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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 or welfare which may be expected from 

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

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

9 incorporated into this assessment. Additional details of the pertinent scientific literature 

10 published since the last review, as well as selected earlier studies of particular interest, 

11 are included. This ISA thus serves to update and revise the evaluation of the scientific 

12 evidence available at the time of the completion of the 2006 O3 AQCD. The current 

13 primary O3 standard includes an 8-hour (h) average (avg) standard set at 75 parts per 

14 billion (ppb). The secondary standard for O3 is set equal to the primary standard. Further 

15 information on the legislative and historical background for the O3 NAAQS is contained 

16 in the Preface to this ISA.

17 This chapter summarizes and synthesizes the available scientific evidence and is intended 

18 to provide a concise synopsis of the ISA conclusions and findings that best inform 

19 consideration of the policy-relevant questions that frame this assessment (U.S. EPA, 

20 2009c). It includes:

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

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

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

24 evidence from the different scientific disciplines and exposure durations.

25  An integration of the evidence on the welfare effects associated with exposure 

26 to O3, including those associated with vegetation and ecosystems, and 

27 discussion of important uncertainties identified in the interpretation of the 

28 scientific evidence.

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

30 populations and concentration-response relationships and how they inform 

31 selection of appropriate exposure metrics/indices. 
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2.1 ISA Development and Scope

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

2 scientific evidence and drawing conclusions and causal judgments regarding air 

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

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

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

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

7 Preamble to the ISA. This section provides a brief overview of the process for 

8 development of this ISA.

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

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

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

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

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

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

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

16 in the ISA, with bibliographic information and abstracts.

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

18 this includes studies pertaining to the atmospheric science of O3, human exposure to 

19 ambient O3, and health, ecological, climate and UV-B effects studies. These include 

20 studies that are related to concentration-response relationships, mode(s) of action (MOA), 

21 and understanding of at-risk populations for effects of O3 exposure. Added to the body of 

22 research were EPA’s analyses of air quality and emissions data, studies on atmospheric 

23 chemistry, transport, and fate of these emissions. 

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

25 body of evidence on both health and welfare effects of O3 exposure, as well as an 

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

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

28 each section, to provide the foundation for consideration of evidence from recent studies. 

29 Results of key studies from previous reviews are included in discussions or tables and 

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

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

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

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

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

35 placed on those studies most relevant to the review of the NAAQS. Studies conducted in 
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1 the United States (U.S.) or Canada are discussed in more detail than those from other 

2 geographical regions, and in regard to human health, particular emphasis is placed on: 

3 (1) recent multicity studies that employ standardized analysis methods for evaluating 

4 effects of O3 and that provide overall estimates for effects, based on combined analyses 

5 of information pooled across multiple cities; (2) studies that help understand quantitative 

6 relationships between exposure concentrations and effects; (3) new studies that provide 

7 evidence on effects in at-risk populations; and (4) studies that consider and report O3 as a 

8 component of a complex mixture of air pollutants. In evaluating toxicological and 

9 controlled human exposure studies, emphasis is placed on studies using concentrations 

10 that are within about an order of magnitude of ambient O3 concentrations. Consideration 

11 of studies important for evaluation of human exposure to ambient O3 places emphasis on 

12 those evaluating the relationship between O3 measured at central site monitors and 

13 personal exposure to ambient O3. Important factors affecting this relationship include 

14 spatial and temporal variations in ambient O3 concentration, and time spent outdoors, 

15 since penetrations of O3 into indoor environments may be limited. 

16 Epidemiologic studies generally present O3-related effect estimates for mortality and 

17 morbidity health outcomes based on an incremental change in exposure, traditionally 

18 equal to the interquartile range in O3 concentrations or some other arbitrary value 

19 (e.g., 10 ppb). Additionally, various averaging times are used in O3 epidemiologic studies, 

20 with the three most common being the maximum 1-hour average within a 24-hour period 

21 (1-h max), the maximum 8-hour average within a 24-h period (8-h max), and 24-hour 

22 average (24-h avg). For the purpose of presenting results from studies that use different 

23 exposure metrics, EPA consistently applies the same O3 increments to facilitate 

24 comparisons between the results of various studies that may use different indices. These 

25 increments were derived using the nationwide distributional data for O3 monitors in U.S. 

26 Metropolitan Statistical Areas and are representative of a low-to-high change in O3

27 concentrations and were approximated on the basis of annual mean to 95th percentile 

28 differences (Langstaff, 2003). Therefore, throughout Chapter 6, efforts were made to 

29 standardize O3-related effect estimates using the increments of 20 ppb for 24-h avg, 

30 30 ppb for 8-h max, and 40 ppb for 1-h max O3 concentrations, except as noted. In long31 term exposure studies, typically, O3 concentrations are lower and less variable when 

32 averaged across longer exposure periods, and differences due to the use of varying 

33 averaging times (e.g., 1-h max, 24-h avg) become less apparent. As such, in the long-term 

34 exposure chapter (Chapter 7) an increment of 10 ppb was consistently applied across 

35 studies, regardless of averaging time, to facilitate comparisons between the results from 

36 these studies. 
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1 This ISA uses a five-level hierarchy that classifies the weight of evidence for causation: 

2  Causal relationship 

3  Likely to be a causal relationship 

4  Suggestive of a causal relationship 

5  Inadequate to infer a causal relationship 

6  Not likely to be a causal relationship 

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

8 environmental risks based on the understanding of the quantitative relationships between 

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

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

11 regarding quantitative relationships include: 

12  What is the concentration-response, exposure-response, or dose-response 

13 relationship?

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

15 are effects observed?

16  What populations appear to be differentially affected i.e., at-risk to effects?

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

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

19 effects?

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

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

22 Section 2.2 discusses the trends in ambient concentrations and sources of O3 and provides 

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

24 Section 2.3 presents the evidence regarding personal exposure to ambient O3 in outdoor 

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

26 concentrations and personal exposure to ambient O3. Section 2.4 provides a discussion of 

27 the dosimetry and mode of action evidence for O3 exposure. Section 2.5 integrates the 

28 evidence for studies that examine the health effects associated with short- and long-term 

29 exposure to O3 and discusses important uncertainties identified in the interpretation of the 

30 scientific evidence. A discussion of policy-relevant considerations, such as potentially at31 risk populations, lag structure, and the O3 concentration-response relationship is also 

32 included in Section 2.5. Finally, Section 2.6 summarizes the evidence for welfare effects 

33 related to O3 exposure, and Section 2.7 reviews the literature on the influence of 

34 tropospheric O3 on climate and exposure to solar ultraviolet radiation. 
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2.2 Atmospheric Chemistry and Ambient Concentrations

2.2.1 Physical and Chemical Processes

1 Ozone in the troposphere is a secondary pollutant; it is formed by photochemical 

2 reactions of precursor gases and is not directly emitted from specific sources. Ozone 

3 precursor gases originate from both anthropogenic (i.e., man-made) and natural source 

4 categories. Ozone attributed to anthropogenic sources is formed in the atmosphere by 

5 photochemical reactions involving sunlight and precursor pollutants including volatile 

6 organic compounds (VOCs), nitrogen oxides (NOX), and carbon monoxide (CO). Ozone 

7 attributed to natural sources is formed through similar photochemical reactions involving 

8 natural emissions of precursor pollutants from vegetation, microbes, animals, biomass 

9 burning, lightning, and geogenic sources. The distinction between natural and 

10 anthropogenic sources of O3 precursors is often difficult to make in practice, as human 

11 activities affect directly or indirectly emissions from what would have been considered 

12 natural sources during the pre-industrial era. A schematic overview of the major 

13 photochemical cycles influencing O3 in the troposphere and the stratosphere is shown in 

14 Figure 2-1. The processes depicted in this figure are fairly well understood, and were 

15 covered in detail in the previous O3 AQCD. The formation of O3, other oxidants, and 

16 oxidation products from these precursors is a complex, nonlinear function of many 

17 factors including: (1) the intensity and spectral distribution of sunlight reaching the lower 

18 troposphere; (2) atmospheric mixing; (3) concentrations of precursors in the ambient air 

19 and the rates of chemical reactions of these precursors; and (4) processing on cloud and 

20 aerosol particles.
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Figure 2-1 Schematic overview of photochemical processes influencing 

stratospheric and tropospheric ozone.

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

2 even in remote areas of the globe. Similar basic processes involving sunlight-driven 

3 reactions of NOX, VOCs and CO contribute to O3 formation throughout the troposphere. 

4 These processes also lead to the formation of other photochemical products, such as 

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

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

7 all important for O3 formation. In non-urban vegetated areas, biogenic VOCs emitted 

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

9 troposphere, methane—structurally the simplest VOC—and CO are the main carbon10 containing precursors to O3 formation. Ozone is subsequently removed from the 
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1 troposphere through a number of gas phase reactions and deposition to surfaces as shown 

2 in Figure 2-1.

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

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

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

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

7 characterized by the development of urban plumes. Meteorological conditions, small8 scale circulation patterns, localized chemistry, and mountain barriers can influence 

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

10 individual urban areas.

11 Furthermore, because the mean tropospheric lifetime of O3 is a few weeks, O3 can be 

12 transported from continent to continent. The degree of influence from intercontinental 

13 transport varies greatly by location and time. For instance, high elevation sites are most 

14 susceptible to the intercontinental transport of pollution, particularly during spring. 

15 However, because the atmospheric chemistry of O3 is quite complex and can be highly 

16 non-linear in environments close to sources of precursors, isolating the influence of 

17 intercontinental transport of O3 and O3 precursors on urban air quality is particularly 

18 problematic.

2.2.2 Atmospheric Modeling of Background Ozone Concentrations

19 A number of recent studies indicate that natural sources such as wildfires and 

20 stratospheric intrusions and the intercontinental transport of pollution can affect O3 air 

21 quality at specific times and in specific locations in the United States. These contributions 

22 are in addition to contributions from dominant local pollution sources. To gain a broader 

23 perspective and to isolate the influence of natural or transported O3, estimates from 

24 chemical transport models (CTMs) must be used. This is because observations within the 

25 U.S.—even at relatively remote monitoring sites—are impacted by transport from 

26 anthropogenic source regions within U.S. borders.

27 In the context of a review of the NAAQS, it is useful to define background O3

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

29 precursor emissions that are relatively less controllable from those that are relatively 

30 more controllable through U.S. policies. For this assessment, three definitions of 

31 background O3 concentrations are considered, including (1) North American (NA) 

32 background (simulated O3 concentrations that would exist in the absence of 

33 anthropogenic emissions from the U.S., Canada and Mexico), (2) United States (U.S.) 

34 background (simulated O3 concentrations that would exist in the absence of 
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1 anthropogenic emissions from the U.S.), and (3) natural background (simulated O3

2 concentrations in the absence of all anthropogenic emissions globally). Each definition of 

3 background O3 includes contributions resulting from emissions from natural sources 

4 (e.g., stratospheric intrusion, wildfires, biogenic methane and more short-lived VOC 

5 emissions) throughout the globe. There is no chemical difference between background O3

6 and O3 attributable to U.S. or North American anthropogenic sources. However, to 

7 inform policy considerations regarding the current or potential alternative standards, it is 

8 useful to understand how total O3 concentrations (i.e., O3 from all sources) can be 

9 attributed to different sources.

10 Since background O3 concentrations as defined above are a construct that cannot be 

11 directly measured, the range of background O3 concentrations is estimated using CTMs. 

12 For the current assessment, the GEOS-Chem model at 0.5°×0.667° (~50 km×50 km) 

13 horizontal resolution and a nested, hybrid GEOS-Chem/CAMx model at finer horizontal 

14 resolution (12 km × 12 km) were used. Results from these two models represent the latest 

15 estimates for background O3 concentrations documented in the peer-reviewed literature 

and are shown in Table 2-1. The R2 16 for both models are generally <0.5, with CAMx 

17 showing generally higher values than GEOS-Chem (Table 3-1). The GEOS-Chem 

18 model-predicted seasonal mean daily maximum 8-h average O3 concentrations for the 

19 base case (i.e., including all anthropogenic and natural sources globally), U.S. 

20 background, and NA background simulations during spring and summer 2006 are shown 

21 in Figure 2-2.

Table 2-1 Comparison of seasonal mean MDA8 ozone concentrations 

simulated by the GEOS-Chem and CAMx base case models for 

2006, with measurements at CASTNET sites.

Region CASTNET GEOS-Chem GEOS-Chem/CAMx

Spring Summer Spring Summer Spring Summer

California (5)a 58 ± 12b 69 ± 14

52 ± 11

38 ± 7c

66 ± 18

37 ± 9

50 ± 10

39 ± 6

66 ± 13

42 ± 6

West (14) 54 ± 9 55 ± 11

53 ± 7

42 ± 6

55 ± 11

40 ± 9

49 ± 8

40 ± 7

57 ± 10

41 ± 8

North Central (6) 47 ± 10 50 ± 12

47 ± 8

33 ± 6

51 ± 14

27 ± 7

45 ± 11

30 ± 6

54 ± 13

31 ± 5

Northeast (5) 48 ± 10 45 ± 14

45 ± 7

33 ± 7

45 ± 13

24 ± 7

46 ± 11

30 ± 5

53 ± 14

27 ± 6

Southeast (9) 52 ± 11 52 ± 16

51 ± 7

32 ± 7

54 ± 9

29 ± 10

54 ± 9

33 ± 6

61 ± 12

30 ± 6

a

Values in parentheses after each region name refer to the number of sites.

b

Shown are seasonal (spring, summer) mean daily maximum 8-h avg O3 concentrations in ppb ± standard deviation. 

c

North American background mean daily maximum 8-h avg O3 concentrations (ppb ± standard deviation) are shown beneath the 
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base case means.

Note: Mean daily average 8-h O3 concentrations were calculated by GEOS-Chem for the base case (top, Base), United States 

background (middle, USB) and North American Background (lower, NAB).

Values in parentheses (above each map) refer to continental U.S. means, and are shown in the color bar as black squares for 

summer and white squares for spring.

Source: Adapted from Zhang et al. (2011).

Figure 2-2 Mean daily average 8-hour ozone concentrations in surface air, for 

spring and summer 2006.
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1 The main results from these modeling efforts can be summarized as follows.

2  Simulated regional and seasonal means of base-case O3 using both models 

3 generally agree to within a few ppb with observations throughout the western 

4 and central U.S., except in California; but GEOS-Chem shows better 

5 agreement than CAMx in the eastern U.S. However, these results are likely to 

6 change with updates to model chemistry and physics.

7  Both models show background concentrations vary spatially and temporally. 

8 NA background concentrations are generally higher in spring than in summer 

9 across the U.S. Simulated mean NA background concentrations are highest in 

10 the Intermountain West (i.e., at high altitude) in spring and in the Southwest in 

11 summer. Lowest estimates of NA background occur in the East in the spring 

12 and the Northeast in summer.

13  NA background concentrations tend to increase with total (i.e., base case) O3

14 concentrations at high elevation, but that tendency is not as clear at low 

15 elevations.

16  Comparison of NA background and natural background indicate that methane 

17 is a major contributor to NA background O3, accounting for slightly less than 

18 half of the increase in background since the preindustrial era and whose 

19 relative contribution is projected to grow in the future.

20  U.S. background concentrations are on average 2.6 ppb higher than NA 

21 background concentrations during spring and 2.7 ppb during summer across 

22 the U.S. with highest increases above NA background over the Northern Tier 

23 of New York State (19.1 ppb higher than NA background) in summer. High 

24 values for U.S. background are also found in other areas bordering Canada 

25 and Mexico.

26  Contributions to background O3 can be episodic or non-episodic; high 

27 background concentrations are driven primarily by the episodic events such as 

28 stratospheric intrusions and wildfires. The most pronounced differences 

29 between these model results and observations are at the upper end of the 

30 concentration distribution, particularly at high elevations.

31 Note that the calculations of background concentrations presented in this chapter were 

32 formulated to answer the question, “what would O3 concentrations be if there were no 

33 anthropogenic sources”. This is different from asking, “how much of the O3 measured or 

34 simulated in a given area is due to background contributions”. Because of potentially 

35 strong non-linearities—particularly in many urban areas—these estimates should not be 

36 used by themselves to answer the second question posed above. The extent of these non37 linearities will generally depend on location and time, the strength of concentrated 
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1 sources, and the nature of the chemical regime. Further work is needed on how these

2 estimates of background concentrations can be used to help determine the contributions 

3 of background sources of O3 to urban concentrations.

2.2.3 Monitoring

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

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

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

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

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

9 and bias goals during this period.

10 In 2010, there were 1250 SLAMS O3 monitors reporting data to AQS. Ozone monitoring 

11 is required at SLAMS sites during the local “ozone season” which varies by state. In 

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

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

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

15 nationwide (See Figure 3-21 and Figure 3-22). The densest concentrations of O3 sites are 

16 located in California and the eastern half of the U.S.

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

18 established to assess trends in acidic deposition and also provides concentration 

19 measurements of O3. CASTNET O3 monitors operate year round and are primarily 

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

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

22 Class-i areas, and provided data to AQS from 20 additional Portable Ozone Monitoring 

23 Systems (POMS) in 2010 (See Figure 3-22). Compared to urban-focused monitors, rural24 focused monitors are relatively scarce across the U.S.

2.2.4 Ambient Concentrations

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

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

27 only measured during special field studies. The concentration analyses in Chapter 3 are 

28 limited to widely available O3 data obtained directly from AQS for the period from 2007 

29 to 2009. The median 24-h average, 8-h daily maximum, and 1-h daily maximum O3

30 concentrations across all U.S. sites reporting data to AQS between 2007 and 2009 were 

31 29, 40, and 44 ppb, respectively.
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1 To investigate O3 variability in urban areas across the U.S., 20 combined statistical areas 

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

3 studies and on their location. Several CSAs had relatively little spatial variability in 

4 8-hour daily maximum O3 concentrations (e.g., inter-monitor correlations ranging from 

5 0.61 to 0.96 in the Atlanta CSA) while other CSAs exhibited considerably more 

6 variability in O3 concentrations (e.g., inter-monitor correlations ranging from -0.06 to 

7 0.97 in the Los Angeles CSA). Uncertainties resulting from the observed variability in O3

8 concentration fields should be considered when using data from the network of ambient 

9 O3 monitors to approximate community-scale exposures.

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

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

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

13 AQS monitors was Great Smoky Mountains National Park where the May-September 

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

15 (564 m) site to 60 ppb at the highest elevation (2,021 m) site. Correlations between sites 

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

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

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

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

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

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

22 O3 tends to persist longer in rural than in urban areas as a result of less chemical 

23 scavenging. This results in a more uniform O3 concentration throughout the day and night 

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

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

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

27 frequently exceed cumulative exposures in urban areas.

28 Nation-wide surface level O3 concentrations have declined over the last decade, with a 

29 particularly noticeable decrease between 2003 and 2004 coinciding with NOX emissions 

30 reductions resulting from implementation of the NOX SIP Call rule, which began in 2003 

31 and was fully implemented in 2004. This rule was designed to reduce NOX emissions 

32 from power plants and other large combustion sources in the eastern U.S. The largest 

33 density of individual monitors showing downward trends in O3 concentrations over the 

34 last decade occur in the Northeast where this rule was focused. In addition to a downward 

35 trend, the nation-wide surface level O3 concentration data also show a general tightening 

36 of the distribution across sites. In contrast to the majority of U.S. surface level monitors 

37 reporting downward trends, a few surface-level monitors and elevated observations along 

38 the Pacific Coast have shown increases in O3 concentrations in recent years, possibly 
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1 resulting from intercontinental transport from Asia. As noted in the 2006 O3 AQCD, 

2 trends in national parks and rural areas are similar to nearby urban areas, reflecting the 

3 regional nature of O3 pollution.

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

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

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

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

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

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

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

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

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

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

14 investigated.

2.3 Human Exposure

15 The widespread presence of O3 in the environment results in exposure as people 

16 participate in normal daily activities. Personal exposure measurements have been found 

17 to be moderately associated with fixed-site ambient O3 concentrations, although a number 

18 of factors affect the relationship between ambient concentration and personal exposure. 

19 These include: infiltration of ambient O3 into indoor microenvironments, which is driven 

20 by air exchange rate; time spent outdoors and activity pattern, which includes changes in 

21 personal behavior by some populations to avoid exposure to O3; and the variation in O3

22 concentrations at various spatial and temporal scales. Personal exposure to O3 is 

23 moderately correlated with ambient O3 concentration, as indicated by studies reporting 

24 correlations generally in the range of 0.3-0.8 (Table 4-2). This suggests that ambient 

25 monitor concentrations are representative of day-to-day changes in personal exposure to 

26 ambient O3. Some studies report lower personal-ambient correlations, a result attributable 

27 in part to low building air exchange rates and O3 concentrations below the personal 

28 sampler detection limit. Low correlations may also occur for individuals or populations 

29 spending increased time indoors. In contrast to correlation, which represents the temporal 

30 association between exposure and concentration, the magnitude of exposure can be 

31 represented as the ratio between personal exposure and ambient concentration. This ratio 

32 varies widely depending on activity patterns, housing characteristics, and season. 

33 Personal-ambient ratios are typically 0.1-0.3 for sampling durations of several hours to 

34 several days, although individuals spending substantial time outdoors (e.g., outdoor 

35 workers) have shown much higher ratios (0.5-0.9) (Table 4-3). Since there are relatively 
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1 few indoor sources of O3, and because of reactions of O3 with indoor surfaces and 

2 airborne constituents, indoor O3 concentrations are often substantially lower than outdoor 

3 concentrations (Section 4.3.2). The lack of indoor sources also suggests that fluctuations 

4 in ambient O3 may be primarily responsible for changes in personal exposure, even under 

5 low-ventilation, low-concentration conditions. 

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

7 avoid O3 exposure by altering their behavior (e.g., reducing outdoor activity levels or 

8 time spent being active outdoors) on high-O3 days. Activity pattern has a substantial 

9 effect on ambient O3 exposure, with time spent outdoors contributing to increased 

10 exposure (Section 4.4.2). Air quality alerts and public health recommendations induce 

11 reductions in time spent outdoors on high-O3 days among some populations, particularly 

12 for children, older adults, and people with respiratory problems. Such effects are less 

13 pronounced in the general population. Limited evidence from an epidemiologic study 

14 conducted in the 1990’s in Los Angeles, CA reports increased asthma hospital 

15 admissions among children and older adults when O3 alert days (1-h max O3

16 concentration >200 ppb) were excluded from the analysis of daily hospital admissions 

17 and O3 concentrations (presumably thereby eliminating averting behavior based on high 

18 O3 forecasts). The lower rate of admissions observed when alert days were included in 

19 the analysis suggests that estimates of health effects based on concentration-response 

20 functions that do not account for averting behavior may be biased towards the null.

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

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

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

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

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

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

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

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

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

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

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

32 different locations within an urban area. The various factors affecting exposure patterns 

33 and quantification of exposure result in uncertainty which may contribute to exposure 

34 measurement error in epidemiologic studies, which typically use fixed-site monitor data 

35 as an indicator of exposure. Low personal-ambient correlations are a source of exposure 

36 error for epidemiologic studies, tending to obscure the presence of potential thresholds,

37 bias effect estimates toward the null, and widen confidence intervals, and this impact may 

38 be more pronounced among populations spending substantial time indoors. The impact of 
Draft – Do Not Cite or Quote 2-15 June 2012

1 this exposure error may tend more toward widening confidence intervals than biasing 

2 effect estimates, since epidemiologic studies evaluating the influence of monitor selection 

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

4 monitoring sites. In addition, in examinations of respiratory endpoints in epidemiologic 

5 studies, associations were similar in magnitude across analyses using several different 

6 exposure assessment methods that likely vary in how well ambient O3 concentrations 

7 represent personal exposures and between-subject variability in exposures. Respiratory 

8 effects were observed with ambient O3 concentrations found to have stronger personal9 ambient relationships, including those measured on-site during long periods of outdoor 

10 activity. However, such effects were also found with ambient O3 measurements expected 

11 to have weaker personal-ambient relationships, including those measured at home or 

12 school, measured at the closest site, averaged from multiple community sites, and 

13 measured at a single site. Overall, there was no clear indication that a particular method 

14 of exposure assessment produced stronger findings.

2.4 Dosimetry and Mode of Action

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

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

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

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

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

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

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

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

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

24 or the junction of the conducting airways with the gas exchange region. 

25 Ozone uptake is sensitive to a number of factors including tidal volume, breathing 

26 frequency, O3 concentration, and exposure time. Interindividual variability also accounts 

27 for a large amount of the variability in local dose due to differences in pulmonary 

28 physiology, anatomy, and biochemistry. An increase in tidal volume and breathing 

29 frequency are both associated with increased physical activity. These changes and a 

30 switch to oronasal breathing during exercise result in deeper penetration of O3 into the 

31 lower respiratory tract in part due to less oral versus nasal uptake efficiency. For these 

32 reasons, increased physical activity acts to move the maximum tissue dose of O3 distally 

33 in the respiratory tract and more into the alveolar region. 
Draft – Do Not Cite or Quote 2-16 June 2012

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

2 barrier and target for inhaled O3 (see Figure 5-7). Distinct products with diverse reactivity 

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

4 ELF components. The thickness of the ELF and that of the mucus layer, within the ELF, 

5 are important determinants of the dose of O3 to the tissues; a thicker ELF generally 

6 results in a lower dose of O3 to the tissues. Additionally, the quenching ability and the 

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

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

9 O3 with underlying tissues and to reduce penetration of O3 distally into the respiratory 

10 tract. 

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

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

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

14 pathways (See Figure 5-8) that provide the mechanistic basis for short- and long-term 

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

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

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

18 bronchial smooth muscle, modification of innate and adaptive immunity, and airways 

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

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

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

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

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

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

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

26 which mediate a mild increase in airways obstruction (i.e., bronchoconstriction) 

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

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

29 Secondary oxidation products also initiate the inflammatory cascade following exposure 

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

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

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

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

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

35 Inflammation further contributes to O3-induced oxidative stress. 

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

37 of O3-induced secondary oxidation product formation. Increased epithelial permeability 
Draft – Do Not Cite or Quote 2-17 June 2012

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

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

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

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

5 bronchial smooth muscle sensitization, while earlier studies demonstrate roles for 

6 eicosanoids, cytokines, and chemokines. 

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

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

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

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

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

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

13 Airways remodeling has been demonstrated following chronic and/or intermittent 

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

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

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

17 relevance to effects in humans is unknown. 

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

19 vascular oxidative/nitrosative stress. The release of diffusible mediators from the 

20 O3-exposed lung into the circulation may initiate or propagate inflammatory responses in 

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

22 extrapulmonary effects, such as vascular dysfunction. 

23 Both dosimetric and mechanistic factors contribute to the understanding of 

24 inter-individual variability in response. Inter-individual variability is influenced by 

25 variability in respiratory tract volume and thus surface area, breathing route, certain 

26 genetic polymorphisms, pre-existing conditions and disease, nutritional status, lifestages, 

27 attenuation, and co-exposures. In particular, very young individuals may be sensitive to 

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

29 development of lung and immune system. 

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

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

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

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

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

35 resting conditions underestimates the dose to the respiratory tract tissue relative to 

36 exercising humans. Further, it should be noted that, with the exception of airways 
Draft – Do Not Cite or Quote 2-18 June 2012

1 remodeling, the mechanistic pathways discussed above have been demonstrated in both 

2 animals and human subjects in response to the inhalation of O3. Even though interspecies 

3 differences limit quantitative comparison between species, the short- and long-term 

4 functional responses of laboratory animals to O3 appear qualitatively homologous to 

5 those of the human making them a useful tool in determining mechanistic and 

6 cause-effect relationships with O3 exposure. Furthermore, animal studies add to a better 

7 understanding of the full range of potential O3-mediated effects.

2.5 Integration of Ozone Health Effects

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

9 epidemiologic studies (which examined the health effects associated with short- and 

10 long-term exposure to O3,) and summarizes the main conclusions of this assessment 

11 regarding the health effects of O3 and the concentrations at which those effects are 

12 observed. The results from the health studies, supported by the synthesis of atmospheric 

13 chemistry (See Section 2.2) and exposure assessment (See Section 2.3) studies, contribute 

14 to the causal determinations made for the health outcomes discussed in this assessment 

15 (See Preamble to this document for details on the causal framework).

2.5.1 Conclusions from Previous Ozone AQCDs

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

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

18 2006b). The causal relationship for respiratory health effects was substantiated by the 

19 coherence of effects observed across controlled human exposure, epidemiologic, and 

20 toxicological studies indicating effects of short-term O3 exposures on a range of 

21 respiratory health endpoints from respiratory tract inflammation to respiratory-related 

22 emergency department (ED) visits and hospital admissions.

23 Across disciplines, short-term O3 exposures induced or were associated with statistically 

24 significant declines in lung function. An equally strong body of evidence from controlled 

25 human exposure and toxicological studies demonstrated O3-induced inflammatory 

26 responses, increased epithelial permeability, and airway hyperresponsiveness (both 

27 specific and nonspecific). Toxicological studies provided additional evidence for 

28 O3-induced impairment of host defenses. Combined, these findings from experimental 

29 studies provided support for epidemiologic evidence, in which short-term increases in 

30 ambient O3 concentration were consistently associated with increases in respiratory 

31 symptoms and asthma medication use in children with asthma, respiratory-related 
Draft – Do Not Cite or Quote 2-19 June 2012

1 hospital admissions, and asthma-related ED visits. Although O3 was consistently 

2 associated with nonaccidental and cardiopulmonary mortality, the contribution of 

3 respiratory causes to these findings was uncertain. 

4 Collectively, there is a vast amount of evidence spanning several decades that 

5 demonstrated that exposure to O3 induces a range of respiratory effects. The majority of 

6 this evidence was derived from studies investigating short-term exposure (i.e., hours to 

7 weeks) to O3. The combined evidence across disciplines led to the causal relationship 

8 between short-term O3 exposure and respiratory effects reported in the 2006 O3 AQCD. 

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

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

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

12 lung function, and the immune system. As summarized in Section 2.4 and fully 

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

14 in humans and animal models. They include formation of secondary oxidation products, 

15 activation of neural reflexes, initiation of inflammation, alteration of epithelial barrier 

16 function, sensitization of bronchial smooth muscle, modification of innate/adaptive 

17 immunity, airways remodeling, and systemic inflammation and oxidative/nitrosative 

18 stress. 

2.5.2 Summary of Causal Determinations

19 Recent studies support or build upon the strong body of evidence presented in the 1996 

20 and 2006 O3 AQCDs that short-term O3 exposure is causally associated with respiratory 

21 health effects. Recent controlled human exposure studies demonstrate statistically

22 significant group mean decreases in pulmonary function to exposures as low as 

23 60-70 ppb O3 in young, healthy adults, and are supported by the strong, cumulative 

24 evidence from epidemiologic studies. Equally strong evidence demonstrated associations 

25 of ambient O3 with respiratory hospital admissions and ED visits across the U.S., Europe, 

26 and Canada. Most effect estimates ranged from a 1.6 to 5.4% increase in daily all 

respiratory-related ED visits or hospital admissions in all-year analyses for unit increases

1 27

28 in ambient O3 concentrations. Several multicity studies and a multicontinent study 

29 reported associations between short-term increases in ambient O3 concentrations and 

30 increases in respiratory mortality. This evidence is supported by a large body of 

31 individual-level epidemiologic panel studies that demonstrate associations of ambient O3

32 with respiratory symptoms in children with asthma. Further support is provided by recent 

33 studies that found O3-associated increases in indicators of airway inflammation and 

 1 Effect estimates were standardized to a 40-, 30-, and 20-ppb unit increase for 1-h max, 8-h max, and 24-h avg O3.
Draft – Do Not Cite or Quote 2-20 June 2012

1 oxidative stress in children with asthma. Across respiratory endpoints, evidence indicates 

2 antioxidant capacity may modify the risk of respiratory morbidity associated with O3

3 exposure. The potentially elevated risk of populations with diminished antioxidant 

4 capacity and the reduced risk of populations with enhanced antioxidant capacity 

5 identified in epidemiologic studies is strongly supported by similar findings from 

6 controlled human exposure studies and by evidence that characterizes O3-induced 

7 decreases in intracellular antioxidant levels as a mode of action for downstream effects. 

8 By demonstrating O3-induced airway hyperresponsiveness, decreased pulmonary 

9 function, allergic responses, lung injury, impaired host defense, and airway inflammation, 

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

11 plausibility for epidemiologic associations of ambient O3 concentrations with lung 

12 function and respiratory symptoms, hospital admissions, ED visits, and mortality. 

13 Together, the evidence integrated across controlled human exposure, epidemiologic, and 

14 toxicological studies and across the spectrum of respiratory health endpoints continues to 

15 demonstrate that there is a causal relationship between short-term O3 exposure and 

16 respiratory health effects.

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

18 health effects (including respiratory symptoms, new-onset asthma, and repiratory 

19 mortality) is contributed by recent studies that demonstrated associations between long20 term measures of O3 exposure and both new-onset asthma in children and increased 

21 respiratory symptom effects in individuals with asthma. While the evidence is limited, a 

22 U.S. multicommunity prospective cohort demonstrates that asthma risk is affected by 

23 interactions among genetic variability, environmental O3 exposure, and behavior. The 

24 evidence relating new-onset asthma to long-term O3 exposure is supported by 

25 toxicological studies of asthma in monkeys. This nonhuman primate evidence of 

26 O3-induced changes supports the biologic plausibility of long-term exposure to O3

27 contributing to the effects of asthma in children. Early life O3 exposure may alter airway 

28 development and lead to the development of asthma. Other recent epidemiologic studies 

29 provide coherent evidence for long-term O3 exposure and respiratory effects such as first 

30 asthma hospitalization, respiratory symptoms in asthmatics, and respiratory mortality. 

31 Generally, the epidemiologic and toxicological evidence provides a compelling case that 

32 supports the hypothesis that a relationship exists between long-term exposure to ambient 

33 O3 and measures of respiratory health effects and mortality. The evidence for short-term 

34 exposure to O3 and effects on respiratory endpoints provides coherence and biological 

35 plausibility for the effects of long-term exposure to O3. Building upon that evidence, the 

36 more recent epidemiologic evidence, combined with toxicological studies in rodents and 

37 nonhuman primates, provides biologically plausible evidence that there is likely to be a 

38 causal relationship between long-term exposure to O3 and respiratory health 

39 effects.
Draft – Do Not Cite or Quote 2-21 June 2012

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

2 that short-term exposure to O3 directly or indirectly contributes to nonaccidental and 

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

4 establish underlying mechanisms by which such effects occur. The evaluation of recent 

5 multicity studies and a multicontinent study that examined the association between short6 term increases in ambient O3 concentration and mortality found evidence that supports 

7 the conclusions of the 2006 O3 AQCD. These recent studies reported consistent positive 

8 associations between short-term increases in ambient O3 concentration and total 

9 (nonaccidental) mortality, with associations being stronger during the warm season, as 

10 well as provided additional support for associations between O3 concentrations and 

11 cardiovascular mortality being similar or larger in magnitude compared to respiratory 

12 mortality. Additionally, these new studies examined previously identified areas of 

13 uncertainty in the O3-mortality relationship, and provide additional evidence supporting 

14 an association between short-term O3 exposure and mortality. Taken together, the body of 

15 evidence indicates that there is likely to be a causal relationship between short-term 

16 O3 exposures and total mortality.

17 The 2006 O3 AQCD concluded that an insufficient amount of evidence existed to suggest 

18 a causal relationship between long-term O3 exposure and mortality (U.S. EPA, 2006b). 

19 A synthesis of the recent and earlier evidence reveals that the strongest evidence for an 

20 association between long-term exposure to ambient O3 concentrations and mortality is 

21 derived from associations for respiratory mortality that remained robust after adjusting 

22 for PM2.5 concentrations. There is inconsistent evidence for an association between long23 term exposure to ambient O3 and cardiopulomary mortality, with several analyses from 

24 the ACS cohort reporting some positive associations, while other studies reported no 

25 association. There is generally limited evidence for an association with long-term 

26 exposure to ambient O3 and total mortality.The findings for respiratory mortality are 

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

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

29 exposure to O3 on respiratory effects. Respiratory mortality is a relatively small portion 

30 of total mortality [about 7.6% of all deaths in 2010 were due to respiratory causes 

31 (Murphy et al., 2012)], thus it is not surprising that the respiratory mortality signal may 

32 be difficult to detect in studies of cardiopulmonary or total mortality. Based on the recent 

33 evidence for respiratory mortality along with limited evidence for total and 

34 cardiopulmonary mortality, the evidence is suggestive of a causal relationship 

35 between long-term O3 exposures and total mortality.

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

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

38 information available. However, studies investigating O3-induced cardiovascular events 
Draft – Do Not Cite or Quote 2-22 June 2012

1 have advanced in the last two decades. Animal toxicological studies provide evidence for 

2 both short- and long-term O3 exposure leading to cardiovascular morbidity. The 

3 toxicological studies demonstrate O3-induced cardiovascular effects, specifically 

4 enhanced atherosclerosis and ischemia/reperfusion injury with or without the 

5 corresponding development of a systemic oxidative, pro-inflammatory environment, 

6 disrupted NO-induced vascular reactivity, decreased cardiac function, and increased heart 

7 rate variability (HRV). The observed increase in HRV is supported by a recent controlled 

8 human exposure study that also found increased high frequency HRV, but not altered 

9 blood pressure, following O3 exposure. It is still uncertain how O3 inhalation may cause 

10 systemic toxicity; however the cardiovascular effects of O3 found in animals correspond 

11 to the development and maintenance of an extrapulmonary oxidative, proinflammatory 

12 environment that may result from pulmonary inflammation.

13 There is limited, inconsistent evidence for cardiovascular morbidity in epidemiologic 

14 studies examining both short- and long-term exposure to O3. This is highlighted by the 

15 multiple studies that examined the association between short-term increases in ambient 

16 O3 concentration and cardiovascular-related hospital admissions and ED visits and other 

17 various cardiovascular effects and found no evidence of a consistent relationship with O3

18 exposure. Positive associations between short-term increases in O3 concentration and 

19 cardiovascular mortality have been consistently reported in multiple epidemiologic 

20 studies. However, the lack of coherence between the results from studies that examined 

21 associations between short-term increases in O3 concentration and cardiovascular 

22 morbidity and subsequently cardiovascular mortality, complicate the interpretation of the 

23 evidence for O3-induced cardiovascular mortality.

24 Overall, animal toxicological studies provide some evidence for O3-induced 

25 cardiovascular effects, but the effects observed were not consistently supported by 

26 controlled human exposure studies or epidemiologic studies. Although the toxicological 

27 evidence provides initial support to the relatively strong body of evidence indicating 

28 O3-induced cardiovascular mortality, there is a lack of coherence with controlled human 

29 exposure and epidemiologic studies of cardiovascular morbidity which together do not 

30 support O3-induced cardiovascular effects. Thus, the overall body of evidence across 

31 disciplines is suggestive of a causal relationship for both relevant short- and long32 term exposures to O3 and cardiovascular effects.

33 In the 2006 O3 AQCD, there were a number of health effects for which an insufficient 

34 amount of evidence existed to adequately characterize the relationships with exposure to 

35 O3. However, recent evidence suggests that O3 may impart health effects through 

36 exposure durations and biological mechanisms not previously considered. For example, 

37 recent toxicological studies add to earlier evidence that short- and long-term exposures to 

38 O3 can produce a range of effects on the central nervous system and behavior. 
Draft – Do Not Cite or Quote 2-23 June 2012

1 Additionally, an epidemiologic study demonstrated that long-term exposure to O3 affects 

2 memory in humans as well. Together the evidence from studies of short- and long-term 

3 exposure to O3 is suggestive of a causal relationship between O3 exposure and 

4 central nervous system effects. There is also limited though positive toxicological 

5 evidence for O3-induced developmental effects. Limited epidemiologic evidence exists 

6 for an association of O3 concentration with decreased sperm concentration and 

7 associations with reduced birth weight and restricted fetal growth. Overall, the evidence 

8 is suggestive of a causal relationship between long-term exposures to O3 and 

9 reproductive and developmental effects.

10 These causal determinations are summarized in Table 2-2, along with the conclusions 

11 from the previous NAAQS review. Special emphasis and additional details are provided 

12 in Table 2-2 for respiratory health outcomes, for which there is the strongest body of 

13 evidence.

Table 2-2 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 2012 3rd 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.

Evidence integrated across controlled human 

exposure, epidemiologic, and toxicological studies 

and across the spectrum of respiratory health 

endpoints continues to demonstrate that there is a 

causal relationship between short-term O3

exposure and respiratory health effects.

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 hour exposures to as low 

as 60 ppb O3. The collective body of epidemiologic 

evidence demonstrates associations between shortterm ambient O3 exposure and decrements in lung 

function, particularly in children with asthma, 

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, healthy adults, 

and at 50 ppb in certain strains of rats.
Draft – Do Not Cite or Quote 2-24 June 2012

Health Outcome Conclusions from 2006 O3 AQCD Conclusions from 2012 3rd Draft ISA

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. Recent controlled 

human exposure studies show O3-induced 

inflammatory responses at 60 ppb, the lowest 

concentration evaluated.

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 shortterm exposure to ambient O3 and respiratory 

symptoms (e.g., cough, wheeze, and shortness of 

breath) in children with asthma. 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 phagocytize microorganisms 

upon exposure to 80 to 100 ppb O3.

Recent controlled human exposure studies 

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 shortterm O3 exposures as low as 80 ppb.

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 controlled human exposure studies 

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.

Respiratory 

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.

Consistent, positive 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 respiratoryrelated 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 

cardiovascular-related morbidity, but much 

remains to be done to more fully substantiate 

the association.

The overall body of evidence across disciplines is 

suggestive of a causal relationship for relevant 

short-term exposures to O3 and cardiovascular 

effects.
Draft – Do Not Cite or Quote 2-25 June 2012

Health Outcome Conclusions from 2006 O3 AQCD Conclusions from 2012 3rd Draft ISA

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.

Together the evidence from studies of short-term 

exposure to O3 is suggestive of a causal 

relationship between O3 exposure and CNS 

effects.

Total Mortality The evidence is highly suggestive that O3

directly or indirectly contributes to nonaccidental and cardiopulmonary-related 

mortality.

Taken together, the body of evidence indicates that 

there is likely to be a causal relationship 

between short-term exposures to O3 and allcause total mortality.

Long-term Exposure to O3

Respiratory effects The current evidence is suggestive but 

inconclusive for respiratory health effects from 

long-term O3 exposure.

Recent epidemiologic evidence, combined with 

toxicological studies in rodents and non-human 

primates, provides biologically plausible evidence 

that there is likely to be a causal relationship 

between long-term exposure to O3 and 

respiratory health effects.

New onset asthma No studies examining this outcome were 

evaluated in the 2006 O3 AQCD.

Evidence that different genetic variants (HMOX, 

GST, ARG), in combination with O3 exposure, are 

related to new onset asthma. These associations 

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 examining this outcome were 

evaluated in the 2006 O3 AQCD.

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, some 

of which were irreversible, 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 

observing positive associations (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.

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.
Draft – Do Not Cite or Quote 2-26 June 2012

Health Outcome Conclusions from 2006 O3 AQCD Conclusions from 2012 3rd Draft ISA

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 examining this outcome were 

evaluated in the 2006 O3 AQCD.

The overall body of evidence across disciplines is 

suggestive of a causal relationship for relevant 

long-term exposures to O3 and cardiovascular 

effects.

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.

Overall, the evidence is suggestive of a causal 

relationship between long-term exposures to O3

and reproductive and developmental effects.

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.

Together the evidence from studies of long-term 

exposure to O3 is suggestive of a causal 

relationship between O3 exposure and CNS 

effects.

Cancer Little evidence for a relationship between 

chronic O3 exposure and increased risk of lung 

cancer.

Overall, the evidence is inadequate to determine 

if a causal relationship exists between ambient 

O3 exposures and cancer.

Total Mortality There is little evidence to suggest a causal 

relationship between chronic O3 exposure and 

increased risk for mortality in humans.

Collectively, the evidence is suggestive of a 

causal relationship between long-term O3

exposures and total mortality.

2.5.3 Integrated Synthesis of Evidence for Health Effects

1 Building off that evaluated in previous O3 AQCDs, recent evidence demonstrates that O3 

2 is associated with a broad range of respiratory effects, including altered development of 

3 the respiratory tract. Recent animal toxicological studies of long-term exposure to O3

4 occurring throughout various lifestages in monkeys, beginning with prenatal and early 

5 life exposures, provide novel evidence for effects on the development of the respiratory 

6 system, including ultrastructural changes in bronchiole development, effects on the 

7 developing immune system, and increased offspring airway hyper-reactivity 

8 (Section 7.4.7). The strongest evidence for O3-induced effects on the developing lung 

9 comes from a series of experiments using infant rhesus monkeys episodically exposed to 

10 500 ppb O3 for approximately 5 months, starting at one month of age. Functional changes 

11 in the conducting airways of infant rhesus monkeys exposed to either O3 alone or O3 + 

12 antigen were accompanied by a number of cellular and morphological changes. In 

13 addition to these functional and cellular changes, substantial structural changes in the 

14 respiratory tract were observed. Importantly, the O3-induced structural pathway changes 

15 persisted after recovery in filtered air for six months after cessation of the O3 exposures. 

16 Exposure to O3 has also been associated with similar types of alterations in pulmonary 

17 structure, including airways remodeling and pulmonary injury and increased 
Draft – Do Not Cite or Quote 2-27 June 2012

1 permeability, in all adult laboratory animal species studied, from rats to monkeys (U.S. 

2 EPA, 1996a). 

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

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

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

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

7 1996a). This inflammatory response to O3 was detected after a single 1-h exposure with 

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

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

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

11 100 ppb O3. Evidence summarized in the 2006 O3 AQCD demonstrated that 

12 inflammatory responses were observed subsequent to 6.6 hours O3 exposure to the lowest 

13 tested level of 80 ppb in healthy human adults, while toxicological studies provided 

14 extensive evidence that short-term (1-3 hours) O3 exposure in the range of 100-500 ppb 

15 could cause lung inflammatory responses. The limited epidemiologic evidence reviewed 

16 in the 2006 O3 AQCD demonstrated an association between short-term increases in 

17 ambient O3 concentration and airways inflammation in children (1-h max O3 of 

18 approximately 100 ppb). Recent studies in animals and in vitro models described 

19 inflammatory and injury responses mediated by Toll-like receptors (e.g., TLR4, TLR2), 

20 receptors for TNF or IL-1, multiple signaling pathways (e.g., p38, JNK, NFκB, 

21 MAPK/AP-1), and oxidative stress (Section 6.2.3.3). Recent epidemiologic studies 

22 provide additional supporting evidence by demonstrating associations of ambient O3 with 

23 mediators of airways inflammation and oxidative stress. 

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 for 2 hours were shown to decrease the ability of alveolar macrophages to 

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

31 from resisting infection with streptococcal bacteria and resulted in infection-related 

32 mortality. Similarly, alveolar macrophages removed from the lungs of human subjects 

33 after 6.6 hours of exposure to 80 and 100 ppb O3 had decreased ability to ingest 

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

35 host defense mechanisms can lead to increased risk of respiratory infections, which can 

36 often predispose individuals to developing asthma when occurring in early life. Despite 

37 the strong toxicological evidence, in the limited body of epidemiologic evidence, ambient 

38 O3 concentrations have not been consistently associated with hospital admissions or ED 
Draft – Do Not Cite or Quote 2-28 June 2012

1 visits for respiratory infection, pneumonia, or influenza (Section 6.2.7.2and 

2 Section 6.2.7.3).

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

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

5 human exposure studies reviewed in previous assessments demonstrated O3-induced 

6 decrements in pulmonary function, characterized by alterations in lung volumes and flow 

7 and airway resistance and responsiveness for multihour exposures (up to 8 hours) to O3

8 concentrations as low as 80 ppb (U.S. EPA, 1996a). A series of mobile laboratory studies 

9 of lung function and respiratory symptoms reported pulmonary function decrements at 

10 mean ambient O3 concentrations of 140 ppb in exercising healthy adolescents and 

11 increased respiratory symptoms and pulmonary function decrements at 150 ppb in 

12 heavily exercising athletes and at 170 ppb in lightly exercising healthy and asthmatic 

13 subjects. Epidemiologic and animal toxicological evidence is coherent with the results of 

14 the controlled human exposure studies, both indicating decrements in lung function upon 

15 O3 exposure. A combined statistical analysis of epidemiologic studies in children at 

16 summer camp with particularly strong exposure assessment demonstrated decrements in 

17 FEV1 of 0.50 mL/ppb with an increase in previous hour O3 concentration. For 

18 preadolescent children exposed to 120 ppb ambient O3, this estimated volume decrease 

19 corresponded to an average decrement of 2.4-3.0% in FEV1. Key studies of lung function 

20 (FEV1) measured before and after well-defined outdoor exercise events in adults yielded 

21 concentration-response slopes of 0.40 and 1.35 mL/ppb ambient O3 after exposure for up 

22 to 1 hour. Animal toxicological studies reported similar respiratory effects in rats at 

23 exposures as low as 200 ppb O3 for 3 hours. The 2006 O3 AQCD characterized the 

24 controlled human exposure and animal toxicological studies as providing clear evidence 

25 of causality for the associations observed between short-term (≤ 24 hours) increases in O3

26 concentration and relatively small, but statistically significant declines in lung function 

27 observed in numerous recent epidemiologic studies. In epidemiologic studies, declines in 

28 lung function were particularly noted in children with and without asthma, and adults 

29 who work or exercise outdoors. 

30 Recent controlled human exposure studies examined lower concentration O3 exposures 

31 (40-80 ppb) and demonstrated that FEV1, respiratory symptoms, and inflammatory 

32 responses were affected by O3 exposures of 6.6 hours as low as 60 to 70 ppb 

33 (Section 6.2.1.1 and Section 6.2.3.1). These studies demonstrated average O3-induced 

34 decreases in FEV1 in the range of 2.8 to 3.6% with O3 exposures to 60 ppb for 6.6 hours. 

35 Further, in the controlled human exposure studies evaluating effects of 60 ppb O3, on 

36 average, 10% of the exposed individuals experienced >10% FEV1 decrements following 

37 6.6 hours of exposure. Considerable intersubject variability has also been reported in 

38 studies at higher exposure concentrations (≥ 70 ppb) with some subjects experiencing 
Draft – Do Not Cite or Quote 2-29 June 2012

1 considerably greater decrements than average. Recent epidemiologic studies provide 

2 greater insight into individual- and population-level factors that may increase for the risk 

3 of O3-associated respiratory morbidity. In addition to lung function decrements 

4 consistently reported in healthy children at summer camp, O3-associated decreases in 

5 lung function were consistently observed in epidemiologic studies that included 

6 potentially at-risk populations (e.g., individuals with asthma with concurrent respiratory 

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

8 antioxidant capacity).

9 Exposure to O3 may also result in respiratory symptoms (e.g., coughing, wheezing, 

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

11 symptoms and increasing ambient O3, particularly among children with asthma. In the 

12 2006 O3 AQCD, symptoms of cough and pain on deep inspiration were well documented 

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

14 moderate exercise. Limited data suggested an increase in respiratory symptoms down to 

15 60 ppb. More recently, these effects have been observed at 70 ppb in healthy adults. 

16 Controlled human exposure studies of healthy adults, have also reported an increased 

17 incidence of cough with O3 exposures as low as 120 ppb and 1-3 hours in duration with 

18 very heavy exercise. The controlled human exposure studies also demonstrated lesser 

19 respiratory symptom responses in children and older adults relative to young healthy 

20 adults. Cumulative epidemiologic evidence adds to the findings from controlled human 

21 exposure studies for healthy adults by demonstrating the effects of ambient O3 exposure 

22 on respiratory symptoms in children with asthma. Increases in ambient O3 concentration 

23 were associated with a wide variety of respiratory symptoms (e.g., cough, wheeze, and 

24 shortness of breath) in children with asthma. Epidemiologic studies also indicated that 

25 short-term increases in O3 concentration are likely associated with increased asthma 

26 medication use in children with asthma. Additionally, epidemiologic studies provide 

27 evidence for an association between long-term exposure to O3 and respiratory symptoms 

28 (Section 7.2.2).

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

30 hyperresponsiveness (AHR). Increased AHR is an important consequence of exposure to 

31 O3 because its presence represents a change in airway smooth muscle reactivity and 

32 implies that the airways are predisposed to narrowing on inhalation of a variety of stimuli 

33 (e.g., specific allergens, SO2, cold air). Specifically, short-term (2 or 3 hours) exposure to 

34 250 or 400 ppb O3 was found to cause increases in AHR in response to allergen 

35 challenges among allergic asthmatic subjects who characteristically already had 

36 somewhat increased AHR at baseline. Increased non-specific AHR has been 

37 demonstrated in healthy young adults down to 80 ppb O3 following 6.6 hours of exposure 

38 during moderate exercise. While AHR has not been widely examined in epidemiologic 
Draft – Do Not Cite or Quote 2-30 June 2012

1 studies, findings for O3-induced increases in AHR in controlled human exposure 

2 (Section 6.2.2.1) and toxicological (Section 6.2.2.2) studies provide biological 

3 plausibility for associations observed between increases in ambient O3 concentration and 

4 increases in respiratory symptoms in subjects with asthma.

5 In addition to asthma exacerbations, recent epidemiologic evidence has indicated that 

6 long-term ambient O3 concentrations may contribute to new onset asthma (Section 7.2.1, 

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

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

9 measures of exposure to ambient O3 and measures of respiratory morbidity. Studies from 

10 two California cohorts have provided evidence for different variants in genes related to 

11 oxidative or nitrosative stress (e.g., HMOX, GSTs, ARG) that, depending on community 

12 long-term O3 concentrations, are related to new onset asthma. This is the first time that 

13 evidence has extended beyond the association of short-term exposure to O3 and asthma 

14 exacerbations to suggest that long-term exposure to O3 may play a role in the 

15 development of the disease and contribute to incident cases of asthma.

16 The frequency of ED visits and hospital admissions due to respiratory symptoms, asthma 

17 exacerbations and other respiratory diseases is associated with short- and long-term 

18 exposure to ambient O3 concentrations. Summertime daily hospital admissions for 

19 respiratory causes in various locations of eastern North America were consistently 

20 associated with ambient concentrations of O3 in studies reviewed in the 1996 O3 AQCD. 

21 This association remained even with examination of only concentrations below 120 ppb 

22 O3. The 2006 O3 AQCD concluded that aggregate population time-series studies 

23 demonstrate a positive and robust association between ambient O3 concentrations and 

24 respiratory-related hospitalizations and asthma ED visits during the warm season. Recent 

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

26 multicontinent study further demonstrate that short-term exposures to ambient O3

27 concentrations are consistently associated with increases in respiratory hospital 

28 admissions and ED visits specifically during the warm/summer months across a range of 

29 O3 concentrations (Section 6.2.7). There is also recent evidence for an association 

30 between respiratory hospital admissions and long-term exposure to O3 (Section 7.2.2).

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

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

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

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

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

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

37 consistent and coherent with the evidence from epidemiologic, controlled human 
Draft – Do Not Cite or Quote 2-31 June 2012

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

2 exposure to O3 on respiratory effects. Additionally, the evidence for respiratory morbidity 

3 after short- and long-term exposure provides biological plausibility for mortality due to 

4 respiratory disease. 

5 There is similar evidence for a positive association between short-term exposure to O3

6 and mortality. This evidence has been substantiated by single-city studies reviewed in the 

7 2006 O3 AQCD and recent multicity and multicontinent studies. When examining 

8 mortality due to cardiovascular disease, epidemiologic studies consistently observe 

9 positive associations with short-term exposure to O3. Additionally, there is some 

10 evidence for an association between long-term exposure to O3 and mortality. However, 

11 the association between long-term ambient O3 concentrations and cardiovascular 

12 mortality may be confounded by other pollutants as evident by a study of cardiovascular 

13 mortality that reported no association after adjustment for PM2.5 concentrations. The lack 

14 of coherence between the results from studies that examined associations between short15 and long-term O3 concentrations and cardiovascular morbidity, and results from studies of 

16 cardiovascular mortality, complicate the interpretation of the evidence for O3-induced 

17 cardiovascular mortality. 

18 Epidemiologic studies evaluating cardiovascular morbidity and short- and long-term 

19 exposure to O3 provide no consistent evidence for an association. This is highlighted by 

20 the multiple studies that examined the association between short- and long-term O3

21 concentrations and cardiovascular-related hospital admissions and ED visits and 

22 cardiovascular disease-related biomarkers. Additionally, a single controlled human 

23 exposure study reported no statistically significant O3-induced differences in 

24 electrocardiogram (ECG), heart rate, or blood pressure in normal or hypertensive subjects 

25 (0.3 ppm for 3 h with intermittent exercise), however an overall increase in myocardial 

26 work and impairment in pulmonary gas exchange was observed. 

27 There is an emerging body of animal toxicological evidence suggesting that autonomic 

28 nervous system alterations (in heart rate and/or heart rate variability) and 

29 proinflammatory signals may mediate cardiovascular effects. Interactions of O3 with ELF 

30 components result in secondary oxidation products and inflammatory mediators that have 

31 the potential to penetrate the epithelial barrier and to initiate toxic effects on the 

32 cardiovascular system. Animal toxicological studies of long-term exposure to O3 provide 

33 evidence enhanced atherosclerosis and ischemia/reperfusion (I/R) injury, corresponding 

34 with development of a systemic oxidative, proinflammatory environment.

35 Overall, animal toxicological studies provide some evidence for O3-induced 

36 cardiovascular effects, but the effects were not consistently supported by controlled 

37 human exposure studies or epidemiologic evidence. Although the toxicological evidence 
Draft – Do Not Cite or Quote 2-32 June 2012

1 provides initial support to the body of evidence indicating an association between short2 term exposure to O3 and cardiovascular mortality, there is a lack of coherence with 

3 controlled human exposure and epidemiologic studies of cardiovascular morbidity. 

4 Together, these findings are suggestive of O3-induced cardiovascular effects.

2.5.4 Policy Relevant Considerations

2.5.4.1 Populations Potentially at Increased Risk

5 Studies were conducted to identify populations that are at increased risk for O3-related 

6 health effects. These studies have investigated factors that can cause populations to be at 

7 increased risk for O3-related health effects by conducting stratified epidemiologic 

8 analyses; by examining individuals with an underlying health condition, genetic 

9 polymorphism, or categorized by age, race, or sex in controlled human exposure studies; 

10 or by developing animal models that mimic the pathophysiological conditions associated 

11 with a health effect. These studies have identified a multitude of factors that could 

12 potentially contribute to whether a population is at increased risk for O3-related health 

13 effects. 

14 The populations identified in Chapter 8 that were examined for their potential for 

15 increased risk of O3-related health effects are listed in Table 8-5 and are classified as 

16 providing adequate, suggestive, inadequate, or no evidence of being an at-risk factor. The 

17 factors that have adequate evidence to be classified as an at-risk factor for O3-related 

18 health effects are individuals with asthma, younger and older age groups, individuals with 

19 reduced intake of certain nutrients (i.e., vitamins C and E), and outdoor workers, based 

20 on consistency in findings across studies and evidence of coherence in results from 

21 different scientific disciplines. Asthma as a factor affecting risk was supported by 

22 controlled human exposure and toxicological studies, as well as some evidence from 

23 epidemiologic studies. Generally, studies comparing age groups also reported greater 

24 associations for respiratory hospital admissions and ED visits among children than for 

25 adults. Biological plausibility for this increased risk is supported by toxicological and 

26 controlled human exposure studies. Also, children have higher exposure and dose due to 

27 increased time spent outdoors and ventilation rate, and childrens’ respiratory systems are 

28 also still undergrowing lung growth. Most studies comparing age groups reported greater 

29 effects of short-term O3 exposure on mortality among older adults, although studies of 

30 other health outcomes had inconsistent findings regarding whether older adults were at 

31 increased risk. Multiple epidemiologic, controlled human exposure, and toxicological 

32 studies reported that diets lower in vitamins E and C are associated with increased risk of 
Draft – Do Not Cite or Quote 2-33 June 2012

1 O3 -related health effects. Previous studies have shown that increased exposure to O3 due 

2 to outdoor work leads to increased risk of O3-related health effects and it is clear that 

3 outdoor workers have higher exposures, and possibly greater internal doses, of O3, which 

4 may lead to increased risk of O3-related health effects. 

5 Other potential factors [genetic variants (such as those in GSTM1, HMOX-1, NQO1, and

6 TNF-α), obesity, sex, and SES] provided some suggestive evidence of increased risk, but 

7 further investigation is needed. Similarly, many factors had inadequate evidence to 

8 determine if they increased the risk of O3-related health effects, including 

9 influenza/infection, COPD, CVD, diabetes, hyperthyroidism, smoking, race/ethnicity, 

10 and air conditioning use. 

2.5.4.2 Exposure Metrics in Epidemiologic Studies

11 Some epidemiologic studies have conducted analyses between O3 concentration and 

12 health effects (i.e., mortality, respiratory or cardiovascular) using various exposure 

13 metrics (i.e., 1-h max, 8-h max, and 24-h avg). No studies of long-term exposure 

14 (i.e., months to years) to O3 have compared the use of different exposure metrics on risk 

15 estimation.

16 Among time-series studies, the limited evidence suggests comparable risk estimates 

17 across exposure metrics with some evidence for smaller O3 risk estimates when using a 

18 24-hour average exposure metric. Several panel studies examined whether associations of 

19 lung function and respiratory symptoms varied depending on the O3 exposure metric 

20 used. Although differences in effect estimates across exposure metrics were found within 

21 some studies, collectively, there was no indication that the consistency or magnitude of 

22 the observed association was stronger for a particular O3 exposure metric. Comparisons 

23 of lung function decrements among O3 exposure metrics were similarly inconsistent in 

24 populations without increased outdoor exposures. It is important to note in these studies, 

25 the degree of exposure measurement error associated with use of central site ambient O3

26 concentrations may vary among O3 averaging times, depending on time spent outdoors. 

27 Among studies that examined associations of multiple respiratory symptoms in children 

28 with multiple O3 exposure metrics, most did not find higher odds ratios for any particular 

29 exposure metric. Overall, the evidence from time-series and panel epidemiologic studies 

30 does not indicate that one exposure metric is more consistently or strongly associated 

31 with mortality or respiratory-related health effects.
Draft – Do Not Cite or Quote 2-34 June 2012

2.5.4.3 Lag Structure in Epidemiologic Studies

1 Epidemiologic studies have attempted to identify the time-frame in which exposure to O3

2 can impart a health effect. The time period between O3 exposure and health effects can 

3 potentially be influenced by a multitude of factors, such as age or existence of 

4 pre-existing diseases. Different lag times have been evaluated for specific health 

5 outcomes. 

6 The epidemiologic evidence evaluated in the 2006 O3 AQCD indicated that one of the 

7 remaining uncertainties in characterizing the O3-mortality relationship was identifying 

8 the appropriate lag structure (e.g., single-day lags versus distributed lag model). An 

9 examination of lag times used in the epidemiologic studies evaluated in this assessment 

10 can provide further insight on the characterization of the relationship between O3

11 exposure and morbidity and mortality outcomes from epidemiologic studies. 

12 The majority of epidemiologic studies that focused on the association between short-term 

13 O3 exposure and mortality (i.e., all-cause, respiratory and cardiovascular) examined the 

14 average of multiday lags with some studies examining single-day lags. Across a range of 

15 multiday lags (i.e., average of 0-1 to 0-6 days), the studies evaluated consistently 

16 demonstrate that the O3 effects on mortality occur within a few days of exposure 

17 (Figure 6-28). 

18 Epidemiologic studies of lung function, respiratory symptoms, and biological markers of 

19 airway inflammation and oxidative stress examined associations with single-day ambient 

20 O3 concentrations (using various averaging times) lagged from 0 to 7 days as well as 

21 concentrations averaged over 2 to 19 days. Lags of 0 and 1 day ambient O3

22 concentrations were associated with decreases in lung function and increases in 

23 respiratory symptoms, airway inflammation, and oxidative stress. Additionally, several 

24 studies found that multiday averages of O3 concentration were associated with these 

25 endpoints, indicating that not only single day, but exposures accumulated over several 

26 days led to a respiratory health effect. In studies of respiratory hospital admissions and 

27 ED visits, investigators either examined the lag structure of associations by including 

28 both single-day and the average of multiday lags, or selecting lags a priori. The collective 

29 evidence indicates a rather immediate response within the first few days of O3 exposure 

30 (i.e., for lags days averaged at 0-1, 0-2, and 0-3 days) for hospital admissions and ED 

31 visits for all respiratory outcomes, asthma, and chronic obstructive pulmonary disease in 

32 all-year and seasonal analyses. 
Draft – Do Not Cite or Quote 2-35 June 2012

2.5.4.4 Ozone Concentration-Response Relationship

1 An important consideration in characterizing the O3-morbidity and mortality association 

2 is whether the concentration-response (C-R) relationship is linear across the full 

3 concentration range that is encountered or if there are concentration ranges where there 

4 are departures from linearity (i.e., nonlinearity). In this ISA studies have been identified 

5 that attempt to characterize the shape of the O3 C-R curve along with possible O3

6 “thresholds” (i.e., O3 concentrations which must be exceeded in order to elicit an 

7 observable health response). The controlled human exposure and epidemiologic studies 

8 that examined the shape of the C-R curve and the potential presence of a threshold have 

9 indicated a generally linear C-R function with no indication of a threshold in analyses 

10 that have examined 8-h max and 24-h avg O3 concentrations. However, there is less 

11 certainty in the shape of the C-R curve at the lower end of the distribution of O3

12 concentrations due to the low density of data in this range.

13 Controlled human exposure studies have provided strong and quantifiable C-R data on 

14 the human health effects of O3. The magnitude of respiratory effects in these studies is 

15 generally a function of O3 exposure, i.e., the product of concentration (C), minute 

ventilation (V̇ 16 E), and exposure duration. Several studies provide evidence for a smooth 

17 C-R curve without indication of a threshold in young healthy adults exposed during 

18 moderate exercise for 6.6 hours to O3 concentrations between 40 and 120 ppb 

19 (Figure 6-1). It is difficult to characterize the C-R relationship below 40 ppb due to 

20 uncertainty associated with the sparse data at these lower concentrations.

21 Although relatively few epidemiologic studies have examined the O3-health effects C-R 

22 relationship, the C-R relationship has been examined across multiple health endpoints 

23 and exposure durations. Some studies of populations engaged in outdoor activity found 

24 that associations between O3 and lung function decrements persisted at lower O3

25 concentrations with some studies showing larger negative associations in analyses limited 

26 to lower O3 concentrations (e.g., 60-80 ppb; Table 6-6) and shorter exposure durations 

27 (i.e., in the range of 30 minutes to less than 8 hours; Table 6-6). A study examining the 

28 C-R relationship between short-term O3 exposure and pediatric asthma ED visits found 

29 no evidence of a threshold with a linear relationship evident down to 8-h max O3

30 concentrations as low as 30 ppb (Figure 6-17). In an additional study, authors used a 

31 smooth function while also accounting for the potential confounding effects of PM2.5, to 

32 examine whether the shape of the C-R curve for short-term exposure to O3 and asthma 

33 hospital admissions is linear. When comparing the curve to a linear fit, the authors found 

34 that the linear fit is a reasonable approximation of the C-R relationship between O3 and 

35 asthma hospital admissions in the mid-range of the data though it can be seen that there is 
Draft – Do Not Cite or Quote 2-36 June 2012

1 greater uncertainty at the lower end of the distribution of ambient O3 concentrations, 

2 generally below 20 ppb (Figure 6-15) due to sparse data at these lower concentrations.

3 Several recent studies applied a variety of statistical approaches to examine the shape of 

4 the O3-mortality C-R relationship and existence of a threshold (Section 6.6.2.4). These 

5 studies suggest that the shape of the O3-mortality C-R curve is linear across the range of 

6 O3 concentrations though uncertainty in the relationship increases at the lower end of the 

7 distribution (Figure 6-35). Generally, the epidemiologic studies that examined the 

8 O3-mortality C-R relationship do not provide evidence for the existence of a threshold 

9 within the range of 24-h average (24-h avg) O3 concentrations most commonly observed 

10 in the U.S. during the O3 season (i.e., above 20 ppb). It should be noted that the 

11 evaluation of the C-R relationship for short-term exposure to O3 and mortality is difficult 

12 due to the evidence from multicity studies indicating highly heterogeneous O3-mortality 

13 associations across regions of the U.S. In addition, there are numerous issues that may 

14 influence the shape of the O3-mortality C-R relationship that need to be taken into 

15 consideration including: multiday effects (distributed lags), and potential adaptation and 

16 mortality displacement (i.e., hastening of death by a short period). Additionally, given the 

17 effect modifiers identified in mortality analyses that are also expected to vary regionally 

18 (e.g., temperature, air conditioning prevalence), a national or combined analysis may not 

19 be appropriate to identify whether a threshold exists in the O3-mortality C-R relationship. 

20 In addition, the C-R relationship of long-term exposure to O3 and birth outcomes has 

21 been evaluated. Evidence from the southern California Children’s Health Study identified 

22 a C-R relationship of birth weight with 24-h avg O3 concentrations averaged over the 

23 entire pregnancy that was clearest above the 30 ppb level (Figure 7-4). 

24 Generally, both short- and long-term exposure studies indicate a linear, no threshold C-R 

25 relationship when examining the association between O3 exposure and multiple health 

26 effects across the range of 8-h max and 24-h avg O3 concentrations most commonly 

27 observed in the U.S. during the O3 season (i.e., greater than 20 ppb). However, evidence 

28 from studies of respiratory health effects and mortality indicates less certainty in the 

29 shape of the C-R curve at the lower end of the distribution of O3 data, which corresponds 

30 to 8-h max and 24-h avg O3 concentrations generally below 20 ppb. 

2.5.4.5 Regional Heterogeneity in Risk Estimates

31 Multicity epidemiologic studies that have examined the relationship between short-term 

32 O3 exposures and mortality have provided evidence of city-to-city and regional 

33 heterogeneity in O3-mortality risk estimates. A possible explanation for this heterogeneity 

34 may be differences in community characteristics (individual- or community-level) across 
Draft – Do Not Cite or Quote 2-37 June 2012

1 cities that could modify the O3 effect. Another possible explanation for the observed 

2 heterogeneity could be effect modification by concentrations of other air pollutants or 

3 interactions with temperature or other meteorological factors that vary regionally in the 

4 U.S.

5 An examination of community characteristics measured at the individual level that may 

6 contribute to the observed heterogeneity in O3-mortality risk estimates indicates increased 

7 risk in older adults (i.e., ≥ 65 years of age), women, African American individuals, 

8 individuals with pre-existing diseases/conditions (e.g., diabetes, atrial fibrillation), and 

9 lower SES. Furthermore, studies have examined community characteristics measured at 

10 the community level and found that higher O3-mortality risk estimates were associated 

11 with higher: percent unemployment, fraction of the population Black/African-American, 

12 percent of the population that take public transportation to work; and with lower: 

13 temperatures and percent of households with central air conditioning. There is also 

14 evidence of greater effects in cities with lower mean O3 concentrations. Additionally, 

15 there is evidence of increased risk of O3-related mortality as percentage unemployed 

16 increases and a reduction in O3-related mortality as mean temperature increased (i.e., a 

17 surrogate for air conditioning rate) in the U.S. The lack of a consistent reduction in 

18 O3-risk estimates in cities with a higher percentage of central air conditioning across 

19 health outcomes complicates the interpretation of the potential modifying effects of air 

20 conditioning use. 

21 Overall, the epidemiologic studies that have examined the city-to-city and regional 

22 heterogeneity observed in multicity studies have identified a variety of factors that may 

23 modify the O3-mortality or -respiratory hospital admission relationship. Some studies 

24 have also examined the correlation with other air pollutants or the potential interactive 

25 effects between O3 and temperature to explain city-to-city heterogeneity in O3-mortality 

26 risk estimates. This includes evidence that O3-mortality risk estimates in the U.S. varied 

27 by mean SO2 concentrations, the ratio between mean NO2/PM10 concentrations, and 

28 temperatures. However, studies have not consistently identified specific community 

29 characteristics that explain the observed heterogeneity. 

2.6 Integration of Effects on Vegetation and Ecosystems

30 Chapter 9 presents the most policy-relevant information related to this review of the 

31 NAAQS for the welfare effects of O3 on vegetation and ecosystems. This section 

32 integrates the key findings from the disciplines evaluated in this assessment of the O3

33 scientific literature, which includes plant physiology, whole plant biology, ecosystems, 

34 and exposure-response. 
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1 Overall, exposure to O3 is causally related or likely to be causally related to effects 

2 observed on vegetation and ecosystems. These effects are observed across the entire 

3 continuum of biological organization; from the cellular and subcellular level to the whole 

4 plant level, and up to ecosystem-level processes. Furthermore, there is evidence that the 

5 effects observed across this continuum are related to one another; effects of O3 at lower 

6 levels of organization, such as the leaf of an individual plant, can result in effects at 

7 higher levels. Ozone enters leaves through stomata, and can alter stomatal conductance 

8 and disrupt CO2 fixation (Section 9.3). These effects can change rates of leaf gas 

9 exchange, growth and reproduction at the individual plant level and result in changes in 

10 ecosystems, such as productivity, C storage, water cycling, nutrient cycling, and 

11 community composition (Section 9.4). Figure 2-3 is a simplified illustrative diagram of 

12 the major pathway through which O3 enters leaves and the major endpoints O3 may affect 

13 in vegetation and ecosystems. 

14 The framework for causal determinations (see Preamble) has been applied to the body of 

15 scientific evidence to examine effects attributed to O3 exposure (Table 2-3). The 

16 summary below provides brief integrated summaries of the evidence that supports the 

17 causal determinations. The detailed discussion of the underlying evidence used to 

18 formulate each causal determination can be found in Chapter 9. This summary ends with 

19 a short discussion of policy relevant considerations.

2.6.1 Visible Foliar Injury

20 Visible foliar injury resulting from exposure to O3 has been well characterized and 

21 documented over several decades of research on many tree, shrub, herbaceous, and crop 

22 species (U.S. EPA, 2006b, 1996b, 1984, 1978a) (Section 9.4.2). Ozone-induced visible 

23 foliar injury symptoms on certain bioindicator plant species are considered diagnostic as 

24 they have been verified experimentally in exposure-response studies, using exposure 

25 methodologies such as continuous stirred tank reactors (CSTRs), open-top chambers 

26 (OTCs), and free-air fumigation. Experimental evidence has clearly established a 

27 consistent association of visible injury with O3 exposure, with greater exposure often 

28 resulting in greater and more prevalent injury. Since publication of the 2006 O3 AQCD, 

29 the results of several multiple-year field surveys of O3-induced visible foliar injury at 

30 National Wildlife Refuges in Maine, Michigan, New Jersey, and South Carolina have 

31 been published. New sensitive species showing visible foliar injury continue to be 

32 identified from field surveys and verified in controlled exposure studies.
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Figure 2-3 An illustrative diagram of the major pathway through which ozone

enters leaves and the major endpoints that ozone 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 2-3 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 estimated risk 

12 of visible foliar injury was high in 65 parks (27%), moderate in 46 parks (19%), and low 

13 in 131 parks (54%). Some of the well-known parks with a high risk of O3-induced visible 

14 foliar injury include Gettysburg, Valley Forge, Delaware Water Gap, Cape Cod, Fire 
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1 Island, Antietam, Harpers Ferry, Manassas, Wolf Trap Farm Park, Mammoth Cave, 

2 Shiloh, Sleeping Bear Dunes, Great Smoky Mountains, Joshua Tree, Sequoia and Kings 

3 Canyon, and Yosemite. Overall, evidence is sufficient to conclude that there is a causal 

4 relationship between ambient O3 exposure and the occurrence of O3-induced 

5 visible foliar injury on sensitive vegetation across the U.S.

2.6.2 Growth, Productivity, Carbon Storage and Agriculture

6 Ambient O3 concentrations have long been known to cause decreases in photosynthetic 

7 rates and plant growth. The O3-induced damages at the plant scale may translate to 

8 damages at the stand, then ecosystem scales, and cause changes in productivity and C 

9 storage. The effects of O3 exposure on photosynthesis, growth, biomass allocation, 

10 ecosystem production, and ecosystem C sequestration were reviewed for the natural 

11 ecosystems, and crop productivity and crop quality were reviewed for the agricultural 

12 ecosystems. 

2.6.2.1 Natural Ecosystems

13 The previous O3 AQCDs concluded that there is strong and consistent evidence that 

14 ambient concentrations of O3 decrease plant photosynthesis and growth in numerous 

15 plant species across the U.S. Studies published since the last review continue to support 

16 that conclusion (Section 9.4.3.1). Recent studies, based on the Aspen free-air carbon17 dioxide/ozone enrichment (FACE) experiment, found that O3 caused reductions in total 

18 biomass relative to the control in aspen, paper birch, and sugar maple communities 

19 during the first seven years of stand development. Overall, the studies at the Aspen FACE 

20 experiment were consistent with the open-top chamber (OTC) studies that were the 

21 foundation of previous O3 NAAQS reviews. These results strengthen the understanding 

22 of O3 effects on forests and demonstrate the relevance of the knowledge gained from 

23 trees grown in OTC studies. 

24 A set of meta-analyses assessed the effects of O3 on plant photosynthesis and growth 

25 across different species and fumigation methods (such as OTC and FACE). Those studies 

26 reported that current O3 concentrations in the northern hemisphere are decreasing 

27 photosynthesis (~11%) across tree species, and the decreases in photosynthesis are 

28 consistent with cumulative uptake of O3 into the leaf. The current ambient O3

29 concentrations (~40 ppb averaged across all hours of exposure) decreased annual total 

30 biomass growth of forest species by an average of 7%, with potentially greater decreases 

31 (11-17%) with elevated O3 exposures (Section 9.4.3.1). The meta-analyses further 
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1 confirmed that reduction of plant photosynthesis and growth under O3 exposure are 

2 coherent across numerous species and various experimental techniques. 

3 Studies during recent decades have also demonstrated O3 alters biomass allocation and 

4 plant reproduction (Section 9.4.3). Recent meta-analyses have generally indicated that O3

5 reduced C allocated to roots. Several recent studies published since the 2006 O3 AQCD 

6 further demonstrate that O3 altered reproductive processes, such as timing of flowering, 

7 number of flowers, fruits and seeds, in herbaceous and woody plant species. However, a 

8 knowledge gap still exists pertaining to the exact mechanism of the responses of 

9 reproductive processes to O3 exposure (Section 9.4.3.3). 

10 Studies at the leaf and plant scales show that O3 decreased photosynthesis and plant 

11 growth, providing coherence and biological plausibility for the reported decreases in 

12 ecosystem productivity. During the previous NAAQS reviews, there were very few 

13 studies that investigated the effect of O3 exposure on ecosystem productivity and 

14 C sequestration. Recent studies from long-term FACE experiments and ecosystem 

15 models provided evidence of the association of O3 exposure and reduced productivity at 

16 the ecosystem scale. Elevated O3 reduced stand biomass at Aspen FACE after 7 years of 

17 O3 exposure, and annual volume growth at the Kranzberg Forest in Germany. Results 

18 across different ecosystem models were consistent with the FACE experimental 

19 evidence, which showed that O3 reduced ecosystem productivity (Section 9.4.3.4). In 

20 addition to primary productivity, other indicators such as net ecosystem productivity 

21 (NEP), net ecosystem CO2 exchange (NEE) and C sequestration were often assessed by 

22 model studies. Model simulations consistently found that O3 exposure caused negative 

23 impacts on these indicators (Section 9.4.3.4, Table 9-3), but the severity of these impacts 

24 was influenced by multiple interactions of biological and environmental factors. The 

25 suppression of ecosystem C sinks results in more CO2 accumulation in the atmosphere. A 

26 recent study suggested that the indirect radiative forcing caused by O3 exposure through 

27 lowering the ecosystem C sink could have an even greater impact on global warming than 

28 the direct radiative forcing of O3.

29 Although O3 generally causes negative effects on ecosystem productivity, the magnitude 

30 of the response varies among plant communities (Section 9.4.3.4). For example, O3 had 

31 little impact on white fir, but greatly reduced growth of ponderosa pine in southern 

32 California. Ozone decreased net primary production (NPP) of most forest types in the 

33 Mid-Atlantic region, but had small impacts on spruce-fir forest. Ozone could also affect 

34 regional C budgets through interacting with multiple factors, such as N deposition, 

35 elevated CO2 and land use history. Model simulations suggested that O3 partially offset 

36 the growth stimulation caused by elevated CO2 and N deposition in both Northeast- and 

37 Mid-Atlantic-region forest ecosystems of the U.S.
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1 Overall, evidence is sufficient to conclude that there is a causal relationship between 

2 ambient O3 exposure and reduced native plant growth and productivity, and a likely 

3 causal relationship between O3 exposure and reduced carbon sequestration in 

4 terrestrial ecosystems.

2.6.2.2 Agricultural Crops

5 The detrimental effect of O3 on crop production has been recognized since the 1960’s and 

6 a large body of research has subsequently stemmed from those initial findings. Previous 

7 O3 AQCDs have extensively reviewed this body of literature. Current O3 concentrations 

8 across the U.S. are high enough to cause yield loss for a variety of agricultural crops 

9 including, but not limited to, soybean, wheat, potato, watermelon, beans, turnip, onion, 

10 lettuce, and tomato (Section 9.4.4.1). Continued increases in O3 concentration may 

11 further decrease yield in these sensitive crops. Despite the well-documented yield losses 

12 due to increasing O3 concentration, there is still a knowledge gap pertaining to the exact 

13 mechanism of O3-induced yield loss. Research has linked increasing O3 concentration to 

14 decreased photosynthetic rates and accelerated senescence, which are related to yield.

15 In addition, recent research has highlighted the effects of O3 on crop quality. Increasing 

16 O3 concentration decreases nutritive quality of grasses, decreases macro- and micro17 nutrient concentrations in fruits and vegetable crops, and decreases cotton fiber quality. 

18 These areas of research require further investigation to determine the mechanism and 

19 dose-responses (Section 9.4.4.2).

20 During the previous NAAQS reviews, there were very few studies that estimated O3

21 impacts on crop yields at large geographical scales (i.e., regional, national or global). 

22 Recent modeling studies found that O3 generally reduced crop yield, but the impacts 

23 varied across regions and crop species (Section 9.4.4.1). For example, the largest 

24 O3-induced crop yield losses occurred in high-production areas exposed to high O3

25 concentrations, such as the Midwest and the Mississippi Valley regions of the U.S. 

26 Among crop species, the estimated yield loss for wheat and soybean were higher than 

27 rice and maize. Satellite and ground-based O3 measurements have been used to assess 

28 yield loss caused by O3 over the continuous tri-state area of Illinois, Iowa, and 

29 Wisconsin. The results showed that O3 concentrations reduced soybean yield, which 

30 correlates well with the previous results from FACE- and OTC-type experiments 

31 (Section 9.4.4.1). 

32 Evidence is sufficient to conclude that there is a causal relationship between O3

33 exposure and reduced yield and quality of agricultural crops.
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2.6.3 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. Regardless of the 

4 mechanism, O3 exposure has been shown to alter stomatal performance, which may affect 

5 plant and stand transpiration and therefore possibly affecting hydrological cycling. 

6 Although the evidence was from a limited number of field and modeling studies, these 

7 findings showed an association of O3 exposure and the alteration of water use and cycling 

8 in vegetation and ecosystems (Section 9.4.5). There is not a clear consensus on the nature 

9 of leaf-level stomatal conductance response to O3 exposure. When measured at steady10 state high light conditions, leaf-level stomatal conductance is often found to be reduced 

11 when exposed to O3. However, measurements of stomatal conductance under dynamic 

12 light and vapor pressure deficit conditions indicate sluggish responses under elevated O3

13 exposure which could potentially lead to increased water loss from vegetation. In 

14 situations where stomata fail to close under low light or water stressed conditions water 

15 loss may be greater over time. In other situations it is possible that sluggish stomata may 

16 fail to completely open in response to environmental stimuli and result in decreased water 

17 loss. Field studies suggested that peak hourly O3 exposure increased the rate of water loss 

18 from several tree species, and led to a reduction in the late-season modeled stream flow in 

19 three forested watersheds in eastern Tennessee. Sluggish stomatal responses during O3

20 exposure was suggested as a possible mechanism for increased water loss during peak O3

21 exposure. Currently, the O3-induced reduction in stomatal aperture is the biological 

22 assumption for most process-based models. Therefore, results of those models normally 

23 found that O3 reduced water loss. For example, one study found that O3 damage and 

24 N limitation together reduced evapotranspiration and increase runoff.

25 Although the direction of the response differed among studies, the evidence is sufficient 

26 to conclude that there is likely to be a causal relationship between O3 exposure and 

27 the alteration of ecosystem water cycling.

2.6.4 Below-Ground Processes

28 Below-ground processes are tightly linked with aboveground processes. The responses of 

29 aboveground process to O3 exposure, such as reduced photosynthetic rates, increased 

30 metabolic cost, and reduced root C allocation, have provided biologically plausible 

31 mechanisms for the alteration of below-ground processes. Since the 2006 O3 AQCD, 

32 more evidence has shown that although the responses are often species specific, O3
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1 altered the quality and quantity of C input to soil, microbial community composition, and 

2 C and nutrient cycling. 

3 Results from Aspen FACE and other experimental studies consistently found that O3

4 reduced litter production and altered C chemistry, such as soluble sugars, soluble 

5 phenolics, condensed tannins, lignin, and macro/micro nutrient concentration in litter 

6 (Section 9.4.6.1). Under elevated O3, the changes in substrate quality and quantity could 

7 alter microbial metabolism, and therefore soil C and nutrient cycling. Several studies 

8 indicated that O3 generally suppressed soil enzyme activities (Section 9.4.6.2). However, 

9 the impact of O3 on litter decomposition was inconsistent and varied among species, 

10 sites, and exposure length. Similarly, O3 had inconsistent impacts on dynamics of micro 

11 and macro nutrients (Section 9.4.6.4). 

12 Studies from the Aspen FACE experiment suggested that the response of below-ground 

13 C cycle to O3 exposure, such as litter decomposition, soil respiration, and soil C content, 

14 changed over time. For example, in the early part of the experiment (1998-2003), O3 had 

15 no impact on soil respiration but reduced the formation rates of total soil C under 

16 elevated CO2. However, after 10 to 11 years of exposure, O3 was found to increase soil 

17 respiration but have no substantial impact on soil C formation under elevated CO2

18 (Section 9.4.6.3). 

19 The evidence is sufficient to infer that there is a causal relationship between O3

20 exposure and the alteration of below-ground biogeochemical cycles.

2.6.5 Community Composition

21 In the 2006 O3 AQCD, the impact of O3 exposure on species competition and community 

22 composition was assessed. Ozone was found to be one of the dominant factors causing a 

23 decline in ponderosa and Jeffrey pine in the San Bernardino Mountains in southern 

24 California. Ozone exposure also tended to shift the grass-legume mixtures in favor of 

25 grass species. Since the 2006 O3 AQCD, more evidence has shown that O3 exposure 

26 changed the competitive interactions and led to loss of O3 sensitive species or genotypes. 

27 Studies found that the severity of O3 damage on growth, reproduction and foliar injury 

28 varied among species (Section 9.4.3), which provided the biological plausibility for the 

29 alteration of community composition. Additionally, research since the last review has 

30 shown that O3 can alter community composition and diversity of soil microbial 

31 communities.

32 The decline of conifer forests under O3 exposure was continually observed in several 

33 regions. Ozone damage was believed to be an important causal factor in the dramatic 
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1 decline of sacred fir in the valley of Mexico, as well as cembran pine in southern France 

2 and the Carpathian Mountains, although several factors, such as drought, insect outbreak 

3 and forest management, may also contribute to or even be the dominant factors causing 

4 the mortality of the conifer trees. Results from the Aspen FACE site indicated that O3

5 could alter community composition of broadleaf forests as well. At the Aspen FACE site, 

6 O3 reduced growth and increased mortality of a sensitive aspen clone, while the O3

7 tolerant clone emerged as the dominant clone in the pure aspen community. In the mixed 

8 aspen-birch and aspen-maple communities, O3 reduced the competitive capacity of aspen 

9 compared to birch and maple (Section 9.4.7.1).

10 The tendency for O3-exposure to shift the biomass of grass-legume mixtures in favor of 

11 grass species was reported in the 2006 O3 AQCD and has been generally confirmed by 

12 recent studies. However, in a high elevation mature/species-rich grass-legume pasture, O3

13 fumigation showed no substantial impact on community composition (Section 9.4.7.2).

14 Ozone exposure not only altered community composition of plant species, but also 

15 microorganisms. The shift in community composition of bacteria and fungi has been 

16 observed in both natural and agricultural ecosystems, although no general patterns could 

17 be identified (Section 9.4.7.3). 

18 The evidence is sufficient to conclude that there is likely to be a causal relationship 

19 between O3 exposure and the alteration of community composition of some 

20 ecosystems.

2.6.6 Policy Relevant Considerations

2.6.6.1 Air Quality Indices

21 Exposure indices are metrics that quantify exposure as it relates to measured plant injury 

22 (e.g., reduced growth). They are summary measures of monitored ambient O3

23 concentrations over time intended to provide a consistent metric for reviewing and 

24 comparing exposure-response effects obtained from various studies. No recent 

25 information is available since 2006 that alters the basic conclusions put forth in the 2006 

26 and 1996 O3 AQCDs. These AQCDs focused on the research used to develop various 

27 exposure indices to help quantify effects on growth and yield in crops, perennials, and 

28 trees (primarily seedlings). The performance of indices was compared through regression 

29 analyses of earlier studies designed to support the estimation of predictive O3 exposure30 response models for growth and/or yield of crops and tree (seedling) species.
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1 Another approach for improving risk assessment of vegetation response to ambient O3 is 

2 based on determining the O3 concentration from the atmosphere that enters the leaf 

3 (i.e., flux or deposition). Interest has been increasing in recent years, particularly in 

4 Europe, in using mathematically tractable flux models for O3 assessments at the regional, 

5 national, and European scale. While some efforts have been made in the U.S. to calculate 

6 O3 flux into leaves and canopies, little information has been published relating these 

7 fluxes to effects on vegetation. There is also concern that not all O3 stomatal uptake 

8 results in a yield reduction, which depends to some degree on the amount of internal 

9 detoxification occurring with each particular species. Species having high detoxification 

10 capacity may show little relationship between O3 stomatal uptake and plant response. The 

11 lack of data in the U.S. and the lack of understanding of detoxification processes have 

12 made this technique less viable for vulnerability and risk assessments in the U.S. 

13 The main conclusions from the 1996 and 2006 O3 AQCDs regarding indices based on 

14 ambient exposure remain valid. These key conclusions can be restated as follows:

15  O3 effects in plants are cumulative;

16  higher O3 concentrations appear to be more important than lower 

17 concentrations in eliciting a response;

18  plant sensitivity to O3 varies with time of day and plant development stage; 

19 and

20  quantifying exposure with indices that cumulate hourly O3 concentrations and 

21 preferentially weight the higher concentrations improves the explanatory 

22 power of exposure/response models for growth and yield, over using indices 

23 based on mean and peak exposure values.

24 Various weighting functions have been used, including threshold-weighted 

25 (e.g., SUM06) and continuous sigmoid-weighted (e.g., W126) functions. Based on 

26 statistical goodness-of-fit tests, these cumulative, concentration-weighted indices could 

27 not be differentiated from one another using data from previous exposure studies. 

28 Additional statistical forms for O3 exposure indices are summarized in Section 9.5 of this 

29 ISA. The majority of studies published since the 2006 O3 AQCD do not change earlier 

30 conclusions, including the importance of peak concentrations, and the duration and 

31 occurrence of O3 exposures in altering plant growth and yield.

32 Given the current state of knowledge and the best available data, exposure indices that 

33 cumulate and differentially weight the higher hourly average concentrations and also 

34 include the mid-level values continue to offer the most defensible approach for use in 

35 developing response functions and comparing studies, as well as for defining future 

36 indices for vegetation protection.
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2.6.6.2 Exposure-Response

1 None of the information on effects of O3 on vegetation published since the 2006 O3

2 AQCD has modified the assessment of quantitative exposure-response relationships that 

3 was presented in that document (U.S. EPA, 2006b). This assessment updates the 2006 

4 exposure-response models by computing them using the W126 metric, cumulated over 

5 90 days. Almost all of the experimental research on the effects of O3 on growth or yield 

6 of plants published since 2006 used only two levels of exposure. In addition, hourly O3

7 concentration data that would allow calculations of exposure using the W126 metric are 

8 generally unavailable. However, two long-term experiments, one with a crop species 

9 (soybean), one with a tree species (aspen), have produced data that are used in 

10 Section 9.6 to validate the exposure-response models presented in the 2006 O3 AQCD, 

11 and the methodology used to derive them. EPA compared predictions from the models 

12 presented in the 2006 O3 AQCD, updated to use the 90 day 12hr W126 metric, with more 

13 recent observations for yield of soybean and biomass growth of trembling aspen. The 

14 models were parameterized using data from the National Crop Loss Assessment Network 

15 (NCLAN) and EPA’s National Health and Environmental Effects Research Laboratory –

16 Western Ecology Division (NHEERL-WED) projects, which were conducted in OTCs. 

17 The more recent observations were from experiments using FACE technology, which is 

18 intended to provide conditions closer to natural environments than OTC. Observations 

19 from these new experiments were exceptionally close to predictions from the models. 

20 The accuracy of model predictions for two widely different plant species, grown under 

21 very different conditions, provides support for the validity of the models for crops and 

22 trees developed using the same methodology and data for other species. However, 

23 variability observed among species in the NCLAN and NHEERL-WED projects indicates 

24 that the range of sensitivity between and among species is likely quite wide.

25 Results from several meta-analyses have provided approximate values for responses of 

26 yield of soybean, wheat, rice and other crops under broad categories of exposure, relative 

27 to charcoal-filtered air. Additional reports have summarized yield data for six crop 

28 species under various broad comparative exposure categories, and reviewed 263 studies 

29 that reported effects on tree biomass. However, these analyses have proved difficult to 

30 compare with exposure-response models, especially given that exposure was not

31 expressed using a common metric (i.e., W126). 
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2.7 The Role of Tropospheric Ozone in Climate Change and UV-B 

Effects

1 Atmospheric O3 plays an important role in the Earth’s energy budget by interacting with 

2 incoming solar radiation and outgoing infrared radiation. Tropospheric O3 makes up only 

3 a small portion of the total column of O3, but it has important incremental effects on the 

4 overall radiation budget. Chapter 10 assesses the specific role of tropospheric O3 in the 

5 earth’s radiation budget and how perturbations in tropospheric O3 might affect (1) climate 

6 through its role as a greenhouse gas, and (2) health, ecology and welfare through its role 

7 in shielding the earth’s surface from solar ultraviolet (UV) radiation.

2.7.1 Tropospheric Ozone as a Greenhouse Gas

8 Ozone is an important greenhouse gas, and increases in its abundance in the troposphere 

9 may contribute to climate change according to the 2007 climate assessment by the 

10 Intergovernmental Panel on Climate Change (IPCC). Models calculate that the global 

11 burden of tropospheric O3 has doubled since the pre-industrial era, while observations 

12 indicate that in some regions O3 may have increased by factors as great as 4 or 5. These 

13 increases are tied to the rise in emissions of O3 precursors from human activity, mainly 

14 fossil fuel consumption and agricultural processes.

15 Figure 2-4 shows the main steps involved in the influence of tropospheric O3 on climate. 

16 Emissions of O3 precursors including CO, VOCs, CH4, and NOX lead to production of 

17 tropospheric O3. A change in the abundance of tropospheric O3 perturbs the radiative 

18 balance of the atmosphere, an effect quantified by the radiative forcing (RF) metric. The 

19 earth-atmosphere-ocean system responds to the forcing with a climate response, typically 

20 expressed as a change in surface temperature. Finally, the climate response causes 

21 downstream climate-related health and ecosystem impacts, such as redistribution of 

22 diseases or ecosystem characteristics due to temperature changes. Feedbacks from both 

23 the climate response and downstream impacts can, in turn, affect the abundance of 

24 tropospheric O3 and O3 precursors through multiple feedback mechanisms as indicated in 

25 Figure 2-4. Direct feedbacks are discussed in Section 10.3.2.4 while downstream climate 

26 impacts and their feedbacks are extremely complex and outside the scope of this 

27 assessment.
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Note: 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 2-4 Schematic illustrating the effects of tropospheric ozone on climate;

including the relationship between precursor emissions, 

tropospheric ozone abundance, radiative forcing, climate response, 

and climate impacts.Tropospheric Ozone and UV-B related effects

1 The impact of the tropospheric O3 change since pre-industrial times on climate has been 

2 estimated to be about 25-40% of the anthropogenic CO2 impact and about 75% of the 

3 anthropogenic CH4 impact according to the IPCC, ranking it third in importance among 

4 the greenhouse gases. There are large uncertainties in the RF estimate attributed to 

5 tropospheric O3, making the impact of tropospheric O3 on climate more uncertain than 

6 the impact of the long-lived greenhouse gases. Overall, the evidence supports a causal 

7 relationship between changes in tropospheric O3 concentrations and radiative 

8 forcing.

9 RF does not take into account the climate feedbacks that could amplify or dampen the 

10 actual surface temperature response. Quantifying the change in surface temperature 

11 requires a complex climate simulation in which all important feedbacks and interactions 

12 are accounted for. As these processes are not well understood or easily modeled, the 

13 surface temperature response to a given RF is highly uncertain and can vary greatly 

14 among models and from region to region within the same model. In light of these 

15 uncertainties, the evidence indicates that there is likely to be a causal relationship 

16 between changes in tropospheric O3 concentrations and effects on climate.
Draft – Do Not Cite or Quote 2-51 June 2012

2.7.3 Tropospheric Ozone and UV-B Related Effects

1 UV radiation emitted from the Sun contains sufficient energy when it reaches the Earth to 

2 break (photolyze) chemical bonds in molecules, thereby leading to damaging effects on 

3 living organisms and materials. Atmospheric O3 plays a crucial role in reducing exposure 

4 to solar UV radiation at the Earth’s surface. Ozone in the stratosphere is responsible for 

5 the majority of this shielding effect, as approximately 90% of total atmospheric O3 is 

6 located there over mid-latitudes. Ozone in the troposphere provides supplemental 

7 shielding of radiation in the wavelength band from 280-315 nm, referred to as UV-B 

8 radiation. UV-B radiation has important effects on human health and ecosystems, and is 

9 associated with materials damage.

10 Human health effects associated with solar UV-B radiation exposure include erythema, 

11 skin cancer, ocular damage, and immune system suppression. A potential human health 

12 benefit of increased UV-B exposure involves the UV-induced production of vitamin D 

13 which may help reduce the risk of metabolic bone disease, type I diabetes, mellitus, and 

14 rheumatoid arthritis, and may provide beneficial immunomodulatory effects on multiple 

15 sclerosis, insulin-dependent diabetes mellitus, and rheumatoid arthritis. Ecosystem and 

16 materials damage effects associated with solar UV-B radiation exposure include 

17 terrestrial and aquatic ecosystem impacts, alteration of biogeochemical cycles, and 

18 degradation of man-made materials. 

19 There is a lack of published studies that critically examine the incremental health or 

20 welfare effects (adverse or beneficial) attributable specifically to changes in UV-B 

21 exposure resulting from perturbations in tropospheric O3 concentrations. The effects are 

22 expected to be small and they cannot yet be critically assessed within reasonable 

23 uncertainty. Overall, the evidence is inadequate to determine if a causal relationship 

24 exists between changes in tropospheric O3 concentrations and effects on health 

25 and welfare related to UV-B shielding.

2.8 Summary of Causal Determinations for Health Effects and 

Welfare Effects

26 This chapter has provided an overview of the underlying evidence used in making the 

27 causal determinations for the health and welfare effects of O3. This review builds upon 

28 the conclusions of the previous AQCDs for O3. 

29 The evaluation of the epidemiologic, toxicological, and controlled human exposure 

30 studies published since the completion of the 2006 O3 AQCD have provided additional 

31 evidence for O3-related health outcomes. Table 2-4 provides an overview of the causal 
Draft – Do Not Cite or Quote 2-52 June 2012

1 determinations for all of the health outcomes evaluated. Causal determinations for O3 and 

2 welfare effects are included in Table 2-5, while causal determinations for climate change 

3 and UV-B effects are in Table 2-6. Detailed discussions of the scientific evidence and 

4 rationale for these causal determinations are provided in subsequent chapters of this ISA. 

Table 2-4 Summary of ozone causal determinations by exposure duration 

and health outcome.

Health Outcome Conclusions from 2006 O3 AQCD

Conclusions from 

2012 3rd 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

Total 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

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

Total 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
Draft – Do Not Cite or Quote 2-53 June 2012

Table 2-5 Summary of ozone causal determination for welfare effects.

Vegetation and 

Ecosystem Effects

Conclusions from 2006 O3 AQCD Conclusions from 

2012 3rd 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 2-6 Summary of ozone causal determination for climate and UV-B 

effects.

Effects Conclusions from 2006 O3 AQCD Conclusions from 

2012 3rd 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 discernible influence on 

climate, leading to surface temperature and hydrological cycle changes.

Likely to be a Causal 

Relationship

Health and Welfare 

Effects Related to UV-B 

Shielding

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
Draft – Do Not Cite or Quote 2-54 June 2012

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