality in Falun, a small city in central Sweden, with a focus on particles and volatile organic compounds (VOC). Falun is located in a valley which makes it sensitive to inversions, when the vertical mixing of air over the city is prevented. When this happens emissions over the city can stay for days and the pollution levels can be high. The report is based upon a literature review, calculation of emissions from traffic and a survey of industrial emissions. Emission of VOCs can be dangerous to people and contributes to the production of ground- level ozone. Particles can be a carrier for other dangerous compounds. The result shows that high pollution levels caused by inversions can happen. The temperature, wind and temperature differences show that inversions during the winter months are possible up to half of the time. Emissions from cars and industries are a problem. The municipality forced to control air pollution and in Swedish law there is a threshold value for both particles and the volatile organic compounds benzene. Spreading of pollution in air in Falun is centered around the emission sourses. Because it´s hard to prevent inversions, the municipality must focus on reducing emission of pollutants. This can be done through road planning and diverting traffic to other routes around the city.</p>

Cloud reflectivity is a function of cloud liquid water content and droplet number concentration. Since cloud droplets form around pre-existing aerosol particles, cloud droplet number concentration depends on the availability of particles that can serve as cloud condensation nuclei. Given constant liquid water amount, increased availability of cloud condensation nuclei leads to clouds with a greater droplet number concentration, greater total droplet surface area and consequently, greater reflectivity. The change in cloud reflectivity resulting from the increased availability of condensation nuclei is known as the aerosol indirect effect. The aerosol indirect effect ranks as one of the largest sources of uncertainty in current estimates of global climate change, largely due to difficulties in measurement. Changes in cloud reflectivity resulting from the aerosol indirect effect are typically much smaller than the natural background variability observed in clouds. As a result, the modification signal is very difficult to detect against the background noise. Additionally, since atmospheric aerosols are ubiquitous, it is difficult to find polluted and nonpolluted clouds that are sufficiently alike for reasonable comparison. However, ship tracks seen in satellite images present one opportunity to study the aerosol indirect effect in relative isolation. Ship tracks are regions of enhanced reflectivity in marine stratus, resulting from the addition of aerosols from ship exhaust plumes to preexisting clouds. Ship tracks are a common feature of satellite images of the North Pacific. Since the marine atmosphere has comparatively low background aerosol concentrations, the addition of ship exhaust particles can lead to distinct increases in cloud reflectivity. Ship tracks allow for sampling of polluted and nonpolluted clouds from adjacent regions with similar solar and viewing geometry, cloud temperatures and surface properties, and consequently provide a unique opportunity to study the effects of aerosol modification of cloud reflectivity. Using satellite images of the North Pacific in July 1999, over 1000 ship tracks were identified, logged and analyzed, yielding 504 sets of radiance data matching polluted clouds with nearby nonpolluted clouds. It was expected that increasing the size of the region for selection of nonpolluted clouds would increase the variability in observed reflectivity, and make detection of the modification signal more difficult. In order to study this potential effect of domain size for selection of nonpolluted clouds on measurements of the aerosol indirect effect, three data sets were collected, using domain sizes for selection of nonpolluted clouds of 15, 50 and 100 km. Analysis of retrieved optical depth and droplet effective radius for modified and control pixels shows evidence of a 1-5% increase in visible optical depth of marine stratus following modification by addition of ship exhaust particles, but unexpectedly, shows only slight increases in uncertainty with increasing domain size. A subsequent study revealed that autocorrelation lengths of radiances and retrieved cloud properties were only 8-15 km. This indicates that even the 15 km control domain captured much of the background variability present. Domain sizes smaller than 15 km are difficult to sample automatically while avoiding the inclusion of polluted clouds in the nonpolluted cloud sample. As a result, it remains necessary to analyze large numbers of ship tracks to separate the aerosol modification signal from the background variability. / Graduation date: 2003

Ambient high-volume (hi-vol) air samples were collected between March 15th and May 30th 2002, at Cheeka Peak Observatory (CPO), located on the tip of the Olympic Peninsula, Washington State. This sampling campaign was in conjunction with the 2002 Inter-Continental Transport and Chemical Transformation (ITCT 2K2) Campaign and the Photochemical Ozone Budget of the Eastern North Pacific Atmosphere (PHOEBA2) experiment, both of which studied the effect of Trans-Pacific transport on the U.S. West Coast. The anthropogenic semi-volatile organic compounds (SOCs) measured during this time period included polycyclic aromatic hydrocarbons (PAHs) and various U.S. current-use and historical-use pesticides. The total PAH concentration ranged from 0.480-4.49 ng/m³, which is comparable to other remote sites throughout the globe. Ten pesticides (hexachlorobenzene, dacthal, chlorothalonil, heptachlor, trans-nonachlor, cis-nonachlor, endosulfan I, triallate, trifluralin, and mirex) were also measured and their concentrations (0.104-57.0 pg/m³) were comparable to other remote sites and less than agricultural areas. Gas-phase/particle-phase partitioning of SOCs was explored, with a significant correlation with temperature found for endosulfan I and retene. A possible relationship at CPO of low total suspended particulate (TSP) concentration with the concentration of non-exchangeable SOCs in the particle phase was found. Principal Component Analysis, as well as a t-test, showed there were elevated concentrations and a unique pattern of anthropogenic SOCs measured during possible Trans-Pacific events on March 15th-16th March 27th-28th and April 22nd-23rd, 2002. These Trans-Pacific events were identified using the GEOS-CHEM model and 10-day back air trajectories. The potential sources of these compounds at CPO were determined using diagnostic ratios of their concentrations, back trajectories calculated using HYSPLIT4, local meteorological conditions, and U.S. pesticide use data. / Graduation date: 2004

In 1990, the Clean Air Act (CAA) Amendments authorized the regulation of 188 hazardous air pollutants (HAP). Exposure to HAPs at sufficient concentrations and durations can increase both cancer and serious adverse non-carcinogenic effects. The purpose of this study was to conduct a human health risk assessment using data of 43 HAPs from five monitor sites in Portland, Oregon during July 1999-August 2000. HAP concentrations were compared to carcinogenic and non-carcinogenic (health) benchmark concentrations; and emission sources were determined for HAPs that exceeded health benchmark concentrations. Additionally, cancer risks were determined for subpopulations and compared to cancer risks generated for the general population. Results of this study indicate that 20 HAPs exceeded carcinogenic benchmark concentrations (corresponding to a risk level of 1 x 10������) in at least one location. Chromium compounds posed the highest cancer risk (3.5 x 10������). Seventeen HAPs exceeded carcinogenic benchmark concentrations at all five sites. Seventy-five percent (%) of the total cumulative cancer risk was contributed by chromium compounds, 1,3-butadiene, formaldehyde and 1,1,2,2-tetrachloroethane. Three HAPs, chromium compounds, acrolein, and formaldehyde, exceeded non-carcinogenic hazard ratios of 1.0. Releases from area sources accounted for the largest percentage of HAPs that exceeded health benchmark concentrations. With respect to subpopulations, asthmatics teenagers (age 11-16) and asthmatic adults (age 18-50), had slightly elevated cancer risks of 1.4 x 10������ and 1.2 x 10������. respectively, compared to the general population risk level of 1 x 10������. Results of this study indicate that several HAPs pose a potential human health concern in Portland and that efforts should be made to reduce their emissions. Additional studies are warranted to further assess potential human health risks and the extent of HAPs in Portland, Oregon. / Graduation date: 2003

Thesis (Doctoral)--Technische Universiteit Delft, 2006. / Includes bibliographical references (p. 221-244). Also issued online.

With the increasing availability of observational data from different sources at a global level, joint analysis of these data is becoming especially attractive. For such an analysis – oftentimes with little prior knowledge about local and global interactions between the different observational variables at hand – an exploratory, data-driven analysis of the data may be of particular relevance. In the present work we used generalized additive models (GAM) in an exemplary study of spatio-temporal patterns in the tropospheric NO2-distribution derived from GOME satellite observations (1996 to 2001) at global scale. We focused on identifying correlations between NO2 and local wind fields, a quantity which is of particular interest in the analysis of spatio-temporal interactions. Formulating general functional, parametric relationships between the observed NO2 distribution and local wind fields, however, is difficult – if not impossible. So, rather than following a modelbased analysis testing the data for predefined hypotheses (assuming, for example, sinusoidal seasonal trends), we used a GAM with non-parametric model terms to learn this functional relationship between NO2 and wind directly from the data. The NO2 observations showed to be affected by winddominated processes over large areas. We estimated the extent of areas affected by specific NO2 emission sources, and were able to highlight likely atmospheric transport “pathways”. General temporal trends which were also part of our model – weekly, seasonal and linear changes – showed to be in good agreement with previous studies and alternative ways of analysing the time series. Overall, using a non-parametric model provided favorable means for a rapid inspection of this large spatio-temporal NO2 data set, with less bias than parametric approaches, and allowing to visualize dynamical processes of the NO2 distribution at a global scale.

Background: Air pollution is associated with negative health effects. Exposure to combustion-derived particulate matter (PM) air pollution has been related to increased incidence of cardiovascular and respiratory morbidity and mortality, specifically in susceptible populations. Ambient particles, with a diameter of less than 2.5 mm, have been suggested to be the strongest contributor to these health effects. Diesel exhaust (DE) is a major source of small combustion-derived PM air pollution world wide.  In healthy volunteers, exposure to DE, has been associated with airway inflammation and impaired vasomotor function and endogenous fibrinolysis. The aims of this thesis were to further elucidate the underlying mechanisms to the reported cardiovascular effects following exposure to DE, with specific focus on endothelin-1 (ET-1). Additionally, the vascular effects of the major gaseous component of DE, nitrogen dioxide (NO2), were assessed together with the impact of an exhaust particle trap to reduce the observed negative vascular effects after DE exposure. Methods: In all studies healthy, non-smoking male volunteers were included and exposed for one hour during intermittent exercise in a randomised double-blind crossover fashion. In studies I-III, subjects were exposed to DE at a particulate matter concentration of approximately 300 μg/m3 and filtered air, on two different occasions. In study V an additional exposure was employed, during which DE was filtered through an exhaust particle trap. In study IV subjects were exposed to nitrogen dioxide (NO2) at 4 ppm or filtered air. In study I, thrombus formation and platelet activation were assessed using the Badimon ex vivo perfusion chamber and flow cytometry. Study II comprised the determination of arterial stiffness including pulse wave analysis and velocity. In studies III-V, vascular assessment was performed using venous occlusion plethysmography. In studies IV and V, the vascular responses to intra-arterially infused endothelial-dependent and endothelial-independent vasodilatators were registered. In study III, vascular responses to intra-arterial infusion of Endothelin-1 (ET-1) and ET-1-receptor antagonists were assessed. Venous occlusion phlethysmography was in all cases performed 4-6 hours following exposures. Blood samples for markers of inflammation, coagulation and platelet activation were collected before and throughout the study periods in studies III and V. Results: Exposure to DE increased ex vivo thrombus formation and arterial stiffness, in terms of augmentation index. DE inhalation impaired vasomotor function and endogenous fibrinolysis. The exhaust particle trap reduced the particle concentration by 98% and abolished the effects on vasomotor function, endogenous fibrinolysis and ex vivo thrombus formation. Plasma concentrations of ET-1 and its precursor big-ET-1 were unchanged following exposure. Dual endothelial receptor antagonism caused similar vasodilatation after both exposures, although vasodilatation to the endothelin-A receptor alone was blunted after DE exposure. ET-1 infusion induced vasoconstriction only following DE exposure. Exposure to nitrogen dioxide did not affect vascular function. Conclusion: Inhalation of diesel exhaust in young healthy men impaired important and complementary aspects of vascular function in humans; regulation of vascular tone and endogenous fibrinolysis as well as increased ex vivo thrombus formation. The use of an exhaust particle trap significantly reduced particle emissions and abolished the DE-induced vascular and prothrombotic effects. The adverse vascular effects following DE exposure do not appear to be directly mediated through the endothelin system. Neither is NO2 suggested to be a major arbiter of the DE-induced cardiovascular responses. Arterial stiffness is a non-invasive and easily accessible method and could thus be employed to address vascular function in larger field studies. Taken together, this thesis has given further knowledge about the mechanisms underlying the DE-induced vascular effects.

It is well established that air pollution has detrimental effects on both human health as well as the environment. Exposure to ozone and particulate matter pollution, is associated with an increase in cardiopulmonary mortality and morbidity. Asthmatics, elderly and children have been indicated as especially sensitive groups. With a global increase in use of vehicles and industry, ambient air pollution represents a crucial health concern as well as a political, economical and environmental dilemma. Both ozone (O3) and diesel exhaust (DE) trigger oxidative stress and inflammation in the airways, causing symptoms such as wheezing, coughing and reduced lung function. The aim of this thesis was to further examine which pro-inflammatory signaling pathways that are initiated in the airways by ozone, as compared to diesel exhaust. Furthermore, to study the effects of these two ambient air pollutants in a sequential exposure, thus mimicking an urban profile. In order to investigate this in healthy as well as asthmatic subjects, walk-in exposure chambers were utilized and various airway compartments were studied by obtaining induced sputum, endobronchial biopsies, or airway lavage fluids. In asthmatic subjects, exposure to 0.2 ppm of O3 induced an increase in the cytokines IL 5, GM-CSF and ENA-78 in the bronchial epithelium six hours post-exposure. The healthy subjects, however, displayed no elevations of bronchial epithelial cytokine expression in response to the ozone exposure. The heightened levels of neutrophil chemoattractants and Th2 cytokines in the asthmatic airway epithelium may contribute to symptom exacerbations following air pollution exposure. When examining an earlier time point post O3 exposure (1½ hours), healthy subjects exhibited a suppression of IL-8 as well as of the transcription factors NFκB and c-jun in the bronchial epithelium, as opposed to after filtered air exposure. This inhibition of early signal transduction in the bronchial epithelium after O3 differs from the response detected after exposure to DE. Since both O3 and DE are associated with generating airway neutrophilia as well as causing direct oxidative damage, it raises the query of whether daily exposure to these two air pollutants creates a synergistic or additive effect. Induced sputum attained from healthy subjects exposed in sequence to 0.2 ppm of O3 five hours following DE at a PM concentration of 300 µg/m3, demonstrated significantly increased neutrophils, and elevated MPO levels, as compared to the sequential DE and filtered air exposure. O3 and DE interactions were further investigated by analyses of bronchoalveolar lavage and bronchial wash. It was demonstrated that pre-exposure to DE, as compared to filtered air, enhances the O3-induced airway inflammation, in terms of an increase in neutrophil and macrophage numbers in BW and higher EPX expression in BAL. In conclusion, this thesis has aspired to expand the knowledge of O3-induced inflammatory pathways in humans, observing a divergence to the previously described DE initiated responses. Moreover, a potentially adverse airway inflammation augmentation has been revealed after exposure to a relevant ambient combination of these air pollutants. This provides a foundation towards an understanding of the cumulative airway effects when exposed to a combination of ambient air pollutants and may have implications regarding future regulations of exposure limits.