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Adaptations to ozone in reference to mucociliary clearance.

Adaptation to ozone in respiratory tract mucociliary clearance was investigated in this study. Eighty rats inhaled insoluble radioactively labeled particles in order to permit monitoring of clearance. The respiratory tract and the feces were counted for radioactivity at fixed intervals to determine clearance rates. A brief challenge to 1.2 ppm of ozone following particle deposition caused a substantial delay in rapid (mucociliary) clearance. This delay (or "ozone effect") however, was eliminated by brief pre-exposure to 0.8 ppm of ozone 3 days prior to deposition of particles. When a 13-day period intervened between the ozone pre-exposure and challenge, a substantial delay (or "ozone effect") was again seen. Thus, the pre-exposure to ozone appeared to afford essentially complete protection at 3 days, and no protection by 13 days.

Animals↗

Antioxidant and inflammatory response after acute nitrogen dioxide and ozone exposures in C57Bl/6 mice.

Ozone (O(3)) and nitrogen dioxide (NO(2)) are highly reactive and toxic oxidant pollutants. The objective of this study is to compare chemokine, cytokine, and antioxidant changes elicited by acute exposures of O(3) and NO(2) in a genetically sensitive mouse. Eight-week-old C57Bl/6J mice were exposed to 1 or 2.5 ppm ozone or 15 or 30 ppm NO(2) for 4 or 24 h. Changes in mRNA abundance in lung were assayed by slot blot and ribonuclease protection assay (RPA). Messages encoding metallothionein (Mt), heme oxygenase I (HO-I), and inducible nitric oxide synthase (iNOS) demonstrated increased message abundance after 4 and 24 h of exposure to either O(3) or NO(2). Furthermore, increases in message abundance were of a similar magnitude for O(3) and NO(2). Messages encoding eotaxin, macrophage inflammatory protein (MIP)-1alpha, and MIP-2 were elevated after 4 and 24 h of exposure to 1 ppm ozone. Interleukin-6 was elevated after 4 h of exposure to ozone. After 4 h of 2.5 ppm ozone exposure, increased mRNAs of eotaxin, MIP-1alpha, MIP-2, Mt, HO-I, and iNOS were elevated to a higher magnitude than were detected after 1 ppm ozone. Monocyte chemoattractant protein (MCP-1) was elevated following 15 ppm NO(2) exposure. After 4 h of 30 ppm NO(2) exposure, messages encoding eotaxin, MIP-1alpha, MIP-2, and MCP-1 were elevated to levels similar to those detected after ozone exposure. Our results demonstrate a similar antioxidant and chemokine response during both O(3) and NO(2) exposure. Induction of these messages is associated with the duration and concentration of exposure. These studies suggest that these gases exert toxic action through a similar mechanism.

Administration, Inhalation↗

An automated system for exposure of cultured cells and other materials to ozone.

Ozone, a highly reactive oxidant gas, is a major constituent of urban air pollution. Studies of the toxic effects of ozone on cultured cells and other materials are most appropriately conducted under conditions of humidity, temperature, and ozone concentration similar to those in which those materials are naturally exposed. An automated system designed for exposure of cultured cells and other materials to environmentally relevant levels of ozone under nearly physiological conditions is described. Although based on time-proven manually controlled systems, this system is automated using computer programming and hardware that allow unattended operations for extended time periods while maintaining tight control over ozone levels, humidity, and temperature. Experiments were conducted to ensure that the distribution of ozone within the exposure chambers was homogeneous. In addition, experiments were performed to ensure that changes in media volume within the tissue culture plates were minimal, in order to prevent either desiccation of the cultured cells or dilution of the cell culture media. A rocker system is described that allows the tissue culture plates within each exposure vessel to be rocked from end to end to promote mixing of both the gas phase and the liquid phase on each side of the cell culture insert membrane. Since automation of the system allows unattended operation of the system for extended periods, safety systems are described that prevent exposure of investigators to elevated levels of ozone under a variety of system failure conditions.

Animals↗

Association between ozone and respiratory admissions among children and the elderly in Vancouver, Canada.

In this study, we examine the impact of ozone on daily respiratory admissions in both young children and the elderly in greater Vancouver, British Columbia. Study subjects included children less than 3 yr of age and adults 65 yr of age or over living in greater Vancouver who had acute hospital admissions for any respiratory diseases (ICD-9 codes 460-519) during the 13-yr period 1986-1998. Bidirectional case-crossover analysis was used to investigate associations between ambient ozone and respiratory hospitalizations after adjustment for other pollutants, including carbon monoxide, nitrogen dioxide, sulfur dioxide, and coefficient of haze. Potential effect modification by socioeconomic status as measured by household income was also examined. Respiratory admissions were associated with ozone levels 2, 3, 4, and 5 days prior to admission in both children and the elderly, with the strongest association observed at a lag of 4 days. Odds ratios for hospital admission of 1.22 (95% CI: 1.15-1.30) for children and 1.13 (1.09-1.18) for the elderly, respectively, were found, based on an increment in exposure corresponding to the interquartile range for ozone. Adjusting for other pollutants did not attenuate the ozone effect on respiratory admissions. Nor did socioeconomic status appear to modify the association between ozone and respiratory admissions in either children or the elderly. We concluded that ambient ozone is positively associated with respiratory hospital admission among young children and the elderly in Vancouver, British Columbia. These associations persisted after adjustment for both copollutant exposures and socioeconomic status.

Age Factors↗

Characterization of humic substances isolated from Han River water and change in the structural and chemical characteristics by ozonation.

This study investigated the characteristics of extracted humic substances, which are ubiquitous in river waters and affect the treatment of water. Humic substances were extracted from the Han River water and analyzed using the samples obtained before/after ozonation with various analytical items. Ozonation was conducted in a batch-type reactor, and ozone was dosed from 0 to 2.0 mg O3 mg(-1) humic substances. The humic fraction was 56.0% of total organic carbon in the Han River and the ratio of fulvic to humic acids was approximately 3.46, including aromatic ring structures and/or various functional groups. Humic substances could not completely be oxidized to CO2, H2O, etc., but partly oxidized to low molecular weight matter, thus low removal efficiencies in terms of dissolved organic carbon (31% at 1.0 mg O3 mg(-1) humic substances) were observed. For UV absorbance at the wavelength 254 nm, ozone dose at 1.0 mg O3 mg(-1) humic substances showed more than 80% removal efficiencies. The molar ratios of H/C and O/C of the humic substances structure relatively increased by ozonation, indicating the degradation of aromatic groups in the humic substances molecule. The Fourier transform infrared spectra and proton nuclear magnetic resonance spectra of humic substances showed the increase in carboxylic acids and the decrease in aromatic protons through ozonation, respectively. As specific reaction sites in the humic substances including aromatic ring structures were reduced through ozone oxidation, contents of carboxylic acids, ketones and quinones in the humic substances molecule increased.

Bioreactors↗

The role of ozonation and activated carbon filtration in the natural organic matter removal from drinking water.

Aquatic natural organic matter is one of the most important problems in the drinking water treatment process design and development. In this study, the removal of the natural organic matter was followed both in the full-scale drinking water treatment process and in the pilot-scale studies. The full-scale process consisted of coagulation, flocculation and flotation, sand filtration, ozonation, activated carbon filtration and disinfection. The aim of the pilot study was to investigate the influence of the dose and contact time of ozonation, and also the impact of activated carbon filtration, on the removal efficiency of organic matter. Several methods, including high-performance size-exclusion chromatography, total organic carbon content and assimilable organic carbon content measurements were used to characterize the behaviour of organic matter and its removal efficiency. On the full-scale process, total organic carbon was removed by over 90 %. According to size-exclusion measurements, chemical coagulation removed the high molar mass organic matter with an efficiency of 98%. The ozonation further removed the smaller molar mass fraction compounds by about 27%, while residual higher molar mass matter remained quite unaltered. Activated carbon filtration removed primarily intermediate and low molar mass organic matter. In the pilot-tests, conducted with sand filtered water from the full-scale process, it was noticed, that the ozonation removed primarily smaller organic compounds. The amount of assimilable organic carbon increased with increasing ozone dose, up to 0.4 mg l(-1) with the highest ozone dose of 4.0 mg 1(-1). The activated carbon filtration removed the assimilable organic carbon. Total organic carbon content was not reduced in ozonation.

Carbon↗

Protection by ozone preconditioning is mediated by the antioxidant system in cisplatin-induced nephrotoxicity in rats.

BACKGROUND: Acute renal failure is a dose-limiting factor of cisplatin chemotherapy. Here, we show the protective effect of ozone oxidative preconditioning against cisplatin-induced renal dysfunction in rats. Ozone oxidative preconditioning is a prophylactic approach, which favors the antioxidant-pro-oxidant balance for preservation of the cell redox state by increasing antioxidant endogenous systems in various in vivo and in vitro experimental models. AIMS: To analyze the protective role of ozone oxidative preconditioning against cisplatin-induced nephrotoxicity. METHODS: Male Sprague-Dawley rats were pretreated with 15 intrarectal applications of ozone/oxygen mixture at 0.36, 0.72, 1.1, 1.8 and 2.5 mg/kg before cisplatin intraperitoneal injection (6 mg/kg). Serum and kidneys were extracted and analyzed 5 days after cisplatin treatment for determinations of the renal content of glutathione, thiobarbituric acid-reactive substances, renal concentration and enzymatic activities of catalase, superoxide dismutase and glutathione peroxidase. RESULTS: Ozone pretreatment prevented the increase in serum creatinine levels, the glutathione depletion and the inhibition of superoxide dismutase, catalase and glutathione peroxidase activities induced by cisplatin in the rat kidney. Also, the renal content of thiobarbituric acid-reactive substances was decreased by ozone therapy. These protective effects of ozone were dose dependent. CONCLUSIONS: Intrarectal ozone therapy prevented effectively the renal antioxidant unbalance induced by cisplatin treatment.

Animals↗

Ozone as Janus: this controversial gas can be either toxic or medically useful.

Ozone is an intrinsically toxic gas and its hazardous employment has led to a poor consideration of ozone therapy. The aim of this review is to indicate that a wrong dogma and several misconceptions thwart progress: in reality, properly performed ozone therapy, carried out by expert physicians, can be very useful when orthodox medicine appears inadequate. The unbelievable versatility of ozone therapy is due to the cascade of ozone-derived compounds able to act on several targets leading to a multifactorial correction of a pathological state. During the past decade, contrary to all expectations, it has been demonstrated that the judicious application of ozone in chronic infectious diseases, vasculopathies, orthopedics and even dentistry has yielded such striking results that it is deplorable that the medical establishment continues to ignore ozone therapy.

Animals↗

Urban ozone plumes and population distribution by income and race: a case study of New York and Philadelphia.

Who lives in the downwind areas of urban ozone plumes? Location theory suggests that the poor should disaproportionately populate the downwind area, while the rich are most likely to live outside urban ozone plumes. Dynamically, we would expect that the downwind area would become poorer over time because the rich would "vote with their feet" under the serious impacts of urban ozone plumes. However, the importance of urban ozone pollution could be discounted due to the public's risk perception. According to risk and air quality perception literature, one would expect that the public would likely perceive ozone air pollution as a relatively low risk, compared with other environmental risks and social concerns. Therefore, actual population distribution might not follow what location theory suggests. Who actually does live in the downwind areas of urban ozone plumes? The results from a case study of New York and Philadelphia show that the ozone downwind areas are currently populated by a considerably larger proportion of upper income households and whites than the source areas. Furthermore, the population dynamics data do not provide any evidence for the "vote with their feet" hypothesis. While these findings deviate from the hypotheses prescribed by location theory, they are consistent with what we could expect from theories of risk perception.

Air Pollutants↗

Application of the Urban Airshed Model to forecasting next-day peak ozone concentrations in Atlanta, Georgia.

Twenty-four to forty-eight-hour ozone air quality forecasts are increasingly being used in metropolitan areas to inform the public about potentially harmful air quality conditions. The forecasts are also behind "ozone action day" programs in which the public and private sectors are encouraged or mandated to alter activities that contribute to the formation of ground-level ozone. Presented here is a low-cost application of the Urban Airshed Model (UAM), an Eulerian 3-dimensional photochemical-transport grid model for generating next-day peak ozone concentration forecasts. During the summer of 1997, next-day peak ozone concentrations in Atlanta, GA, were predicted both by a team of eight forecasters and by the Urban Airshed Model in Forecast Mode (UAM-FM). Results are presented that compare the accuracy of the team and the UAM-FM. The results for the summer of 1997 indicate that the UAM-FM may be a better predictor of peak ozone concentrations when concentrations are high (> 0.095 ppmv), and the team may be a better predictor of ozone concentrations when concentrations are low (< or = 0.095 ppmv). The UAM-FM is also discussed in the context of other forecasting tools, primarily linear regression models and a no-skill, persistence-based technique.

Forecasting↗

Ozone injection into an activated carbon bed to remove hydrogen sulfide in the presence of concurrent substances.

Adsorption using activated carbon is one of the most reliable techniques for preventing odor by substances such as H2S. Concurrent substances in effluent gas often reduce the removal capacity of activated carbon for H2S. As a means of restoring capacity under such conditions, ozone injection into an activated carbon column was examined. When activated carbon was saturated with substances such as toluene, ethanol, n-butanol, or iso-butanol, its capacity to remove H2S decreased in proportion to the amount of the saturating substance. Under such conditions, ozone injection greatly increased capacity. Toluene, which is not easily decomposed by ozone, was displaced by ozone and by oxidized products of H2S. Ethanol, which is adsorbed in small amounts by activated carbon and easily decomposed by ozone, was removed by ozone injection. Butanols, which are also decomposed by ozone and adsorbed in large quantities by activated carbon, showed intermediate behavior between that of toluene and ethanol.

Adsorption↗

Modeling the effects of VOC/NOx emissions on ozone synthesis in the cascadia airshed of the Pacific Northwest.

A modeling system consisting of MM5, Calmet, and Calgrid was used to investigate the sensitivity of anthropogenic volatile organic compound (VOC) and oxides of nitrogen (NOx) reductions on ozone formation within the Cascadia airshed of the Pacific Northwest. An ozone episode that occurred on July 11-14, 1996, was evaluated. During this event, high ozone levels were recorded at monitors downwind of Seattle, WA, and Portland, OR, with one monitor exceeding the 1 hr/120 ppb National Ambient Air Quality Standard (at 148 ppb), and six monitors above the proposed 8 hr/80 ppb standard (at 82-130 ppb). For this particular case, significant emissions reductions, between 25 and 75%, would be required to decrease peak ozone concentrations to desired levels. Reductions in VOC emissions alone, or a combination of reduced VOC and NOx emissions, were generally found to be most effective; reducing NOx emissions alone resulted in increased ozone in the Seattle area. When only VOC emissions were curtailed, ozone reductions occurred in the immediate vicinity of densely populated areas, while NOx reductions resulted in more widespread ozone reductions.

Air Movements↗

Mechanisms of ozone toxicity in cultured cells. I. Reduced clonogenic ability of polyunsaturated fatty acid-supplemented fibroblasts. Effect of vitamin E.

The direct action of ozone on viability and survival of normal and modified mouse lung fibroblasts has been studied. By cell manipulation of fibroblasts in culture, the content of polyunsaturated fatty acids (PUFA) in the phospholipids was increased from about 6% to about 40%. The cellular content of alpha-tocopherol (alpha-T) (vitamin E) could be drastically enhanced. Vitamin E supplementation to the cell did not influence the PUFA manipulation. Normal, PUFA, and PUFA(alpha-T) fibroblasts were exposed to ozone by bubbling 10 ppm through the cell suspensions for different periods of time (0-6 h). No significant effects of the ozone exposure could be established when normal fibroblasts were used. The PUFA fibroblasts, however, were very vulnerable to ozone toxicity, both in terms of dye uptake (Trypan blue) and cell death (clonogenic ability). When alpha-tocopherol was present in the cell (200 ng/10(6) cells), a clear protection against ozone toxicity was found. It is concluded that ozone toxicity might be higher under conditions of a relative high amount of polyunsaturated fatty acids in the membrane phospholipids of the cell and a low cellular antioxidant capacity. Cellular membranes are probably an important target for ozone-induced cell death.

Animals↗

Surface-tension measurements of pulmonary lavage from ozone-exposed rats.

Ozone, an important component of photochemical air pollution, has been shown to cause morphological and functional changes in the lung after acute, high-level exposure in controlled animal studies. Previous exposures of rats to 0.8 ppm ozone for 18 h showed trends toward decreased lung volumes, as well as modifications in phospholipid composition of lung lavage fluid. These results suggested that exposure to ozone may have diminished the ability of surfactant to reduce surface tension. The purpose of this pilot study was to determine if changes in the surface tension of lavaged pulmonary surfactant occur with ozone exposure. The lavage fluid from rats exposed to ozone at 0.8 ppm for 18 h had a 360% increase in protein and a 30% increase in lipid phosphorus content. Lung lavage samples from ozone-exposed rats were more potent in reducing surface tension as measured on a Wilhelmy plate balance. This difference was evident whether determined with half the total lavage or with equivalent microgram amounts of lipid phosphorus. It is concluded that at this dose and duration of ozone exposure, contrary to our hypothesis, surface-tension-lowering ability of surfactant increases and therefore does not appear to be a contributory factor in the previously observed changes in pulmonary function.

Animals↗

Acute and subchronic ozone inhalation in the rabbit: response of alveolar macrophages.

Ozone is a potent oxidant gas and a common constituent of photochemical smog. This investigation evaluated the numbers and functional capabilities of alveolar macrophages (AM) recovered from rabbits undergoing acute and subchronic ozone exposure. Bronchoalveolar lavage was performed immediately, 24 h, and 7 d after acute (2-h) exposure to 0.1 or 1.2 ppm ozone, and on d 3, 7, and 14 during subchronic (2 h/d X 13 d) exposure to 0.1 ppm ozone. After acute exposure to 1.2 ppm, a marked increase in lavaged neutrophils was observed at 24 h. A single exposure to 0.1 ppm resulted in increased AM at 7 d, while repeated exposures resulted in an increase in AM and neutrophils on d 7 and 14. AM phagocytosis was depressed immediately and 24 h after acute exposure to 0.1 ppm, and at all time points after exposure to 1.2 ppm. Repeated exposures to 0.1 ppm produced reductions in the numbers of phagocytically active AM on d 3 and 7, with a return to control levels by d 14. Substrate attachment by AM was impaired immediately after exposure to 1.2 ppm; AM mobility was not altered by any of the ozone exposures. The results of these studies demonstrated significant alterations in the numbers and functional properties of AM as a result of single or repeated exposure to 0.1 ppm ozone, a level below the current National Ambient Air Quality Standard. These findings indicate that levels of ozone frequently encountered in areas of high photochemical air pollution can elicit a pulmonary inflammatory response and can impair pulmonary defense capabilities.

Administration, Inhalation↗

Response of T-cell-deficient mice to ozone exposure.

The number, appearance, and functional reactivity of T-lymphocytes of mediastinal lymph nodes are altered during experimental ozone inhalation. The purpose of the present work is to determine how the lymph nodes and lungs of a mutant strain of animal, which lacks this type of cell, differ in their response to ozone exposure when compared with animals that possess a normal complement of lymphocytes. We exposed athymic nude (nu/nu) mice or heterozygous (nu/+) euthymic mice to 0.7 ppm ozone for 20 h/d for 7 or 14 d while maintaining control groups in clean air. At 7 d the lymph-node hyperplastic response normally seen in euthymic, ozone-exposed animals was greatly reduced in exposed athymic animals. By both 7 and 14 d, greater damage had occurred in the lungs of ozone-exposed, athymic animals than in similarly exposed euthymic animals. Lung wet weight divided by body weight, which was used as a general indicator of lung damage, increased by substantially more in athymic animals than in conventional animals. In a parallel manner, quantitative microscopic analysis, a more sensitive indicator, revealed a marked increase in the lung lesion volumes. Qualitative histologic analysis showed that the change in the response in the athymic animal was most prominent in the peripheral region of the lung extending from the alveolar duct to the alveoli, and was characterized by a greater acute inflammatory cell reaction. Possible mechanisms by which the T-cell could produce the observed effect include secretion of factors that enhance inherent resistance of the lung's target cells, or alterations in the way the inflammatory response to ozone-mediated damage occurs. The results support the idea that the mediastinal lymph node lymphocyte response is adaptive in nature and aids in protecting the lung from ozone-mediated effects.

Animals↗

Qualitative and quantitative changes in cytochrome P-450-dependent xenobiotic metabolism in pulmonary microsomes and isolated Clara cell populations derived from ozone-exposed rats.

The effect of a prolonged ozone exposure (1.6 mg ozone/m3; 7 d; 24 h/d) on pulmonary cytochrome P-450-dependent xenobiotic metabolism was studied both in whole rat lung as well as in isolated bronchiolar Clara cell preparations. Ozone exposure was demonstrated to result in significant quantitative but also qualitative changes. All components of the pulmonary microsomal electron transport system appeared to be significantly increased in the lungs of exposed animals both per lung and per gram lung, although increases were no longer observed when expressed per milligram microsomal lung protein. Remarkably, it was demonstrated that the increases in the components of the pulmonary cytochrome P-450 system were not accompanied by a concomitant increase in all cytochrome P-450-dependent substrate conversions. In whole-lung microsomes ethoxycoumarin O-deethylase and ethoxyresorufin O-deethylase activities were unchanged or even significantly reduced when expressed per lung, per gram lung, per milligram microsomal protein, or per picomole cytochrome P-450. In contrast to these observations, pentoxyresorufin O-dealkylation appeared to be significantly increased upon ozone exposure when expressed per lung, per gram lung, and even per picomole cytochrome P-450. Clara cell populations isolated from ozone exposed rats showed a comparable qualitative shift in cytochrome P-450-dependent substrate conversion characteristics. On a cellular basis, ozone exposure resulted in a significant reduction of ethoxycoumarin and ethoxyresorufin O-deethylation and did not affect pentoxyresorufin O-dealkylase activity. Additional experiments, in which ozone-mediated inactivation of microsomal cytochrome P-450-dependent substrate metabolism was studied in vitro, demonstrated that the qualitative changes observed after in vivo exposure cannot be ascribed to a disproportional inactivation of different cytochrome P-450 isoenzymes. Based on these results and on lung morphometrics and cell isolation data presented, the observed effects should rather be ascribed to (1) the proliferation of cytochrome P-450 containing cell populations and (2) intrinsic cellular biochemical changes. The quantitative and qualitative ozone-induced changes in pulmonary cytochrome P-450-linked enzyme characteristics in whole lung and within specific lung cells, as demonstrated in the present study, may be expected to have important implications for the toxicity of xenobiotics whose (de)toxification depends on pulmonary cytochrome P-450-dependent metabolism.

Animals↗

Preexposure to ozone blocks the antigen-induced late asthmatic response of the canine peripheral airways.

The influence of exposure of the airways to ozone on acute allergic responsiveness has been investigated in several species. Little is known, however, about the effect of this environmental pollutant on the late asthmatic response (LAR) in animals in which it is exhibited. The purpose of this study was to evaluate this effect in the canine peripheral airways and to assess the potential role of mast cells in modulating the effect. A series of experiments on seven mongrel dogs demonstrated that the numbers of mast cells at the base of the epithelial region of small subsegmental airways exposed to 1 ppm ozone for 5 min were significantly (p less than .01) increased 3 h following exposure compared to air exposed or nonexposed control airways. In a second series of experiments performed on eight additional mongrel dogs with inherent sensitivity to Ascaris suum antigen, antigen aerosol was administered to the sublobar segment 3 h following ozone preexposure when mast cell numbers were presumed to be increased. These experiments were performed to determine whether ozone preexposure could enhance the late-phase response to antigen by virtue of acutely increasing the number of mast cells available to bind the antigen. Four of the eight dogs tested displayed a late-phase response to antigen following air-sham preexposure. In these four dogs, simultaneous ozone preexposure of a contralateral lobe completely blocked the late-phase response to antigen. These results indicate that the consequences of a single exposure to ozone persist beyond its effects on acute antigen-induced bronchoconstriction and extend to the complex processes involved with the late response. This attenuating effect of ozone is seen under conditions where mast-cell numbers in the airways are increased above baseline levels.

Administration, Inhalation↗