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2 INTEGRATIVE SUMMARY

1 This Integrated Science Assessment (ISA) forms the scientific foundation for the review 

2 of the national ambient air quality standards (NAAQS) for ozone (O3). The ISA is a 

3 concise evaluation and synthesis of the most policy-relevant science, and it 

4 communicates critical science judgments relevant to the review of the NAAQS for O3. 

5 The ISA accurately reflects “the latest scientific knowledge useful in indicating the kind 

6 and extent of identifiable effects on public health which may be expected from the 

7 presence of [a] pollutant in ambient air” (CAA, 1990a). Key information and judgments 

8 contained in prior Air Quality Criteria Documents (AQCD) for O3 are incorporated into 

9 this assessment. Additional details of the pertinent scientific literature published since the 

10 last review, as well as selected older studies of particular interest, are included. This ISA 

11 thus serves to update and revise the evaluation of the scientific evidence available at the 

12 time of the completion of the 2006 O3 AQCD. The current primary O3 standard includes 

13 an 8-hour (h) average (avg) standard set at 75 parts per billion (ppb). The secondary 

14 standard for O3 is set equal to the primary standard. Further information on the legislative 

15 and historical background for the O3 NAAQS is contained in the Preface to this ISA.

16 This chapter summarizes and synthesizes the newly available scientific evidence and is 

17 intended to provide a concise synopsis of the ISA conclusions and findings that best 

18 inform consideration of the policy-relevant questions that frame this assessment 

19 (presented in Section 2.1). It includes:

20  An integration of the evidence on the health effects associated with short- and 

21 long-term exposure to O3, discussion of important uncertainties identified in 

22 the interpretation of the scientific evidence, and an integration of health 

23 evidence from the different scientific disciplines and exposure durations.

24  An integration of the evidence on the ecological and welfare effects associated 

25 with exposure to O3, and discussion of important uncertainties identified in the 

26 interpretation of the scientific evidence.

27  Discussion of policy-relevant considerations, such as potentially at-risk 

28 populations and concentration-response relationships. 

2.1 Policy-Relevant Questions for O3 NAAQS Review

29 The draft Integrated Review Plan for the Ozone National Ambient Air Quality Standards 

30 (IRP) (U.S. EPA, 2009c) identified key policy-relevant questions that provide a 

31 framework for this assessment of the scientific evidence. These questions frame the entire 
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1 review of the NAAQS for O3 and thus are informed by both science and policy 

2 considerations. The ISA organizes, presents, and integrates the scientific evidence which 

3 is considered along with findings from risk analyses and policy considerations to help the 

4 U.S. Environmental Protection Agency (EPA) address these questions during the 

5 NAAQS review. In evaluating the health evidence, the focus of this assessment is on 

6 scientific evidence that is most relevant to the following questions taken directly from the 

7 Integrated Review Plan:

8  To what extent has new scientific information become available that alters or 

9 substantiates our understanding of the health effects associated with various 

10 time periods of exposure to ambient O3, including short-term (1-3 hours), 

11 prolonged (6-8 hours), and chronic (months to years) exposures?

12  To what extent has new scientific information become available that alters or 

13 substantiates our understanding of the health effects of O3 on at-risk 

14 populations, including those with potentially increased susceptibility such as 

15 children and disadvantaged populations?

16  To what extent has new scientific information become available that alters or 

17 substantiates conclusions from previous reviews regarding the plausibility of 

18 adverse health effects caused by O3 exposure?

19  At what levels of O3 exposure are health effects observed? Is there evidence of 

20 effects at exposure levels lower than those previously observed, and what are 

21 the important uncertainties associated with that evidence? What is the nature 

22 of the exposure-response relationships of O3 for the various health effects 

23 evaluated?

24  To what extent has new scientific information become available that alters or 

25 substantiates our understanding of non-O3-exposure factors that might 

26 influence the associations between O3 levels and health effects being 

27 considered (e.g., weather-related factors; behavioral factors such as heating/air 

28 conditioning use; driving patterns; and time-activity patterns)?

29  To what extent do risk and/or exposure analyses suggest that exposures of 

30 concern for O3-related health effects are likely to occur with current ambient 

31 levels of O3 or with levels that just meet the O3 standard? Are these 

32 risks/exposures of sufficient magnitude such that the health effects might 

33 reasonably be judged to be important from a public health perspective? What 

34 are the important uncertainties associated with these risk/exposure estimates?

35  To what extent have important uncertainties identified in the last rulemaking 

36 been addressed and/or have new uncertainties emerged?
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1 In evaluating the welfare evidence, the available scientific evidence will focus on key 

2 policy-relevant issues by addressing a series of questions including the following:

3  To what extent has new scientific information become available that alters or 

4 substantiates our understanding of the effects on vegetation and other welfare 

5 effects following exposures to levels of O3 found in the ambient air?

6  To what extent has new scientific information become available to inform our 

7 understanding of the nature of the exposures that are associated with such 

8 effects in terms of biologically relevant cumulative, seasonal exposure 

9 indices?

10  To what extent has new scientific information become available that alters or 

11 substantiates our understanding of the effects of O3 on sensitive plant species, 

12 ecological receptors, or ecosystem processes?

13  To what extent has new scientific information become available that alters or 

14 substantiates our understanding of exposure factors other than O3 that might 

15 influence the associations between O3 levels and welfare effects being 

16 considered (e.g., site specific features such as elevation, soil moisture level, 

17 presence of co-occurring competitors, pests, pathogens, other pollutant 

18 stressors, weather-related factors)?

19  To what extent has new scientific information become available that alters or 

20 substantiates conclusions regarding the occurrence of adverse welfare effects 

21 at levels of O3 as low as or lower than those observed previously? What is the 

22 nature of the exposure-response relationships of O3 for the various welfare

23 effects evaluated?

24  Given recognition in the last review that the significance of O3-induced effects 

25 to the public welfare depends in part on the intended use of the plants or 

26 ecosystems on which those effects occurred, to what extent has new scientific 

27 evidence become available to suggest additional locations where the 

28 vulnerability of sensitive species or ecosystems would have special 

29 significance to the public welfare and should be given increased focus in this 

30 review?

31  To what extent do risk and/or exposure analyses suggest that exposures of 

32 concern for O3-related welfare effects are likely to occur with current ambient 

33 levels of O3 or with levels that just meet the O3 standard? Are these 

34 risks/exposures of sufficient magnitude such that the welfare effects might 

35 reasonably be judged to be important from a public welfare perspective? What 

36 are the important uncertainties associated with these risk/exposure estimates?
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1  To what extent have important uncertainties identified in the last review been 

2 addressed and/or have new uncertainties emerged?

3  To what extent does newly available information reinforce or call into 

4 question any of the basic elements of the current O3 standard?

2.2 ISA Development and Scope

5 EPA has a developed a robust, consistent, and transparent process for evaluating the 

6 scientific evidence and drawing conclusions and causal judgments regarding air 

7 pollution-related health and environmental effects. The ISA development process 

8 includes literature search strategies, criteria for selecting and evaluating studies, 

9 approaches for evaluating weight of the evidence, and a framework for making causality 

10 determinations. The process and causality framework are described in more detail in the 

11 Preamble to the ISA [website]. This section provides a brief overview of the process for 

12 development of this ISA.

13 EPA initiated the current review of the NAAQS for O3 on September 29, 2008, with a 

14 call for information from the public (U.S. EPA, 2008f). Literature searches were 

15 conducted routinely to identify studies published since the last review, focusing on 

16 studies published from 2005 (close of previous scientific assessment) through July 2011. 

17 References that were considered for inclusion in this ISA can be found using the HERO 

18 website (http://hero.epa.gov/ozone). This site contains HERO links to lists of references

19 that are cited in the ISA, as well as those that were considered for inclusion, but not cited 

20 in the ISA, with bibliographic information and abstracts.

21 This review has endeavored to evaluate all relevant data published since the last review 

22 pertaining to the atmospheric science of O3, human exposure to ambient O3, 

23 epidemiologic, controlled human exposure, toxicological, and ecological or welfare 

24 effects studies, including studies related to exposure-response relationships, mode(s) of 

25 action (MOA), and understanding of at-risk or susceptible populations for effects of O3

26 exposure. Added to the body of research were EPA’s analyses of air quality and 

27 emissions data, studies on atmospheric chemistry, transport, and fate of these emissions, 

28 as well as issues related to exposure to O3. 

29 Previous AQCDs (U.S. EPA, 2006b, 1996a, b, 1984, 1978a) have included an extensive 

30 body of evidence on both health and ecological effects of O3 exposure, as well as an 

31 understanding of the atmospheric chemistry of O3 (U.S. EPA, 2006b). In this ISA, the 

32 conclusions and key findings from previous reviews are summarized at the beginning of 

33 each section, to provide the foundation for consideration of evidence from recent studies. 
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1 Results of key studies from previous reviews are included in discussions or tables and 

2 figures, as appropriate, and conclusions are drawn based on the synthesis of evidence 

3 from recent studies with the extensive literature summarized in previous reviews. 

4 The Preamble discusses the general framework for conducting the science assessment 

5 and developing an ISA, including criteria for evaluating studies and developing scientific 

6 conclusions. For selection of epidemiologic studies in the O3 ISA, particular emphasis is 

7 placed on those studies most relevant to the review of the NAAQS. Studies conducted in 

8 the United States (U.S.) or Canada are discussed in more detail than those from other 

9 geographical regions, and particular emphasis is placed on: (1) recent multicity studies 

10 that employ standardized analysis methods for evaluating effects of O3 and that provide 

11 overall estimates for effects, based on combined analyses of information pooled across 

12 multiple cities; (2) studies that help understand quantitative relationships between 

13 exposure concentrations and effects; (3) new studies that provide evidence on effects in 

14 susceptible populations; and (4) studies that consider and report O3 as a component of a 

15 complex mixture of air pollutants. In evaluating toxicological and controlled human 

16 exposure studies, emphasis is placed on studies using concentrations or doses that are 

17 within about an order of magnitude of ambient O3 concentrations. Consideration of issues 

18 important for evaluation of human exposure to ambient O3 include the relationship 

19 between O3 measured at central site monitors and personal exposure to ambient O3

20 environments, since penetration of O3 into indoor environments may be limited. 

21 This ISA uses a five-level hierarchy that classifies the weight of evidence for causation: 

22  Causal relationship 

23  Likely to be a causal relationship 

24  Suggestive of a causal relationship 

25  Inadequate to infer a causal relationship 

26  Not likely to be a causal relationship 

27 Beyond judgments regarding causality are questions relevant to quantifying health or 

28 environmental risks based on our understanding of the quantitative relationships between 

29 pollutant exposures and health or welfare effects. Once a determination is made regarding 

30 the causal relationship between the pollutant and outcome category, important questions 

31 regarding quantitative relationships include: 

32  What is the concentration-response or dose-response relationship?

33  Under what exposure conditions (dose or concentration, duration and pattern) 

34 are effects observed?
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1  What populations appear to be differentially affected i.e., more susceptible to 

2 effects?

3  What elements of the ecosystem (e.g., types, regions, taxonomic groups, 

4 populations, functions, etc.) appear to be affected or are more sensitive to 

5 effects?

6 This chapter summarizes and integrates the newly available scientific evidence that best 

7 informs consideration of the policy-relevant questions that frame this assessment. 

8 Section 2.3 discusses the trends in ambient concentrations and sources of O3 and provides 

9 a brief summary of ambient air quality for short- and long-term exposure durations. 

10 Section 2.4 presents the evidence regarding personal exposure to ambient O3 in outdoor 

11 and indoor microenvironments, and it discusses the relationship between ambient O3

12 concentrations and personal exposure to O3 from ambient sources. Section 2.5 provides a 

13 discussion of the dosimetry and mode of action evidence for O3 exposure. Section 2.6 

14 integrates the evidence for studies that examine the health effects associated with short15 and long-term exposure to O3 and discusses important uncertainties identified in the 

16 interpretation of the scientific evidence. Section 2.7 provides a discussion of policy17 relevant considerations, such as potentially at-risk populations, lag structure, and the O3

18 concentration-response relationship. Section 2.8 integrates the health evidence from the 

19 different scientific disciplines and exposure durations. Finally, Section 2.9 summarizes 

20 the evidence for welfare effects related to O3 exposure, and Section 2.10 reviews the 

21 literature on the influence of tropospheric O3 on climate and exposure to solar ultraviolet 

22 radiation. 

2.3 Atmospheric Chemistry and Ambient Concentrations

2.3.1 Physical and Chemical Processes

23 Ozone in the troposphere originates from both anthropogenic (i.e., man-made) and 

24 natural source categories. Ozone attributed to anthropogenic sources is formed in the 

25 atmosphere by photochemical reactions involving sunlight and precursor pollutants 

26 including volatile organic compounds (VOCs), nitrogen oxides (NOX), and carbon 

27 monoxide (CO). Ozone attributed to natural sources is formed through the same 

28 photochemical reactions involving natural emissions of precursor pollutants from 

29 vegetation, microbes, animals, biomass burning, lightning, and geogenic sources. A 

30 schematic overview of the major photochemical cycles influencing O3 in the troposphere 

31 and the stratosphere is shown in Figure 2-1. The processes depicted in this figure are 

32 fairly well understood, and were covered in detail in the previous O3 AQCD. The 
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1 formation of O3, other oxidants, and oxidation products from these precursors is a 

2 complex, nonlinear function of many factors including: (1) the intensity and spectral 

3 distribution of sunlight; (2) atmospheric mixing; (3) concentrations of precursors in the 

4 ambient air and the rates of chemical reactions of these precursors; and (4) processing on 

5 cloud and aerosol particles.

Figure 2-1 Schematic overview of photochemical processes influencing 

stratospheric and tropospheric ozone.

6 Ozone is present not only in polluted urban atmospheres but throughout the troposphere, 

7 even in remote areas of the globe. The same basic processes involving sunlight-driven 

8 reactions of NOX, VOCs and CO contribute to O3 formation throughout the troposphere. 
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1 These processes also lead to the formation of other photochemical products, such as 

2 peroxyacetyl nitrate, nitric acid, and sulfuric acid, and to other compounds, such as 

3 formaldehyde and other carbonyl compounds. In urban areas, NOX, VOCs and CO are all 

4 important for O3 formation. In nonurban vegetated areas, biogenic VOCs emitted from 

5 vegetation tend to be the most important precursor to O3 formation. In the remote 

6 troposphere, methane – structurally the simplest VOC – and CO are the main carbon7 containing precursors to O3 formation. Throughout the troposphere, O3 is subsequently 

8 lost through a number of gas phase reactions and deposition to surfaces as shown in 

9 Figure 2-1.

10 Convective processes and turbulence transport O3 and other pollutants both upward and 

11 downward throughout the planetary boundary layer and the free troposphere. In many 

12 areas of the U.S., O3 and its precursors can be transported over long distances, aided by 

13 vertical mixing. The transport of pollutants downwind of major urban centers is 

14 characterized by the development of urban plumes. Meteorological conditions, small15 scale circulation patterns, localized chemistry, and mountain barriers can influence 

16 mixing on a smaller scale, resulting in frequent heterogeneous O3 concentrations across 

17 an individual urban area.

18 Furthermore, the mean tropospheric lifetime of O3 is long enough that it can be 

19 transported from continent to continent and latitudinally around the globe. The degree of 

20 influence from intercontinental transport varies greatly by location and time. For 

21 instance, high elevation sites are most susceptible to the intercontinental transport of 

22 pollution, particularly during spring. Given the nonlinear chemistry involving O3

23 formation, the task of isolating the influence of intercontinental transport of O3 and O3

24 precursors on regional air quality is quite complex and the topic of the next section.

2.3.2 Atmospheric Modeling of Background Ozone Concentrations

25 Background concentrations of O3 have been given various definitions in the literature 

26 over time. In the context of a review of the NAAQS, it is useful to define background O3

27 concentrations in a way that distinguishes between concentrations that result from 

28 precursor emissions that are relatively less directly controllable from those that are 

29 relatively more directly controllable through U.S. policies. North American (NA) 

30 background O3 can include contributions that result from emissions from natural sources 

31 (e.g., stratospheric intrusion, biogenic methane and more short-lived VOC emissions), 

32 emissions of pollutants that contribute to global concentrations of O3 (e.g., anthropogenic 

33 methane) from countries outside North America. In previous NAAQS reviews, a specific 

34 definition of background concentrations was used and referred to as policy relevant 
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1 background (PRB). In those previous reviews, PRB concentrations were defined by EPA 

2 as those concentrations that would occur in the U.S. in the absence of anthropogenic 

3 emissions in continental North America (CNA), defined here as the U.S., Canada, and 

4 Mexico. For this document, we have focused on the sum of those background 

5 concentrations from natural sources everywhere in the world and from anthropogenic 

6 sources outside CNA. North American background concentrations so defined facilitate 

7 separation of pollution that can be controlled directly by U.S. regulations or through 

8 international agreements with neighboring countries from that which would require more 

9 comprehensive international agreements, such as are being discussed as part of the 

10 United Nations sponsored Convention on Long Range Transboundary Air Pollution Task 

11 Force on Hemispheric Air Pollution. There is no chemical difference between 

12 background O3 and O3 attributable to CNA anthropogenic sources, and background 

13 concentrations can contribute to the risk of health effects. However, to inform policy 

14 considerations regarding the current or potential alternative standards, it is useful to 

15 understand how total O3 concentrations can be attributed to different source.

16 Since North American background as defined above is a construct that cannot be directly 

17 measured, the range of background O3 concentrations are estimated using chemistry 

18 transport models (CTMs). The 2006 O3 AQCD provided regional estimates of PRB O3

19 concentrations based on a coarse resolution (2°×2.5°, or ~200 km×200 km) GEOS-Chem 

20 model. For the current assessment, updated results from a finer resolution (0.5°×0.667°, 

21 or ~50 km×50 km) GEOS-Chem model were used. Base-case model performance 

22 evaluations comparing 2006 predicted to observed mean O3 concentrations from March 

23 to August showed general agreement to within ~5 ppb at most (26 out of 28) sites 

24 investigated. Exceptions included over-prediction of mean O3 during the summer at a site 

25 on the Atlantic coast of Florida and under-prediction of mean O3 year-round at a site in 

26 Yosemite NP. The finer resolution GEOS-Chem model agrees more closely with 

27 observations in the intermountain West than earlier versions.

28 The GEOS-Chem model-predicted North American O3 seasonal mean concentrations for 

29 spring and summer, 2006 are shown in Figure 2-2. As can be seen, North American 

30 background concentrations are generally higher in spring than in summer across the U.S., 

31 with exception in the Southwest where predictions peak in the summer. Highest estimates 

32 are found in the Intermountain West during the spring (less than 47 ppb) and in the 

33 Southwest during the summer (less than 49 ppb). Lowest estimates occur over the East in 

34 the spring (greater than 23 ppb) and over the Northeast in the summer (greater than 

35 15 ppb).
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2.3.3 Monitoring

1 The federal reference method (FRM) for O3 measurement is based on the detection of 

2 chemiluminescence resulting from the reaction of O3 with ethylene gas. However, almost 

3 all of the state and local air monitoring stations (SLAMS) that reported data to the EPA’s 

4 Air Quality System (AQS) database from 2005 to 2009 used the federal equivalence 

5 method (FEM) UV absorption photometer. More than 96% of O3 monitors met precision 

6 and bias goals during this period.

7 In 2010, there were 1250 SLAMS O3 monitors reporting data to AQS. Ozone is required 

8 to be monitored at SLAMS during the local “ozone season” which varies by state. In 

9 addition, National Core (NCore) is a new multipollutant monitoring network 

10 implemented to meet multiple monitoring objectives and each state is required to operate 

11 at least one NCore site. The NCore network consists of 60 urban and 20 rural sites 

12 nationwide (See Figure 3-16). The densest concentrations of O3 sites are located in 

13 California and the eastern half of the U.S.

Source: Zhang et al. (In Press)

Figure 2-2 GEOS-Chem modeled U.S. policy relevant background seasonalmean surface ozone concentrations in spring (left) and summer 

(right), 2006.

14 The Clean Air Status and Trends Network (CASTNET) is a regional monitoring network 

15 established to assess trends in acidic deposition and also provides concentration 
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1 measurements of O3. CASTNET O3 monitors operate year round and are primarily 

2 located in rural areas; in 2010, there were 80 CASTNET sites reporting O3 data to AQS. 

3 The National Park Service (NPS) operates 23 CASTNET sites in national parks and other 

4 Class-I areas, and provided data to AQS from 20 additional Portable Ozone Monitoring 

5 Systems (POMS) in 2010 (See Figure 3-17). Compared to urban-focused monitors, rural6 focused monitors are relatively scarce across the U.S.

2.3.4 Ambient Concentrations

7 Ozone is the only photochemical oxidant other than NO2 that is routinely monitored and

8 for which a comprehensive database exists. Other photochemical oxidants are typically 

9 only measured during special field studies. Therefore, the concentration analyses in 

10 Chapter 3 are limited to widely available O3 data obtained directly from AQS for the

11 period from 2007 to 2009. The median 24-h average, 8-h daily maximum, and 1-h daily 

12 maximum O3 concentrations across all U.S. sites reporting data to AQS between 2007 

13 and 2009 were 29, 40, and 44 ppb, respectively.

14 To investigate O3 variability in urban areas across the U.S., 20 combined statistical areas 

15 (CSAs) were selected for closer analysis based on their importance in O3 epidemiology 

16 studies and on their location. Several CSAs had relatively little spatial variability in 8-h 

17 daily maximum O3 concentrations (e.g., inter-monitor correlations ranging from 0.61 to 

18 0.96 in the Atlanta CSA) while other CSAs exhibited considerably more variability in O3

19 concentrations (e.g., inter-monitor correlations ranging from -0.06 to 0.97 in the 

20 Los Angeles CSA). As a result, caution should be observed in using data from the 

21 network of ambient O3 monitors to approximate community-scale exposures.

22 To investigate O3 variability in rural settings across the U.S., six focus areas were 

23 selected for closer analysis based on the impact of O3 or O3 precursor transport from 

24 upwind urban areas. The selected rural focus area with the largest number of available 

25 AQS monitors was Great Smoky Mountain National Park where the May-September 

26 median 8-h daily maximum O3 concentration ranged from 47 ppb at the lowest elevation 

27 (564 m) site to 60 ppb at the highest elevation (2,021 m) site. Correlations between sites 

28 within each rural focus area ranged from 0.78 to 0.92. Ozone in rural areas is produced 

29 from emissions of O3 precursors emitted directly within the rural areas, from emissions in 

30 urban areas that are processed during transport, and from occasional stratospheric 

31 intrusions. Factors contributing to variations observed within these rural focus areas 

32 include proximity to local O3 precursor emissions, local scale circulations related to 

33 topography, and possibly stratospheric intrusions as a function of elevation. In addition, 

34 O3 tends to persist longer in rural than in urban areas as a result of less chemical 
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1 scavenging. This results in a more uniform O3 concentration throughout the day and night 

2 without the typical nocturnal decrease in O3 concentration observed in urban areas. 

3 Persistently high O3 concentrations observed at many of the rural sites investigated here 

4 indicate that cumulative exposures for humans and vegetation in rural areas can be 

5 substantial and often higher than cumulative exposures in urban areas.

6 According to the 2010 National Air Quality Status and Trends report (U.S. EPA, 2010e), 

7 O3 concentrations have declined over the last decade; with the majority of this decline 

8 occurring before 2004. A noticeable decrease in O3 between 2003 and 2004 coincides 

9 with NOX emissions reductions resulting from implementation of the NOX SIP Call rule, 

10 which began in 2003 and was fully implemented in 2004. This rule was designed to 

11 reduce NOX emissions from power plants and other large combustion sources in the 

12 eastern U.S. As noted in the 2006 O3 AQCD, trends in national parks and rural areas are 

13 similar to nearby urban areas, reflecting the regional nature of O3 pollution.

14 Since O3 is a secondary pollutant, it is not expected to be highly correlated with primary 

15 pollutants such as CO and NOX. Furthermore, O3 formation is strongly influenced by 

16 meteorology, entrainment, and transport of both O3 and O3 precursors, resulting in a 

17 broad range in correlations with other pollutants which can vary substantially with 

18 season. Correlations between 8-h daily maximum O3 and other criteria pollutants exhibit 

19 mostly negative correlations in the winter and mostly positive correlations in the summer. 

20 The median seasonal correlations are modest at best with the highest positive correlation 

21 at 0.52 for PM2.5 in the summer and the highest negative correlation at -0.38 for PM2.5 in 

22 the winter. As a result, statistical analyses that may be sensitive to correlations between 

23 copollutants need to take seasonality into consideration, especially when O3 is being 

24 investigated.

2.4 Human Exposure

25 Ozone is ubiquitous throughout the environment, originating from both natural and 

26 anthropogenic sources. As such, people are routinely exposed to O3 as they participate in 

27 normal day-to-day activities. A number of factors affect the pattern of personal O3

28 exposure. These include: the variation in O3 concentrations at various spatial and 

29 temporal scales; individuals’ activity patterns, particularly time spent outdoors, which 

30 may involve changes in personal behavior to avoid exposure to O3; and infiltration of 

31 ambient O3 into indoor microenvironments, which is driven by air exchange rate. 

32 Similarly, several approaches have been used to measure or quantify exposure to ambient 

33 O3, giving an indication of the impact of these factors. These approaches include 

34 characterizing the correlation and ratio between personal exposure and ambient O3
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1 concentration, determining the ratio between indoor and outdoor concentrations, and 

2 using models to estimate exposure to O3 based on ambient concentrations. Both the 

3 factors affecting the pattern of exposure as well as the type of approaches used for 

4 quantification of exposure may have implications for epidemiologic studies.

5 Variations in O3 concentrations occur over multiple spatial and temporal scales. Near 

6 roadways, O3 concentrations are reduced due to reaction with NO and other species 

7 (Section 4.3.4.2). Over spatial scales of a few kilometers and away from roads, O3 may 

8 be somewhat more homogeneous due to its formation as a secondary pollutant, while 

9 over scales of tens of kilometers, additional atmospheric processing can result in higher 

10 concentrations downwind of an urban area. Although local-scale variability impacts the 

11 magnitude of O3 concentrations, O3 formation rates are influenced by factors that vary 

12 over larger spatial scales, such as temperature (Section 3.2), suggesting that urban 

13 monitors may track one another temporally but miss small-scale variability. This 

14 variation in concentrations changes the pattern of exposure people experience as they 

15 move through different microenvironments and affects the magnitude of exposures in 

16 different locations within an urban area. 

17 Another factor that may influence the pattern of exposure is the tendency for people to 

18 avoid O3 exposure by altering their behavior (e.g., reducing time spent outdoors) on high19 O3 days. Activity pattern has a substantial effect on ambient O3 exposure, with time spent 

20 outdoors contributing to increased exposure (Section 4.4.2). Air quality alerts and public 

21 health recommendations induce reductions in outdoor activity on high-O3 days among 

22 some populations, particularly for children, older adults, and people with respiratory 

23 problems. Such effects are less pronounced in the general population, possibly due to the 

24 opportunity cost of behavior modification. Preliminary epidemiologic evidence reports 

25 increased asthma hospital admissions among children and older adults when O3 alert days 

26 were excluded from the analysis of daily hospital admissions and O3 concentrations 

27 (presumably thereby eliminating averting behavior based on high O3 forecasts). The 

28 lower rate of admissions observed when alert days were included in the analysis suggests 

29 that estimates of health effects based on dose-response functions which do not account 

30 for averting behavior may be biased towards the null.

31 Personal exposure to O3 is moderately correlated with ambient O3 concentration, as 

32 indicated by studies reporting correlations generally in the range of 0.3-0.8 (Table 4-2). 

33 To the extent that relative changes in central-site monitor concentration are associated 

34 with relative changes in exposure concentration, this indicates that ambient monitor 

35 concentrations are representative of day-to-day changes in average total personal 

36 exposure and in personal exposure to ambient O3. The ratio between personal exposure 

37 and ambient concentration varies widely depending on activity patterns, housing 
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1 characteristics, and season. Personal-ambient ratios are typically 0.1-0.3, although 

2 individuals spending substantial time outdoors (e.g., outdoor workers) have shown much 

3 higher ratios (0.5-0.9) (Table 4-3). Thus, applying personal-ambient ratios for outdoor 

4 workers to the general population or susceptible populations spending substantial time 

5 indoors can result in overestimates of the magnitude of personal exposure for these 

6 groups. Some studies report much lower personal-ambient correlations, a result 

7 attributable in part to low air exchange rate and O3 concentrations below the sampler 

8 detection limit, conditions often encountered during wintertime. Low correlations may 

9 also occur for individuals or populations spending increased time indoors. Since there are 

10 relatively few indoor sources of O3, indoor O3 concentrations are often substantially 

11 lower than outdoor concentrations due to reactions of O3 with indoor surfaces and 

12 airborne constituents (Section 4.3.2). The lack of indoor sources also suggests that 

13 fluctuations in ambient O3 may be primarily responsible for changes in personal 

14 exposure, even under low-ventilation, low-concentration conditions. 

15 The factors affecting exposure patterns and quantification of exposure result in 

16 uncertainty which may contribute to exposure measurement error in epidemiologic 

17 studies. Low personal-ambient correlations are a source of exposure error for 

18 epidemiologic studies, tending to obscure the presence of thresholds, bias effect estimates 

19 toward the null, and widen confidence intervals, and this impact may be more

20 pronounced among populations spending substantial time indoors. The impact of this 

21 exposure error may tend more toward widening confidence intervals than biasing effect 

22 estimates, since epidemiologic studies evaluating the influence of monitor selection 

23 indicate that effect estimates are similar across different spatial averaging scales and 

24 monitoring sites.

2.5 Dosimetry and Mode of Action

25 Upon inspiration, O3 uptake in the respiratory tract is affected by a number of factors 

26 including respiratory tract morphology, and breathing route, frequency, and volume. 

27 Additionally, physicochemical properties of O3 itself and how it is transported, as well as 

28 the physical and chemical properties of the extracellular lining fluid (ELF) and tissue 

29 layers in the respiratory tract can influence O3 uptake. Experimental studies and models 

30 have suggested that there are differences between the total absorption of O3 from the 

31 inhaled air and the O3 dose reaching the respiratory tract tissues. The total O3 absorption 

32 gradually decreases with distal progression into the respiratory tract. In contrast, the 

33 primary site of O3 delivery to the lung epithelium is believed to be the centriacinar region 

34 or the junction of the conducting airways with the gas exchange region. 
Draft – Do Not Cite or Quote 2-15 September 2011

1 Ozone uptake efficiency is sensitive to a number of factors including tidal volume, 

2 minute volume, breathing frequency, O3 concentration, and exposure time. However, the 

3 greatest source of variability in uptake efficiency is interindividual variability, primarily 

4 due to differences in tracheobronchial volume and thus surface area. An increase in tidal 

5 volume and breathing frequency are both associated with increased physical activity. 

6 These changes and a switch to oronasal breathing during exercise result in deeper 

7 penetration of O3 into the lung with a higher absorbed fraction in the upper respiratory 

8 tract, tracheobronchial, and alveolar airways. For these reasons, increased physical 

9 activity acts to move the maximum tissue dose of O3 distally in the respiratory tract and 

10 into the alveolar region. 

11 The ELF is a complex mixture of lipids, proteins, and antioxidants that serves as the first 

12 barrier and target for inhaled O3 (see Figure 5-8). Distinct products with diverse reactivity 

13 (i.e., secondary oxidation products), are formed by reactions of O3 with soluble ELF 

14 components or plasma membranes. The thickness of the ELF and that of the mucus layer, 

15 within the ELF, are important determinants of the dose of O3 to the tissues; a thicker ELF 

16 generally results in a lower dose of O3 to the tissues. Additionally, the quenching ability 

17 and the concentrations of antioxidants and other ELF components are determinants of the 

18 formation of secondary oxidation products. These reactions appear to limit interaction of 

19 O3 with underlying tissues and to prevent penetration of O3 distally into the respiratory 

20 tract. 

21 In addition to contributing to the driving force for O3 uptake, formation of secondary 

22 oxidation products contributes to oxidative stress which may lead to cellular injury and 

23 altered cell signaling in the respiratory tract. Secondary oxidation products initiate 

24 pathways (See Figure 5-9) that provide the mechanistic basis for short- and long-term 

25 health effects described in detail in Chapters 6 and 7. Other key events involved in the 

26 mode of action of O3 in the respiratory tract include the activation of neural reflexes, 

27 initiation of inflammation, alterations of epithelial barrier function, sensitization of 

28 bronchial smooth muscle, modification of innate and adaptive immunity, and airway 

29 remodeling. Another key event, systemic inflammation and vascular oxidative/nitrosative 

30 stress, may be critical to the extrapulmonary effects of O3.

31 Secondary oxidation products can transmit signals to respiratory tract cells resulting in 

32 the activation of neural reflexes. Nociceptive sensory nerves mediate the involuntary 

33 truncation of respiration, resulting in decreases in lung function (i.e., FVC, FEV1, and 

34 tidal volume), and pain upon deep inspiration. Studies implicate TRPA1 receptors on 

35 bronchial C-fibers in this reflex. Another neural reflex involves vagal sensory nerves, 

36 which mediate a mild increase in airways obstruction (i.e., bronchoconstriction) 
Draft – Do Not Cite or Quote 2-16 September 2011

1 following exposure to O3 via parasympathetic pathways. Substance P release from 

2 bronchial C-fibers and the SP-NK receptor pathway may also contribute to this response. 

3 Secondary oxidation products also initiate the inflammatory cascade following exposure 

4 to O3. Studies have implicated eicosanoids, chemokines and cytokines, vascular 

5 endothelial adhesion molecules, and tachykinins in mediating this response. 

6 Inflammation is characterized by airways neutrophilia as well as the influx of other 

7 inflammatory cell types. Recent studies demonstrate a later phase of inflammation 

8 characterized by increased numbers of macrophages, which is mediated by hyaluronan. 

9 Inflammation further contributes to O3-induced oxidative stress. 

10 Alteration of the epithelial barrier function of the respiratory tract also occurs as a result 

11 of O3-induced secondary oxidation product formation. Increased epithelial permeability 

12 may lead to enhanced sensitization of bronchial smooth muscle, resulting in airways 

13 hyperresponsiveness (AHR). Neurally-mediated sensitization also occurs and is mediated 

14 by cholinergic postganglionic pathways and bronchial C-fiber release of substance P. 

15 Recent studies implicate hyaluronan and toll-like receptor 4 (TLR4) signaling in 

16 bronchial smooth muscle sensitization, while older studies demonstrate roles for 

17 eicosanoids, cytokines, and chemokines. 

18 Evidence is accumulating that exposure to O3 modifies innate and adaptive immunity 

19 through effects on macrophages, monocytes, and dendritic cells. Enhanced antigen 

20 presentation, adjuvant activity, and altered responses to endotoxin have been 

21 demonstrated. TLR4 signaling contributes to some of these responses. Effects on innate 

22 and adaptive immunity may result in both short- and longer-term consequences related to 

23 the exacerbation and/or induction of asthma and to alterations in host defense. 

24 Airway remodeling has been demonstrated following chronic and/or intermittent 

25 exposure to O3 by mechanisms which are not well understood. However, the TGF-β 

26 signaling pathway has recently been implicated in O3-induced deposition of collagen in 

27 the airways wall. These studies were conducted in adult animal models and their 

28 relevance to effects in humans is unknown. 

29 Evidence is also accumulating that O3 exposure results in systemic inflammation and 

30 vascular oxidative/nitrosative stress. The release of diffusible mediators from the O3-

31 exposed lung into the circulation may initiate or propagate inflammatory responses in the 

32 vascular or in systemic compartments. This may provide a mechanistic basis for 

33 extrapulmonary effects, such as vascular dysfunction. 

34 Both dosimetric and mechanistic factors contribute to the understanding of inter35 individual variability in response. Inter-individual variability is influenced by variability 

36 in respiratory tract volume and thus surface area, breathing route, certain genetic 
Draft – Do Not Cite or Quote 2-17 September 2011

1 polymorphisms, pre-existing conditions and disease, nutritional status, lifestages, 

2 attenuation, and coexposures. In particular, functional genetic polymorphisms of genes 

3 associated with antioxidant defense have been implicated in O3-mediated health effects. 

4 Pre-existing asthma, allergic airways disease, and obesity modulate immune and 

5 inflammatory responses to O3. Older adults exhibit diminished spirometric responses to 

6 O3 compared with younger adults. Very young individuals may be sensitive to 

7 developmental effects of O3 since studies in animal models demonstrated altered 

8 development of lung and other organ systems. 

9 Some of these factors are also influential in understanding species homology and 

10 sensitivity. Qualitatively, animal models exhibit a similar pattern of tissue dose 

11 distribution for O3 with the largest tissue dose delivered to the centriacinar region. 

12 However, due to anatomical and biochemical respiratory tract differences, the actual O3

13 dose delivered differs between humans and animal models. Animal data obtained in 

14 resting conditions underestimates the dose to the respiratory tract relative to exercising 

15 humans. Further, it should be noted that, with the exception of airways remodeling, the 

16 mechanistic pathways discussed above have been demonstrated in both animals and 

17 human subjects in response to the inhalation of O3. Even though interspecies differences 

18 limit quantitative comparison between species, the short- and long-term functional 

19 responses of laboratory animals to O3 appear qualitatively homologous to those of the 

20 human making them a useful tool in determining mechanistic and cause-effect 

21 relationships with O3 exposure.

2.6 Integration of Ozone Health Effects

22 This section evaluates the evidence from toxicological, controlled human exposure, and 

23 epidemiologic studies that examined the health effects associated with short- and long24 term exposure to O3, and summarizes the main conclusions of this assessment regarding 

25 the health effects of O3 and the concentrations at which those effects are observed. The 

26 conclusions from the previous NAAQS review and the causality determinations from this 

27 review are summarized in Table 2-1. The results from the health studies evaluated in 

28 combination with the evidence from atmospheric chemistry and exposure assessment 

29 studies contribute to the causal determinations made for the health outcomes discussed in 

30 this assessment (See Preamble to this document). In the following sections a discussion 

31 of the causal determinations will be presented by exposure duration (i.e., short-term [i.e., 

32 hours, days, weeks] or long-term [i.e., months to years] exposure) for the health effects 

33 for which sufficient evidence was available to conclude a causal, likely to be causal or 

34 suggestive relationship. This section also integrates the evidence from short- and long35 term exposure studies across scientific disciplines (i.e., controlled human exposure 
Draft – Do Not Cite or Quote 2-18 September 2011

1 studies, toxicology, and epidemiology) in interpreting the health effects evidence that 

2 spans from prenatal development to death. 

Table 2-1 Summary of evidence from epidemiologic, controlled human 

exposure, and animal toxicological studies on the health effects 

associated with short- and long-term exposure to ozone

Health Outcome Conclusions from 2006 O3 AQCD Conclusions from 2011 2nd Draft ISA

Short-Term Exposure to O3

Respiratory effects The overall evidence supports a causal relationship 

between acute ambient O3 exposures and increased 

respiratory morbidity outcomes.

Causal relationship

Lung function Results from controlled human exposure studies and 

animal toxicological studies provide clear evidence of 

causality for the associations observed between acute 

(≤ 24 h) O3 exposure and relatively small, but 

statistically significant declines in lung function 

observed in numerous recent epidemiologic studies. 

Declines in lung function are particularly noted in 

children, asthmatics, and adults who work or exercise 

outdoors.

Recent controlled human exposure studies demonstrate 

group mean decreases in FEV1 in the range of 2 to 3% with 

6.6 h exposures to as low as 60 ppb O3. The collective body 

of epidemiologic evidence demonstrates associations 

between short-term ambient O3 exposure and decrements in 

lung function, particularly in asthmatics, children, and adults 

who work or exercise outdoors.

Airway 

hyperresponsiveness

Evidence from human clinical and animal toxicological 

studies clearly indicate that acute exposure to O3 can 

induce airway hyperreactivity, thus likely placing atopic 

asthmatics at greater risk for more prolonged bouts of 

breathing difficulties due to airway constriction in 

response to various airborne allergens or other 

triggering stimuli.

A limited number of studies have observed airway 

hyperresponsiveness in rodents and guinea pigs after 

exposure to less than 300 ppb O3. As previously reported in 

the 2006 O3 AQCD, increased airway responsiveness has 

been demonstrated at 80 ppb in young, health adults, and at 

50 ppb in certain strains of rats, suggesting a genetic 

component. 

Pulmonary inflammation, 

injury and oxidative 

stress

The extensive human clinical and animal toxicological 

evidence, together with the limited available 

epidemiologic evidence, is clearly indicative of a causal 

role for O3 in inflammatory responses in the airways.

Epidemiologic studies provided new evidence for 

associations of ambient O3 with mediators of airway 

inflammation and oxidative stress and indicate that higher

antioxidant levels may reduce pulmonary inflammation 

associated with O3 exposure. Generally, these studies had 

mean 8-h max O3 concentrations less than 73 ppb.

Respiratory symptoms 

and medication use

Young healthy adult subjects exposed in clinical 

studies to O3 concentrations ≥ 80 ppb for 6 to 8 h 

during moderate exercise exhibit symptoms of cough 

and pain on deep inspiration. The epidemiologic 

evidence shows significant associations between acute 

exposure to ambient O3 and increases in a wide variety 

of respiratory symptoms (e.g., cough, wheeze, 

production of phlegm, and shortness of breath) and 

medication use in asthmatic children.

The collective body of epidemiologic evidence demonstrates 

positive associations between short-term exposure to 

ambient O3 and respiratory symptoms (e.g., cough, wheeze, 

production of phlegm, and shortness of breath) in asthmatic 

children. Generally, these studies had mean 8-h max O3

concentrations less than 69 ppb.

Lung host defenses Toxicological studies provided extensive evidence that 

acute O3 exposures as low as 80 to 500 ppb can cause 

increases in susceptibility to infectious diseases due to 

modulation of lung host defenses. A single controlled 

human exposure study found decrements in the ability 

of alveolar macrophages to phagocytose 

microorganisms upon exposure to 80 to 100 ppb O3.

Recent studies in human subjects demonstrate the 

increased expression of cell surface markers and alterations 

in sputum leukocyte markers related to innate adaptive 

immunity with short-term O3 exposures of 80-400 ppb. 

Recent studies demonstrating altered immune responses 

and natural killer cell function build on prior evidence that O3

can affect multiple aspects of innate and acquired immunity 

with short-term O3 exposures as low as 80 ppb.
Draft – Do Not Cite or Quote 2-19 September 2011

Health Outcome Conclusions from 2006 O3 AQCD Conclusions from 2011 2nd Draft ISA

Allergic and asthma 

related responses

Previous toxicological evidence indicated that O3

exposure skews immune responses toward an allergic 

phenotype, and enhances the development and 

severity of asthma-related responses such as AHR. 

Recent studies in human subjects demonstrate enhanced 

allergic cytokine production in atopic individuals and 

asthmatics, increased IgE receptors in atopic asthmatics, 

and enhanced markers of innate immunity and antigen 

presentation in health subjects or atopic asthmatics with 

short-term exposure to 80-400 ppb O3, all of which may 

enhance allergy and/or asthma. Further evidence for O3-

induced allergic skewing is provided by a few recent studies 

in rodents using exposure concentrations as low as 

200 ppb.

Hospital admissions, ED 

visits, and physician 

visits

Aggregate population time-series studies observed that 

ambient O3 concentrations are positively and robustly 

associated with respiratory-related hospitalizations and 

asthma ED visits during the warm season.

Strong evidence demonstrated associations of ambient O3

with respiratory hospital admissions and ED visits in the 

U.S., Europe, and Canada with supporting evidence from 

single city studies. Generally, these studies had mean 8-h 

max O3 concentrations less than 60 ppb.

Respiratory Mortality Aggregate population time-series studies specifically 

examining mortality from respiratory causes were 

limited in number and showed inconsistent 

associations between acute exposure to ambient O3

exposure and respiratory mortality.

Recent multicity time-series studies and a multicontinent 

study consistently demonstrated associations between 

ambient O3 and respiratory-related mortality visits across the 

U.S., Europe, and Canada with supporting evidence from 

single city studies. Generally, these studies had mean 8-h 

max O3 concentrations less than 63 ppb.

Cardiovascular effects The limited evidence is highly suggestive that O3

directly and/or indirectly contributes to cardiovascularrelated morbidity, but much remains to be done to 

more fully substantiate the association.

Suggestive of a Causal Relationship

Central nervous system 

effects

Toxicological studies report that acute exposures to O3

are associated with alterations in neurotransmitters, 

motor activity, short- and long-term memory, sleep 

patterns, and histological signs of neurodegeneration.

Suggestive of a Causal Relationship

Mortality The evidence is highly suggestive that O3 directly or 

indirectly contributes to non-accidental and 

cardiopulmonary-related mortality.

Likely to be a Causal Relationship

Long-term Exposure to O3

Respiratory effects The current evidence is suggestive but inconclusive for 

respiratory health effects from long-term O3 exposure.

Likely to be a Causal Relationship

New onset asthma No studies at this time. Evidence for a relationship between different genetic 

variants (HMOX, GST, ARG) that, in combination with O3

exposure, are related to new onset asthma. These results 

were observed when subjects living in areas where the 

mean annual 8-h max O3 concentration was 55.2 ppb, 

compared to those who lived where it was 38.4 ppb.

Asthma hospital 

admissions

No studies at this time. Chronic O3 exposure was related to first childhood asthma 

hospital admissions in a positive concentration-response 

relationship. Generally, these studies had mean annual 8-h 

max O3 concentrations less than 41 ppb.

Pulmonary structure and 

function

Epidemiologic studies observed that reduced lung 

function growth in children was associated with 

seasonal exposure to O3; however, cohort studies of 

annual or multiyear O3 exposure observed little clear 

evidence for impacts of longer-term, relatively low-level 

O3 exposure on lung function development in children. 

Animal toxicological studies reported chronic O3-

induced structural alterations in several regions of the 

respiratory tract including the centriacinar region. 

Morphologic evidence from studies using exposure 

regimens that mimic seasonal exposure patterns report 

increased lung injury compared to conventional chronic 

stable exposures.

Evidence for pulmonary function effects is inconclusive, with 

some new epidemiologic studies (mean annual 8-h max O3

concentrations less than 65 ppb). Information from 

toxicological studies indicates that long-term maternal 

exposure during gestation (100 ppb) or development (500 

ppb) can result in irreversible morphological changes in the 

lung, which in turn can influence pulmonary function.

Pulmonary inflammation, 

injury and oxidative 

stress

Extensive human clinical and animal toxicological 

evidence, together with limited epidemiologic evidence 

available, suggests a causal role for O3 in inflammatory 

responses in the airways.

Several epidemiologic studies (mean 8-h max O3

concentrations less than 69 ppb) and toxicology studies (as 

low as 500 ppb) add to observations of O3-induced 

inflammation and injury.
Draft – Do Not Cite or Quote 2-20 September 2011

Health Outcome Conclusions from 2006 O3 AQCD Conclusions from 2011 2nd Draft ISA

Lung host defenses Toxicological studies provided evidence that chronic O3

exposure as low as 100 ppb can cause increases in 

susceptibility to infectious diseases due to modulation 

of lung host defenses, but do not cause greater effects 

on infectivity than short exposures. 

Consistent with decrements in host defenses observed in 

rodents exposed to 100 ppb O3, recent evidence 

demonstrates a decreased ability to respond to pathogenic 

signals in infant monkeys exposed to 500 ppb O3.

Allergic responses Limited epidemiologic evidence supported an 

association between ambient O3 and allergic 

symptoms. Little if any information was available from 

toxicological studies.

Evidence relates positive outcomes of allergic response and 

O3 exposure but with variable strength for the effect 

estimates; exposure to O3 may increase total IgE in adult 

asthmatics. Allergic indicators in monkeys were increased by 

exposure to O3 concentrations of 500 ppb.

Respiratory mortality Studies of cardio-pulmonary mortality were insufficient 

to suggest a causal relationship between chronic O3

exposure and increased risk for mortality in humans.

A single study demonstrated that exposure to O3 (long-term 

mean O3 less than 104 ppb) elevated the risk of death from 

respiratory causes and this effect was robust to the inclusion 

of PM2.5.

Cardiovascular Effects No studies at this time. Suggestive of a Causal Relationship

Reproductive and 

developmental effects

Limited evidence for a relationship between air 

pollution and birth-related health outcomes, including 

mortality, premature births, low birth weights, and birth 

defects, with little evidence being found for O3 effects.

Suggestive of a Causal Relationship

Central nervous system 

effects

Toxicological studies reported that acute exposures to 

O3 are associated with alterations in neurotransmitters, 

motor activity, short and long term memory, sleep 

patterns, and histological signs of neurodegeneration. 

Evidence regarding chronic exposure and 

neurobehavioral effects was not available.

Suggestive of a Causal Relationship

Cancer Little evidence for a relationship between chronic O3

exposure and increased risk of lung cancer.

Inadequate to infer a Causal Relationship

Mortality There is little evidence to suggest a causal relationship 

between chronic O3 exposure and increased risk for 

mortality in humans.

Suggestive of a Causal Relationship

2.6.1 Respiratory Effects

1 The clearest evidence for health effects associated with exposure to O3 is provided by 

2 studies of respiratory effects. Collectively, there is a vast amount of evidence spanning 

3 several decades that supports a causal association between exposure to O3 and a 

4 continuum of respiratory effects (Figure 2-3). The majority of this evidence is derived 

5 from studies investigating short-term exposure (i.e., hours to weeks) to O3, although 

6 animal toxicological studies and recent epidemiologic evidence demonstrate that long7 term exposure (i.e., months to years) may also be detrimental to the respiratory system.

8 The 2006 O3 AQCD concluded that there was clear, consistent evidence of a causal 

9 relationship between short-term exposure to O3 and respiratory health effects (U.S. EPA, 

10 2006b). This causal association was substantiated by the coherence of effects observed 

11 across controlled human exposure, epidemiologic, and toxicological studies indicating 

12 associations of short-term O3 exposures with a range of respiratory health endpoints from 

13 respiratory tract inflammation to respiratory emergency department (ED) visits and 

14 hospital admissions. Across disciplines, short-term O3 exposures induced or were 

15 associated with statistically significant declines in lung function. An equally strong body 
Draft – Do Not Cite or Quote 2-21 September 2011

1 of evidence from controlled human exposure and toxicological studies demonstrated O3-

2 induced inflammatory responses, increased epithelial permeability, and airway 

3 hyperresponsiveness (both specific and nonspecific). Toxicological studies provided 

4 additional evidence for O3-induced impairment of host defenses. Combined, these 

5 findings from experimental studies provided support for epidemiologic evidence, in 

6 which short-term O3 exposure was consistently associated with increases in respiratory 

7 symptoms and asthma medication use in asthmatic children, respiratory-related hospital 

8 admissions, and asthma-related ED visits. Although O3 was consistently associated with 

9 non-accidental and cardiopulmonary mortality, the contribution of respiratory causes to 

10 these findings was uncertain. The combined evidence across disciplines supports a causal 

11 relationship between short-term O3 exposure and respiratory effects. 

12 Mechanistic evidence for the effects of O3 on the respiratory system was characterized in 

13 the 1996 O3 AQCD, which identified O3-induced changes in a variety of lung lipid 

14 species whose numerous biologically active metabolites, in turn, can affect host defenses, 

15 lung function, and the immune system. As summarized in Section 2.5 and fully 

16 characterized in Chapter 5, key events in the toxicity pathway of O3 have been identified 

17 in humans and animal models. They include activation of neural reflexes, initiation of 

18 inflammation, alteration of epithelial barrier function, sensitization of bronchial smooth 

19 muscle, modification of innate/adaptive immunity, airway remodeling, and systemic 

20 inflammation and oxidative/nitrosative stress. 

21 As demonstrated in Figure 2-3, O3 is associated with a continuum of respiratory effects, 

22 including altered development of the respiratory tract. Recent toxicological studies of 

23 long-term exposure to O3 occurring throughout various lifestages, beginning with 

24 prenatal and early life exposures, provide novel evidence for effects on the development 

25 of the respiratory system, including ultrastructural changes in bronchiole development, 

26 effects on the developing immune system, and increased offspring airway hyper27 reactivity (Section 7.4.7. The strongest evidence for O3-induced effects on the developing 

28 lung comes from a series of experiments using infant rhesus monkeys episodically 

29 exposed to 500 ppb O3 for approximately 5 months, starting at one month of age. 

30 Functional changes in the conducting airways of infant rhesus monkeys exposed to either 

31 O3 alone or O3 + antigen were accompanied by a number of cellular and morphological 

32 changes. In addition to these functional and cellular changes, significant structural 

33 changes in the respiratory tract were observed. Importantly, the O3-induced structural 

34 pathway changes persisted after recovery in filtered air for six months after cessation of 

35 the O3 exposures. Exposure to O3 has also been associated with similar types of 

36 alterations in pulmonary structure, including airway remodeling and pulmonary injury 

37 and increased permeability, in all adult laboratory animal species studied, from rats to 

38 monkeys (U.S. EPA, 1996a). 
Draft – Do Not Cite or Quote 2-22 September 2011

Green=Animal Toxicological Studies; Blue=Controlled Human Exposure Studies; Purple=Epidemiologic Studies; AM=Alveolar 

Macrophage.

Figure 2-3 Snapshot of evidence for the association of O3 with the continuum 

of respiratory effects, including sub-clinical effects (bottom level of 

the pyramid) and clinical effects, increasing in severity moving up 

the pyramid. 
Draft – Do Not Cite or Quote 2-23 September 2011

1 In addition to effects on the development and structure of the respiratory tract, there is 

2 extensive evidence for the effects of short-term exposure to O3 on pulmonary 

3 inflammation and oxidative stress. Previous evidence from controlled human exposure 

4 studies indicated that O3 causes an inflammatory response in the lungs (U.S. EPA, 

5 1996a). This inflammatory response to O3 was detected after a single 1-h exposure with 

6 exercise to O3 concentrations of 300 ppb; the increased levels of some inflammatory cells 

7 and mediators persisted for at least 18 hours. Toxicological studies provided additional 

8 evidence for increases in permeability and inflammation in rabbits at levels as low as 100 

9 ppb O3. Evidence summarized in the 2006 O3 AQCD demonstrated that inflammatory 

10 responses were observed subsequent to 6.6 hours O3 exposure to the lowest tested level 

11 of 80 ppb in healthy human adults, while toxicological studies provided extensive 

12 evidence that short-term (1-3 hours) O3 exposure in the range of 100-500 ppb could cause 

13 lung inflammatory responses. The limited epidemiologic evidence reviewed in the 2006 

14 O3 AQCD demonstrated an association between short-term ambient O3 exposure and 

15 airway inflammation in children (1-h max O3 of approximately 100 ppb). Recent studies 

16 in animals and in vitro models described inflammatory and injury responses mediated by 

17 toll-like receptors (e.g., TLR4, TLR2), receptors for TNF or IL-1, multiple signaling 

18 pathways (e.g., p38, JNK, NFκB, MAPK/AP-1), and oxidative stress (Section 6.2.3.3). 

19 The most recent epidemiologic studies provide additional supporting evidence by 

20 demonstrating associations of ambient O3 with mediators of airway inflammation and 

21 indicating that populations with diminished antioxidant capacity may have increased 

22 susceptibility to pulmonary inflammation and oxidative stress associated with O3

23 exposure (Sections 6.2.4 and 8.1). 

24 The normal inflammatory response in lung tissue is part of host defense that aids in 

25 removing microorganisms or particles that have reached the distal airways and alveolar 

26 surface. The 1996 O3 AQCD concluded that short-term exposure to elevated 

27 concentrations of O3 resulted in alterations in these host defense mechanisms in the 

28 respiratory system. Specifically, toxicological studies of short-term exposures as low as 

29 100 ppb O3 were shown to decrease the ability of alveolar macrophages to ingest 

30 particles, and short-term exposures as low as 80 ppb for 3 hours prevented mice from 

31 resisting infection with streptococcal bacteria and resulted in infection-related mortality. 

32 Similarly, alveolar macrophages removed from the lungs of human subjects after 6.6 

33 hours of exposure to 80 and 100 ppb O3 had decreased ability to ingest microorganisms, 

34 indicating some impairment of host defense capability. These altered host defense 

35 mechanisms can lead to susceptibility to respiratory infections, which are associated with 

36 increased risk of developing asthma when occurring in early life. Despite the strong 

37 toxicological evidence, in the limited body of epidemiologic evidence, O3 exposure has 

38 not been consistently associated with hospital admissions or ED visits for respiratory 

39 infection, pneumonia, or influenza (Sections 6.2.7.2 and 6.2.7.3).
Draft – Do Not Cite or Quote 2-24 September 2011

1 The most commonly observed and strongest evidence for respiratory effects associated 

2 with short-term exposure to O3 is transient decrements in pulmonary function. Controlled 

3 human exposure studies characterized in previous NAAQS reviews demonstrated O3-

4 induced decrements in pulmonary function, characterized by alterations in lung volumes 

5 and flow and airway resistance and responsiveness for multihour exposures (up to 8 

6 hours) to O3 concentrations as low as 80 ppb (U.S. EPA, 1996a). A series of mobile 

7 laboratory studies of lung function and respiratory symptoms reported pulmonary 

8 function decrements at mean ambient O3 concentrations of 140 ppb in exercising healthy 

9 adolescents and increased respiratory symptoms and pulmonary function decrements at 

10 150 ppb in heavily exercising athletes and at 170 ppb in lightly exercising healthy and 

11 asthmatic subjects. Epidemiologic and animal toxicological evidence is coherent with the 

12 results of the controlled human exposure studies, both indicating decrements in lung 

13 function upon O3 exposure. A combined statistical analysis of epidemiologic studies in 

14 children at summer camp demonstrated decrements in FEV1 of 0.50 mL/ppb with 

15 previous hour O3 concentration. For preadolescent children exposed to 120 ppb ambient 

16 O3, this amounted to an average decrement of 2.4-3.0% in FEV1. Key studies of lung 

17 function measurements (FEV1) taken before and after well-defined outdoor exercise 

18 events in adults yielded exposure-response slopes of 0.40 and 1.35 mL/ppb ambient O3

19 after exposure for up to 1 hour. Animal toxicological studies reported similar respiratory 

20 effects in rats at exposures as low as 200 ppb O3 for 3 hours. The 2006 O3 AQCD 

21 characterized the controlled human exposure and animal toxicological studies as 

22 providing clear evidence of causality for the associations observed between short-term (≤ 

23 24 hours) O3 exposure and relatively small, but statistically significant declines in lung 

24 function observed in numerous recent epidemiologic studies. Declines in lung function 

25 were particularly noted in children, asthmatics, and adults who work or exercise 

26 outdoors. 

27 Recent controlled human exposure studies examined lower concentration O3 exposures 

28 (40-80 ppb) and demonstrated that FEV1, respiratory symptoms, and inflammatory 

29 responses were affected by O3 exposures of 6.6 hours and in the range of 60 to 80 ppb 

30 (Section 6.2.1.1 and 6.2.3.1). These studies demonstrated average decreases in FEV1 in 

31 the range of 2.8 to 3.6% with O3 exposures 6.6 hours in duration and as low as 60 ppb in 

32 concentration. However, considerable intersubject variability has been reported with 

33 some subjects experiencing considerably greater decrements than average. Recent 

34 epidemiologic studies provide greater insight into subject factors that may increase 

35 susceptibility for O3-associated respiratory morbidity. It was in these potentially 

36 susceptible populations (e.g., individuals with asthma with concurrent respiratory 

37 infection, older adults with AHR or elevated body mass index, or groups with diminished 

38 antioxidant capacity) that O3-associated decreases in lung function were consistently 

39 observed.
Draft – Do Not Cite or Quote 2-25 September 2011

1 In addition to alterations in lung volumes and flow, changes in pulmonary function due to 

2 exposure to O3 may manifest as respiratory symptoms (e.g., coughing, wheezing, 

3 shortness of breath). The 1996 O3 AQCD identified an association between respiratory 

4 symptoms and increasing ambient O3, particularly among asthmatic children. In the 2006 

5 O3 AQCD, symptoms of cough and pain on deep inspiration were well documented in 

6 young healthy adult subjects after exposure of ≥80 ppb O3 for 6-8 hours during moderate 

7 exercise. Limited data suggested an increase in respiratory symptoms down to 60 ppb. 

8 More recently, these effects have been observed at 70 ppb in healthy adults. Controlled 

9 human exposure studies of healthy adults, have also reported an increased incidence of 

10 cough with O3 exposures as low as 120 ppb and 1-3 hours in duration with very heavy 

11 exercise. The controlled human exposure studies also demonstrated lesser respiratory 

12 symptom responses in children and older adults relative to young healthy adults. Previous 

13 epidemiologic evidence showed significant associations between short-term exposure to 

14 ambient O3 and increases in a wide variety of respiratory symptoms (e.g., cough, wheeze, 

15 production of phlegm, and shortness of breath) in asthmatic children (U.S. EPA, 2006b). 

16 Epidemiologic studies also indicated that short-term O3 exposure is likely associated with 

17 increased asthma medication use in asthmatic children. Similar to what was observed for 

18 pulmonary function, recent epidemiologic studies provided insight into additional subject 

19 factors that may increase susceptibility for O3-associated respiratory symptoms. It was in 

20 these potentially susceptible populations (e.g., asthmatics with diminished antioxidant 

21 capacity and infants with asthmatic mothers) where the recent evidence of O3-associated 

22 increases in respiratory symptoms was the strongest. Additionally, recent epidemiologic 

23 studies provide evidence for an association between long-term exposure to O3 and 

24 respiratory symptoms (Section 7.2.2).

25 Ozone exposure has been shown to result in both specific and non-specific airway 

26 hyperresponsiveness. Increased airway responsiveness is an important consequence of 

27 exposure to O3 because its presence represents a change in airway smooth muscle 

28 reactivity and implies that the airways are predisposed to narrowing on inhalation of a 

29 variety of stimuli (e.g., specific allergens, SO2, cold air). Specifically, short-term (2 or 

30 3 hours) exposure to 250 or 400 ppb O3 was found to cause increases in airway 

31 responsiveness in response to allergen challenges among allergic asthmatic subjects who 

32 characteristically already had somewhat increased airway responsiveness at baseline. 

33 Increased non-specific airway responsiveness has been demonstrated in healthy young 

34 adults down to 80 ppb O3 following 6.6 hours of exposure during moderate exercise. 

35 While AHR has not been widely examined in epidemiologic studies, findings for O3-

36 induced increases in AHR in controlled human exposure (Section 6.2.2.1) and 

37 toxicological (Section 6.2.2.2) studies provide biological plausibility for associations 

38 observed between ambient O3 exposure and increases in respiratory symptoms in subjects 

39 with asthma.
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1 In addition to asthma exacerbations, recent epidemiologic evidence has revealed an 

2 association between long-term exposure to O3 and new onset asthma (Section 7.2.1, 

3 Table 7-2). The new epidemiologic evidence base consists of studies using a variety of 

4 designs and analysis methods evaluating the relationship between long-term annual 

5 measures of exposure to ambient O3 and measures of respiratory morbidity conducted by 

6 different research groups in different locations. Studies from two California cohorts have 

7 provided evidence for a relationship between different variants in genes related to 

8 oxidative or nitrosative stress (e.g., HMOX, GSTs, ARG) that, in combination with O3

9 exposure, are related to new onset asthma. This is the first time that evidence has 

10 extended beyond the association of exposure to O3 and asthma exacerbations to suggest 

11 that long-term exposure to O3 may play a role in the development of the disease and 

12 contribute to incident cases of asthma.

13 When respiratory symptoms, asthma exacerbations, or other respiratory diseases become 

14 too serious to be cared for at home, they can result in ED visits or hospital admissions. 

15 The frequency of these types of ED visits and hospital admissions is associated with 

16 short-term changes in ambient O3 concentrations. Summertime daily hospital admissions 

17 for respiratory causes in various locations of eastern North America were consistently 

18 associated with ambient levels of O3 in studies reviewed in the 1996 O3 AQCD. This 

19 association remained even when considering only concentrations below 120 ppb O3. The 

20 2006 O3 AQCD concluded that aggregate population time-series studies demonstrate a 

21 positive and robust association between ambient O3 concentrations and respiratory22 related hospitalizations and asthma ED visits during the warm season. Recent 

23 epidemiologic time-series studies that include additional multicity studies and a 

24 multicontinent study further support that short-term exposures to ambient O3

25 concentrations are consistently associated with increases in respiratory hospital 

26 admissions and ED visits specifically during the warm/summer months in multiple 

27 geographic locations and across a range of O3 concentrations (Section 6.2.7). There is 

28 also recent evidence for an association between respiratory hospital admissions and long29 term exposure to O3 (Section 7.2.2).

30 Finally, O3 exposure may contribute to death from respiratory causes. Recent evidence 

31 from several multicity studies and a multicontinent study demonstrate consistent positive 

32 associations between short-term exposure to ambient O3 concentrations and increases in 

33 respiratory mortality (Section 6.6.2.5). Similarly, a study of long-term exposure to 

34 ambient O3 concentrations also demonstrated an association between O3 and increases in 

35 respiratory mortality (Section 7.7.1). Evidence from these recent mortality studies is 

36 consistent and coherent with the evidence from epidemiologic, controlled human 

37 exposure, and animal toxicological studies for the effects of short- and long-term 

38 exposure to O3 on respiratory effects. Additionally, the evidence for respiratory morbidity 
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1 after short- and long-term exposure provides biological plausibility for mortality due to 

2 respiratory disease. 

3 In summary, recent studies support or build upon the strong body of evidence presented 

4 in the 1996 and 2006 O3 AQCDs that short-term O3 exposure is causally associated with 

5 adverse respiratory health effects. Recent controlled human exposure studies demonstrate 

6 statistically significant group mean decreases in pulmonary function to exposures as low 

7 as 60-70 ppb O3 in young, healthy adults. Equally strong evidence demonstrated 

8 associations of ambient O3 with respiratory hospital admissions and ED visits across the 

9 U.S., Europe, and Canada. Most effect estimates ranged from a 1.6 to 5.4% increase in 

10 daily all respiratory-related ED visits or hospital admissions in all-year analyses for 

11 standardized increases in ambient O3 concentrations. Several multicity studies and a 

12 multicontinent study reported associations between short-term exposure to ambient O3

13 concentrations and increases in respiratory mortality. This evidence is supported by 

14 individual-level epidemiologic studies that provide new evidence for associations of 

15 ambient O3 with mediators of airway inflammation and oxidative stress, and across 

16 endpoints, they indicate that groups with diminished antioxidant capacity or 

17 comorbidities such as atopy, AHR, or elevated body mass index may have increased 

18 susceptibility to respiratory morbidity associated with O3 exposure. The potential 

19 susceptibility of these populations identified in recent epidemiologic studies are strongly 

20 supported by findings from experimental studies that demonstrated O3-induced decreases 

21 in intracellular antioxidant levels, increases in airway responses with co-exposures to 

22 allergens, and increases in airway responses in animal models of obesity. By 

23 demonstrating O3-induced airway hyperresponsiveness, decreased pulmonary function, 

24 allergic responses, lung injury, impaired host defense, and airway inflammation, 

25 toxicological studies have characterized O3 modes of action and have provided biological 

26 plausibility for epidemiologic associations of ambient O3 exposure with lung function 

27 and respiratory symptoms, hospital admissions, ED visits, and mortality. Together, the 

28 evidence integrated across controlled human exposure, epidemiologic, and toxicological 

29 studies and across the spectrum of respiratory health endpoints continues to demonstrate 

30 that there is a causal relationship between short-term O3 exposure and respiratory 

31 health effects.

32 The strongest evidence for a relationship between long-term O3 exposure and respiratory 

33 morbidity is contributed by recent studies from a single cohort demonstrating 

34 associations between long-term measures of O3 exposure and new-onset asthma in 

35 children and increased respiratory symptom effects in asthmatics. While the evidence is 

36 limited, this U.S. multicommunity prospective cohort demonstrates that asthma risk is 

37 affected by interactions among genetic variability, environmental O3 exposure, and 

38 behavior. Other recent studies provide coherent evidence for long-term O3 exposure and 
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1 respiratory morbidity effects such as first asthma hospitalization and respiratory 

2 symptoms in asthmatics. Generally, the epidemiologic and toxicological evidence 

3 provides a compelling case that supports the hypothesis that a relationship exists between 

4 long-term exposure to ambient O3 and measures of respiratory morbidity. The evidence 

5 for short-term exposure to O3 and effects on respiratory endpoints provides coherence 

6 and biological plausibility for the effects of long-term exposure to O3. Building upon that 

7 evidence, the more recent epidemiologic evidence, combined with toxicological studies 

8 in rodents and non-human primates, provides biologically plausible evidence that there 

9 is likely to be a causal relationship between long-term exposure to O3 and 

10 respiratory health effects.

2.6.2 Mortality Effects

11 The 2006 O3 AQCD concluded that the overall body of evidence was highly suggestive 

12 that short-term exposure to O3 directly or indirectly contributes to non-accidental and 

13 cardiopulmonary-related mortality, but additional research was needed to more fully 

14 establish underlying mechanisms by which such effects occur. The evaluation of new 

15 multicity studies that examined the association between short-term O3 exposure and 

16 mortality found evidence which supports the conclusions of the 2006 O3 AQCD. These 

17 new studies reported consistent positive associations between short-term O3 exposure and 

18 total (nonaccidental) mortality, with associations being stronger during the warm season, 

19 as well as additional support for associations between O3 exposure and cardiovascular 

20 mortality being similar or larger in magnitude compared to respiratory mortality. 

21 Additionally, these new studies examined previously identified areas of uncertainty in the 

22 O3-mortality relationship. Taken together, the body of evidence indicates that there is 

23 likely to be a causal relationship between short-term exposures to O3 and all-cause 

24 mortality.

25 The 2006 O3 AQCD concluded that an insufficient amount of evidence existed “to 

26 suggest a causal relationship between chronic O3 exposure and increased risk for 

27 mortality in humans” (U.S. EPA, 2006b). Several additional studies have been conducted 

28 since the last review, an ecologic study that finds no association between mortality and 

29 O3, and a reanalysis of the ACS cohort that specifically points to a relationship between 

30 long-term O3 exposure and an increased risk of respiratory mortality. The findings from 

31 the reanalysis of the ACS study are consistent and coherent with the evidence from 

32 epidemiologic, controlled human exposure, and animal toxicological studies for the 

33 effects of short- and long-term exposure to O3 on respiratory effects. Additionally, the 

34 evidence for short- and long-term respiratory morbidity provides biological plausibility 
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1 for mortality due to respiratory disease. Collectively, the evidence is suggestive of a 

2 causal relationship between long-term O3 exposures and mortality.

2.6.3 Cardiovascular Health Effects

3 In past O3 AQCDs the effects of short- and long-term exposure to O3 on the 

4 cardiovascular system could not be thoroughly evaluated due to the paucity of 

5 information available. However, studies investigating O3-induced cardiovascular events 

6 have advanced in the last two decades. Overall, there is limited, inconsistent evidence for 

7 cardiovascular morbidity in epidemiologic studies examining both short- and long-term 

8 exposure to O3. Positive associations between short-term O3 exposure and cardiovascular 

9 mortality have been consistently reported in multiple epidemiologic studies. Animal 

10 toxicological studies provide more evidence for both short- and long-term O3 exposure 

11 leading to cardiovascular morbidity. The toxicological studies demonstrate O3-induced 

12 cardiovascular effects, specifically enhanced atherosclerosis and ischemia/reperfusion 

13 injury with or without the corresponding development of a systemic oxidative, pro14 inflammatory environment, disrupted NO-induced vascular reactivity, decreased cardiac 

15 function, and increased HRV. Taking into consideration the positive toxicological studies 

16 and evidence for an association between O3 exposure and cardiovascular mortality, the 

17 generally limited body of evidence is suggestive of a causal relationship for both 

18 relevant short- and long-term exposures to O3 and cardiovascular effects.

2.6.4 Central Nervous System Effects

19 In rodents, O3 exposure has been shown to cause physicochemical changes in the brain 

20 indicative of oxidative stress and inflammation. Recent toxicological studies add to 

21 earlier evidence that short- and long-term exposures to O3 can produce a range of effects 

22 on the central nervous system and behavior. Previously observed effects, including 

23 neurodegeneration, alterations in neurotransmitters, short- and long-term memory, and 

24 sleep patterns, have been further supported by recent studies. In instances where 

25 pathology and behavior are both examined, animals exhibit decrements in behaviors tied 

26 to the brain regions or chemicals found to be affected or damaged. The single 

27 epidemiologic study conducted showed that long-term exposure to O3 affects memory in 

28 humans as well. Notably, exposure to O3 levels as low as 250 ppb has resulted in 

29 progressive neurodegeneration and deficits in both short- and long-term memory in 

30 rodents. Additionally, changes in the CNS, including biochemical, cellular, and 

31 behavioral effects, have been observed in animals whose sole exposure occurred in utero, 

32 at levels as a low as 300 ppb. Together the evidence from studies of short- and long-term 
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1 exposure to O3 is suggestive of a causal relationship between O3 exposure and 

2 adverse CNS effects.

2.6.5 Reproductive and Developmental Effects

3 There is limited though positive toxicological evidence for O3-induced developmental 

4 effects, including effects on pulmonary structure and function and central nervous system 

5 effects after developmental exposure to O3. Limited epidemiologic evidence exists for an 

6 association with O3 concentration and decreased sperm concentration. A recent 

7 toxicological study provides limited evidence for a possible biological mechanism 

8 (histopathology showing impaired spermatogenesis and rescue with antioxidants) for 

9 such an association. Additionally, though the evidence for an association between O3

10 concentrations and adverse birth outcomes is generally inconsistent, there are several 

11 influential studies that indicate an association with reduced birth weight and restricted 

12 fetal growth. Overall, the evidence is suggestive of a causal relationship between 

13 long-term exposures to O3 and reproductive and developmental effects.

2.6.6 Cancer and Mutagenicity and Genotoxicity

14 The 2006 O3 AQCD reported that evidence did not support ambient O3 as a pulmonary 

15 carcinogen. Since the 2006 O3 AQCD, very few epidemiologic and toxicological studies 

16 have been published that examine O3 as a carcinogen, but collectively, study results 

17 indicate that O3 may contribute to DNA damage. Overall, the evidence is inadequate to 

18 determine if a causal relationship exists between ambient O3 exposures and 

19 cancer.

2.6.7 Policy Relevant Considerations

2.6.7.1 Populations at Increased Risk

20 Upon evaluating the association between short- and long-term exposure to O3 and various 

21 health outcomes, studies also attempted to identify populations that are at increased risk

22 for O3-related health effects. These studies did so by conducting stratified epidemiologic 

23 analyses; by examining individuals with an underlying health condition, genetic 

24 polymorphism, or categorized by age, race, or sex in controlled human exposure studies; 

25 or by developing animal models that mimic the pathophysiological conditions associated 

26 with an adverse health effect. These studies identified a multitude of factors that could 
Draft – Do Not Cite or Quote 2-31 September 2011

1 potentially contribute to whether an individual is at increased risk for O3-related health 

2 effects. The examination of at risk populations for O3 exposure allows for the NAAQS to 

3 provide an adequate margin of safety for both the general population and for sensitive 

4 populations. 

5 The populations identified in Chapter 8 that are most at risk for O3-related health effects 

6 are individuals with influenza/infection, individuals with asthma, and younger and older 

7 age groups. There were a small number of studies on influenza/infection but both 

8 reported influenza/infection to modify the association between O3 exposure and 

9 respiratory effects, with individuals having influenza or an infection being at increased 

10 risk. Asthma as a factor affecting risk was supported by controlled human exposure and 

11 toxicological studies, as well as some evidence from epidemiologic studies. Most studies 

12 comparing age groups reported greater effects of short-term O3 exposure on mortality 

13 among older adults, although studies of other health outcomes had inconsistent findings 

14 regarding whether older adults were at increased risk. Generally, studies of age groups 

15 also reported positive associations for respiratory hospital admissions and ED visits 

16 among children. Biological plausibility for this increased risk is supported by 

17 toxicological and clinical research. Diet and obesity are also both likely factors that affect 

18 risk. Multiple epidemiologic, controlled human exposure, and toxicological studies 

19 reported that diets deficient in vitamins E and C are associated with risk of O3 -related 

20 health effects. Similarly, studies of effect measure modification by body mass index 

21 (BMI) observed greater O3 -related respiratory decrements for individuals who were 

22 obese. 

23 Other potential factors [preexisting conditions (such as chronic obstructive pulmonary 

24 disease and cardiovascular disease), sex, and multiple genes (such as GSTM1, GSTP1, 

25 HMOX-1, NQO1, and TNF-α)] provided some evidence of susceptibility, but further 

26 investigation is warranted. In addition, examination of modification of the associations 

27 between O3 exposure and health effects by SES and race were available in a limited 

28 number of studies, and demonstrated possible increased odds of health effects related to 

29 O3 exposure among those with low SES and black race. 

30 Individuals with increased ambient exposure were examined in a recent study of outdoor 

31 workers, in which no effect modification was observed, and in studies of air conditioning 

32 prevalence, which demonstrated inconsistent findings. However, previous evidence along 

33 with biological plausibility from toxicological and controlled human studies has shown 

34 individuals exposed to more outdoor air to be at increased risk of O3-related health 

35 effects. Studies of physical conditioning and smoking were conducted but little evidence 

36 was available to determine whether increased risk of O3-related health effects is present 

37 for these factors. The only studies examining effect measure modification by diabetes 
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1 examined O3 exposure and cardiovascular outcomes and none reported increased risks for 

2 individuals with diabetes. Toxicological studies also identified hyperthyroidism to be a 

3 factor warranting further examination. Future research will provide additional insight into 

4 whether these factors affect risk of O3-related health effects. 

2.6.7.2 Lag Structure in Epidemiologic Studies

5 Epidemiologic studies have attempted to identify the time-frame in which exposure to O3

6 can impart a health effect. Although O3 exposure-response relationships have 

7 traditionally been examined using air quality data for a defined lag period (e.g., 1 day or 

8 average of 0-1 days), the relationship can potentially be influenced by a multitude of 

9 factors, such as the underlying susceptibility of an individual (e.g., age, pre-existing 

10 diseases), which could increase or decrease the lag times observed. Different lag times 

11 have been evaluated for specific health outcomes. 

12 The epidemiologic evidence evaluated in the 2006 O3 AQCD indicated that one of the 

13 remaining uncertainties in characterizing the O3-mortality relationship was identifying 

14 the appropriate lag structure (e.g., single-day lags versus distributed lag model). An 

15 examination of lag times used in the epidemiologic studies evaluated in this assessment 

16 can provide further insight on the relationship between O3 exposure and morbidity and 

17 mortality outcomes. 

18 Collectively, recent epidemiologic studies of lung function, respiratory symptoms, and 

19 biological markers of airway inflammation and oxidative stress examined associations 

20 with single-day ambient O3 exposures (using various averaging times) lagged from 0 to 7 

21 days as well as concentrations averaged over 2 to 19 days. Lags of 0 and 1 day ambient 

22 O3 exposures were associated with decreases in lung function and increases in respiratory 

23 symptoms, airway inflammation, and oxidative stress. Additionally, several studies found 

24 that multiday averages of O3 exposure were associated with these endpoints, indicating 

25 that not only single day, but exposures accumulated over several days led to a respiratory 

26 health effect. In studies of respiratory hospital admissions and ED visits, investigators 

27 either examined the lag structure of associations by including both single-day and the 

28 average of multiday lags, or selecting lags a priori. Of the studies evaluated, the 

29 collective evidence indicates a rather immediate response within the first few days of O3

30 exposure (i.e., for lags days averaged at 0-1, 0-2, and 0-3 days) for hospital admissions 

31 and ED visits for all respiratory outcomes, asthma, and chronic obstructive pulmonary 

32 disease in all-year and seasonal analyses. 

33 The majority of epidemiologic studies that focused on the association between short-term 

34 O3 exposure and mortality (i.e., all-cause, respiratory and cardiovascular) examined the 
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1 average of multiday lags with some studies examining single-day lags. Across a range of 

2 multiday lags (i.e., average of 0-1 to 0-6 days), the studies evaluated consistently 

3 demonstrate that the O3 effects on mortality occur within a few days of exposure (Figure 

4 6-28). Additionally, several recent studies have conducted more extensive analysis of lag 

5 structure to investigate “mortality displacement” (i.e., deaths are occurring in frail 

6 individuals and exposure is only moving the day of death to a day slightly earlier), which 

7 also inform upon the lag structure of associations (Section 6.6.2.4). Collectively, these 

8 studies suggest that the positive associations between O3 and mortality are observed 

9 mainly in the first few days after exposure. 

2.6.7.3 Ozone Concentration-Response Relationship

10 An important consideration in characterizing the O3-morbidity and mortality association 

11 is whether the C-R relationship is linear across the full concentration range that is 

12 encountered or if there are concentration ranges where there are departures from linearity 

13 (i.e., nonlinearity). In this ISA studies have been identified that attempt to characterize 

the shape of the O3 C-R curve along with possible O3 “thresholds” (i.e., O3 14 levels which 

15 must be exceeded in order to elicit a health response). The controlled human exposure 

16 and epidemiologic studies that examined the shape of the C-R curve and the potential 

17 presence of a threshold have indicated a generally linear C-R function with no indication 

18 of a threshold for O3 concentrations greater than 30 or 40 ppb, which corresponds with 

19 PRB and the lower bound of O3 concentrations included in the C-R functions.

20 Controlled human exposure studies have provided strong and quantifiable C-R data on 

21 the human health effects of O3. The magnitude of respiratory effects in these studies is 

22 generally a function of O3 exposure, i.e., the product of concentration (C), minute 

23 ventilation (VE), and exposure duration. Recent studies provide evidence for a smooth C24 R curve without indication of a threshold in young healthy adults, exposed during 

25 moderate exercise for 6.6 hours to O3 concentrations between 40 and 120 ppb 

26 (Figure 6-1). 

27 Although relatively few epidemiologic studies have examined the O3-health effects C-R 

28 relationship, the C-R relationship has been examined across multiple health endpoints 

29 and exposure durations. Some studies of populations engaged in outdoor activity found 

30 that associations between O3 and lung function decrements persisted at lower O3

31 concentrations (Table 6-5). For example, a study found ambient O3 exposure (10-min to 

32 1-h) during outdoor exercise to be associated with decreases in lung function in analyses 

33 restricted to concentrations less than 51 ppb, though effect estimates were near zero with 

34 O3 concentrations less than 41 ppb. In contrast, a subsequent study found associations 
Draft – Do Not Cite or Quote 2-34 September 2011

1 persisted with 1-h max O3 concentrations less than 40 ppb. A study examining the C-R 

2 relationship between short-term O3 exposure and pediatric asthma ED visits found no 

3 evidence of a threshold. In both quintile and loess dose-response analyses this study 

4 found evidence that suggests that there are elevated associations for pediatric asthma ED 

5 visits with O3 concentrations as low as 30 ppb (Figure 6-11). In an additional study, 

6 authors used a smooth function while also accounting for the potential confounding 

7 effects of PM2.5, to examine whether the shape of the C-R curve for short-term exposure 

8 to O3 and asthma hospital admissions (i.e., both general and ICU for all ages) is linear. 

9 When comparing the curve to a linear fit, the authors found that the linear fit is a 

10 reasonable approximation of the C-R relationship between O3 and asthma hospital 

11 admissions around and below the current NAAQS (Figure 6-9). Although the C-R 

12 relationship between short-term O3 exposure and respiratory-related hospital admissions 

13 and ED visits has not been extensively examined, these preliminary examinations 

14 indicate a linear, no threshold relationship between short-term O3 exposure and pediatric 

15 asthma ED visits and asthma hospitalizations. 

16 The O3-health effects C-R relationship was further examined in studies of short-term O3

17 exposure and mortality. Evaluation of the C-R relationship for short-term exposure to O3

18 and mortality is difficult due to the evidence from multicity studies indicating highly 

19 heterogeneous O3-mortality associations across regions of the U.S. In addition, there are 

20 numerous issues that may influence the shape of the O3-mortality C-R relationship that 

21 need to be taken into consideration including: multiday effects (distributed lags), 

22 potential adaptation and mortality displacement (i.e., hastening of death by a short 

23 period). Several recent studies applied a variety of statistical approaches to examine the 

24 shape of the O3-mortality C-R relationship and whether a threshold exists. These studies 

25 did not find any evidence that supports a threshold for the association between short-term 

26 exposure to O3 and mortality within a range of O3 concentrations observed in the U.S. 

27 Recent evidence also suggests that the shape of the O3-mortality C-R curve remains 

28 linear across the full range of the O3 concentrations. However, studies have also 

29 demonstrated heterogeneity in the O3-mortality relationship across cities (or regions), 

30 which complicates the interpretation of a combined C-R curve and threshold analysis. 

31 Additionally, given the effect modifiers identified in mortality analyses that are also 

32 expected to vary regionally (e.g., temperature, air conditioning prevalence), a national or 

33 combined analysis may not be appropriate to identify whether a threshold exists in the 

34 O3-mortality C-R relationship. 

35 An evaluation of long-term exposure studies identified studies of long-term exposure to 

36 O3 and birth outcomes that have characterized the C-R relationship. Evidence from the 

37 southern California Children’s Health Study identified a C-R relationship of birth weight 

38 with 24-h avg O3 concentrations averaged over the entire pregnancy that was clearest 
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1 above the 30 ppb level (Figure 7-4). Relative to the lowest decile of 24-h avg O3, 

2 estimates for the next 5 lowest deciles were approximately -40 g to -50 g, with no clear 

3 trend and with 95% confidence bounds that included zero. The highest four deciles of O3

4 exposure showed an approximately linear decrease in birth weight, and all four 95% CIs 

5 excluded zero, and ranged from mean decreases of 74 grams to decreases of 148 grams. 

6 Another study conducted in southern California reported increased risks for cardiac birth 

7 defects in a dose-response manner with second-month O3 exposure.

8 Collectively, both short- and long-term exposure studies that examined the O3-health 

9 effects C-R relationship have provided no evidence of a threshold. Additionally, these 

10 studies indicate a linear C-R relationship across the full range of O3 concentrations 

11 observed in the U.S.

2.7 Integration of Effects on Vegetation and Ecosystems

12 Chapter 9 presents the most policy-relevant information related to this review of the 

13 NAAQS for the effects of O3 on vegetation and ecosystems. This section integrates the 

14 key findings from the disciplines evaluated in this assessment of the O3 scientific 

15 literature, which includes plant physiology, whole plant biology, ecosystems, and 

16 exposure-response. 

17 Ozone effects at small spatial scales, such as the leaf of an individual plant, can result in 

18 effects at a continuum of larger spatial scales. Figure 2-4 is a simplified illustrative 

19 diagram of the major pathway through which O3 enters leaves and the major endpoints O3

20 may affect in vegetation and ecosystems. The sections of Chapter 9 are organized 

21 according to increasing spatial scales, starting with the cellular and subcellular level, then 

22 the whole plant and finally, ecosystem-level processes. Ozone enters leaves through 

23 stomata, and can alter stomatal conductance and disrupt CO2 fixation (Section 9.3). These 

24 effects can change rates of leaf gas exchange, growth and reproduction at the individual 

25 plant level and result in changes in ecosystems, such as productivity, C storage, water 

26 cycling, nutrient cycling, and community composition (Section 9.4). The framework for 

27 causal determinations has been applied to the body of scientific evidence to collectively 

28 examine effects attributed to O3 exposure (Table 2-2). The summary below provides brief 

29 integrated summaries of the evidence that supports the causal determinations. The 

30 detailed discussion of the underlying evidence used to formulate each causal 

31 determination can be found in Chapters 9. This summary ends with a short discussion of 

32 policy relevant considerations.
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2.7.1 Visible Foliar Injury

1 Visible foliar injury resulting from exposure to O3 has been well characterized and 

2 documented over several decades of research on many tree, shrub, herbaceous, and crop 

3 species (U.S. EPA, 2006b, 1996b, 1984, 1978a) (Section 9.4.2). Ozone-induced visible 

4 foliar injury symptoms on certain bioindicator plant species are considered diagnostic as 

5 they have been verified experimentally in exposure-response studies, using exposure 

6 methodologies such as continuous stirred tank reactors (CSTRs), open-top chambers 

7 (OTCs), and free-air fumigation. Experimental evidence has clearly established a 

8 consistent association of visible injury with O3 exposure, with greater exposure often 

9 resulting in greater and more prevalent injury. Since the 2006 O3 AQCD, several 

10 multiple-year field surveys of O3-induced visible foliar injury have been conducted at 

11 National Wildlife Refuges in Maine, Michigan, New Jersey, and South Carolina. New 

12 sensitive species showing visible foliar injury continue to be identified from field surveys 

13 and verified in controlled exposure studies.

Figure 2-4 An illustrative diagram of the major pathway through which O3

enters leaves and the major endpoints that O3 may affect in plants 

and ecosystems.

O3 exposure

O3 uptake & physiology (Fig 9-2) •Antioxidant metabolism up-regulated

•Decreased photosynthesis

•Decreased stomatal conductance 

or sluggish stomatal response

Effects on leaves

•Visible leaf injury

•Altered leaf production 

•Altered leaf chemical composition

Plant growth (Fig 9.8) •Decreased biomass accumulation

•Altered reproduction

•Altered carbon allocation

•Altered crop quality

Belowground processes (Fig 9.8) •Altered litter production and decomposition

•Altered soil carbon and nutrient cycling

•Altered soil fauna and microbial communities

Differential O3 sensitivity

Affected ecosystem services

•Decreased productivity 

•Decreased C sequestration

•Altered water cycling (Fig 9-7)

•Altered community composition 

(i.e., plant, insect & microbe)
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Table 2-2 Summary of ozone causal determinations for vegetation and 

ecosystem effects

Vegetation and 

Ecosystem Effects Conclusions from 2006 O3 AQCD Conclusions from 2011 2nd Draft ISA

Visible Foliar Injury Effects on 

Vegetation 

Data published since the 1996 O3 AQCD strengthen previous conclusions that 

there is strong evidence that current ambient O3 concentrations cause impaired 

aesthetic quality of many native plants and trees by increasing foliar injury.

Causal Relationship

Reduced Vegetation Growth Data published since the 1996 O3 AQCD strengthen previous conclusions that 

there is strong evidence that current ambient O3 concentrations cause 

decreased growth and biomass accumulation in annual, perennial and woody 

plants, including agronomic crops, annuals, shrubs, grasses, and trees.

Causal Relationship

Reduced Productivity in 

Terrestrial Ecosystems

There is evidence that O3 is an important stressor of ecosystems and that the 

effects of O3 on individual plants and processes are scaled up through the 

ecosystem, affecting net primary productivity.

Causal Relationship

Reduced Carbon (C) 

Sequestration in Terrestrial 

Ecosystems

Limited studies from previous review Likely to be a Causal 

Relationship

Reduced Yield and Quality of 

Agricultural Crops

Data published since the 1996 O3 AQCD strengthen previous conclusions that 

there is strong evidence that current ambient O3 concentrations cause 

decreased yield and/or nutritive quality in a large number of agronomic and 

forage crops.

Causal Relationship

Alteration of Terrestrial 

Ecosystem Water Cycling

Ecosystem water quantity may be affected by O3 exposure at the landscape 

level.

Likely to be a Causal 

Relationship

Alteration of Below-ground 

Biogeochemical Cycles

Ozone-sensitive species have well known responses to O3 exposure, including 

altered C allocation to below-ground tissues, and altered rates of leaf and root 

production, turnover, and decomposition. These shifts can affect overall C and N 

loss from the ecosystem in terms of respired C, and leached aqueous dissolved 

organic and inorganic C and N.

Causal Relationship

Alteration of Terrestrial 

Community Composition 

Ozone may be affecting above- and below -ground community composition 

through impacts on both growth and reproduction. Significant changes in plant 

community composition resulting directly from O3 exposure have been 

demonstrated.

Likely to be a Causal 

Relationship

1 The use of biological indicators in field surveys to detect phytotoxic levels of O3 is a 

2 longstanding and effective methodology. The USDA Forest Service through the Forest 

3 Health Monitoring (FHM) Program (1990-2001) and currently the Forest Inventory and 

4 Analysis (FIA) Program has been collecting data regarding the incidence and severity of 

5 visible foliar injury on a variety of O3 sensitive plant species throughout the U.S. The 

6 network has provided evidence that O3 concentrations were high enough to induce visible 

7 symptoms on sensitive vegetation. From repeated observations and measurements made 

8 over a number of years, specific geographical patterns of visible O3 injury symptoms can 

9 be identified. In addition, a study assessed the risk of O3-induced visible foliar injury on 

10 bioindicator plants in 244 national parks in support of the National Park Service’s Vital 

11 Signs Monitoring Network. The results of the study demonstrated that the risk of visible 

12 foliar injury was high in 65 parks (27%), moderate in 46 parks (19%), and low in 131 

13 parks (54%). Some of the well-known parks with a high risk of O3-induced visible foliar 

14 injury include Gettysburg, Valley Forge, Delaware Water Gap, Cape Cod, Fire Island, 

15 Antietam, Harpers Ferry, Manassas, Wolf Trap Farm Park, Mammoth Cave, Shiloh, 
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1 Sleeping Bear Dunes, Great Smoky Mountains, Joshua Tree, Sequoia and Kings Canyon, 

2 and Yosemite. Overall, evidence is sufficient to conclude that there is a causal 

3 relationship between ambient O3 exposure and the occurrence of O3-induced

4 visible foliar injury on sensitive vegetation across the U.S.

2.7.2 Growth, Productivity, Carbon Storage and Agriculture

5 Ambient O3 concentrations have long been known to cause decreases in photosynthetic 

6 rates and plant growth. The O3-induced damages at the plant scale may translate to the 

7 ecosystem scale, and cause changes in productivity and C storage. The effects of O3

8 exposure on photosynthesis, growth, biomass allocation, ecosystem production and 

9 ecosystem C sequestration were reviewed for the natural ecosystems, and crop 

10 productivity and crop quality were reviewed for the agricultural ecosystems. 

2.7.2.1 Natural Ecosystems

11 The previous O3 AQCDs concluded that there is strong and consistent evidence that 

12 ambient concentrations of O3 decrease plant photosynthesis and growth in numerous 

13 plant species across the U.S. Studies published since the last review continue to support 

14 that conclusion (Section 9.4.3.1). New studies, based on the Aspen free-air carbon15 dioxide/ozone enrichment (FACE) experiment, found that O3 caused reductions in total 

16 biomass relative to the control in aspen, paper birch, and sugar maple communities 

17 during the first seven years of stand development. Overall, the studies at the Aspen FACE 

18 experiment were consistent with the open-top chamber (OTC) studies that were the 

19 foundation of previous O3 NAAQS reviews. These results strengthen our understanding 

20 of O3 effects on forests and demonstrate the relevance of the knowledge gained from 

21 trees grown in open-top chamber studies. 

22 A set of meta-analyses assessed the effects of O3 on plant photosynthesis and growth 

23 across different species and fumigation methods (such as OTC and FACE). Those studies 

24 reported that current O3 concentrations in the northern hemisphere are decreasing 

25 photosynthesis (~11%) across tree species, and the decreases in photosynthesis are 

26 consistent with cumulative uptake of O3 into the leaf. The current ambient O3

27 concentrations (~40 ppb) significantly decreased annual total biomass growth of forest 

28 species by an average of 7%, with potentially greater decreases (11-17%) in areas that 

29 have higher O3 concentrations (Section 9.4.3.1). The meta-analyses further confirmed 

30 that reduction of plant photosynthesis and growth under O3 exposure are coherent across

31 numerous species and various experimental techniques. 
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1 Studies during recent decades have also demonstrated O3 alters biomass allocation and 

2 plant reproduction (Section 9.4.3). Recent meta-analyses have generally indicated that O3

3 reduced C allocated to roots, although the findings of individual studies were mixed. 

4 Several recent studies published since the 2006 O3 AQCD further demonstrate that O3

5 altered reproductive processes, such as timing of flowering, number of flowers, fruits and 

6 seeds, in herbaceous and woody plant species. However, a knowledge gap still exists 

7 pertaining to the exact mechanism of the responses of reproductive processes to O3

8 exposure (Section 9.4.3.3). 

9 Studies at the leaf and plant scales showed that O3 reduced photosynthesis and plant 

10 growth, providing coherence and biological plausibility for the reported decreases in 

11 ecosystem productivity. During the previous NAAQS reviews, there were very few 

12 studies that investigated the effect of O3 exposure on ecosystem productivity and C 

13 sequestration. Recent studies from long-term FACE experiments and ecosystem models 

14 provided evidence of the association of O3 exposure and reduced productivity at the 

15 ecosystem scale. Elevated O3 reduced stand biomass at Aspen FACE after 7 years of O3

16 exposure, and annual volume growth at the Kranzberg Forest in Germany. Results across 

17 different ecosystem models were consistent with the FACE experimental evidence, which 

18 showed that O3 reduced ecosystem productivity (Section 9.4.3.4). In addition to primary 

19 productivity, other indicators such as net ecosystem CO2 exchange (NEE) and C 

20 sequestration were often assessed by model studies. Model simulations consistently 

21 found that O3 exposure caused negative impacts on those indicators (Section 9.4.3.4, 

22 Table 9-3), but the severity of these impacts was influenced by multiple interactions of 

23 biological and environmental factors. The suppression of ecosystem C sinks results in 

24 more CO2 accumulation in the atmosphere. A recent study suggested that the indirect 

25 radiative forcing caused by O3 exposure through lowering ecosystem C sink could have 

26 an even greater impact on global warming than the direct radiative forcing of O3.

27 Although O3 generally causes negative effects on ecosystem productivity, the magnitude 

28 of the response varies among plant communities (Section 9.4.3.4). For example, O3 had 

29 little impact on white fir, but greatly reduced growth of ponderosa pine in southern 

30 California. Ozone decreased net primary production (NPP) of most forest types in Mid31 Atlantic region, but had small impacts on spruce-fir forest. Ozone could also affect 

32 regional C budgets through interacting with multiple factors, such as N deposition, 

33 elevated CO2 and land use history. Model simulations suggested that O3 partially offset 

34 the growth stimulation caused by elevated CO2 and N deposition in both Northeast- and 

35 Mid-Atlantic-region forest ecosystems of the U.S.

36 Overall, evidence is sufficient to conclude that there is a causal relationship 

37 between O3 exposure and reduced plant growth and productivity, and a likely 
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1 causal relationship between O3 exposure and reduced carbon sequestration in 

2 terrestrial ecosystems.

2.7.2.2 Agricultural Crops

3 The detrimental effect of O3 on crop production has been recognized since the 1960’s and 

4 a large body of research has subsequently stemmed from those initial findings. Previous 

5 O3 AQCDs have extensively reviewed this body of literature. Current O3 concentrations 

6 across the U.S. are high enough to cause yield loss for a variety of agricultural crops 

7 including, but not limited to, soybean, wheat, potato, watermelon, beans, turnip, onion, 

8 lettuce, and tomato (Section 9.4.4.1). Continued increases in O3 concentration may 

9 further decrease yield in these sensitive crops. Despite the well-documented yield losses 

10 due to increasing O3 concentration, there is still a knowledge gap pertaining to the exact 

11 mechanism of O3-induced yield loss. Research has linked increasing O3 concentration to 

12 decreased photosynthetic rates and accelerated senescence, which are related to yield.

13 In addition, new research has highlighted the effects of O3 on crop quality. Increasing O3

14 concentration decreases nutritive quality of grasses, decreases macro- and micro-nutrient 

15 concentrations in fruits and vegetable crops, and decreases cotton fiber quality. These 

16 areas of research require further investigation to determine the mechanism and dose17 responses (Section 9.4.4.2).

18 During the previous NAAQS reviews, there were very few studies that estimate O3

19 impacts on crop yields at large spatial scales. Recent modeling studies found that O3

20 generally reduced crop yield, but the impacts varied across regions and crop species 

21 (Section 9.4.4.1). For example, the largest O3-induced crop yield losses occurred in high22 production areas exposed to high O3 concentrations, such as the Midwest and the 

23 Mississippi Valley regions of the U.S. Among crop species, the estimated yield loss for 

24 wheat and soybean were higher than rice and maize. Satellite and ground-based O3

25 measurements have been used to assess yield loss caused by O3 over the continuous tri26 state area of Illinois, Iowa and Wisconsin. The results showed that O3 concentrations 

27 significantly reduced soybean yield, which correlates well with the previous results from 

28 FACE-type experiments and OTC experiments (Section 9.4.4.1). 

29 Evidence is sufficient to conclude that there is a causal relationship between O3

30 exposure and reduced yield and quality of agricultural crops.
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2.7.3 Water Cycling

1 Ozone can affect water use in plants and ecosystems through several mechanisms 

2 including damage to stomatal functioning and loss of leaf area. Section 9.3.6 reviewed 

3 possible mechanisms for O3 exposure effects on stomatal functioning including the build4 up of CO2 in substomatal cavity, impacts on signal transduction pathways and direct O3

5 impact on guard cells. Regardless of the mechanism, O3 exposure has been shown to alter 

6 stomatal performance, which may affect plant and stand transpiration and therefore 

7 possibly affecting hydrological cycling. 

8 Although the evidence was from a limited number of field and modeling studies, these 

9 findings showed an association of O3 exposure and the alteration of water use and cycling 

10 in vegetation and ecosystem level (Section 9.4.5). There is not a clear consensus on the 

11 nature of leaf-level stomatal conductance response to O3 exposure. When measured at 

12 steady-state high light conditions, leaf-level stomatal conductance is often found to be 

13 reduced when exposed to O3. However, measurements of stomatal conductance under 

14 dynamic light and vapor pressure deficit conditions indicate sluggish responses under 

15 elevated O3 exposure which could potentially lead to increased water loss from 

16 vegetation. Field studies suggested that peak hourly O3 exposure increased the rate of 

17 water loss from several tree species, and led to a reduction in the late-season modeled 

18 stream flow in three forested watersheds in eastern Tennessee. Sluggish stomatal 

19 responses during O3 exposure was suggested as a possible mechanism for increased water 

20 loss during peak O3 exposure. Currently, the O3-induced reduction in stomatal aperture is 

21 the biological assumption for most process-based models. Therefore, results of those 

22 models normally found that O3 reduced water loss. For example, one study found that O3

23 damage and N limitation together reduced evapotranspiration and increase runoff.

24 Although the direction of the response differed among studies, the evidence is 

25 sufficient to conclude that there is likely to be a causal relationship between O3

26 exposure and the alteration of ecosystem water cycling.

2.7.4 Below-Ground Processes

27 Below-ground processes are tightly linked with aboveground processes. The responses of 

28 aboveground process to O3 exposure, such as reduced photosynthetic rates, increased 

29 metabolic cost, and reduced root C allocation, have provided biologically plausible 

30 mechanisms for the alteration of below-ground processes. Since the 2006 O3 AQCD, 

31 more evidence has shown that although the responses are often species specific, O3

32 altered the quality and quantity of C input to soil, microbial community composition, and 

33 C and nutrient cycling. 
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1 Results from Aspen FACE and other experimental studies consistently found that O3

2 reduced litter production and altered C chemistry, such as soluble sugars, soluble 

3 phenolics, condensed tannins, lignin, and macro/micro nutrient concentration in litter 

4 (Section 9.4.6.1). The changes in substrate quality and quantity could alter microbial 

5 metabolism under elevated O3, and therefore soil C and nutrient cycling. Several studies 

6 indicated that O3 generally suppressed soil enzyme activities (Section 9.4.6.2). However, 

7 the impact of O3 on litter decomposition was inconsistent and varied among species, sites 

8 and exposure length. Similarly, O3 had inconsistent impacts on dynamics of micro and 

9 macro nutrients (Section 9.4.6.4). 

10 Studies from the Aspen FACE experiment suggested that the response of below-ground 

11 C cycle to O3 exposure, such as litter decomposition, soil respiration and soil C content, 

12 changed over time. For example, in the early part of the experiment (1998-2003), O3 had 

13 no impact on soil respiration but reduced the formation rates of total soil C under 

14 elevated CO2. However, after 10 to 11 years of exposure, O3 was found to increase soil 

15 respiration but have no significant impact on soil C formation under elevated CO2

16 (Section 9.4.6.3). 

17 The evidence is sufficient to infer that there is a causal relationship between O3

18 exposure and the alteration of below-ground biogeochemical cycles.

2.7.5 Community Composition

19 In the 2006 O3 AQCD, the impact of O3 exposure on species competition and community 

20 composition was assessed. Ozone was found to be one of the dominant factors causing a 

21 significant decline in ponderosa and Jeffrey pine in the San Bernardino Mountains in 

22 southern California. Ozone exposure also tended to shift the grass-legume mixtures in 

23 favor of grass species. Since the 2006 O3 AQCD, more evidence has shown that O3

24 exposure changed the competitive interactions and led to loss of O3 sensitive species or 

25 genotypes. Studies found that the severity of O3 damage on growth, reproduction and 

26 foliar injury varied among species (Section 9.4.3), which provided the biological 

27 plausibility for the alteration of community composition. Additionally, research since the 

28 last review has shown that O3 can alter community composition and diversity of soil 

29 microbial communities.

30 The decline of conifer forests under O3 exposure was continually observed in several 

31 regions. Ozone damage was believed to be an important causal factor in the dramatic 

32 decline of sacred fir in the valley of Mexico, as well as cembran pine in southern France 

33 and Carpathian Mountains, although several factors, such as drought, insect outbreak and 

34 forest management, may also contribute to or even be the dominant factors causing the 
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1 mortality of the conifer trees. Results from the Aspen FACE site indicated that O3 could 

2 alter community composition of broadleaf forests as well. At the Aspen FACE site, O3

3 reduced growth and increased mortality of a sensitive aspen clone, while the O3 tolerant 

4 clone emerged as the dominant clone in the pure aspen community. In the mixed aspen5 birch and aspen-maple communities, O3 reduced the competitive capacity of aspen 

6 compared to birch and maple (Section 9.4.7.1).

7 The tendency for O3-exposure to shift the biomass of grass-legume mixtures in favor of 

8 grass species was reported in the 2006 O3 AQCD and has been generally confirmed by 

9 recent studies. However, in a high elevation mature/species-rich grass-legume pasture, O3

10 fumigation showed no significant impact on community composition (Section 9.4.7.2).

11 Ozone exposure not only altered community composition of plant species, but also 

12 microorganisms. The shift in community composition of bacteria and fungi has been 

13 observed in both natural and agricultural ecosystems, although no general patterns could 

14 be identified (Section 9.4.7.3). 

15 The evidence is sufficient to conclude that there is likely a causal relationship 

16 between O3 exposure and the alteration of community composition.

2.7.6 Policy Relevant Considerations

2.7.6.1 Air Quality Indices

17 Exposure indices are metrics that quantify exposure as it relates to measured plant 

18 damage (e.g., reduced growth). They are summary measures of monitored ambient O3

19 concentrations over time intended to provide a consistent metric for reviewing and 

20 comparing exposure-response effects obtained from various studies. No new information 

21 is available since 2006 that alters the basic conclusions put forth in the 2006 and 1996 O3

22 AQCDs. These AQCDs focused on the research used to develop various exposure indices 

23 to help quantify effects on growth and yield in crops, perennials, and trees (primarily 

24 seedlings). The performance of indices was compared through regression analyses of 

25 earlier studies designed to support the estimation of predictive O3 exposure-response 

26 models for growth and/or yield of crops and tree (seedling) species.

27 Another approach for improving risk assessment of vegetation response to ambient O3 is 

28 based on determining the O3 concentration from the atmosphere that enters the leaf (i.e., 

29 flux or deposition). Interest has been increasing in recent years, particularly in Europe, in 

30 using mathematically tractable flux models for O3 assessments at the regional, national, 

31 and European scale. While some efforts have been made in the U.S. to calculate O3 flux 
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1 into leaves and canopies, little information has been published relating these fluxes to 

2 effects on vegetation. There is also concern that not all O3 stomatal uptake results in a 

3 yield reduction, which depends to some degree on the amount of internal detoxification 

4 occurring with each particular species. Species having high detoxification capacity may 

5 show little relationship between O3 stomatal uptake and plant response. The lack of data 

6 in the U.S. and the lack of understanding of detoxification processes have made this 

7 technique less viable for vulnerability and risk assessments in the U.S. 

8 The main conclusions from the 1996 and 2006 O3 AQCDs regarding indices based on 

9 ambient exposure remain valid. These key conclusions can be restated as follows:

10  O3 effects in plants are cumulative;

11  higher O3 concentrations appear to be more important than lower 

12 concentrations in eliciting a response;

13  plant sensitivity to O3 varies with time of day and plant development stage; 

14 and

15  exposure indices that cumulate hourly O3 concentrations and preferentially 

16 weight the higher concentrations have better statistical fits to growth/yield 

17 response data than do the mean and peak indices.

18 Various weighting functions have been used, including threshold-weighted (e.g., 

19 SUM06) and continuous sigmoid-weighted (e.g., W126) functions. Based on statistical 

20 goodness-of-fit tests, these cumulative, concentration-weighted indices could not be 

21 differentiated from one another using data from previous exposure studies. Additional 

22 statistical forms for O3 exposure indices are summarized in Section 9.5 of this ISA. The 

23 majority of studies published since the 2006 O3 AQCD do not change earlier conclusions, 

24 including the importance of peak concentrations, and the duration and occurrence of O3

25 exposures in altering plant growth and yield.

26 Given the current state of knowledge and the best available data, exposure indices that 

27 cumulate and differentially weight the higher hourly average concentrations and also 

28 include the mid-level values continue to offer the most defensible approach for use in 

29 developing response functions and comparing studies, as well as for defining future 

30 indices for vegetation protection.

2.7.6.2 Exposure-Response

31 None of the information on effects of O3 on vegetation published since the 2006 O3

32 AQCD has modified the assessment of quantitative exposure-response relationships that 

33 was presented in that document (U.S. EPA, 2006b). This assessment updates the 2006 
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1 exposure-response models by computing them using the W126 metric, cumulated over 

2 90 days. Almost all of the experimental research on the effects of O3 on growth or yield 

3 of plants published since 2006 used only two levels of exposure. In addition, hourly O3

4 concentration data that would allow calculations of exposure using the W126 metric are 

5 generally unavailable. However, two long-term experiments, one with a crop species 

6 (soybean), one with a tree species (aspen), have produced data that are used in Section 

7 9.6 to validate the exposure-response models presented in the 2006 O3 AQCD, and the 

8 methodology used to derive them. EPA compared predictions from the models presented 

9 in the 2006 O3 AQCD, updated to use the 90 day 12hr W126 metric, with more recent 

10 observations for yield of soybean and biomass growth of trembling aspen. The models 

11 were parameterized using data from the NCLAN and NHEERL-WED projects, which 

12 were conducted in OTCs. The more recent observations were from experiments using 

13 FACE technology, which is intended to provide conditions closer to natural environments 

14 than OTC. Observations from these new experiments were exceptionally close to 

15 predictions from the models. The accuracy of model predictions for two widely different 

16 plant species, grown under very different conditions, provides support for the validity of 

17 the models for crops and trees developed using the same methodology and data for other 

18 species. However, variability observed among species in the NCLAN and NHEERL19 WED projects indicates that the range of sensitivity between and among species is likely 

20 quite wide.

21 Results from several meta-analyses have provided approximate values for responses of 

22 yield of soybean, wheat, rice and other crops under broad categories of exposure, relative 

23 to charcoal-filtered air. Additional reports have summarized yield data for six crop 

24 species under various broad comparative exposure categories, and reviewed 263 studies 

25 that reported effects on tree biomass. However, these analyses have proved difficult to 

26 compare with exposure-response models, especially given that exposure was not 

27 expressed on the same W126 scale. 

2.8 The Role of Tropospheric Ozone in Climate Change and UV-B 

Effects

28 Atmospheric O3 plays an important role in the Earth’s energy budget by interacting with 

29 incoming solar radiation and outgoing infrared radiation. Tropospheric O3 makes up only 

30 a small portion of the total column of O3, but it has important incremental effects on the 

31 overall radiation budget. Chapter 10 assesses the specific role of tropospheric O3 in the 

32 earth’s radiation budget and how perturbations in tropospheric O3 might affect (1) climate 

33 through its role as a greenhouse gas, and (2) health, ecology and welfare through its role 

34 in shielding the earth’s surface from solar ultraviolet (UV) radiation.
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2.8.1 Tropospheric Ozone as a Greenhouse Gas

1 Ozone is an important greenhouse gas, and increases in its abundance in the troposphere 

2 may contribute to climate change according to the 2007 climate assessment by the 

3 Intergovernmental Panel on Climate Change (IPCC). Models calculate that the global

4 burden of tropospheric O3 has doubled since the preindustrial era, while observations 

5 indicate that in some regions O3 may have increased by factors as great as 4 or 5. These 

6 increases are tied to the rise in emissions of O3 precursors from human activity, mainly 

7 fossil fuel consumption and agricultural processes.

8 Units shown are those typical for each quantity illustrated. Feedbacks from both the 

9 climate response and climate impacts can, in turn, affect the abundance of tropospheric 

10 O3 and O3 precursors through multiple feedback mechanisms. Climate impacts are 

11 deemphasized in the figure since these downstream effects are extremely complex and 

12 outside the scope of this assessment.

13 Figure 2-5 shows the main steps involved in the influence of tropospheric O3 on climate. 

14 Emissions of O3 precursors including CO, VOCs, CH4, and NOX lead to production of 

15 tropospheric O3. A change in the abundance of tropospheric O3 perturbs the radiative 

16 balance of the atmosphere, an effect quantified by the radiative forcing (RF) metric. The 

17 earth-atmosphere-ocean system responds to the forcing with a climate response, typically 

18 expressed as a change in surface temperature. Finally, the climate response causes 

19 downstream climate-related health and ecosystem impacts, such as redistribution of 

20 diseases or ecosystem characteristics due to temperature changes. Feedbacks from both 

21 the climate response and downstream impacts can, in turn, affect the abundance of 

22 tropospheric O3 and O3 precursors through multiple feedback mechanisms as indicated in 

23 Figure 2-5. Direct feedbacks are discussed in Section 10.2.3.4 while downstream climate 

24 impacts and their feedbacks are extremely complex and outside the scope of this 

25 assessment.

26 The impact of the tropospheric O3 change since preindustrial times on climate has been 

27 estimated to be about 25-40% of anthropogenic CO2 impact and about 75% of 

28 anthropogenic CH4 impact according to the IPCC, ranking it third in importance among 

29 the greenhouse gases. There are large uncertainties in the RF estimate attributed to 

30 tropospheric O3, however, making the impact of tropospheric O3 on climate more 

31 uncertain than the impact of the long-lived greenhouse gases. Despite these uncertainties, 

32 the evidence supports a causal relationship between changes in tropospheric O3

33 concentrations and radiative forcing.

34 RF does not take into account the climate feedbacks that could amplify or dampen the

35 actual surface temperature response. Quantifying the change in surface temperature 
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1 requires a complex climate simulation in which all important feedbacks and interactions 

2 are accounted for. As these processes are not well understood or easily modeled, the

3 surface temperature response to a given RF is highly uncertain and can vary greatly 

4 among models and from region to region within the same model. In light of these 

5 uncertainties, the evidence supports a likely to be a causal relationship between 

6 changes in tropospheric O3 concentrations and climate change.

Units shown are those typical for each quantity illustrated. Feedbacks from both the climate response and climate impacts can, in 

turn, affect the abundance of tropospheric O3 and O3 precursors through multiple feedback mechanisms. Climate impacts are 

deemphasized in the figure since these downstream effects are extremely complex and outside the scope of this assessment.

Figure 2-5 Schematic illustrating the effects of tropospheric O3 on climate

including the relationship between precursor emissions, 

tropospheric O3 abundance, radiative forcing, climate response, 

and climate impacts. Tropospheric Ozone and UV-B related effects

7 UV radiation emitted from the Sun contains sufficient energy when it reaches the Earth to 

8 break (photolyze) chemical bonds in molecules, thereby leading to damaging effects on 

9 living organisms and materials. Atmospheric O3 plays a crucial role in reducing exposure 

10 to solar UV radiation at the Earth’s surface. Ozone in the stratosphere is responsible for 

11 the majority of this shielding effect, as approximately 90% of total atmospheric O3 is 

12 located there over mid-latitudes. Ozone in the troposphere provides supplemental 

13 shielding of radiation in the wavelength band from 280-315 nm, referred to as UV-B 
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1 radiation. UV-B radiation has important effects on human health and ecosystems, and is 

2 associated with materials damage.

3 Adverse human health effects associated with solar UV-B radiation exposure include 

4 erythema, skin cancer, ocular damage, and immune system suppression. A potential 

5 human health benefit of increased UV-B exposure involves the UV-induced production 

6 of vitamin D which may help reduce the risk of metabolic bone disease, type I diabetes, 

7 mellitus, and rheumatoid arthritis, and may provide beneficial immunomodulatory effects 

8 on multiple sclerosis, insulin-dependent diabetes mellitus, and rheumatoid arthritis.

9 Adverse ecosystem and materials damage effects associated with solar UV-B radiation 

10 exposure include terrestrial and aquatic ecosystem impacts, alteration of biogeochemical 

11 cycles, and degradation of man-made materials. Terrestrial ecosystem effects from 

12 increased UV-B radiation include reduced plant productivity and plant cover, changes in 

13 biodiversity, susceptibility to infection, and increases in natural UV protective responses. 

14 In general, however, these effects are small for moderate UV-B increases at mid15 latitudes. Aquatic ecosystem effects from increased UV-B radiation include sensitivity in 

16 growth, immune response, and behavioral patterns of aquatic organisms and the potential 

17 for increased catalysis and mobility of trace metals. Biogeochemical cycles, particularly 

18 the carbon cycle, can also be influenced by increased UV-B radiation with effects ranging 

19 from UV-induced increases in CO2 uptake through soil respiration to UV-induced release 

20 of CO2 through photodegradation of above-ground plant litter. Changes in solar UV 

21 radiation may also have effects on carbon cycling and CO2 uptake in the oceans as well 

22 as release of dissolved organic matter from sediment and algae. Finally, materials damage 

23 from increased UV-B radiation includes UV-induced photodegradation of wood and 

24 plastics.

25 There is a lack of published studies that critically examine the incremental health or 

26 welfare effects (adverse or beneficial) attributable specifically to changes in UV-B 

27 exposure resulting from perturbations in tropospheric O3 concentrations. The effects are 

28 expected to be small and they cannot yet be critically assessed within reasonable 

29 uncertainty. Overall, the evidence is inadequate to determine if a causal relationship 

30 exists between tropospheric O3 and UV-B related health and welfare effects.
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2.9 Summary of Causal Determinations for Health Effects and 

Welfare Effects 

1 This chapter has provided an overview of the underlying evidence used in making the 

2 causal determinations for the health and welfare effects of O3. This review builds upon 

3 the conclusions of the previous AQCDs for O3. 

4 The evaluation of the epidemiologic, toxicological, and controlled human exposure 

5 studies published since the completion of the 2006 O3 AQCD have provided additional 

6 evidence for O3-related health outcomes. Table 2-3 provides an overview of the causal 

7 determinations for all of the health outcomes evaluated. Causal determinations for O3 and 

8 welfare effects are included in Table 2-4, while causal determinations for climate change 

9 and UV-B effects are in Table 2-5. Detailed discussions of the scientific evidence and 

10 rationale for these causal determinations are provided in subsequent chapters of this ISA. 

Table 2-3 Summary of ozone causal determinations by exposure duration 

and health outcome

Health Outcome Conclusions from 2006 O3 AQCD Conclusions from 

2011 1st Draft ISA

Short-Term Exposure to O3

Respiratory effects The overall evidence supports a causal relationship between acute ambient O3

exposures and increased respiratory morbidity outcomes.

Causal Relationship

Cardiovascular effects The limited evidence is highly suggestive that O3 directly and/or indirectly contributes to 

cardiovascular-related morbidity, but much remains to be done to more fully 

substantiate the association.

Suggestive of a Causal 

Relationship

Central nervous system 

effects

Toxicological studies report that acute exposures to O3 are associated with alterations in 

neurotransmitters, motor activity, short and long term memory, sleep patterns, and 

histological signs of neurodegeneration.

Suggestive of a Causal 

Relationship

Mortality The evidence is highly suggestive that O3 directly or indirectly contributes to nonaccidental and cardiopulmonary-related mortality.Likely to be a Causal 

Relationship

Long-term Exposure to O3

Respiratory effects The current evidence is suggestive but inconclusive for respiratory health effects from 

long-term O3 exposure.

Likely to be a Causal 

Relationship

Cardiovascular Effects No studies from previous review Suggestive of a Causal 

Relationship

Reproductive and 

developmental effects

Limited evidence for a relationship between air pollution and birth-related health 

outcomes, including mortality, premature births, low birth weights, and birth defects, with 

little evidence being found for O3 effects.

Suggestive of a Causal 

Relationship

Central nervous system 

effects

Evidence regarding chronic exposure and neurobehavioral effects was not available. Suggestive of a Causal 

Relationship

Cancer Little evidence for a relationship between chronic O3 exposure and increased risk of 

lung cancer.

Inadequate to infer a 

Causal Relationship

Mortality There is little evidence to suggest a causal relationship between chronic O3 exposure 

and increased risk for mortality in humans.

Suggestive of a Causal 

Relationship
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Table 2-4 Summary of ozone causal determination for welfare effects

Vegetation and 

Ecosystem Effects Conclusions from 2006 O3 AQCD Conclusions from 2011 2nd Draft ISA

Visible Foliar Injury Effects on 

Vegetation 

Data published since the 1996 O3 AQCD strengthen previous conclusions that 

there is strong evidence that current ambient O3 concentrations cause impaired 

aesthetic quality of many native plants and trees by increasing foliar injury.

Causal Relationship

Reduced Vegetation Growth Data published since the 1996 O3 AQCD strengthen previous conclusions that 

there is strong evidence that current ambient O3 concentrations cause 

decreased growth and biomass accumulation in annual, perennial and woody 

plants, including agronomic crops, annuals, shrubs, grasses, and trees.

Causal Relationship

Reduced Productivity in 

Terrestrial Ecosystems

There is evidence that O3 is an important stressor of ecosystems and that the 

effects of O3 on individual plants and processes are scaled up through the 

ecosystem, affecting net primary productivity.

Causal Relationship

Reduced Carbon (C) 

Sequestration in Terrestrial 

Ecosystems

Limited studies from previous review Likely to be a Causal 

Relationship

Reduced Yield and Quality of 

Agricultural Crops

Data published since the 1996 O3 AQCD strengthen previous conclusions that 

there is strong evidence that current ambient O3 concentrations cause 

decreased yield and/or nutritive quality in a large number of agronomic and 

forage crops.

Causal Relationship

Alteration of Terrestrial 

Ecosystem Water Cycling

Ecosystem water quantity may be affected by O3 exposure at the landscape 

level.

Likely to be a Causal 

Relationship

Alteration of Below-ground 

Biogeochemical Cycles

Ozone-sensitive species have well known responses to O3 exposure, including 

altered C allocation to below-ground tissues, and altered rates of leaf and root 

production, turnover, and decomposition. These shifts can affect overall C and N 

loss from the ecosystem in terms of respired C, and leached aqueous dissolved 

organic and inorganic C and N.

Causal Relationship

Alteration of Terrestrial 

Community Composition 

Ozone may be affecting above- and below -ground community composition 

through impacts on both growth and reproduction. Significant changes in plant 

community composition resulting directly from O3 exposure have been 

demonstrated.

Likely to be a Causal 

Relationship

Table 2-5 Summary of ozone causal determination for climate change and 

UV-B effects

Effects Conclusions from 2006 O3 AQCD Conclusions from 

2011 1st Draft ISA

Radiative Forcing Climate forcing by O3 at the regional scale may be its most important impact on climate. Causal Relationship

Climate Change While more certain estimates of the overall importance of global-scale forcing due to 

tropospheric O3 await further advances in monitoring and chemical transport modeling, 

the overall body of scientific evidence suggests that high concentrations of O3 on the 

regional scale could have a discernable influence on climate, leading to surface 

temperature and hydrological cycle changes.

Likely to be a Causal 

Relationship

UV-B Related Health and 

Welfare Effects 

UV-B has not been studied in sufficient detail to allow for a credible health benefits 

assessment. In conclusion, the effect of changes in surface-level O3 concentrations on 

UV-induced health outcomes cannot yet be critically assessed within reasonable 

uncertainty.

Inadequate to Determine if 

a Causal Relationship 

Exists

1
Draft – Do Not Cite or Quote 2-51 September 2011

2.10 References

CAA. (Air quality criteria and control techniques, Section 108 of the Clean Air Act). 42. § 7408, (1990a).

U.S. EPA. (U.S. Environmental Protection Agency). (1978a). Air quality criteria for ozone and other 

photochemical oxidants. (EPA/600/8-78/004). Washington, DC.

U.S. EPA. (U.S. Environmental Protection Agency). (1984). Air quality criteria for ozone and other 

photochemical oxidants, Vol. 3. (EPA/600/8-84/020A). Research Triangle Park, NC. 

http://nepis.epa.gov/Exe/ZyPURL.cgi?Dockey=2000AVEV.txt.

U.S. EPA. (U.S. Environmental Protection Agency). (1996a). Air quality criteria for ozone and related 

photochemical oxidants. (EPA/600/P-93/004AF). Research Triangle Park, NC.

U.S. EPA. (U.S. Environmental Protection Agency). (1996b). Air quality criteria for ozone and related 

photochemical oxidants, Vol. II of III. (EPA/600/P-93/004BF). Research Triangle Park, NC.

U.S. EPA. (U.S. Environmental Protection Agency). (2006b). Air quality criteria for ozone and related 

photochemical oxidants. (EPA/600/R-05/004AF). Research Triangle Park, NC: U.S. Environmental 

Protection Agency, Office of Research and Development. 

http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=149923.

U.S. EPA. (U.S. Environmental Protection Agency). (2008f). Notice of workshop and call for information on 

integrated science assessment for ozone. Fed Reg 73: 56581-56583. 

U.S. EPA. (U.S. Environmental Protection Agency). (2009c). Integrated review plan for the ozone National 

Ambient Air Quality Standards review (external review draft). (EPA 452/D-09-001). Washington, DC. 

http://www.epa.gov/ttnnaaqs/standards/ozone/data/externalreviewdraftO3IRP093009.pdf.

U.S. EPA. (U.S. Environmental Protection Agency). (2010e). Our nation's air: Status and trends through 2008. 

(EPA-454/R-09-002). Research Triangle Park, NC. 

http://www.epa.gov/airtrends/2010/report/fullreport.pdf.

Zhang, L; Jacob, DJ; Downey, NV; Wood, DA; Blewitt, D; Carouge, CC; Van donkelaar, A; Jones, DBA; Murray, 

LT; Wang, Y. (In Press) Improved estimate of the policy-relevant background ozone in the United States 

using the GEOS-Chem global model with 1/2° × 2/3° horizontal resolution over North America. Atmos 

Environ. http://dx.doi.org/10.1016/j.atmosenv.2011.07.054.