Oxidant Air Pollution Research Articles

Ozone Reactivity and Free Radical Scavenging Behavior of Phenolic Secondary Metabolites in Lichens Exposed to Chronic Oxidant Air Pollution from Mexico City

Lichen secondary metabolites putatively protect lichens from a variety of environmental stress factors, but it is unknown whether these substances respond to air pollution. To assess such a possibility, the three major phenolics of two epiphytic lichen species with contrasting tolerance to chronic air pollution from Mexico City were studied by combining experimental reactivity data and measured field contents. The antioxidant activity and antiradical power of boninic (BO), 2-O-methylsekikaic (MA), and usnic (US) acids, isolated from the tolerant Ramalina asahinae and salazinic acid (SA), atranorin (AT), and chloroatranorin (CA), from the sensitive Parmotrema stuppeum, were determined in vitro by kinetic experiments with ozone and the free radical diphenyl picryl hidrazyl (DPPH*), respectively. In addition, the field contents of these phenolics in the lichens, and the potential antioxidant capacity (PAC) they provide, were compared among three forested sites exposed to urban emissions and a similar, relatively clean site. The six phenolics had antioxidant activity and antiradical power according to these trends: CA >> AT > US > SA > or = BO > or = MA for O(3); and CA > AT > US > MA > SA = BO for DPPH*. The three most reactive phenolics are cortical compounds, located in the lichen portion most exposed to the surrounding environment. In contrast, the less reactive SA, BO, and MA are medullary. Such reactivity patterns indicate that some phenolics may provide antioxidative protection at the air-lichen interface. The higher antioxidant power of CA and AT may be due to the reactive hydroxyl groups at positions 2 and 4 of ring A, instead of the less reactive methoxyl at the same positions in both BO and MA. In the field comparisons, total quantified phenolics were significantly higher near Mexico City for both lichens, except for the tolerant R. asahinae at one site. Nevertheless, only the latter species had significantly increased PAC values at all sites near the city. This result is explained by species-dependent changes in individual phenolics. At the polluted sites, R. asahinae had consistently higher contents of its most reactive phenolic, US, with values approximately twice that of the control site. In contrast, P. stuppeum only increased its less reactive SA (26-35%), but this was counteracted by CA and, to a lesser extent, AT degradation. Thus, the substantial increase in US at the polluted sites appears to be associated with the current ecological success of R. asahinae near the city. On the other hand, the inability of P. stuppeum to overcome degradation of its most reactive phenolic (CA) at the same sites seems to partially explain the declining status of this lichen. These results provide evidence for a protective mechanism in lichens against air pollution based on secondary metabolites, which may eventually determine which species survive in forests stressed by oxidative air pollution.

Mortality Effects of a Copper Smelter Strike and Reduced Ambient Sulfate Particulate Matter Air Pollution

BackgroundNumerous studies have reported associations between fine particulate and sulfur oxide air pollution and human mortality. Yet there continues to be concern that public policy efforts to improve air quality may not produce actual improvement in human health.ObjectivesThis study retrospectively explored a natural experiment associated with a copper smelter strike from 15 July 1967 through the beginning of April 1968.MethodsIn the 1960s, copper smelters accounted for approximately 90% of all sulfate emissions in the four Southwest states of New Mexico, Arizona, Utah, and Nevada. Over the 8.5-month strike period, a regional improvement in visibility accompanied an approximately 60% decrease in concentrations of suspended sulfate particles. We collected monthly mortality counts for 1960–1975 and analyzed them using Poisson regression models.ResultsThe strike-related estimated percent decrease in mortality was 2.5% (95% confidence interval, 1.1–4.0%), based on a Poisson regression model that controlled for time trends, mortality counts in bordering states, and nationwide mortality counts for influenza/pneumonia, cardiovascular, and other respiratory deaths.ConclusionsThese results contribute to the growing body of evidence that ambient sulfate particulate matter and related air pollutants are adversely associated with human health and that the reduction in this pollution can result in reduced mortality.

Multivariate Statistical Analysis of Meteorological and Air Pollution Data in the ‘Campo De Gibraltar’ Region, Spain

A complete statistical analysis of meteorological and air pollution data was carried out in the 'Campo de Gibraltar' region (in the South of Spain) from 1999 to 2002. This is a heavy industrialized area where, up to date, very few air pollution studies have been made. The main objectives of the study presented here have been the characterization of the meteorological and (gaseous and particulate) air pollution conditions in the area, and the relations between them. Multivariate statistical techniques, such as Principal Component Analysis (PCA), have been applied to the data. The results show that air quality in the area is highly dependent on meteorological conditions such as wind persistence and direction, dispersion capability of the atmosphere, and humidity content. On average, sulphur dioxide and nitrogen oxide air pollution, mainly caused by fuel-oil combustion and traffic, respectively, is not very high. However, an important number of exceedences of the limits established by the EU Directive 1999 for PM10 (particulate matter with a diameter less than 10 microm) have been observed in some points of the area. A significant percentage of these exceedences (about 22% on average) are likely caused by African dust intrusions, which usually take place from May to August. From gaseous and particulate air correlations, it seems that anthropogenic activities contribute with about 19% on average.

Cyclic exposure to ozone alters distal airway development in infant rhesus monkeys

Inner city children exposed to high levels of ozone suffer from an increased prevalence of respiratory diseases. Lung development in children is a long-term process, and there is a significant period of time during development when children growing up in urban areas are exposed to oxidant air pollution. This study was designed to test whether repeating cycles of injury and repair caused by episodes of ozone exposure lead to chronic airway disease and decreased lung function by altering normal lung maturation. We evaluated postnatal lung morphogenesis and function of infant monkeys after 5 mo of episodic exposure of 0.5 parts per million ozone beginning at 1 mo of age. Nonhuman primates were chosen because their airway structure and postnatal lung development is similar to those of humans. Airway morphology and structure were evaluated at the end of the 5-mo exposure period. Compared with control infants, ozone-exposed animals had four fewer nonalveolarized airway generations, hyperplastic bronchiolar epithelium, and altered smooth muscle bundle orientation in terminal and respiratory bronchioles. These results suggest that episodic exposure to environmental ozone compromises postnatal morphogenesis of tracheobronchial airways.

Vitamin supplementation does not protect against symptoms in ozone-responsive subjects

Vitamin supplements have been reported to reduce the magnitude of symptoms in subjects exposed to oxidant air pollution. To confirm whether supplementation with vitamins C and E could reduce lung function decrements, airway inflammation, and epithelial injury in subjects sensitive to ozone, a double-blinded, crossover control study was performed. Fourteen ozone-responsive subjects were randomly exposed to both air and ozone (0.2 ppm for 2 h) after 7 days of either placebo treatment or supplementation with vitamin C (500 mg/day) and E (100 mg/day). Lung function was assessed pre- and immediately postexposure and blood samples were taken at set intervals. Inflammatory, tissue injury, and antioxidant responses were examined in lavage fluid obtained by bronchoscopy 6 h postexposure. Exposure to ozone resulted in significant ( P < 0.01) decrements in FEV 1 with no protection observed following vitamin supplementation (−8.5%) versus placebo (−7.3%) treatment. Similarly, ozone-induced neutrophilia were of a similar magnitude after both treatments ( P < 0.05). This lack of protection was observed despite elevated plasma vitamin C (+60.1%) and vitamin E (+51.4%) concentrations following supplementation, and increased vitamin C concentrations in the airways after supplementation following ozone exposure. These data do not therefore support the contention that acute ozone-induced symptoms can be attenuated through the use of dietary antioxidants in well-nourished individuals.

EFFECTS OF OZONE EXPOSURE ON NONSPECIFIC PHAGOCYTIC CAPACITY OF PULMONARY MACROPHAGES FROM AN AMPHIBIAN, BUFO MARINUS

Pulmonary macrophages are an important component of immune defense against inhaled foreign particles and microorganisms. In humans and other mammals, exposure to moderate amounts of ozone (O3) can inhibit functional capacities of alveolar macrophages. In many wilderness areas downwind of urban centers, ozone levels frequently exceed national standards. We report results of 4-h inhalation exposures to 0.8 parts per million O3 on pulmonary macrophage viability and phagocytosis capacity in marine toads, Bufo marinus. At 1 and 24 h after ozone exposure, macrophages had reduced in vitro capacity to phagocytize fluorescent polystyrene microspheres. By 48 h postexposure, there were no differences in these macrophage functions between ozone- and air-exposed toads. Macrophage yield did not differ among exposure groups nor did exposure to elevated temperatures (30 degrees C) for up to 48 h affect recovery of macrophages. However, compared with the millions of macrophages per milliliter recovered in mammals by similar procedures, pulmonary macrophage yield was typically in the range of 50 to 200 x 10(3) per milliliter extracted fluid. These results are the first to report effects of an air pollutant on amphibian immune system function and suggest a possible role of oxidant air pollutants in regional declines of amphibian populations.

Respiratory and behavioral effects of ozone on a lizard and a frog

Ozone at concentrations found in urban air pollution is known to have significant physiological effects on humans and other mammals. Exposure of the lizard, Sceloporus occidentalis, to 0.6 ppm ozone for 4 h at 25 °C induced 1.6 °C of behavioral hypothermia immediately following exposure, but selected body temperature recovered to control 35.3 °C the next day. Lizards exposed at 35 °C to 0.6 ppm ozone for 4 h selected body temperatures 1.9 °C below controls after exposure, and the behavioral hypothermic response persisted and increased to 3.3 °C the following day. Four-hour exposures of the frog, Pseudacris cadaverina, to 0.2 to 0.8 ppm ozone resulted in concentration-dependent alterations of respiration including depression of lung ventilation and oxygen consumption and the adoption of a low profile posture that reduced the exposed body surface. Ozone levels in wilderness habitats downwind of urban sources can potentially have stressful physiological effects on wildlife. Defensive physiological and behavioral reactions to ozone exposure may interfere with routine activities, and oxidant air pollution may be in part responsible for observed wildlife population declines.

In vivo ozone exposure induces antioxidant/stress-related responses in murine lung and skin

Lung and skin are the organs directly exposed to environmental pollution. Ozone (O 3) is a toxic, oxidant air pollutant, and exposure has been shown to induce antioxidant depletion as well as oxidation of lipids and proteins within the outermost skin layer (stratum corneum) and the lung respiratory tract lining fluids (RTLFs). To further define skin and lung responses to O 3 exposure, SKH-1 hairless mice were exposed to either 0.8 ppm of O 3 (a level occasionally reached in very polluted areas) or ambient air 6 h/day for 6 consecutive days. O 3 exposure resulted in the depletion of α-tocopherol in lung and plasma and induction in both skin and lung of heme oxygenase 1, cyclooxygenase 2, and proliferating cell nuclear antigen. O 3-exposed animals showed a similar extent of upregulation of COX-2 and PCNA in lung and skin, whereas HO-1 was more responsive in skin than in lung (7-fold induction vs. 2-fold induction). In addition to these measures of response to oxidative stress, O 3 exposure led to the activation of nuclear factor κB measured as IκBα phosphorylation in both tissues. We conclude that in this model, O 3 at high pollutant levels is able to affect both lung and skin biology, inducing depletion of α-tocopherol and inducing stress-related responses in both skin epidermis and respiratory tract epithelium.

Respiratory tract responses to repeated inhalation of an oxidant and acid gas-particle air pollutant mixture.

The purpose of this study was to examine a broad range of toxicologic responses in rats exposed to a multi-component pollutant atmosphere. Cumulative and adaptive respiratory tract responses to 3 concentrations of an inhaled particle-oxidant mixture were examined in Fisher 344 N rats exposed 4 h/day, 3 days/week for 4 weeks. The mixtures contained O3, NO2, NH4HSO4, carbon particles, and HNO3 vapor. Irritant-induced, rapid-shallow breathing responses were present during the first 4-h exposure to medium and high concentrations. Successive exposures showed diminished responses in medium concentrations and exacerbated responses in high concentrations. At the end of 4 weeks, rats exposed to high concentrations exhibited lung lesions. Lavaged pulmonary macrophages showed dose-dependent depressions of Fc-receptor binding and phagocytosis. Lung tissue macrophages showed dose-dependent increases in acid phosphatase staining density and carbon particles. Respiratory tract clearance of tracer particles was not significantly affected by the exposures. Broncho-alveolar epithelial permeability was increased by the high concentration. Epithelial cell-proliferation labeling showed a dose-dependent increase at all levels of the respiratory tract. Progressively exacerbated breathing-pattern responses at high concentrations were associated with lung lesions and high cell-proliferation labeling in the nose transitional epithelium and terminal bronchioles. Attenuating or adaptive breathing-pattern responses occurred in the presence of smaller, but in many cases still significant, compromise of respiratory functions. Either attenuating or exacerbated breathing-pattern responses can occur in the presence of a significant dose-dependent compromise of other respiratory functions and lung tissue injury.

Oxidant Air Pollution Impacts in the Montane Forests of Southern California

Oxidant Air Pollution Impacts in the Montane Forests of Southern California

Airway inflammatory and antioxidant responses to oxidative and particulate air pollutants - experimental exposure studies in humans.

Airway inflammatory and antioxidant responses to oxidative and particulate air pollutants - experimental exposure studies in humans.

Attenuation of ozone-induced lung injury by interleukin-10

Ozone (O 3), an oxidant air pollutant, is capable of producing pulmonary inflammation and injury. Exposure to O 3 results in the release of inflammatory cytokines including tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) by alveolar macrophages. In addition, O 3 exposure results in an increased expression of the inducible isoform of nitric oxide synthetase (iNOS). Interleukin-10 (IL-10) is an anti-inflammatory cytokine which inhibits the synthesis of TNF-α and IL-1 by macrophages and decreases the expression of iNOS. To test the protective properties of IL-10 in vivo, on the pulmonary injury induced by O 3 exposure, we intratracheally instilled rat recombinant IL-10 1 h prior to O 3 exposure (0.8 ppm×3 h). Approximately 10–12 h following exposure, the animals were sacrificed and the bronchoalveolar lavage fluid (BALF) collected. The quantification of albumin, protein and fibronectin in the BALF provided a means of assessing pulmonary injury while the analysis of the BALF cells reflected the inflammatory response. Ozone exposure resulted in a significant ( P<0.05) increase in BALF albumin, protein and fibronectin content as compared to air-exposed controls. In addition, significant increases in the percentage of BALF polymorphonuclear leukocytes (PMNs) and tissue expression of fibronectin mRNA were observed. The intratracheal instillation of IL-10 prior to O 3 exposure resulted in a significant reduction in BALF albumin, protein and fibronectin content, and lung fibronectin mRNA as compared to O 3 exposure alone. The data shows that IL-10, when given intratracheally, significantly reduces the pulmonary injury following O 3 exposure in the rat. However, since the PMNs and the levels of albumin, protein and fibronectin in the IL-10 treated group did not reach baseline values, we conclude that other mediators of inflammation and injury not regulated by IL-10 also contribute to the pathophysiology of O 3-induced lung injury.

ALTERATION OF EPITHELIAL INTEGRITY, ALKALINE PHOSPHATASE ACTIVITY, AND FIBRONECTIN EXPRESSION IN LUNGS OF RATS EXPOSED TO OZONE

The deleterious effects of ozone (O3), an oxidant air pollutant, in the lung are dependent on dose and exposure duration and generally evolve with time postexposure. This study characterized the time sequence of epithelial injury and fibronectin expression in the lungs of rats exposed to O3. Bronchoalveolar lavage (BAL) fluid was analyzed for alkaline phosphatase and total protein as markers of epithelial injury and increased permeability, and fibronectin for its role in inflammation and lung injury. The results revealed a time-related increase in total protein in the BAL fluid following a 3-h exposure of rats to 1 ppm O3. The increased protein concentrations peaked at 12 h and then declined, but remained significantly higher than control at 24 h postexposure. A similar time-related significant increase also occurred for BAL fibronectin and alkaline phosphatase activity. However, the return of alkaline phosphatase levels to baseline prior to a comparable reduction in protein levels suggests repair of injured cells, but a delay in the formation of epithelial junctions that limit the transfer of serum proteins to air spaces. By cytochemistry, alkaline phosphatase activity was detected in association with lung type II epithelial cells and in BAL polymorphonuclear leukocytes (PMNs), but not in macrophages. While a significant increase in cytochemically detectable alkaline phosphatase resulted from the increase in PMN number following O3 exposure, mononuclear cells constituted the primary cell type responsible for fibronectin mRNA upregulation. While the cytochemical observations support the role of inflammatory cells in the injury process, the comparability of temporal changes in BAL protein, fibronectin, and alkaline phosphatase suggests a mechanistic role for fibronectin in lung injury.

OZONE-INDUCED LUNG INFLAMMATION AND MUCOSAL BARRIER DISRUPTION: TOXICOLOGY, MECHANISMS, AND IMPLICATIONS

The airway epithelial lining serves as an efficient barrier against penetration of exogenous particles and macromolecules. Disruption of this barrier following O3 exposure represents a state of compromised epithelial defenses leading to increased transmucosal permeability. Although the barrier disruption following an acute exposure is transient in nature, the brief period of disruption caused by O3, an oxidant air pollutant, provides an opportunity for facilitated entry of a potentially toxic particulate copollutant(s) across the airway epithelia. The subsequent deposition and retention of the copollutant(s) in the subepithelial compartment for prolonged periods adds the risk of injury due to chronic exposure following an acute episode. Toxicological studies from several laboratories have demonstrated alterations in epithelial permeability, suggestive of barrier disruption, in animals and humans exposed to O3. Inflammatory cells represent another important component of pulmonary defenses, but upon activation these cells can both induce and sustain injury. The recruitment of these cells into the lung following O3 exposure presents a risk of tissue damage through the release of toxic mediators by activated inflammatory cells. Several studies have reported concomitant changes in permeability and recruitment of the inflammatory cells in the lung following O3 exposure. In these studies, an inflammatory response, as detected by an increase in the number of polymorphonuclear leukocytes in the bronchoalveolar lavage (BAL) or in lung parenchyma, was accompanied by either an increased tracer transport across the airway mucosa or an elevation in the levels of total protein and/or albumin in the BAL. The magnitude of response and the time at which the permeability changes and inflammatory response peaked varied with O3 concentration, exposure duration, and the mode of analysis. The responsiveness to O3 also appeared to vary with the animal species, and increased under certain conditions such as physical activity and pregnancy. Some of the effects seen after an acute exposure to O3 were modified upon repeated exposures. The responses following repeated exposures included attenuation, persistence, or elevation of permeability and inflammation. Mechanistic studies implicate chemotactic factors, cellular mediators, and cell-surface-associated molecules in the induction of inflammation and lung injury. In discussing these studies, this review serves to introduce the mucosal barrier functions in the lung, evaluates inflammatory and permeability consequences of O3, addresses mechanisms of inflammatory reactions, and offers alternate viewpoints.

Soluble Carbohydrates and Secondary Phytochemicals in Betula as Affected by SO2-Pollution

Seedlings of closely related birch species Betula pendula and B. resinifera, which have moderate similarity in their phytochemical composition, were exposed to a SO2 concentration of 200 μg m-3 for 24 days to detect their sensitivity and possible induced changes in the amount of primary and secondary phytochemicals. The species deviated from each other in the production of biomass and phytochemicals. The SO2 pollution induced no changes in growth nor in the soluble sugar concentrations in the species. However, the chromatographic analyses showed the moderate reduction in the amount of antioxidative and defensive phenolics, i.e. myricitrin, (+)-catechin, 3,4'-dihydroxypropiophenone and proanthocyanidins in both birch species. These results indicate more pronounced sensitivity of secondary metabolism to SO2 pollution compared with primary metabolism, and the reduced tolerance of birches to other oxidative air pollutants as well as to herbivores in polluted environments.

Genetic analysis of ozone-induced acute lung injury in sensitive and resistant strains of mice.

Epidemiological studies have found air pollution to be associated with excessive mortality, particularly death from respiratory and cardiovascular causes. Interpretation of these findings is controversial, however, because toxicological mechanisms controlling mortality are uncertain. Susceptibility to many air pollutants entails an oxidative stress response. Accordingly, the best-characterized oxidant air pollutant is ozone, which causes direct oxidative damage of lung biomolecules. An underlying characteristic derived from clinical and epidemiological studies of healthy and asthmatic individuals of all ages is marked variability in the respiratory effects of ozone. This susceptibility difference among humans suggests that genetic determinants may control predisposition to the harmful effects of ozone. Mice also vary considerably in their response to ozone. Moreover, ozone-induced differences in strain responses indicate that susceptibility in mice can be genetically determined. Therefore, we used inbred mice to investigate the genetic determinants of acute lung injury. Recombinant inbred (RI) strains derived from A/J (A) mice (sensitive) and C57BL/6J (B) mice (resistant) showed a continuous phenotypic pattern, suggesting a multigenic trait. Quantitative trait locus and RI analyses suggested three major loci linked to ozone susceptibility. Differences in phenotype ratios among the reciprocal back-crosses were consistent with parental imprinting. These findings implicate various genetic and epigenetic factors in individual susceptibility to air pollution.

Effects of oxidant air pollutants on western pine beetle (Coleoptera: Scolytidae) populations in southern California

The attack rates, brood survival, and emergence rates of the western pine beetle, Dendroctonus brevicomis LeConte, and incidence of entomophagus associates, were compared between photochemical oxidant damaged, and apparently healthy, ponderosa pine trees, Pinus ponderosa Dougl. ex Laws in the San Bernardino Forest in Southern California. The results from this study suggest that oxidant-damaged trees attacked by western pine beetle produced about the same total brood with lower initial attacks when compared with healthier trees, whereas the numbers of predators and parasitoids were higher in the healthier trees. This higher productivity trend for western pine beetle is most evident in trees attacked by the first beetle generation. Trees attacked by the second generation, both damaged and healthy, produced much less western pine beetle brood than generation 1 attacked trees, regardless of oxidant damage. The implication of these results is that, in stands with a higher proportion of oxidant damaged trees, a given population of western pine beetle could kill more trees, and increase at a greater rate, than in a stand with a lower proportion of damaged trees.

Chronic inhalation exposure to ozone and nitric acid elevates stress-inducible heat shock protein 70 in the rat lung

The ability of urban oxidant and acid air pollutants to induce heat shock proteins (HSPs) in the mammalian lung is not known. Such proteins are known to be correlated with environmental stress and pathophysiological conditions. In this study, stress-inducible HSP 70 was assessed by slot-blotting in rat lungs ( N = 10 per group) following inhalation exposures for 4 h per day, 3 days per week for 40 weeks to the following pollutants: (a) purified air; (b) 0.15 ppm ozone (O 3); (c) 50 μg/m 3 nitric acid (HNO 3); or (d) a combination of both 0.15 ppm O 3 and 50 μg/m 3 HNO 3. At 24 h following the last exposure, samples from the right apical lobe of the lung were obtained for either slot-blotting or gel electrophoretic separation, subsequent protein immunoblotting, and chemiluminescence detection of HSP 70 levels. Experiments demonstrate that stress-inducible HSP 70 was present constitutively in the control lungs and was separable from the constitutive form of HSP 70. Slot-blotting analysis demonstrate that the O 3 and HNO 3 exposures alone produced significant elevations of HSP 70. Specifically, either O 3 or HNO 3 alone significantly elevated lung stress-inducible HSP 70 levels by 277% and 221%, respectively, above control levels. The group exposed to combined O 3 and HNO 3 showed a 177% elevation in lung stress-inducible HSP 70 that was significantly greater than the group inhaling purified air, but this effect was less than the effects of either pollutant component alone. Moreover, all exposure groups were significantly different from one another. These results indicate that stress-inducible HSP 70 in the rat lung is highly elevated after chronic inhalation exposures to both O 3 and HNO 3 when administered either alone or in combination within the range of urban ambient concentrations.

Effects of oxidant air pollution on Pinus maximartinezii Rzedowski in the México City region

The response of Pinus maximartinezii Rzedowski to photochemical oxidant air pollution was examined using 100 trees, during a 1 year cycle, at Vivero de Coyoacán, a tree nursery located in the south central part of México City, where exposure to polluted air masses has been continuous. The tree response assessment method was based upon documented symptoms of pollutant injury on the foliage. The results showed a homogeneous pattern of health and vigor and only medium sensitivity (based on foliar injury) to photochemical oxidants, although the trees maintained their needles through a three and not the normal 5 year period as at its geographic location of origin (different habitat or environment). Nevertheless, these data suggest that this species of pine could be proposed as good planting material for reforestation in the urban metropolitan area of México city.

Dose-effect models for ozone

Short-term ozone exposure causes lung function decrements, increased airway reactivity, airway inflammation, increased respiratory symptoms and hospital admissions. Exposure to long-term elevated ozone levels seems to be associated with reduced lung function (aging), increase of respiratory symptoms, exacerbation of asthma, and airway cell and tissue changes. Health risk caused by exposure to ozone has been evaluated mainly in a qualitative way by comparing ozone air quality data with health-based guidelines or standards. A preliminary approach to quantifying health risk from short-term exposure to oxidant air pollution has been taken by expert judgement, describing known or expected effects at specific levels of ozone. For quantitative assessment of the health impact of distinct ozone exposure conditions (acute, repeated daily, chronic) specific exposure-dose-response models are being developed which can be linked to human exposure data. Exposure-(dose-)response models using data from epidemiological, human-clinical and animal toxicity studies are presented.