Draft

– Do Not Cite or Quote 2

- 1 September 2011 

## 2 INTEGRATIVE SUMMARY

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

### 1

of the national ambient air quality standards (NAAQS) for ozone (O 3 ). The ISA is a 

### 2

concise evaluation and synthesis of the most policy

- relevant science, and it 

### 3

communicates critical science judgments relevant to the review of the NAAQS for O 3

. 

### 4

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

### 5

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

### 6

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

### 7

contained in prior Air Quality Criteria Documents (AQCD) for O 3 are incorporated into 

### 8

thi s assessment. Additional details of the pertinent scientific literature published since the 

### 9

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

### 10

thus serves to update and revise the evaluation of the scientific evid ence available at the 

### 11

time of the completion of the 2006 O 3 AQCD. The current primary O 3 standard includes 

### 12

an 8

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

### 13

standard for O 3 is set equal to the primary standard. Further i nformation on the legislative 

### 14

and historical background for the O 3 NAAQS is contained in the Preface to this ISA. 

### 15

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

### 16

intended to provide a concise synopsis of the ISA concl usions and findings that best 

### 17

inform consideration of the policy

- relevant questions that frame this assessment 

### 18

(presented in Section 2.1). It includes: 

### 19

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

- and 

### 20

long

- term exposure to O 3 , discussion of important uncertainties identified in 

### 21

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

### 22

evidence from the different scientific disciplines and exposure durations. 

### 23

 An integration of the evidence on the ecological an d welfare effects associated 

### 24

with exposure to O 3 , and discussion of important uncertainties identified in the 

### 25

interpretation of the scientific evidence. 

### 26

 Discussion of policy

- relevant considerations, such as potentially at

- risk 

### 27

populations and concentration

- response relationships. 

### 28



## 2.1 Policy

- Relevant Questions for O 3 

## NAAQS Review

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

### 29

(IRP) ( U.S. EPA, 2009c ) identified key policy

- relevant questions that provide a 

### 30

framework for this assessment of the scientific evidence. These questions frame the entire 

### 31Draft

– Do Not Cite or Quote 2

- 2 September 2011 review of the NAAQS for O 3 and thus are informed by both science and policy 

### 1

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

### 2

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

### 3

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

### 4

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

### 5

scientific evidence that is most relevant to the following q uestions taken directly from the 

### 6

Integrated Review Plan: 

### 7

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

### 8

substantiates our understanding of the health effects associated with various 

### 9

time periods of exposure to ambient O 3 , inc luding short

- term (1

- 3 hours), 

### 10

prolonged (6

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

### 11

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

### 12

substantiates our understanding of the health effects of O 3 on at

- risk 

### 13

populations, including those with potentially increased susceptibility such as 

### 14

children and disadvantaged populations? 

### 15

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

### 16

substantiates conclusions from previous reviews regarding the plausibi lity of 

### 17

adverse health effects caused by O 3 exposure? 

### 18

 At what levels of O 3 exposure are health effects observed? Is there evidence of 

### 19

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

### 20

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

### 21

of the exposure

- response relationships o f O 3 for the various health effects 

### 22

evaluated? 

### 23

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

### 24

substantiates our understanding of non

- O 3 - exposure factors that might 

### 25

influence the associations between O 3 levels and health effec ts being 

### 26

considered (e.g., weather

- related factors; behavioral factors such as heating/air 

### 27

conditioning use; driving patterns; and time

- activity patterns)? 

### 28

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

### 29

concern for O 3 - related hea lth effects are likely to occur with current ambient 

### 30

levels of O 3 or with levels that just meet the O 3 standard? Are these 

### 31

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

### 32

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

### 33

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

### 34

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

### 35

been addressed and/or have new uncertainties emerged? 

### 36Draft

– Do Not Cite or Quote 2

- 3 September 2011 In evaluating the welfare e vidence, the available scientific evidence will focus on key 

### 1

policy

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

### 2

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

### 3

substantiates our understanding o f the effects on vegetation and other welfare 

### 4

effects following exposures to levels of O 3 found in the ambient air? 

### 5

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

### 6

understanding of the nature of the exposures that are associate d with such 

### 7

effects in terms of biologically relevant cumulative, seasonal exposure 

### 8

indices? 

### 9

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

### 10

substantiates our understanding of the effects of O 3 on sensitive plant species, 

### 11

ecol ogical receptors, or ecosystem processes? 

### 12

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

### 13

substantiates our understanding of exposure factors other than O 3 that might 

### 14

influence the associations between O 3 levels and welfare ef fects being 

### 15

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

### 16

presence of co

- occurring competitors, pests, pathogens, other pollutant 

### 17

stressors, weather

- related factors)? 

### 18

 To what extent has new scientific information become a vailable that alters or 

### 19

substantiates conclusions regarding the occurrence of adverse welfare effects 

### 20

at levels of O 3 as low as or lower than those observed previously? What is the 

### 21

nature of the exposure

- response relationships of O 3 for the various welfare 

### 22

effects evaluated? 

### 23

 Given recognition in the last review that the significance of O 3 - induced effects 

### 24

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

### 25

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

### 26

ev idence become available to suggest additional locations where the 

### 27

vulnerability of sensitive species or ecosystems would have special 

### 28

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

### 29

review? 

### 30

 To what extent do risk and/or expos ure analyses suggest that exposures of 

### 31

concern for O 3 - related welfare effects are likely to occur with current ambient 

### 32

levels of O 3 or with levels that just meet the O 3 standard? Are these 

### 33

risks/exposures of sufficient magnitude such that the welfare effec ts might 

### 34

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

### 35

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

### 36Draft

– Do Not Cite or Quote 2

- 4 September 2011  To what extent have important uncertainties identified in the last review been 

### 1

addressed an d/or have new uncertainties emerged? 

### 2

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

### 3

question any of the basic elements of the current O 3 standard? 

### 4



## 2.2 ISA Development and Scope

EPA has a developed a robust, consistent, and transparent p rocess for evaluating the 

### 5

scientific evidence and drawing conclusions and causal judgments regarding air 

### 6

pollution

- related health and environmental effects. The ISA development process 

### 7

includes literature search strategies, criteria for selecting and evalu ating studies, 

### 8

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

### 9

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

### 10

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

### 11

development of this ISA. 

### 12

EPA initiated the current review of the NAAQS for O 3 on September 29, 2008, with a 

### 13

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

### 14

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

### 15

studies published from 2005 (close of previous s cientific assessment) through July 2011. 

### 16

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

### 17

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

### 18

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

### 19

in the ISA, with bibliographic information and abstracts. 

### 20

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

### 21

pertaining to the atmospheric science of O 3 , human exposure to ambient O 3 , 

### 22

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

### 23

effects studies, including studies related to exposure

- response relationships, mode(s) of 

### 24

action (MOA), and unde rstanding of at

- risk or susceptible populations for effects of O 3 

### 25

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

### 26

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

### 27

as well as issues rel ated to exposure to O 3

. 

### 28

Previous AQCDs ( U.S. EPA, 2006b

, 1996a

, b

, 1984

, 1978a ) have included an extensive 

### 29

body of evidence on both health and ecological effects of O 3 exposure, as well as an 

### 30

understanding of the atmospheric chemistry of O 3 ( U.S. E PA, 2006b ) . In this ISA, the 

### 31

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

### 32

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

### 33Draft

– Do Not Cite or Quote 2

- 5 September 2011 Results of key studies from previous reviews ar e included in discussions or tables and 

### 1

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

### 2

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

### 3

The Preamble discusses the general framework fo r conducting the science assessment 

### 4

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

### 5

conclusions. For selection of epidemiologic studies in the O 3 ISA, particular emphasis is 

### 6

placed on those studies most relevant t o the review of the NAAQS. Studies conducted in 

### 7

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

### 8

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

### 9

that employ standardized analysis methods for evaluating effects of O 3 and that provide 

### 10

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

### 11

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

### 12

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

### 13

susceptible populations; and (4) studies that consider and report O 3 as a component of a 

### 14

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

### 15

exposure studies, empha sis is placed on studies using concentrations or doses that are 

### 16

within about an order of magnitude of ambient O 3 concentrations. Consideration of issues 

### 17

important for evaluation of human exposure to ambient O 3 include the relationship 

### 18

between O 3 measured a t central site monitors and personal exposure to ambient O 3 

### 19

environments, since penetration of O 3 into indoor environments may be limited. 

### 20

This ISA uses a five

- level hierarchy that classifies the weight of evidence for causation: 

### 21

 Causal relationship 

### 22

 Lik ely to be a causal relationship 

### 23

 Suggestive of a causal relationship 

### 24

 Inadequate to infer a causal relationship 

### 25

 Not likely to be a causal relationship 

### 26

Beyond judgments regarding causality are questions relevant to quantifying health or 

### 27

environmental risk s based on our understanding of the quantitative relationships between 

### 28

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

### 29

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

### 30

regardi ng quantitative relationships include: 

### 31

 What is the concentration

- response or dose

- response relationship? 

### 32

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

### 33

are effects observed? 

### 34Draft

– Do Not Cite or Quote 2

- 6 September 2011  What populations appear to be differentially affect ed i.e., more susceptible to 

### 1

effects? 

### 2

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

### 3

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

### 4

effects? 

### 5

This chapter summarizes and integrates the newly available s cientific evidence that best 

### 6

informs consideration of the policy

- relevant questions that frame this assessment. 

### 7

Section 2.3 discusses the trends in ambient concentrations and sources of O 3 and provides 

### 8

a brief summary of ambient air quality for short

- and long

- term exposure durations. 

### 9

Section 2.4 presents the evidence regarding personal exposure to ambient O 3 in outdoor 

### 10

and indoor microenvironments, and it discusses the relationship between ambient O 3 

### 11

concentrations and personal exposure to O 3 from ambient sources. Section 2.5 provides a 

### 12

discussion of the dosimetry and mode of action evidence for O 3 exposure. Section 2.6 

### 13

integrates the evidence for studies that examine the health effects associated with short



### 14

and long

- term exposure to O 3 and discusses impor tant uncertainties identified in the 

### 15

interpretation of the scientific evidence. Section 2.7 provides a discussion of policy



### 16

relevant considerations, such as potentially at

- risk populations, lag structure, and the O 3 

### 17

concentration

- response relationship. Sec tion 2.8 integrates the health evidence from the 

### 18

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

### 19

the evidence for welfare effects related to O 3 exposure, and Section 2.10 reviews the 

### 20

literature on the influence of t ropospheric O 3 on climate and exposure to solar ultraviolet 

### 21

radiation. 

### 22



## 2.3 Atmospheric Chemistry and Ambient Concentrations

2.3.1 Physical and Chemical Processes

Ozone in the troposphere originates from both anthropogenic (i.e., man

- made) and 

### 23

natural source categor ies. Ozone attributed to anthropogenic sources is formed in the 

### 24

atmosphere by photochemical reactions involving sunlight and precursor pollutants 

### 25

including volatile organic compounds (VOCs), nitrogen oxides (NO X ), and carbon 

### 26

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

### 27

photochemical reactions involving natural emissions of precursor pollutants from 

### 28

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

### 29

schematic overview of the major photochemical cycles influencing O 3 in the troposphere 

### 30

and the stratosphere is shown in Figure 2

- 1 . The processes depicted in this figure are 

### 31

fairly well understood, and were covered in detail in the previous O 3 AQCD. The 

### 32Draft

– Do Not Cite or Quote 2

- 7 September 2011 formation of O 3 , other oxidants, and oxidation products from these p recursors is a 

### 1

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

### 2

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

### 3

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

### 4

cloud and aerosol particles. 

### 5

Figure 2

- 1 Schematic overview of photochemical processes influencing stratospheric and tropospheric ozone.

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

### 6

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

- driven 

### 7

reactions of NO X , VOCs and CO contribute to O 3 formation throughout the troposphere. 

### 8Draft

– Do Not Cite or Quote 2

- 8 September 2011 These processes also lead to the formatio n of other photochemical products, such as 

### 1

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

### 2

formaldehyde and other carbonyl compounds. In urban areas, NO X , VOCs and CO are all 

### 3

important for O 3 formation. In nonurban veg etated areas, biogenic VOCs emitted from 

### 4

vegetation tend to be the most important precursor to O 3 formation. In the remote 

### 5

troposphere, methane

– structurally the simplest VOC

– and CO are the main carbon



### 6

containing precursors to O 3 formation. Throughout t he troposphere, O 3 is subsequently 

### 7

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

### 8

Figure 2

- 1

. 

### 9

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

### 10

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

### 11

areas of the U.S., O 3 and its precursors can be transported over long distances, aided by 

### 12

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

### 13

characterized by the development of urban plumes. Meteorological conditions, small



### 14

scale circulation patterns, localized chemistry, and mountain barriers can influence 

### 15

mixing on a smaller scale , resulting in frequent heterogeneous O 3 concentrations across 

### 16

an individual urban area. 

### 17

Furthermore, the mean tropospheric lifetime of O 3 is long enough that it can be 

### 18

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

### 19

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

### 20

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

### 21

pollution, particularly during spring. Given the nonlinear chemistry involving O 3 

### 22

formation, the task of isolating the influence of intercontinental transport of O 3 and O 3 

### 23

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

### 24

2.3.2 Atmospheric Modeling of Background Ozone Concentrations

Background concentrations of O 3 have been given various definitions in the literature 

### 25

over time. In the context of a review of the NAAQS, it is useful to define background O 3 

### 26

concentrations in a way that distinguishes between concentrations that result from 

### 27

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

### 28

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

### 29

background O 3 can include contributions that result from emissions from natural sources 

### 30

(e.g., st ratospheric intrusion, biogenic methane and more short

- lived VOC emissions), 

### 31

emissions of pollutants that contribute to global concentrations of O 3 (e.g., anthropogenic 

### 32

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

### 33

de finition of background concentrations was used and referred to as policy relevant 

### 34Draft

– Do Not Cite or Quote 2

- 9 September 2011 background (PRB). In those previous reviews, PRB concentrations were defined by EPA 

### 1

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

### 2

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

### 3

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

### 4

concentrations from natural sources everywhere in the world and from anthropogenic 

### 5

sources outside CNA. North American background concentrations so defined facilitate 

### 6

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

### 7

international agreements with neighboring countries from that which would require more 

### 8

comprehensive inte rnational agreements, such as are being discussed as part of the 

### 9

United Nations sponsored Convention on Long Range Transboundary Air Pollution Task 

### 10

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

### 11

background O 3 and O 3 attributabl e to CNA anthropogenic sources, and background 

### 12

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

### 13

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

### 14

understand how total O 3 concentra tions can be attributed to different source. 

### 15

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

### 16

measured, the range of background O 3 concentrations are estimated using chemistry 

### 17

transport models (CTMs). The 2006 O 3 AQCD provided regional estimates of PRB O 3 

### 18

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

- Chem 

### 19

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

### 20

or ~50 km×50 km) GEOS

- Chem model were used. B ase

- case model performance 

### 21

evaluations comparing 2006 predicted to observed mean O 3 concentrations from March 

### 22

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

### 23

investigated. Exceptions included over

- prediction of mean O 3 duri ng the summer at a site 

### 24

on the Atlantic coast of Florida and under

- prediction of mean O 3 year

- round at a site in 

### 25

Yosemite NP. The finer resolution GEOS

- Chem model agrees more closely with 

### 26

observations in the intermountain West than earlier versions. 

### 27

The GE OS

- Chem model

- predicted North American O 3 seasonal mean concentrations for 

### 28

spring and summer, 2006 are shown in Figure 2

- 2 . As can be seen, North Amer ican 

### 29

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

### 30

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

### 31

are found in the Intermountain West during the spring (less than 47 ppb) a nd in the 

### 32

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

### 33

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

### 34

15 ppb). 

### 35Draft

– Do Not Cite or Quote 2

- 10 September 2011 

### 2.3.3 Monitoring

The federal reference method (FRM) for O 3 measurement is based on the detection of 

### 1

chemiluminescence resulting from the reaction of O 3 with ethylene gas. However, almost 

### 2

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

### 3

Air Quality System (AQS) database fr om 2005 to 2009 used the federal equivalence 

### 4

method (FEM) UV absorption photometer. More than 96% of O 3 monitors met precision 

### 5

and bias goals during this period. 

### 6

In 2010, there were 1250 SLAMS O 3 monitors reporting data to AQS. Ozone is required 

### 7

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

### 8

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

### 9

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

### 10

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

### 11

nationwide (See Figure 3

- 16). The densest concentrations of O 3 sites are located in 

### 12

California and the eastern half of the U.S. 

### 13

Source: Zhang et al. ( In Press )



### Figure 2

- 2 GEOS

- Chem modeled U.S. policy relevant background seasonal

mean surface ozone concentrations in spring (left) and su mmer (right), 2006.

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

### 14

established to assess trends in acidic deposition and also provides concentration 

### 15Draft

– Do Not Cite or Quote 2

- 11 September 2011 measurements of O 3 . CASTNET O 3 monitors operate year round and are prim arily 

### 1

located in rural areas; in 2010, there were 80 CASTNET sites reporting O 3 data to AQS. 

### 2

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

### 3

Class

- I areas, and provided data to AQS from 20 additional Portable Ozone Mon itoring 

### 4

Systems (POMS) in 2010 (See Figure 3

- 17). Compared to urban

- focused monitors, rural



### 5

focused monitors are relatively scarce across the U.S. 

### 6

2.3.4 Ambient Concentrations

Ozone is the only photochemical oxidant other than NO 2 that is routinely monitored and 

### 7

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

### 8

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

### 9

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

### 10

period from 2007 to 2009. The median 24

- h average, 8

- h daily maximum, and 1

- h daily 

### 11

maximum O 3 concentrations across all U.S. sites reporting data to AQS between 2007 

### 12

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

### 13

To investigate O 3 variability in urban a reas across the U.S., 20 combined statistical areas 

### 14

(CSAs) were selected for closer analysis based on their importance in O 3 epidemiology 

### 15

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

- h 

### 16

daily maximum O 3 concentr ations (e.g., inter

- monitor correlations ranging from 0.61 to 

### 17

0.96 in the Atlanta CSA) while other CSAs exhibited considerably more variability in O 3 

### 18

concentrations (e.g., inter

- monitor correlations ranging from

- 0.06 to 0.97 in the 

### 19

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

### 20

network of ambient O 3 monitors to approximate community

- scale exposures. 

### 21

To investigate O 3 variability in rural settings across the U.S., six focus areas were 

### 22

selected for closer analysis based on t he impact of O 3 or O 3 precursor transport from 

### 23

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

### 24

AQS monitors was Great Smoky Mountain National Park where the May

- September 

### 25

median 8

- h daily maximum O 3 concentration ranged from 47 ppb at the lowest elevation 

### 26

(564 m) site to 60 ppb at the highest elevation (2

, 021 m) site. Correlations between sites 

### 27

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

### 28

from emissions of O 3 precursors emitted directly within the rural areas, from emissions in 

### 29

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

### 30

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

### 31

include proximity to local O 3 precursor emissions, local scale circulations related to 

### 32

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

### 33

O 3 tends to persist longer in rural than in urban areas as a result of less chemical 

### 34Draft

– Do Not Cite or Quote 2

- 12 September 2011 scaveng ing. This results in a more uniform O 3 concentration throughout the day and night 

### 1

without the typical nocturnal decrease in O 3 concentration observed in urban areas. 

### 2

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

### 3

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

### 4

substantial and often higher than cumulative exposures in urban areas. 

### 5

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

, 

### 6

O 3 concentrations have declined over the last decade; with the majority of this decline 

### 7

occurring before 20 04. A noticeable decrease in O 3 between 2003 and 2004 coincides 

### 8

with NO X emissions reductions resulting from implementation of the NO X SIP Call rule, 

### 9

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

### 10

reduce NO X emissions from power plants and other large combustion sources in the 

### 11

eastern U.S. As noted in the 2006 O 3 AQCD, trends in national parks and rural areas are 

### 12

similar to nearby urban areas, reflecting the regional nature of O 3 pollution. 

### 13

Since O 3 is a secondary pollutant , it is not expected to be highly correlated with primary 

### 14

pollutants such as CO and NO X . Furthermore, O 3 formation is strongly influenced by 

### 15

meteorology, entrainment, and transport of both O 3 and O 3 precursors, resulting in a 

### 16

broad range in correlations wi th other pollutants which can vary substantially with 

### 17

season. Correlations between 8

- h daily maximum O 3 and other criteria pollutants exhibit 

### 18

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

### 19

The median seasonal cor relations are modest at best with the highest positive correlation 

### 20

at 0.52 for PM 2.5 in the summer and the highest negative correlation at

- 0.38 for PM 2.5 in 

### 21

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

### 22

copoll utants need to take seasonality into consideration, especially when O 3 is being 

### 23

investigated. 

### 24



## 2.4 Human Exposure

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

### 25

anthropogenic sources. As such, people are routinely exposed to O 3 as they participate in 

### 26

normal day

- to

- day activities. A number of factors affect the pattern of personal O 3 

### 27

exposure. These include: the variation in O 3 concentrations at various spatial and 

### 28

temporal scales; individuals ’ activity patterns, particularly ti me spent outdoors, which 

### 29

may involve changes in personal behavior to avoid exposure to O 3 ; and infiltration of 

### 30

ambient O 3 into indoor microenvironments, which is driven by air exchange rate. 

### 31

Similarly, several approaches have been used to measure or quanti fy exposure to ambient 

### 32

O 3 , giving an indication of the impact of these factors. These approaches include 

### 33

characterizing the correlation and ratio between personal exposure and ambient O 3 

### 34Draft

– Do Not Cite or Quote 2

- 13 September 2011 concentration, determining the ratio between indoor and outdoor conce ntrations, and 

### 1

using models to estimate exposure to O 3 based on ambient concentrations. Both the 

### 2

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

### 3

quantification of exposure may have implications for epidemiologic studies

. 

### 4

Variations in O 3 concentrations occur over multiple spatial and temporal scales. Near 

### 5

roadways, O 3 concentrations are reduced due to reaction with NO and other species 

### 6

(Section 4.3.4.2). Over spatial scales of a few kilometers and away from roads, O 3 may 

### 7

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

### 8

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

### 9

concentrations downwind of an urban area. Although local

- scale variability impa cts the 

### 10

magnitude of O 3 concentrations, O 3 formation rates are influenced by factors that vary 

### 11

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

### 12

monitors may track one another temporally but miss small

- scale variability. This 

### 13

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

### 14

move through different microenvironments and affects the magnitude of exposures in 

### 15

different locations within an urban area. 

### 16

Another factor that may influence the p attern of exposure is the tendency for people to 

### 17

avoid O 3 exposure by altering their behavior (e.g., reducing time spent outdoors) on high



### 18

O 3 days. Activity pattern has a substantial effect on ambient O 3 exposure, with time spent 

### 19

outdoors contributing to i ncreased exposure (Section 4.4.2). Air quality alerts and public 

### 20

health recommendations induce reductions in outdoor activity on high

- O 3 days among 

### 21

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

### 22

problems. Such effect s are less pronounced in the general population, possibly due to the 

### 23

opportunity cost of behavior modification. Preliminary epidemiologic evidence reports 

### 24

increased asthma hospital admissions among children and older adults when O 3 alert days 

### 25

were excluded from the analysis of daily hospital admissions and O 3 concentrations 

### 26

(presumably thereby eliminating averting behavior based on high O 3 forecasts). The 

### 27

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

### 28

that estimates of health effects based on dose

- response functions which do not account 

### 29

for averting behavior may be biased towards the null. 

### 30

Personal exposure to O 3 is moderately correlated with ambient O 3 concentration, as 

### 31

indicated by studies reporting correlations ge nerally in the range of 0.3

- 0.8 (Table 4

- 2). 

### 32

To the extent that relative changes in central

- site monitor concentration are associated 

### 33

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

### 34

concentrations are representative of day

- to

- day changes in average total personal 

### 35

exposure and in personal exposure to ambient O 3 . The ratio between personal exposure 

### 36

and ambient concentration varies widely depending on activity patterns, housing 

### 37Draft

– Do Not Cite or Quote 2

- 14 September 2011 characteristics, and season. Personal

- ambient ratios are typically 0.1

- 0.3, although 

### 1

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

### 2

higher ratios (0.5

- 0.9) (Table 4

- 3). Thus, applying personal

- ambient ratios for outdoor 

### 3

workers to the general population or susce ptible populations spending substantial time 

### 4

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

### 5

groups. Some studies report much lower personal

- ambient correlations, a result 

### 6

attributable in part to low air exchange rate an d O 3 concentrations below the sampler 

### 7

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

### 8

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

### 9

relatively few indoor sources of O 3 , indo or O 3 concentrations are often substantially 

### 10

lower than outdoor concentrations due to reactions of O 3 with indoor surfaces and 

### 11

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

### 12

fluctuations in ambient O 3 may be primarily responsible for changes in personal 

### 13

exposure, even under low

- ventilation, low

- concentration conditions. 

### 14

The factors affecting exposure patterns and quantification of exposure result in 

### 15

uncertainty which may contribute to exposure measurement error in epid emiologic 

### 16

studies. Low personal

- ambient correlations are a source of exposure error for 

### 17

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

### 18

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

### 19

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

### 20

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

### 21

estimates, since epidemiologic studies evaluating the influence of monitor selection 

### 22

i ndicate that effect estimates are similar across different spatial averaging scales and 

### 23

monitoring sites. 

### 24



## 2.5 Dosimetry and Mode of Action

Upon inspiration, O 3 uptake in the respiratory tract is affected by a number of factors 

### 25

including respiratory tract morph ology, and breathing route, frequency, and volume. 

### 26

Additionally, physicochemical properties of O 3 itself and how it is transported, as well as 

### 27

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

### 28

layers in the respiratory tract can influence O 3 uptake. Experimental studies and models 

### 29

have suggested that there are differences between the total absorption of O 3 from the 

### 30

inhaled air and the O 3 dose reaching the respiratory tract tissues. The total O 3 absorption 

### 31

gradually decr eases with distal progression into the respiratory tract. In contrast, the 

### 32

primary site of O 3 delivery to the lung epithelium is believed to be the centriacinar region 

### 33

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

### 34Draft

– Do Not Cite or Quote 2

- 15 September 2011 Ozone uptake ef ficiency is sensitive to a number of factors including tidal volume, 

### 1

minute volume, breathing frequency, O 3 concentration, and exposure time. However, the 

### 2

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

### 3

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

### 4

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

### 5

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

### 6

penetr ation of O 3 into the lung with a higher absorbed fraction in the upper respiratory 

### 7

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

### 8

activity acts to move the maximum tissue dose of O 3 distally in the respiratory tract an d 

### 9

into the alveolar region. 

### 10

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

### 11

barrier and target for inhaled O 3 (see Figure 5

- 8). Distinct products with diverse reactivity 

### 12

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

### 13

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

### 14

within the ELF, are important determinants of the dose of O 3 to the tissues; a thicker ELF 

### 15

generally results in a lower dose o f O 3 to the tissues. Additionally, the quenching ability 

### 16

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

### 17

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

### 18

O 3 with underlying ti ssues and to prevent penetration of O 3 distally into the respiratory 

### 19

tract. 

### 20

In addition to contributing to the driving force for O 3 uptake, formation of secondary 

### 21

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

### 22

alt ered cell signaling in the respiratory tract. Secondary oxidation products initiate 

### 23

pathways (See Figure 5

- 9) that provide the mechanistic basis for short

- and long

- term 

### 24

health effects described in detail in Chapters 6 and 7. Other key events involved in t he 

### 25

mode of action of O 3 in the respiratory tract include the activation of neural reflexes, 

### 26

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

### 27

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

### 28

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

### 29

stress, may be critical to the extrapulmonary effects of O 3

. 

### 30

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

### 31

the activa tion of neural reflexes. Nociceptive sensory nerves mediate the involuntary 

### 32

truncation of respiration, resulting in decreases in lung function (i.e., FVC, FEV 1 , and 

### 33

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

### 34

bronchi al C

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

### 35

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

### 36Draft

– Do Not Cite or Quote 2

- 16 September 2011 following exposure to O 3 via parasympathetic pathways. Substance P release from 

### 1

bronchial C

- fi bers and the SP

- NK receptor pathway may also contribute to this response. 

### 2

Secondary oxidation products also initiate the inflammatory cascade following exposure 

### 3

to O 3 . Studies have implicated eicosanoids, chemokines and cytokines, vascular 

### 4

endothelial adh esion molecules, and tachykinins in mediating this response. 

### 5

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

### 6

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

### 7

characterized by increased n umbers of macrophages, which is mediated by hyaluronan. 

### 8

Inflammation further contributes to O 3 - induced oxidative stress. 

### 9

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

### 10

of O 3 - induced secondary oxidation produ ct formation. Increased epithelial permeability 

### 11

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

### 12

hyperresponsiveness (AHR). Neurally

- mediated sensitization also occurs and is mediated 

### 13

by cholinergic postganglionic pathway s and bronchial C

- fiber release of substance P. 

### 14

Recent studies implicate hyaluronan and toll

- like receptor 4 (TLR4) signaling in 

### 15

bronchial smooth muscle sensitization, while older studies demonstrate roles for 

### 16

eicosanoids, cytokines, and chemokines. 

### 17

Evide nce is accumulating that exposure to O 3 modifies innate and adaptive immunity 

### 18

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

### 19

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

### 20

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

### 21

and adaptive immunity may result in both short

- and longer

- term consequences related to 

### 22

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

### 23

Airway remodeling h as been demonstrated following chronic and/or intermittent 

### 24

exposure to O 3 by mechanisms which are not well understood. However, the TGF

- β 

### 25

signaling pathway has recently been implicated in O 3 - induced deposition of collagen in 

### 26

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

### 27

relevance to effects in humans is unknown. 

### 28

Evidence is also accumulating that O 3 exposure results in systemic inflammation and 

### 29

vascular oxidative/nitrosative stress. The release of diffusible mediators from the O 3 - 

### 30

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

### 31

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

### 32

extrapulmonary effects, such as vascular dysfunction. 

### 33

Both dosimetric and mech anistic factors contribute to the understanding of inter



### 34

individual variability in response. Inter

- individual variability is influenced by variability 

### 35

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

### 36Draft

– Do Not Cite or Quote 2

- 17 September 2011 polymorphisms, pre

- ex isting conditions and disease, nutritional status, lifestages, 

### 1

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

### 2

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

### 3

Pre

- existing asthm a, allergic airways disease, and obesity modulate immune and 

### 4

inflammatory responses to O 3 . Older adults exhibit diminished spirometric responses to 

### 5

O 3 compared with younger adults. Very young individuals may be sensitive to 

### 6

developmental effects of O 3 since studies in animal models demonstrated altered 

### 7

development of lung and other organ systems. 

### 8

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

### 9

sensitivity. Qualitatively, animal models exhibit a similar pattern of tissu e dose 

### 10

distribution for O 3 with the largest tissue dose delivered to the centriacinar region. 

### 11

However, due to anatomical and biochemical respiratory tract differences, the actual O 3 

### 12

dose delivered differs between humans and animal models. Animal data obtai ned in 

### 13

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

### 14

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

### 15

mechanistic pathways discussed above have been demonstrated in both an imals and 

### 16

human subjects in response to the inhalation of O 3 . Even though interspecies differences 

### 17

limit quantitative comparison between species, the short

- and long

- term functional 

### 18

responses of laboratory animals to O 3 appear qualitatively homologous to t hose of the 

### 19

human making them a useful tool in determining mechanistic and cause

- effect 

### 20

relationships with O 3 exposure. 

### 21



## 2.6 Integration of Ozone Health Effects

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

### 22

epidemiologic studies that examined the health effects associated with short

- and long



### 23

term exposure to O 3, and summarizes the main conclusions of this assessment regarding 

### 24

the health effects of O 3 and the concentrations at which those effects are observed. The 

### 25

conclus ions from the previous NAAQS review and the causality determinations from this 

### 26

review are summarized in Table 2

- 1 . The results from the health studies evaluated in 

### 27

combination with the evidence from atmospheric chemistry and exposure assessment 

### 28

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

### 29

this assessment (See Preamble to this document). In the following sectio ns a discussion 

### 30

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

- term [i.e., 

### 31

hours, days, weeks] or long

- term [i.e., months to years] exposure) for the health effects 

### 32

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

### 33

suggestive relationship. This section also integrates the evidence from short

- and long



### 34

term exposure studies across scientific disciplines (i.e., controlled human exposure 

### 35Draft

– Do Not Cite or Quote 2

- 18 September 2011 studies, toxicology, and epidemiology) in interpret ing the health effects evidence that 

### 1

spans from prenatal development to death. 

### 2

Table 2

- 1 Summary of evidence from epidemiologic, controlled human exposure, and animal toxicological studies on the health effec ts

associated with short

- and long

- term exposure to ozone

Health Outcome Conclusions from 2006 O 3 AQCD Conclusions from 2011 2nd Draft ISA

Short

- Term Exposure to O 3
Respiratory effects The overall evidence supports a causal relationship

between acute ambient O 3 exposures and increased respiratory morbidity outcomes. Causal relationship

Lung function Results from controlled human exposure studies and animal toxicological studies provide clear evidence of causality for the associations observed between acute (≤ 24 h) O 3 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 ex ercise

outdoors. Recent controlled human exposure studies demonstrate group mean decreases in FEV 1 in the range of 2 to 3% with 6.6 h exposures to as low as 60 ppb O 3 . The collective body of epidemiologic evidence demonstrates associations

between short

- te rm ambient O 3 exposure and decrements in lung function, particularly in asthmatics, children, and adults

who work or exercise outdoors.

Airway

hyperresponsiveness Evidence from human clinical and animal toxicological studies clearly indicate that acute e xposure to O 3 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 O 3 . As previously reported in

the 2006 O 3 AQCD, increased airway responsiveness has

been demonstrated at 80 ppb in young, he alth adults, and at

50 ppb in certain strains of rats, suggesting a genetic
component.

Pulmonary inflammation,

injury and oxidative

stress The extensive human clinical and animal toxicological evidence, together with the limited available epidemiologic evidence, is clearly indicative of a causal

role for O 3 in inflammatory responses in the airways. Epidemiologic studies provided new evidence for

associations of ambient O 3 with mediators of airway inflammation and oxidative stress and indicate that higher antioxidant levels may reduce pulmonary inflammation

associated with O 3 exposure. Generally, these studies had

mean 8

- h max O 3 concentrations less than 73 ppb

. Respiratory symptoms

and medication use Young healthy adult subjects exposed in clinical

stud ies to O 3 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 O 3 and increases in a wide variety

o f respiratory symptoms (e.g., cough, wheeze, production of phlegm, and shortness of breath) and

medication use in asthmatic children. The collective body of epidemiologic evidence demonstrates positive associations between short

- term exposure to
ambient O 3 and respiratory symptoms (e.g., cough, wheeze, production of phlegm, and shortness of breath) in asthmatic children. Generally, these studies had mean 8

- h max O 3 concentrations less than 69 ppb

.

Lung host defenses Toxicological studies provided extensiv e evidence that

acute O 3 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 macrophage s to phagocytose microorganisms upon exposure to 80 to 100 ppb O 3

. Recent studies in human subjects demonstrate the increased expression of cell surface markers and alterations in sputum leukocyte markers related to innate adaptive immunity with short

- term O 3 exposures of 80

- 400 ppb

. Recent studies demonstrating altered immune responses and natural killer cell function build on prior evidence that O 3 can affect multiple aspects of innate and acquired immunity

with short

- term O 3 exposures as low as 80 ppb

.Draft

– Do Not Cite or Quote 2

- 19 September 2011 Health Outcome Conclusions from 2006 O 3 AQCD Conclusions from 2011 2nd Draft ISA

Allergic and asthma

related responses Previous toxicological evidence indicated that O 3 exposure skews immune responses toward an allergic phenotype, and enhances the development and severity of asthma

- related responses such as AHR. Recent studies in human subjects demonstrate enhanced allergic cytokine production in atopic individuals and asthmatics, increased IgE receptors in atopic asthmatics, and enhanced markers of innate immunity and antigen presentation in health subjects or at opic asthmatics with

short

- term exposure to 80

- 400 ppb O 3 , all of which may enhance allergy and/or asthma. Further evidence for O 3 - induced allergic skewing is provided by a few recent studies in rodents using exposure concentrations as low as

200 ppb

.
Ho spital admissions, ED

visits, and physician

visits Aggregate population time

- series studies observed that

ambient O 3 concentrations are positively and robustly associated with respiratory

- related hospitalizations and asthma ED visits during the warm season

. Strong evidence demonstrated associations of ambient O 3 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 O 3 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 O 3 exposure and respirator y mortality. Recent multicity time

- series studies and a multicontinent study consistently demonstrated associations between

ambient O 3 and respiratory

- related mortality visits across the U.S., Europe, and Canada with supporting evidence from single city st udies. Generally, these studies had mean 8

- h

max O 3 concentrations less than 63 ppb

. Cardiovascular effects The limited evidence is highly suggestive that O 3 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 O 3 are associated with alterations in neurotransmitters, motor activity, short

- and long

- term memory, sleep patterns, and histological signs of neurodegeneration. Suggestive of a Causal Relationship

Mortality The evidence is highly suggestiv e that O 3 directly or indirectly contributes to non

- accidental and cardiopulmonary

- related mortality. Likely to be a Causal Relationship

Long

- term Exposure to O 3
Respiratory effects The current evidence is suggestive but inconclusive for respiratory health effects from long

- term O 3 exposure. Likely to be a Causal Relationship

New onset asthma No studies at this time. Evidence for a relationship between different genetic variants (HMOX, GST, ARG) that, in combination with O 3 exposure, are related to new onset asthma. These results were observed when subjects living in areas where the

mean annual 8

- h max O 3 concentration was 55.2 ppb

, compared to those who lived where it was 38.4 ppb

. Asthma hospital

admissions No studies at this time. Chronic O 3 exposure was related to first childhood asthma hospital admissions in a positive concentration

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

- h

max O 3 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 O 3 ; however, cohort studies of annual or multiyear O 3 exposure observed little clear evidence for impacts of longer

- term, relatively low

- level

O 3 exposu re on lung function development in children. Animal toxicological studies reported chronic O 3 - induced structural alterations in several regions of the respiratory tract including the centriacinar region. Morphologic evidence from studies using exposure

reg imens that mimic seasonal exposure patterns report increased lung injury compared to conventional chronic stable exposures. Evidence for pulmonary function effects is inconclusive, with some new epidemiologic studies (mean annual 8

- h max O 3 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 fun ction.

Pulmonary inflammation,

injury and oxidative

stress Extensive human clinical and animal toxicological evidence, together with limited epidemiologic evidence available, suggests a causal role for O 3 in inflammatory responses in the airways. Several epidemiologic studies (mean 8

- h max O 3 concentrations less than 69 ppb ) and toxicology studies (as

low as 500 ppb ) add to observations of O 3 - induced inflammation and injury.Draft

– Do Not Cite or Quote 2

- 20 September 2011 Health Outcome Conclusions from 2006 O 3 AQCD Conclusions from 2011 2nd Draft ISA

Lung host defenses Toxicological studies provided evidence that chronic O 3 expo sure 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

rode nts exposed to 100 ppb O 3 , recent evidence demonstrates a decreased ability to respond to pathogenic signals in infant monkeys exposed to 500 ppb O 3

.

Allergic responses Limited epidemiologic evidence supported an

association between ambient O 3 and allerg ic symptoms. Little if any information was available from toxicological studies. Evidence relates positive outcomes of allergic response and

O 3 exposure but with variable strength for the effect estimates; exposure to O 3 may increase total IgE in adult

ast hmatics. Allergic indicators in monkeys were increased by exposure to O 3 concentrations of 500 ppb

. Respiratory mortality Studies of cardio

- pulmonary mortality were insufficient to suggest a causal relationship between chronic O 3 exposure and increased risk for mortality in humans. A single study demonstrated that exposure to O 3 (long

- term
mean O 3 less than 104 ppb ) elevated the risk of death from respiratory causes and this effect was robust to the inclusion

of PM 2.5

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

Reproductive and developmental effects Limited evidence for a relationship between air pollution and birth

- related health outcomes, including mortality, premature births, low birth weights, and birth defects, with little evidence being found for O 3 effects. Suggestive of a Causal Relationship

Central nervous system

effects Toxicological studies reported that acute exposures to

O 3 are associated with alterations in neurotransmitters, motor activity, short and long term memory, sleep patterns, and histological signs of neurodegeneration. Evidence regarding chronic exposure and

neurobehavioral effects was not available. Suggestive of a Causal Relationship

Cancer Little evidence for a relationship between chronic O 3 exposure and increased risk of lung cancer. Inadequate to infer a Causal Relationship

Mortality There is little evidence to suggest a causal relationship

between chronic O 3 exposure and increased risk for mortality in humans. Suggestive of a Causal Relationship



### 2.6.1 Respiratory Effects

The clearest evidence for health effects associated with exposure to O 3 is provided by 

### 1

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

### 2

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

### 3

continuum of respiratory effects (Figure 2

- 3). The majority of this evidence is derived 

### 4

from studies investigating short

- term exposure (i. e., hours to weeks) to O 3 , although 

### 5

animal toxicological studies and recent epidemiologic evidence demonstrate that long



### 6

term exposure (i.e., months to years) may also be detrimental to the respiratory system. 

### 7

The 2006 O 3 AQCD concluded that there was clea r, consistent evidence of a causal 

### 8

relationship between short

- term exposure to O 3 and respiratory health effects ( U.S. EPA, 

### 9

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

### 10

across controlled human ex posure, epidemiologic, and toxicological studies indicating 

### 11

associations of short

- term O 3 exposures with a range of respiratory health endpoints from 

### 12

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

### 13

hospital admissions. Ac ross disciplines, short

- term O 3 exposures induced or were 

### 14

associated with statistically significant declines in lung function. An equally strong body 

### 15Draft

– Do Not Cite or Quote 2

- 21 September 2011 of evidence from controlled human exposure and toxicological studies demonstrated O 3 - 

### 1

induced inflammatory responses, increased epithelial permeability, and airway 

### 2

hyperresponsiveness (both specific and nonspecific). Toxicological studies provided 

### 3

additional evidence for O 3 - induced impairment of host defenses. Combined, these 

### 4

findings from experimental studies provided support for epidemiologic evidence, in 

### 5

which short

- term O 3 exposure was consistently associated with increases in respiratory 

### 6

symptoms and asthma medication use in asthmatic children, respiratory

- related hospital 

### 7

admissions, and asthma

- related ED visits. Although O 3 was consistently associated with 

### 8

non

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

### 9

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

### 10

relationship between short

- term O 3 exposure and respiratory effects. 

### 11

Mechanistic evidence for the effects of O 3 on the respiratory system was characterized in 

### 12

the 1996 O 3 AQCD, which identified O 3 - induced changes in a variety of lung lipid 

### 13

species whose numerous biologically acti ve metabolites, in turn, can affect host defenses, 

### 14

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

### 15

characterized in Chapter 5, key events in the toxicity pathway of O 3 have been identified 

### 16

in humans and animal models. They incl ude activation of neural reflexes, initiation of 

### 17

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

### 18

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

### 19

inflammation and oxidative/nitrosa tive stress. 

### 20

As demonstrated in Figure 2

- 3, O 3 is associated with a continuum of respiratory effects, 

### 21

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

### 22

long

- term exposure to O 3 occurring throughout various lifestages , beginning with 

### 23

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

### 24

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

### 25

effects on the developing immune system, and increased offspri ng airway hyper



### 26

reactivity (Section 7.4.7. The strongest evidence for O 3 - induced effects on the developing 

### 27

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

### 28

exposed to 500 ppb O 3 for approximately 5 months, starting at one mo nth of age. 

### 29

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

### 30

O 3 alone or O 3 + antigen were accompanied by a number of cellular and morphological 

### 31

changes. In addition to these functional and cellular changes, significa nt structural 

### 32

changes in the respiratory tract were observed. Importantly, the O 3 - induced structural 

### 33

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

### 34

the O 3 exposures. Exposure to O 3 has also been associated with s imilar types of 

### 35

alterations in pulmonary structure, including airway remodeling and pulmonary injury 

### 36

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

### 37

monkeys ( U.S. EPA, 1996a )

. 

### 38Draft

– Do Not Cite or Quote 2

- 22 September 2011 Green=Animal Toxicological Studies; Blue=Controlled Human Exposure Studies; Purple=Epidemiologic Studies; AM=Alveolar Macrophage.



### Figure 2

- 3 Snapshot of evidence for the association of O 3 

### with the continuum of respiratory effec t s , including sub

- clinical effects (bottom level of the pyramid) and clinical effects, increasing in severity moving up the pyramid.Draft

– Do Not Cite or Quote 2

- 23 September 2011 In addition to effects on the development and structure o f the respiratory tract, there is 

### 1

extensive evidence for the effects of short

- term exposure to O 3 on pulmonary 

### 2

inflammation and oxidative stress. Previous evidence from controlled human exposure 

### 3

studies indicated that O 3 causes an inflammatory response in the lungs ( U.S. EPA, 

### 4

1996a ) . This inflammatory response to O 3 was detected after a single 1

- h exposure with 

### 5

exercise to O 3 concentrations o f 300 ppb; the increased levels of some inflammatory cells 

### 6

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

### 7

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

### 8

ppb O 3 . Evidence summarized in the 2006 O 3 AQCD demonstrated that inflammatory 

### 9

responses were observed subsequent to 6.6 hours O 3 exposure to the lowest tested level 

### 10

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

### 11

evidence that short

- term (1

- 3 hours) O 3 exposure in the range of 100

- 500 ppb could cause 

### 12

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

### 13

O 3 AQCD demonstrated an association between short

- term ambient O 3 exposure and 

### 14

airway inflammation in child ren (1

- h max O 3 of approximately 100 ppb). Recent studies 

### 15

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

### 16

toll

- like receptors (e.g., TLR4, TLR2), receptors for TNF or IL

- 1, multiple signaling 

### 17

pathways (e.g., p38, JNK, NFκB, MAPK/AP

- 1), and oxidative stress (Section 6.2.3.3). 

### 18

The most recent epidemiologic studies provide additional supporting evidence by 

### 19

demonstrating associations of ambient O 3 with mediators of airway inflammation and 

### 20

indicating that populations with d iminished antioxidant capacity may have increased 

### 21

susceptibility to pulmonary inflammation and oxidative stress associated with O 3 

### 22

exposure (Sections 6.2.4 and 8.1). 

### 23

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

### 24

remo ving microorganisms or particles that have reached the distal airways and alveolar 

### 25

surface. The 1996 O 3 AQCD concluded that short

- term exposure to elevated 

### 26

concentrations of O 3 resulted in alterations in these host defense mechanisms in the 

### 27

respiratory sys tem. Specifically, toxicological studies of short

- term exposures as low as 

### 28

100 ppb O 3 were shown to decrease the ability of alveolar macrophages to ingest 

### 29

particles, and short

- term exposures as low as 80 ppb for 3 hours prevented mice from 

### 30

resisting infect ion with streptococcal bacteria and resulted in infection

- related mortality. 

### 31

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

### 32

hours of exposure to 80 and 100 ppb O 3 had decreased ability to ingest microorganisms, 

### 33

indicatin g some impairment of host defense capability. These altered host defense 

### 34

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

### 35

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

### 36

toxicol ogical evidence, in the limited body of epidemiologic evidence, O 3 exposure has 

### 37

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

### 38

infection, pneumonia, or influenza (Sections 6.2.7.2 and 6.2.7.3). 

### 39Draft

– Do Not Cite or Quote 2

- 24 September 2011 The most commonly obse rved and strongest evidence for respiratory effects associated 

### 1

with short

- term exposure to O 3 is transient decrements in pulmonary function. Controlled 

### 2

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

### 3

induced decrements in pul monary function, characterized by alterations in lung volumes 

### 4

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

### 5

hours) to O 3 concentrations as low as 80 ppb ( U.S. EPA, 1996a ) . A series of mobile 

### 6

laboratory studies of lung function and respiratory symptoms reported pulmonary 

### 7

function decrements at mean ambient O 3 concentrations of 140 ppb in exercising healthy 

### 8

adolescents and increased respirato ry symptoms and pulmonary function decrements at 

### 9

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

### 10

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

### 11

results of the controlled huma n exposure studies, both indicating decrements in lung 

### 12

function upon O 3 exposure. A combined statistical analysis of epidemiologic studies in 

### 13

children at summer camp demonstrated decrements in FEV 1 of 0.50 mL/ppb with 

### 14

previous hour O 3 concentration. For pr eadolescent children exposed to 120 ppb ambient 

### 15

O 3 , this amounted to an average decrement of 2.4

- 3.0% in FEV 1 . Key studies of lung 

### 16

function measurements (FEV 1 ) taken before and after well

- defined outdoor exercise 

### 17

events in adults yielded exposure

- response slopes of 0.40 and 1.35 mL/ppb ambient O 3 

### 18

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

### 19

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

### 20

characterized the controlled human exposure and animal toxicological studies as 

### 21

providing clear evidence of causality for the associations observed between short

- term (≤ 

### 22

24 hours) O 3 exposure and relatively small, but statistically significant declin es in lung 

### 23

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

### 24

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

### 25

outdoors. 

### 26

Recent controlled human exposure studies examined lower concentrati on O 3 exposures 

### 27

(40

- 80 ppb) and demonstrated that FEV 1 , respiratory symptoms, and inflammatory 

### 28

responses were affected by O 3 exposures of 6.6 hours and in the range of 60 to 80 ppb 

### 29

(Section 6.2.1.1 and 6.2.3.1). These studies demonstrated average decreases in FEV 1 in 

### 30

the range of 2.8 to 3.6% with O 3 exposures 6.6 hours in duration and as low as 60 ppb in 

### 31

concentration. However, considerable intersubject variability has been reported with 

### 32

some subjects experiencing considerably greater decrements than averag e. Recent 

### 33

epidemiologic studies provide greater insight into subject factors that may increase 

### 34

susceptibility for O 3 - associated respiratory morbidity. It was in these potentially 

### 35

susceptible populations (e.g., individuals with asthma with concurrent respir atory 

### 36

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

### 37

antioxidant capacity) that O 3 - associated decreases in lung function were consistently 

### 38

observed. 

### 39Draft

– Do Not Cite or Quote 2

- 25 September 2011 In addition to alterations in lung volumes and flow, changes in pu lmonary function due to 

### 1

exposure to O 3 may manifest as respiratory symptoms (e.g., coughing, wheezing, 

### 2

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

### 3

symptoms and increasing ambient O 3 , particularly among asthmatic chi ldren. In the 2006 

### 4

O 3 AQCD, symptoms of cough and pain on deep inspiration were well documented in 

### 5

young healthy adult subjects after exposure of ≥80 ppb O 3 for 6

- 8 hours during moderate 

### 6

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

### 7

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

### 8

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

### 9

cough with O 3 exposures as low as 120 ppb and 1

- 3 hours in durati on with very heavy 

### 10

exercise. The controlled human exposure studies also demonstrated lesser respiratory 

### 11

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

### 12

epidemiologic evidence showed significant associations between short

- term exposure to 

### 13

ambient O 3 and increases in a wide variety of respiratory symptoms (e.g., cough, wheeze, 

### 14

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

. 

### 15

Epidemiologic studies also indicated that short

- term O 3 exposure is likely associated with 

### 16

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

### 17

pulmonary function, recent epidemiologic studies provided insight into additional subject 

### 18

factors that may increa se susceptibility for O 3 - associated respiratory symptoms. It was in 

### 19

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

### 20

capacity and infants with asthmatic mothers) where the recent evidence of O 3 - associated 

### 21

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

### 22

studies provide evidence for an association between long

- term exposure to O 3 and 

### 23

respiratory symptoms (Section 7.2.2). 

### 24

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

- specific airway 

### 25

hyperresponsiveness. Increased airway responsiveness is an important consequence of 

### 26

exposure to O 3 because its presence represents a change in airway smooth muscle 

### 27

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

### 28

variety of stimuli (e.g., specific allergens, SO 2 , cold air). Specifically, short

- term (2 or 

### 29

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

### 30

responsiveness in response to allergen challenges among allergic asth matic subjects who 

### 31

characteristically already had somewhat increased airway responsiveness at baseline. 

### 32

Increased non

- specific airway responsiveness has been demonstrated in healthy young 

### 33

adults down to 80 ppb O 3 following 6.6 hours of exposure during mode rate exercise. 

### 34

While AHR has not been widely examined in epidemiologic studies, findings for O 3 - 

### 35

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

### 36

toxicological (Section 6.2.2.2) studies provide biological plausibility for associat ions 

### 37

observed between ambient O 3 exposure and increases in respiratory symptoms in subjects 

### 38

with asthma. 

### 39Draft

– Do Not Cite or Quote 2

- 26 September 2011 In addition to asthma exacerbations, recent epidemiologic evidence has revealed an 

### 1

association between long

- term exposure to O 3 and new onset asthma (S ection 7.2.1, 

### 2

Table 7

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

### 3

designs and analysis methods evaluating the relationship between long

- term annual 

### 4

measures of exposure to ambient O 3 and measures of respiratory morbidity conducted by 

### 5

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

### 6

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

### 7

oxidative or nitrosative stress (e.g., HMOX, GSTs, ARG ) that, in com bination with O 3 

### 8

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

### 9

extended beyond the association of exposure to O 3 and asthma exacerbations to suggest 

### 10

that long

- term exposure to O 3 may play a role in the development of the disease and 

### 11

contribute to incident cases of asthma. 

### 12

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

### 13

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

### 14

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

### 15

short

- term changes in ambient O 3 concentrations. Summertime daily hospital admissions 

### 16

for respiratory causes in various locations of eastern North America w ere consistently 

### 17

associated with ambient levels of O 3 in studies reviewed in the 1996 O 3 AQCD. This 

### 18

association remained even when considering only concentrations below 120 ppb O 3 . The 

### 19

2006 O 3 AQCD concluded that aggregate population time

- series studies de monstrate a 

### 20

positive and robust association between ambient O 3 concentrations and respiratory



### 21

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

### 22

epidemiologic time

- series studies that include additional multicity studies and a 

### 23

mul ticontinent study further support that short

- term exposures to ambient O 3 

### 24

concentrations are consistently associated with increases in respiratory hospital 

### 25

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

### 26

geographic locations and across a range of O 3 concentrations (Section 6.2.7). There is 

### 27

also recent evidence for an association between respiratory hospital admissions and long



### 28

term exposure to O 3 (Section 7.2.2). 

### 29

Finally, O 3 exposure may contribute to death from respiratory c auses. Recent evidence 

### 30

from several multicity studies and a multicontinent study demonstrate consistent positive 

### 31

associations between short

- term exposure to ambient O 3 concentrations and increases in 

### 32

respiratory mortality (Section 6.6.2.5). Similarly, a st udy of long

- term exposure to 

### 33

ambient O 3 concentrations also demonstrated an association between O 3 and increases in 

### 34

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

### 35

consistent and coherent with the evidence from epidem iologic, controlled human 

### 36

exposure, and animal toxicological studies for the effects of short

- and long

- term 

### 37

exposure to O 3 on respiratory effects. Additionally, the evidence for respiratory morbidity 

### 38Draft

– Do Not Cite or Quote 2

- 27 September 2011 after short

- and long

- term exposure provides biological plausibility for mortality due to 

### 1

respiratory disease. 

### 2

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

### 3

in the 1996 and 2006 O 3 AQCDs that short

- term O 3 exposure is causally associated with 

### 4

adverse respiratory health effects. Recent controlled human exposure studies demonstrate 

### 5

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

### 6

as 60

- 70 ppb O 3 in young, healthy adults. Equally strong evidence demonstrated 

### 7

associations of ambient O 3 with respiratory hospital admissions and ED visits across the 

### 8

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

### 9

daily all respiratory

- related ED visits or hospital admissions in all

- year analyses for 

### 10

standardized incre ases in ambient O 3 concentrations. Several multicity studies and a 

### 11

multicontinent study reported associations between short

- term exposure to ambient O 3 

### 12

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

### 13

individual

- level ep idemiologic studies that provide new evidence for associations of 

### 14

ambient O 3 with mediators of airway inflammation and oxidative stress, and across 

### 15

endpoints, they indicate that groups with diminished antioxidant capacity or 

### 16

comorbidities such as atopy, AH R, or elevated body mass index may have increased 

### 17

susceptibility to respiratory morbidity associated with O 3 exposure. The potential 

### 18

susceptibility of these populations identified in recent epidemiologic studies are strongly 

### 19

supported by findings from expe rimental studies that demonstrated O 3 - induced decreases 

### 20

in intracellular antioxidant levels, increases in airway responses with co

- exposures to 

### 21

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

### 22

demonstrating O 3 - induced airway hyp erresponsiveness, decreased pulmonary function, 

### 23

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

### 24

toxicological studies have characterized O 3 modes of action and have provided biological 

### 25

plausibility for epidemiologic associa tions of ambient O 3 exposure with lung function 

### 26

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

### 27

evidence integrated across controlled human exposure, epidemiologic, and toxicological 

### 28

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

### 29

that there is a causal relationship between short

- term O 3 exposure and respiratory 

### 30

health effects. 

### 31

The strongest evidence for a relationship between long

- term O 3 exposure and respiratory 

### 32

morbidity is c ontributed by recent studies from a single cohort demonstrating 

### 33

associations between long

- term measures of O 3 exposure and new

- onset asthma in 

### 34

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

### 35

limited, this U.S. multic ommunity prospective cohort demonstrates that asthma risk is 

### 36

affected by interactions among genetic variability, environmental O 3 exposure, and 

### 37

behavior. Other recent studies provide coherent evidence for long

- term O 3 exposure and 

### 38Draft

– Do Not Cite or Quote 2

- 28 September 2011 respiratory morbidity eff ects such as first asthma hospitalization and respiratory 

### 1

symptoms in asthmatics. Generally, the epidemiologic and toxicological evidence 

### 2

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

### 3

long

- term exposure to ambie nt O 3 and measures of respiratory morbidity. The evidence 

### 4

for short

- term exposure to O 3 and effects on respiratory endpoints provides coherence 

### 5

and biological plausibility for the effects of long

- term exposure to O 3 . Building upon that 

### 6

evidence, the more r ecent epidemiologic evidence, combined with toxicological studies 

### 7

in rodents and non

- human primates, provides biologically plausible evidence that there 

### 8

is likely to be a causal relationship between long

- term exposure to O 3 and 

### 9

respiratory health effects. 

### 10

2.6.2 Mortality Effects

The 2006 O 3 AQCD concluded that the overall body of evidence was highly suggestive 

### 11

that short

- term exposure to O 3 directly or indirectly contributes to non

- accidental and 

### 12

cardiopulmonary

- related mortality, but additional research was need ed to more fully 

### 13

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

### 14

multicity studies that examined the association between short

- term O 3 exposure and 

### 15

mortality found evidence which supports the conclusions of the 2006 O 3 AQCD. These 

### 16

new studies reported consistent positive associations between short

- term O 3 exposure and 

### 17

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

### 18

as well as additional support for associations between O 3 exposu re and cardiovascular 

### 19

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

### 20

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

### 21

O 3 - mortality relationship. Taken together, the body of eviden ce indicates that there is 

### 22

likely to be a causal relationship between short

- term exposures to O 3 and all

- cause 

### 23

mortality. 

### 24

The 2006 O 3 AQCD concluded that an insufficient amount of evidence existed “ to 

### 25

suggest a causal relationship between chronic O 3 exposu re and increased risk for 

### 26

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

### 27

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

### 28

O 3 , and a reanalysis of the ACS coh ort that specifically points to a relationship between 

### 29

long

- term O 3 exposure and an increased risk of respiratory mortality. The findings from 

### 30

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

### 31

epidemiologic, controlled huma n exposure, and animal toxicological studies for the 

### 32

effects of short

- and long

- term exposure to O 3 on respiratory effects. Additionally, the 

### 33

evidence for short

- and long

- term respiratory morbidity provides biological plausibility 

### 34Draft

– Do Not Cite or Quote 2

- 29 September 2011 for mortality due to resp iratory disease. Collectively, the evidence is suggestive of a 

### 1

causal relationship between long

- term O 3 exposures and mortality. 

### 2

2.6.3 Cardiovascular Health Effects

In past O 3 AQCDs the effects of short

- and long

- term exposure to O 3 on the 

### 3

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

### 4

information available. However, studies investigating O 3 - induced cardiovascular events 

### 5

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

### 6

cardiovascular morbid ity in epidemiologic studies examining both short

- and long

- term 

### 7

exposure to O 3 . Positive associations between short

- term O 3 exposure and cardiovascular 

### 8

mortality have been consistently reported in multiple epidemiologic studies. Animal 

### 9

toxicological studi es provide more evidence for both short

- and long

- term O 3 exposure 

### 10

leading to cardiovascular morbidity. The toxicological studies demonstrate O 3 - induced 

### 11

cardiovascular effects, specifically enhanced atherosclerosis and ischemia/reperfusion 

### 12

injury with or w ithout the corresponding development of a systemic oxidative, pro



### 13

inflammatory environment, disrupted NO

- induced vascular reactivity, decreased cardiac 

### 14

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

### 15

and evidence f or an association between O 3 exposure and cardiovascular mortality, the 

### 16

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

### 17

relevant short

- and long

- term exposures to O 3 and cardiovascular effects. 

### 18

2.6.4 Central Nervous System Effe cts

In rodents, O 3 exposure has been shown to cause physicochemical changes in the brain 

### 19

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

### 20

earlier evidence that short

- and long

- term exposures to O 3 can produce a range of effects 

### 21

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

### 22

neurodegeneration, alterations in neurotransmitters, short

- and long

- term memory, and 

### 23

sleep patterns, have been further supported by recent studies. In instances whe re 

### 24

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

### 25

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

### 26

epidemiologic study conducted showed that long

- term exposure to O 3 affects memory in 

### 27

hum ans as well. Notably, exposure to O 3 levels as low as 250 ppb has resulted in 

### 28

progressive neurodegeneration and deficits in both short

- and long

- term memory in 

### 29

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

### 30

behavioral effec ts, have been observed in animals whose sole exposure occurred in utero

, 

### 31

at levels as a low as 300 ppb. Together the evidence from studies of short

- and long

- term 

### 32Draft

– Do Not Cite or Quote 2

- 30 September 2011 exposure to O 3 is suggestive of a causal relationship between O 3 exposure and 

### 1

adverse CNS effects. 

### 2

2.6.5 Reproductive and Developmental Effects

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

### 3

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

### 4

effects after developmental exposure to O 3 . Limited epidemiologic evidence exists for an 

### 5

association with O 3 concentration and decreased sperm concentration. A recent 

### 6

toxicological study provides limited evidence for a possible biological mechanism 

### 7

(histopatholog y showing impaired spermatogenesis and rescue with antioxidants) for 

### 8

such an association. Additionally, though the evidence for an association between O 3 

### 9

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

### 10

influential stu dies that indicate an association with reduced birth weight and restricted 

### 11

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

### 12

long

- term exposures to O 3 and reproductive and developmental effects. 

### 13

2.6.6 Cancer and Mutagenicity and Genotoxicity

The 2006 O 3 AQCD reported that evidence did not support ambient O 3 as a pulmonary 

### 14

carcinogen. Since the 2006 O 3 AQCD, very few epidemiologic and toxicological studies 

### 15

have been published that examine O 3 as a carcinogen, but collectively, study results 

### 16

indicate that O 3 may contribute to DNA damage. Overall, the evidence is inadequate to 

### 17

determine if a causal relationship exists between ambient O 3 exposures and 

### 18

cancer. 

### 19

2.6.7 Policy Relevant Considerations

2.6.7.1 Populations at Increased Risk

Upon evaluating t he association between short

- and long

- term exposure to O 3 and various 

### 20

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

### 21

for O 3 - related health effects. These studies did so by conducting stratified epidemiologic 

### 22

ana lyses; by examining individuals with an underlying health condition, genetic 

### 23

polymorphism, or categorized by age, race, or sex in controlled human exposure studies; 

### 24

or by developing animal models that mimic the pathophysiological conditions associated 

### 25

with an adverse health effect. These studies identified a multitude of factors that could 

### 26Draft

– Do Not Cite or Quote 2

- 31 September 2011 potentially contribute to whether an individual is at increased risk for O 3 - related health 

### 1

effects. The examination of at risk populations for O 3 exposure allows for the NAAQS to 

### 2

provide an adequate margin of safety for both the general population and for sensitive 

### 3

populations. 

### 4

The populations identified in Chapter 8 that are most at risk for O 3 - related health effects 

### 5

are individuals with influenza/infection, individuals with asthma, and younger and older 

### 6

age groups. There were a small number of studies on influenza/infection but both 

### 7

reported influenza/infection to modify the association between O 3 exposure and 

### 8

respiratory effects, with individuals having influenza or an infection being at increased 

### 9

risk. Asthma as a factor affecting risk was supported by controlled human exposure and 

### 10

toxicological studies, as well as some evidence from epidemiologic studies. Most studies 

### 11

comparing age groups reported greater effects of sh ort

- term O 3 exposure on mortality 

### 12

among older adults, although studies of other health outcomes had inconsistent findings 

### 13

regarding whether older adults were at increased risk. Generally, studies of age groups 

### 14

also reported positive associations for respir atory hospital admissions and ED visits 

### 15

among children. Biological plausibility for this increased risk is supported by 

### 16

toxicological and clinical research. Diet and obesity are also both likely factors that affect 

### 17

risk. Multiple epidemiologic, controlled human exposure, and toxicological studies 

### 18

reported that diets deficient in vitamins E and C are associated with risk of O 3 - related 

### 19

health effects. Similarly, studies of effect measure modification by body mass index 

### 20

(BMI) observed greater O 3 - related resp iratory decrements for individuals who were 

### 21

obese. 

### 22

Other potential factors [preexisting conditions (such as chronic obstructive pulmonary 

### 23

disease and cardiovascular disease), sex, and multiple genes (such as GSTM1, GSTP1, 

### 24

HMOX

- 1, NQO1, and TNF

- α) ] provided some evidence of susceptibility, but further 

### 25

investigation is warranted. In addition, examination of modification of the associations 

### 26

between O 3 exposure and health effects by SES and race were available in a limited 

### 27

number of studies, and demonst rated possible increased odds of health effects related to 

### 28

O 3 exposure among those with low SES and black race. 

### 29

Individuals with increased ambient exposure were examined in a recent study of outdoor 

### 30

workers, in which no effect modification was observed, a nd in studies of air conditioning 

### 31

prevalence, which demonstrated inconsistent findings. However, previous evidence along 

### 32

with biological plausibility from toxicological and controlled human studies has shown 

### 33

individuals exposed to more outdoor air to be at increased risk of O 3 - related health 

### 34

effects. Studies of physical conditioning and smoking were conducted but little evidence 

### 35

was available to determine whether increased risk of O 3 - related health effects is present 

### 36

for these factors. The only studies examining effect measure modification by diabetes 

### 37Draft

– Do Not Cite or Quote 2

- 32 September 2011 examined O 3 exposure and cardiovascular outcomes and none reported increased risks for 

### 1

individuals with diabetes. Toxicological studies also identified hyperthyroidism to be a 

### 2

factor warranting further examination. Future research will provide additional insight into 

### 3

whether these factors affect risk of O 3 - related health effects. 

### 4

2.6.7.2 Lag Structure in Epidemiologic Studies

Epidemiologic studi es have attempted to identify the time

- frame in which exposure to O 3 

### 5

can impart a health effect. Although O 3 exposure

- response relationships have 

### 6

traditionally been examined using air quality data for a defined lag period (e.g., 1 day or 

### 7

average of 0

- 1 day s), the relationship can potentially be influenced by a multitude of 

### 8

factors, such as the underlying susceptibility of an individual (e.g., age, pre

- existing 

### 9

diseases), which could increase or decrease the lag times observed. Different lag times 

### 10

have been evaluated for specific health outcomes. 

### 11

The epidemiologic evidence evaluated in the 2006 O 3 AQCD indicated that one of the 

### 12

remaining uncertainties in characterizing the O 3 - mortality relationship was identifying 

### 13

the appropriate lag structure (e.g., single

- day lags versus distributed lag model). An 

### 14

examination of lag times used in the epidemiologic studies evaluated in this assessment 

### 15

can provide further insight on the relationship between O 3 exposure and morbidity and 

### 16

mortality outcomes. 

### 17

Collectively, rece nt epidemiologic studies of lung function, respiratory symptoms, and 

### 18

biological markers of airway inflammation and oxidative stress examined associations 

### 19

with single

- day ambient O 3 exposures (using various averaging times) lagged from 0 to 7 

### 20

days as well a s concentrations averaged over 2 to 19 days. Lags of 0 and 1 day ambient 

### 21

O 3 exposures were associated with decreases in lung function and increases in respiratory 

### 22

symptoms, airway inflammation, and oxidative stress. Additionally, several studies found 

### 23

that multiday averages of O 3 exposure were associated with these endpoints, indicating 

### 24

that not only single day, but exposures accumulated over several days led to a respiratory 

### 25

health effect. In studies of respiratory hospital admissions and ED visits, invest igators 

### 26

either examined the lag structure of associations by including both single

- day and the 

### 27

average of multiday lags, or selecting lags a priori. Of the studies evaluated, the 

### 28

collective evidence indicates a rather immediate response within the first fe w days of O 3 

### 29

exposure (i.e., for lags days averaged at 0

- 1, 0

- 2, and 0

- 3 days) for hospital admissions 

### 30

and ED visits for all respiratory outcomes, asthma, and chronic obstructive pulmonary 

### 31

disease in all

- year and seasonal analyses. 

### 32

The majority of epidemi ologic studies that focused on the association between short

- term 

### 33

O 3 exposure and mortality (i.e., all

- cause, respiratory and cardiovascular) examined the 

### 34Draft

– Do Not Cite or Quote 2

- 33 September 2011 average of multiday lags with some studies examining single

- day lags. Across a range of 

### 1

multiday lags (i.e., average of 0

- 1 to 0

- 6 days), the studies evaluated consistently 

### 2

demonstrate that the O 3 effects on mortality occur within a few days of exposure (Figure 

### 3

6

- 28). Additionally, several recent studies have conducted more extensive analysis of lag 

### 4

struc ture to investigate “ mortality displacement ” (i.e., deaths are occurring in frail 

### 5

individuals and exposure is only moving the day of death to a day slightly earlier), which 

### 6

also inform upon the lag structure of associations (Section 6.6.2.4). Collectively, these 

### 7

studies suggest that the positive associations between O 3 and mortality are observed 

### 8

mainly in the first few days after exposure. 

### 9

2.6.7.3 Ozone Concentration

- Response Relationship

An important consideration in characterizing the O 3 - morbidity and mortality association 

### 10

is whether the C

- R relationship is linear across the full concentration range that is 

### 11

encountered or if there are concentration ranges where there are departures from linearity 

### 12

(i.e., nonlinearity). In this ISA studies have been identified that attempt to characterize 

### 13

the shape of the O 3 C

- R curve along with possible O 3 “ thresholds ” (i.e., O 3 levels which 

### 14

must be exceeded in order to elicit a health response). The controlled human exposure 

### 15

and epidemiologic studies that examined the shape of the C

- R curve and the potential 

### 16

presence of a threshold have indicated a generally linear C

- R function with no indication 

### 17

of a threshold for O 3 concentrations greater than 30 or 40 ppb, which corresponds with 

### 18

PRB and the lower bound of O 3 concentrations inclu ded in the C

- R functions. 

### 19

Controlled human exposure studies have provided strong and quantifiable C

- R data on 

### 20

the human health effects of O 3 . The magnitude of respiratory effects in these studies is 

### 21

generally a function of O 3 exposure, i.e., the product of concentration (C), minute 

### 22

ventilation (V E ), and exposure duration. Recent studies provide evidence for a smooth C



### 23

R curve without indication of a threshold in young healthy adults, exposed during 

### 24

moderate exercise for 6.6 hours to O 3 concentrations betwee n 40 and 120 ppb 

### 25

(Figure 6

- 1). 

### 26

Although relatively few epidemiologic studies have examined the O 3 - health effects C

- R 

### 27

relationship, the C

- R relationship has been examined across multiple health endpoints 

### 28

and exposure durations. Some studies of populations engaged in outdoor activity found 

### 29

that associations between O 3 and lung function decrements persisted at lower O 3 

### 30

concentrations (Table 6

- 5). For example, a study found ambient O 3 exposure (10

- min to 

### 31

1

- h) during outdoor exercise to be associated with decre ases in lung function in analyses 

### 32

restricted to concentrations less than 51 ppb, though effect estimates were near zero with 

### 33

O 3 concentrations less than 41 ppb. In contrast, a subsequent study found associations 

### 34Draft

– Do Not Cite or Quote 2

- 34 September 2011 persisted with 1

- h max O 3 concentrations les s than 40 ppb. A study examining the C

- R 

### 1

relationship between short

- term O 3 exposure and pediatric asthma ED visits found no 

### 2

evidence of a threshold. In both quintile and loess dose

- response analyses this study 

### 3

found evidence that suggests that there are e levated associations for pediatric asthma ED 

### 4

visits with O 3 concentrations as low as 30 ppb (Figure 6

- 11). In an additional study, 

### 5

authors used a smooth function while also accounting for the potential confounding 

### 6

effects of PM 2.5 , to examine whether the s hape of the C

- R curve for short

- term exposure 

### 7

to O 3 and asthma hospital admissions (i.e., both general and ICU for all ages) is linear. 

### 8

When comparing the curve to a linear fit, the authors found that the linear fit is a 

### 9

reasonable approximation of the C

- R relationship between O 3 and asthma hospital 

### 10

admissions around and below the current NAAQS (Figure 6

- 9). Although the C

- R 

### 11

relationship between short

- term O 3 exposure and respiratory

- related hospital admissions 

### 12

and ED visits has not been extensively examine d, these preliminary examinations 

### 13

indicate a linear, no threshold relationship between short

- term O 3 exposure and pediatric 

### 14

asthma ED visits and asthma hospitalizations. 

### 15

The O 3 - health effects C

- R relationship was further examined in studies of short

- term O 3 

### 16

exposure and mortality. Evaluation of the C

- R relationship for short

- term exposure to O 3 

### 17

and mortality is difficult due to the evidence from multicity studies indicating highly 

### 18

heterogeneous O 3 - mortality associations across regions of the U.S. In additi on, there are 

### 19

numerous issues that may influence the shape of the O 3 - mortality C

- R relationship that 

### 20

need to be taken into consideration including: multiday effects (distributed lags), 

### 21

potential adaptation and mortality displacement (i.e., hastening of dea th by a short 

### 22

period). Several recent studies applied a variety of statistical approaches to examine the 

### 23

shape of the O 3 - mortality C

- R relationship and whether a threshold exists. These studies 

### 24

did not find any evidence that supports a threshold for the as sociation between short

- term 

### 25

exposure to O 3 and mortality within a range of O 3 concentrations observed in the U.S. 

### 26

Recent evidence also suggests that the shape of the O 3 - mortality C

- R curve remains 

### 27

linear across the full range of the O 3 concentrations. How ever, studies have also 

### 28

demonstrated heterogeneity in the O 3 - mortality relationship across cities (or regions), 

### 29

which complicates the interpretation of a combined C

- R curve and threshold analysis. 

### 30

Additionally, given the effect modifiers identified in mort ality analyses that are also 

### 31

expected to vary regionally (e.g., temperature, air conditioning prevalence), a national or 

### 32

combined analysis may not be appropriate to identify whether a threshold exists in the 

### 33

O 3 - mortality C

- R relationship. 

### 34

An evaluation of long

- term exposure studies identified studies of long

- term exposure to 

### 35

O 3 and birth outcomes that have characterized the C

- R relationship. Evidence from the 

### 36

southern California Children ’ s Health Study identified a C

- R relationship of birth weight 

### 37

with 24

- h avg O 3 concentrations averaged over the entire pregnancy that was clearest 

### 38Draft

– Do Not Cite or Quote 2

- 35 September 2011 above the 30 ppb level (Figure 7

- 4). Relative to the lowest decile of 24

- h avg O 3 , 

### 1

estimates for the next 5 lowest deciles were approximately

- 40 g to

- 50 g, with no clear 

### 2

trend a nd with 95% confidence bounds that included zero. The highest four deciles of O 3 

### 3

exposure showed an approximately linear decrease in birth weight, and all four 95% CIs 

### 4

excluded zero, and ranged from mean decreases of 74 grams to decreases of 148 grams. 

### 5

Ano ther study conducted in southern California reported increased risks for cardiac birth 

### 6

defects in a dose

- response manner with second

- month O 3 exposure. 

### 7

Collectively, both short

- and long

- term exposure studies that examined the O 3 - health 

### 8

effects C

- R relatio nship have provided no evidence of a threshold. Additionally, these 

### 9

studies indicate a linear C

- R relationship across the full range of O 3 concentrations 

### 10

observed in the U.S. 

### 11



## 2.7 Integration of Effects on Vegetation and Ecosystems

Chapter 9 presents the most p olicy

- relevant information related to this review of the 

### 12

NAAQS for the effects of O 3 on vegetation and ecosystems. This section integrates the 

### 13

key findings from the disciplines evaluated in this assessment of the O 3 scientific 

### 14

literature, which includes pl ant physiology, whole plant biology, ecosystems, and 

### 15

exposure

- response. 

### 16

Ozone effects at small spatial scales, such as the leaf of an individual plant, can result in 

### 17

effects at a continuum of larger spatial scales. Figure 2

- 4 is a simplified illustrative 

### 18

diagram of the major pathway through which O 3 enters leaves and the major endpoints O 3 

### 19

may affect in vegetation and ecosystems. The sections of Chapte r 9 are organized 

### 20

according to increasing spatial scales, starting with the cellular and subcellular level, then 

### 21

the whole plant and finally, ecosystem

- level processes. Ozone enters leaves through 

### 22

stomata, and can alter stomatal conductance and disrupt CO 2 fixation (Section 9.3). These 

### 23

effects can change rates of leaf gas exchange, growth and reproduction at the individual 

### 24

plant level and result in changes in ecosystems, such as productivity, C storage, water 

### 25

cycling, nutrient cycling, and community composi tion (Section 9.4). The framework for 

### 26

causal determinations has been applied to the body of scientific evidence to collectively 

### 27

examine effects attributed to O 3 exposure ( Table 2

- 2 ). The summary below provides brief 

### 28

integrated summaries of the evidence that supports the causal determinations. The 

### 29

detailed discussion of the underlying evidence used to formulate each causal 

### 30

determination can be found in Chapters 9. This summary ends with a short discussion of 

### 31

policy relevant considerations. 

### 32Draft

– Do Not Cite or Quote 2

- 36 September 2011 

### 2.7.1 Visible Foliar Injury

Visible foliar injury resulting from exposure to O 3 has been well characterized and 

### 1

documented over several decades of research on many tree, shr ub, herbaceous, and crop 

### 2

species ( U.S. EPA, 2006b

, 1996b

, 1984

, 1978a ) (Section 9.4.2). Ozone

- induced visible 

### 3

foliar injury symptoms on certain bioindicator plant species are considered diagnostic as 

### 4

they have been verified experimentally in exposure

- response studies, using expos ure 

### 5

methodologies such as continuous stirred tank reactors (CSTRs), open

- top chambers 

### 6

(OTCs), and free

- air fumigation. Experimental evidence has clearly established a 

### 7

consistent association of visible injury with O 3 exposure, with greater exposure often 

### 8

re sulting in greater and more prevalent injury. Since the 2006 O 3 AQCD, several 

### 9

multiple

- year field surveys of O 3 - induced visible foliar injury have been conducted at 

### 10

National Wildlife Refuges in Maine, Michigan, New Jersey, and South Carolina. New 

### 11

sensitive species showing visible foliar injury continue to be identified from field surveys 

### 12

and verified in controlled exposure studies. 

### 13

Figure 2

- 4 An illustrative diagram of the major pathway through which O 3 

### ente rs leaves and the major endpoints that O 3 

### may affect in plants and ecosystems

. O 3 exposure

O 3 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 communitiesDifferential O3sensitivity

Affected ecosystem services

• Decreased productivity

• Decreased C sequestration

• Altered water cycling (Fig 9

- 7)

• Altered community composition (i.e., plant, insect & microbe)Draft

– Do Not Cite or Quote 2

- 37 September 2011 

### Table 2

- 2 Summary of ozone causal determinations for vegetation and ecosystem effects

Vegetation and Ecosystem Effects Conclusions from 2006 O 3 AQCD Conclusions from

2011 2nd Draft ISA

Visible Foliar Injury Effects on Vegetation Data published since the 1996 O 3 AQCD strengthen previous conclusions that there is strong evidence that current ambient O 3 concentrations cause impaired

a esthetic quality of many native plants and trees by increasing foliar injury. Causal Relationship

Reduced Vegetation Growth Data published since the 1996 O 3 AQCD strengthen previous conclusions that there is strong evidence that current ambient O 3 concent rations 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 O 3 is an important stressor of ecosystems and that the

effects of O 3 on individual plants and processes are scaled up through the ecosystem, affecting net primary productivity. Causal Relationship

Reduced Carbon (C) Sequestration in Terrestrial Ecosystems L imited studies from previous review Likely to be a Causal Relationship

Reduced Yield and Quality of Agricultural Crops Data published since the 1996 O 3 AQCD strengthen previous conclusions that there is strong evidence that current ambient O 3 concentratio ns 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 O 3 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 O 3 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 aff ecting above

- and below

- ground community composition through impacts on both growth and reproduction. Significant changes in plant community composition resulting directly from O 3 exposure have been

demonstrated. Likely to be a Causal Relationship

T he use of biological indicators in field surveys to detect phytotoxic levels of O 3 is a 

### 1

longstanding and effective methodology. The USDA Forest Service through the Forest 

### 2

Health Monitoring (FHM) Program (1990

- 2001) and currently the Forest Inventory and 

### 3

An alysis (FIA) Program has been collecting data regarding the incidence and severity of 

### 4

visible foliar injury on a variety of O 3 sensitive plant species throughout the U.S. The 

### 5

network has provided evidence that O 3 concentrations were high enough to induce v isible 

### 6

symptoms on sensitive vegetation. From repeated observations and measurements made 

### 7

over a number of years, specific geographical patterns of visible O 3 injury symptoms can 

### 8

be identified. In addition, a study assessed the risk of O 3 - induced visible foliar injury on 

### 9

bioindicator plants in 244 national parks in support of the National Park Service ’ s Vital 

### 10

Signs Monitoring Network. The results of the study demonstrated that the risk of visible 

### 11

foliar injury was high in 65 parks (27%), moderate in 46 par ks (19%), and low in 131 

### 12

parks (54%). Some of the well

- known parks with a high risk of O 3 - induced visible foliar 

### 13

injury include Gettysburg, Valley Forge, Delaware Water Gap, Cape Cod, Fire Island, 

### 14

Antietam, Harpers Ferry, Manassas, Wolf Trap Farm Park, Mam moth Cave, Shiloh, 

### 15Draft

– Do Not Cite or Quote 2

- 38 September 2011 Sleeping Bear Dunes, Great Smoky Mountains, Joshua Tree, Sequoia and Kings Canyon, 

### 1

and Yosemite. Overall, evidence is sufficient to conclude that there is a causal 

### 2

relationship between ambient O 3 exposure and the occurrence of O 3 - induced 

### 3

visible foliar injury on sensitive vegetation across the U.S. 

### 4

2.7.2 Growth, Productivity, Carbon Storage and Agriculture

Ambient O 3 concentrations have long been known to cause decreases in photosynthetic 

### 5

rates and plant growth. The O 3 - induced damages at the pl ant scale may translate to the 

### 6

ecosystem scale, and cause changes in productivity and C storage. The effects of O 3 

### 7

exposure on photosynthesis, growth, biomass allocation, ecosystem production and 

### 8

ecosystem C sequestration were reviewed for the natural ecos ystems, and crop 

### 9

productivity and crop quality were reviewed for the agricultural ecosystems. 

### 10

2.7.2.1 Natural Ecosystems

The previous O 3 AQCDs concluded that there is strong and consistent evidence that 

### 11

ambient concentrations of O 3 decrease plant photosynthesis and growth in numerous 

### 12

plant species across the U.S. Studies published since the last review continue to support 

### 13

that conclusion (Section 9.4.3.1). New studies, based on the Aspen free

- air carbon



### 14

dioxide/ozone enrichment (FAC E) experiment, found that O 3 caused reductions in total 

### 15

biomass relative to the control in aspen, paper birch, and sugar maple communities 

### 16

during the first seven years of stand development. Overall, the studies at the Aspen FACE 

### 17

experiment were consistent with the open

- top chamber (OTC) studies that were the 

### 18

foundation of previous O 3 NAAQS reviews. These results strengthen our understanding 

### 19

of O 3 effects on forests and demonstrate the relevance of the knowledge gained from 

### 20

trees grown in open

- top chamber st udies. 

### 21

A set of meta

- analyses assessed the effects of O 3 on plant photosynthesis and growth 

### 22

across different species and fumigation methods (such as OTC and FACE). Those studies 

### 23

reported that current O 3 concentrations in the northern hemisphere are decrea sing 

### 24

photosynthesis (~11%) across tree species, and the decreases in photosynthesis are 

### 25

consistent with cumulative uptake of O 3 into the leaf. The current ambient O 3 

### 26

concentrations (~40 ppb) significantly decreased annual total biomass growth of forest 

### 27

spe cies by an average of 7%, with potentially greater decreases (11

- 17%) in areas that 

### 28

have higher O 3 concentrations (Section 9.4.3.1). The meta

- analyses further confirmed 

### 29

that reduction of plant photosynthesis and growth under O 3 exposure are coherent across 

### 30

numerous species and various experimental techniques. 

### 31Draft

– Do Not Cite or Quote 2

- 39 September 2011 Studies during recent decades have also demonstrated O 3 alters biomass allocation and 

### 1

plant reproduction (Section 9.4.3). Recent meta

- analyses have generally indicated that O 3 

### 2

reduced C allocated to r oots, although the findings of individual studies were mixed. 

### 3

Several recent studies published since the 2006 O 3 AQCD further demonstrate that O 3 

### 4

altered reproductive processes, such as timing of flowering, number of flowers, fruits and 

### 5

seeds, in herbaceou s and woody plant species. However, a knowledge gap still exists 

### 6

pertaining to the exact mechanism of the responses of reproductive processes to O 3 

### 7

exposure (Section 9.4.3.3). 

### 8

Studies at the leaf and plant scales showed that O 3 reduced photosynthesis and plant 

### 9

growth, providing coherence and biological plausibility for the reported decreases in 

### 10

ecosystem productivity. During the previous NAAQS reviews, there were very few 

### 11

studies that investigated the effect of O 3 exposure on ecosystem productivity and C 

### 12

s equestration. Recent studies from long

- term FACE experiments and ecosystem models 

### 13

provided evidence of the association of O 3 exposure and reduced productivity at the 

### 14

ecosystem scale. Elevated O 3 reduced stand biomass at Aspen FACE after 7 years of O 3 

### 15

expos ure, and annual volume growth at the Kranzberg Forest in Germany. Results across 

### 16

different ecosystem models were consistent with the FACE experimental evidence, which 

### 17

showed that O 3 reduced ecosystem productivity (Section 9.4.3.4). In addition to primary 

### 18

p roductivity, other indicators such as net ecosystem CO 2 exchange (NEE) and C 

### 19

sequestration were often assessed by model studies. Model simulations consistently 

### 20

found that O 3 exposure caused negative impacts on those indicators (Section 9.4.3.4, 

### 21

Table 9

- 3), but the severity of these impacts was influenced by multiple interactions of 

### 22

biological and environmental factors. The suppression of ecosystem C sinks results in 

### 23

more CO 2 accumulation in the atmosphere. A recent study suggested that the indirect 

### 24

radiativ e forcing caused by O 3 exposure through lowering ecosystem C sink could have 

### 25

an even greater impact on global warming than the direct radiative forcing of O 3

. 

### 26

Although O 3 generally causes negative effects on ecosystem productivity, the magnitude 

### 27

of the res ponse varies among plant communities (Section 9.4.3.4). For example, O 3 had 

### 28

little impact on white fir, but greatly reduced growth of ponderosa pine in southern 

### 29

California. Ozone decreased net primary production (NPP) of most forest types in Mid



### 30

Atlantic r egion, but had small impacts on spruce

- fir forest. Ozone could also affect 

### 31

regional C budgets through interacting with multiple factors, such as N deposition, 

### 32

elevated CO 2 and land use history. Model simulations suggested that O 3 partially offset 

### 33

the growt h stimulation caused by elevated CO 2 and N deposition in both Northeast

- and 

### 34

Mid

- Atlantic

- region forest ecosystems of the U.S. 

### 35

Overall, evidence is sufficient to conclude that there is a causal relationship 

### 36

between O 3 exposure and reduced plant growth and productivity, and a likely 

### 37Draft

– Do Not Cite or Quote 2

- 40 September 2011 causal relationship between O 3 exposure and reduced carbon sequestration in 

### 1

terrestrial ecosystems. 

### 2

2.7.2.2 Agricultural Crops

The detrimental effect of O 3 on crop production has been recognized since the 1960 ’ s and 

### 3

a large body of research has subsequently stemmed from those initial findings. Previous 

### 4

O 3 AQCDs have extensively reviewed this body of literature. Current O 3 concentrations 

### 5

across the U.S. are high enough to cause yield loss for a variety of agricultural crops 

### 6

including, but not limited to, soybean, wheat, potato, watermelon, beans, turnip, onion, 

### 7

lettuce, and tomato (Section 9.4.4.1). Continued increases in O 3 concentration may 

### 8

further decrease yield in these sensitive crops. Despite the well

- documented yield losses 

### 9

due to increasing O 3 concentration, there is still a knowledge gap pertaining to the exact 

### 10

mechanism of O 3 - induced yield loss. Research has linked increasing O 3 concentration to 

### 11

decreased photosynthetic rates and accelerated senescence, which are related to yi eld. 

### 12

In addition, new research has highlighted the effects of O 3 on crop quality. Increasing O 3 

### 13

concentration decreases nutritive quality of grasses, decreases macro

- and micro

- nutrient 

### 14

concentrations in fruits and vegetable crops, and decreases cotton fib er quality. These 

### 15

areas of research require further investigation to determine the mechanism and dose



### 16

responses (Section 9.4.4.2). 

### 17

During the previous NAAQS reviews, there were very few studies that estimate O 3 

### 18

impacts on crop yields at large spatial scale s. Recent modeling studies found that O 3 

### 19

generally reduced crop yield, but the impacts varied across regions and crop species 

### 20

(Section 9.4.4.1). For example, the largest O 3 - induced crop yield losses occurred in high



### 21

production areas exposed to high O 3 conc entrations, such as the Midwest and the 

### 22

Mississippi Valley regions of the U.S. Among crop species, the estimated yield loss for 

### 23

wheat and soybean were higher than rice and maize. Satellite and ground

- based O 3 

### 24

measurements have been used to assess yield los s caused by O 3 over the continuous tri



### 25

state area of Illinois, Iowa and Wisconsin. The results showed that O 3 concentrations 

### 26

significantly reduced soybean yield, which correlates well with the previous results from 

### 27

FACE

- type experiments and OTC experiments (Section 9.4.4.1). 

### 28

Evidence is sufficient to conclude that there is a causal relationship between O 3 

### 29

exposure and reduced yield and quality of agricultural crops. 

### 30Draft

– Do Not Cite or Quote 2

- 41 September 2011 

### 2.7.3 Water Cycling

Ozone can affect water use in plants and ecosystems through several mechanism s 

### 1

including damage to stomatal functioning and loss of leaf area. Section 9.3.6 reviewed 

### 2

possible mechanisms for O 3 exposure effects on stomatal functioning including the build



### 3

up of CO 2 in substomatal cavity, impacts on signal transduction pathways and di rect O 3 

### 4

impact on guard cells. Regardless of the mechanism, O 3 exposure has been shown to alter 

### 5

stomatal performance, which may affect plant and stand transpiration and therefore 

### 6

possibly affecting hydrological cycling. 

### 7

Although the evidence was from a li mited number of field and modeling studies, these 

### 8

findings showed an association of O 3 exposure and the alteration of water use and cycling 

### 9

in vegetation and ecosystem level (Section 9.4.5). There is not a clear consensus on the 

### 10

nature of leaf

- level stomat al conductance response to O 3 exposure. When measured at 

### 11

steady

- state high light conditions, leaf

- level stomatal conductance is often found to be 

### 12

reduced when exposed to O 3 . However, measurements of stomatal conductance under 

### 13

dynamic light and vapor pressu re deficit conditions indicate sluggish responses under 

### 14

elevated O 3 exposure which could potentially lead to increased water loss from 

### 15

vegetation. Field studies suggested that peak hourly O 3 exposure increased the rate of 

### 16

water loss from several tree speci es, and led to a reduction in the late

- season modeled 

### 17

stream flow in three forested watersheds in eastern Tennessee. Sluggish stomatal 

### 18

responses during O 3 exposure was suggested as a possible mechanism for increased water 

### 19

loss during peak O 3 exposure. Curr ently, the O 3 - induced reduction in stomatal aperture is 

### 20

the biological assumption for most process

- based models. Therefore, results of those 

### 21

models normally found that O 3 reduced water loss. For example, one study found that O 3 

### 22

damage and N limitation toge ther reduced evapotranspiration and increase runoff. 

### 23

Although the direction of the response differed among studies, the evidence is 

### 24

sufficient to conclude that there is likely to be a causal relationship between O 3 

### 25

exposure and the alteration of ecosystem water cycling. 

### 26

2.7.4 Below

- Ground Processes

Below

- ground processes are tightly linked with aboveground processes. The responses of 

### 27

aboveground process to O 3 exposure, such as reduced photosynthetic rates, increased 

### 28

metabolic cost, and reduced root C allocation, have provided biologically plausible 

### 29

mechanisms for the alteration of below

- ground processes. Since the 2006 O 3 AQCD, 

### 30

more evidence has shown that although the responses are often species specific, O 3 

### 31

altered the quality and quantity of C input to soil, mi crobial community composition, and 

### 32

C and nutrient cycling. 

### 33Draft

– Do Not Cite or Quote 2

- 42 September 2011 Results from Aspen FACE and other experimental studies consistently found that O 3 

### 1

reduced litter production and altered C chemistry, such as soluble sugars, soluble 

### 2

phenolics, condensed tannins, lignin, and macro/micro nutrient concentration in litter 

### 3

(Section 9.4.6.1). The changes in substrate quality and quantity could alter microbia l 

### 4

metabolism under elevated O 3 , and therefore soil C and nutrient cycling. Several studies 

### 5

indicated that O 3 generally suppressed soil enzyme activities (Section 9.4.6.2). However, 

### 6

the impact of O 3 on litter decomposition was inconsistent and varied among species, sites 

### 7

and exposure length. Similarly, O 3 had inconsistent impacts on dynamics of micro and 

### 8

macro nutrients (Section 9.4.6.4). 

### 9

Studies from the Aspen FACE experiment suggested that the response of below

- ground 

### 10

C cycle to O 3 exposure, such as litte r decomposition, soil respiration and soil C content, 

### 11

changed over time. For example, in the early part of the experiment (1998

- 2003), O 3 had 

### 12

no impact on soil respiration but reduced the formation rates of total soil C under 

### 13

elevated CO 2 . However, after 1 0 to 11 years of exposure, O 3 was found to increase soil 

### 14

respiration but have no significant impact on soil C formation under elevated CO 2 

### 15

(Section 9.4.6.3). 

### 16

The evidence is sufficient to infer that there is a causal relationship between O 3 

### 17

exposure and t he alteration of below

- ground biogeochemical cycles. 

### 18

2.7.5 Community Composition

In the 2006 O 3 AQCD, the impact of O 3 exposure on species competition and community 

### 19

composition was assessed. Ozone was found to be one of the dominant factors causing a 

### 20

significant decline in ponderosa and Jeffrey pine in the San Bernardino Mountains in 

### 21

southern California. Ozone exposure also tended to shift the grass

- legume mixtures in 

### 22

favor of grass species. Since the 2006 O 3 AQCD, more evidence has shown that O 3 

### 23

exposure changed the competitive interactions and led to loss of O 3 sensitive species or 

### 24

genotypes. Studies found that the severity of O 3 damage on growth, reproduction and 

### 25

foliar injury varied among species (Section 9.4.3), which provided the biological 

### 26

plausibility for the alteration of community composition. Additionally, research since the 

### 27

last review has shown that O 3 can alter community composition and diversity of soil 

### 28

microbial communities. 

### 29

The decline of conifer forests under O 3 exposure was continually observed i n several 

### 30

regions. Ozone damage was believed to be an important causal factor in the dramatic 

### 31

decline of sacred fir in the valley of Mexico, as well as cembran pine in southern France 

### 32

and Carpathian Mountains, although several factors, such as drought, ins ect outbreak and 

### 33

forest management, may also contribute to or even be the dominant factors causing the 

### 34Draft

– Do Not Cite or Quote 2

- 43 September 2011 mortality of the conifer trees. Results from the Aspen FACE site indicated that O 3 could 

### 1

alter community composition of broadleaf forests as well. At the Aspen FACE site, O 3 

### 2

reduced growth and increased mortality of a sensitive aspen clone, while the O 3 tolerant 

### 3

clone emerged as the dominant clone in the pure aspen community. In the mixed aspen



### 4

birch and aspen

- maple communities, O 3 reduced the competitive capacity of aspen 

### 5

compared to birch and maple (Section 9.4.7.1). 

### 6

The tendency for O 3 - exposure to shift the biomass of grass

- legume mixtures in favor of 

### 7

grass species was reported in the 2006 O 3 AQCD and has been generally confirmed by 

### 8

recent studies. Howev er, in a high elevation mature/species

- rich grass

- legume pasture, O 3 

### 9

fumigation showed no significant impact on community composition (Section 9.4.7.2). 

### 10

Ozone exposure not only altered community composition of plant species, but also 

### 11

microorganisms. The sh ift in community composition of bacteria and fungi has been 

### 12

observed in both natural and agricultural ecosystems, although no general patterns could 

### 13

be identified (Section 9.4.7.3). 

### 14

The evidence is sufficient to conclude that there is likely a causal rela tionship 

### 15

between O 3 exposure and the alteration of community composition. 

### 16

2.7.6 Policy Relevant Considerations

2.7.6.1 Air Quality Indices

Exposure indices are metrics that quantify exposure as it relates to measured plant 

### 17

damage (e.g., reduced growth). They are summary measures of monitored ambient O 3 

### 18

concentrations over time intended to provide a consistent metric for reviewing and 

### 19

comparing exposure

- response effects obtained from various studies. No new information 

### 20

is available since 2006 that alters the basic conclus ions put forth in the 2006 and 1996 O 3 

### 21

AQCDs. These AQCDs focused on the research used to develop various exposure indices 

### 22

to help quantify effects on growth and yield in crops, perennials, and trees (primarily 

### 23

seedlings). The performance of indices was co mpared through regression analyses of 

### 24

earlier studies designed to support the estimation of predictive O 3 exposure

- response 

### 25

models for growth and/or yield of crops and tree (seedling) species. 

### 26

Another approach for improving risk assessment of vegetation re sponse to ambient O 3 is 

### 27

based on determining the O 3 concentration from the atmosphere that enters the leaf (i.e., 

### 28

flux or deposition). Interest has been increasing in recent years, particularly in Europe, in 

### 29

using mathematically tractable flux models for O 3 assessments at the regional, national, 

### 30

and European scale. While some efforts have been made in the U.S. to calculate O 3 flux 

### 31Draft

– Do Not Cite or Quote 2

- 44 September 2011 into leaves and canopies, little information has been published relating these fluxes to 

### 1

effects on vegetation. There is also co ncern that not all O 3 stomatal uptake results in a 

### 2

yield reduction, which depends to some degree on the amount of internal detoxification 

### 3

occurring with each particular species. Species having high detoxification capacity may 

### 4

show little relationship betwe en O 3 stomatal uptake and plant response. The lack of data 

### 5

in the U.S. and the lack of understanding of detoxification processes have made this 

### 6

technique less viable for vulnerability and risk assessments in the U.S. 

### 7

The main conclusions from the 1996 and 2006 O 3 AQCDs regarding indices based on 

### 8

ambient exposure remain valid. These key conclusions can be restated as follows: 

### 9

 O 3 effects in plants are cumulative; 

### 10

 higher O 3 concentrations appear to be more important than lower 

### 11

concentrations in eliciting a re sponse; 

### 12

 plant sensitivity to O 3 varies with time of day and plant development stage; 

### 13

and 

### 14

 exposure indices that cumulate hourly O 3 concentrations and preferentially 

### 15

weight the higher concentrations have better statistical fits to growth/yield 

### 16

response data than do the mean and peak indices. 

### 17

Various weighting functions have been used, including threshold

- weighted (e.g., 

### 18

SUM06) and con tinuous sigmoid

- weighted (e.g., W126) functions. Based on statistical 

### 19

goodness

- of

- fit tests, these cumulative, concentration

- weighted indices could not be 

### 20

differentiated from one another using data from previous exposure studies. Additional 

### 21

statistical for ms for O 3 exposure indices are summarized in Section 9.5 of this ISA. The 

### 22

majority of studies published since the 2006 O 3 AQCD do not change earlier conclusions, 

### 23

including the importance of peak concentrations, and the duration and occurrence of O 3 

### 24

exposur es in altering plant growth and yield. 

### 25

Given the current state of knowledge and the best available data, exposure indices that 

### 26

cumulate and differentially weight the higher hourly average concentrations and also 

### 27

include the mid

- level values continue to off er the most defensible approach for use in 

### 28

developing response functions and comparing studies, as well as for defining future 

### 29

indices for vegetation protection. 

### 30

2.7.6.2 Exposure

- Response

None of the information on effects of O 3 on vegetation published since the 2 006 O 3 

### 31

AQCD has modified the assessment of quantitative exposure

- response relationships that 

### 32

was presented in that document ( U.S. EPA, 2006b ) . This assessment updates the 2006 

### 33Draft

– Do Not Cite or Quote 2

- 45 September 2011 exposure

- response models by computing them using the W126 met ric, cumulated over 

### 1

90 days. Almost all of the experimental research on the effects of O 3 on growth or yield 

### 2

of plants published since 2006 used only two levels of exposure. In addition, hourly O 3 

### 3

concentration data that would allow calculations of exposur e using the W126 metric are 

### 4

generally unavailable. However, two long

- term experiments, one with a crop species 

### 5

(soybean), one with a tree species (aspen), have produced data that are used in Section 

### 6

9.6 to validate the exposure

- response models presented in the 2006 O 3 AQCD, and the 

### 7

methodology used to derive them. EPA compared predictions from the models presented 

### 8

in the 2006 O 3 AQCD, updated to use the 90 day 12hr W126 metric, with more recent 

### 9

observations for yield of soybean and biomass growth of trembli ng aspen. The models 

### 10

were parameterized using data from the NCLAN and NHEERL

- WED projects, which 

### 11

were conducted in OTCs. The more recent observations were from experiments using 

### 12

FACE technology, which is intended to provide conditions closer to natural env ironments 

### 13

than OTC. Observations from these new experiments were exceptionally close to 

### 14

predictions from the models. The accuracy of model predictions for two widely different 

### 15

plant species, grown under very different conditions, provides support for the v alidity of 

### 16

the models for crops and trees developed using the same methodology and data for other 

### 17

species. However, variability observed among species in the NCLAN and NHEERL



### 18

WED projects indicates that the range of sensitivity between and among species is likely 

### 19

quite wide. 

### 20

Results from several meta

- analyses have provided approximate values for responses of 

### 21

yield of soybean, wheat, rice and other crops under broad categories of exposure, relative 

### 22

to charcoal

- filtered air. Additional reports have summarize d yield data for six crop 

### 23

species under various broad comparative exposure categories, and reviewed 263 studies 

### 24

that reported effects on tree biomass. However, these analyses have proved difficult to 

### 25

compare with exposure

- response models, especially given that exposure was not 

### 26

expressed on the same W126 scale. 

### 27



## 2.8 The Role of Tropospheric Ozone in Climate Change and UV

- B

Effects

Atmospheric O 3 plays an important role in the Earth ’ s energy budget by interacting with 

### 28

incoming solar radiation and outgoing infrare d radiation. Tropospheric O 3 makes up only 

### 29

a small portion of the total column of O 3 , but it has important incremental effects on the 

### 30

overall radiation budget. Chapter 10 assesses the specific role of tropospheric O 3 in the 

### 31

earth ’ s radiation budget and how perturbations in tropospheric O 3 might affect (1) climate 

### 32

through its role as a greenhouse gas, and (2) health, ecology and welfare through its role 

### 33

in shielding the earth ’ s surface from solar ultraviolet (UV) radiation. 

### 34Draft

– Do Not Cite or Quote 2

- 46 September 2011 

### 2.8.1 Tropospheric Ozone as a Greenhouse Gas

Ozone is an important greenhouse gas, and increases in its abundance in the troposphere 

### 1

may contribute to climate change according to the 2007 climate assessment by the 

### 2

Intergovernmental Panel on Climate Change (IPCC). Models calculate that the global 

### 3

burden of tropospheric O 3 has doubled since the preindustrial era, while observations 

### 4

indicate that in some regions O 3 may have increased by factors as great as 4 or 5. These 

### 5

increases are tied to the rise in emissions of O 3 precursors from human activity , mainly 

### 6

fossil fuel consumption and agricultural processes. 

### 7

Units shown are those typical for each quantity illustrated. Feedbacks from both the 

### 8

climate response and climate impacts can, in turn, affect the abundance of tropospheric 

### 9

O 3 and O 3 precursors through multiple feedback mechanisms. Climate impacts are 

### 10

deemphasized in the figure since these downstream effects are extremely complex and 

### 11

outside the scope of this assessment. 

### 12

Figure 2

- 5 shows the main steps involved in the influence of tropospheric O 3 on climate. 

### 13

Emissions of O 3 precursors including CO, VOCs, CH 4 , and NO X lead to production of 

### 14

tropospheric O 3 . A change in th e abundance of tropospheric O 3 perturbs the radiative 

### 15

balance of the atmosphere, an effect quantified by the radiative forcing (RF) metric. The 

### 16

earth

- atmosphere

- ocean system responds to the forcing with a climate response, typically 

### 17

expressed as a change i n surface temperature. Finally, the climate response causes 

### 18

downstream climate

- related health and ecosystem impacts, such as redistribution of 

### 19

diseases or ecosystem characteristics due to temperature changes. Feedbacks from both 

### 20

the climate response and do wnstream impacts can, in turn, affect the abundance of 

### 21

tropospheric O 3 and O 3 precursors through multiple feedback mechanisms as indicated in 

### 22

Figure 2

- 5. Direct feedbacks are discussed in Section 10.2.3.4 while downstream climate 

### 23

impacts and their feedback s are extremely complex and outside the scope of this 

### 24

assessment. 

### 25

The impact of the tropospheric O 3 change since preindustrial times on climate has been 

### 26

estimated to be about 25

- 40% of anthropogenic CO 2 impact and about 75% of 

### 27

anthropogenic CH 4 impact acco rding to the IPCC, ranking it third in importance among 

### 28

the greenhouse gases. There are large uncertainties in the RF estimate attributed to 

### 29

tropospheric O 3 , however, making the impact of tropospheric O 3 on climate more 

### 30

uncertain than the impact of the lon g

- lived greenhouse gases. Despite these uncertainties, 

### 31

the evidence supports a causal relationship between changes in tropospheric O 3 

### 32

concentrations and radiative forcing. 

### 33

RF does not take into account the climate feedbacks that could amplify or dampen the 

### 34

actual surface temperature response. Quantifying the change in surface temperature 

### 35Draft

– Do Not Cite or Quote 2

- 47 September 2011 requires a complex climate simulation in which all important feedbacks and interactions 

### 1

are accounted for. As these processes are not well understood or easily modeled, the 

### 2

surface temperature response to a given RF is highly uncertain and can vary greatly 

### 3

among models and from region to region within the same model. In light of these 

### 4

uncertainties, the evidence supports a likely to be a causal relationship between 

### 5

changes i n tropospheric O 3 concentrations and climate change. 

### 6

Units s hown are those typical for each quantity illustrated. Feedbacks from both the climate response and climate impacts can, in turn, affect the abundance of tropospheric O 3 and O 3 precursors through multiple feedback mechanisms. Climate impacts are deemphasized in the figure since these downstream effects are extremely complex and outside the scope of this assessment.



### Figure 2

- 5 Schem atic illustrating the effects of tropospheric O 3 

### on climat e including the relationship between precursor emissions, tropospheric O 3 

### abundance, radiative forcing, climate response, and climate impacts. Tropospheric Ozone and UV

- B related effects

UV radiation emitted from the Sun contains sufficient energy when it reaches the Earth to 

### 7

break (photolyze) chemical bonds in molecules, thereby leading to damaging effects on 

### 8

living organisms and materials. Atmospheric O 3 plays a crucial role in reducing exp osure 

### 9

to solar UV radiation at the Earth ’ s surface. Ozone in the stratosphere is responsible for 

### 10

the majority of this shielding effect, as approximately 90% of total atmospheric O 3 is 

### 11

located there over mid

- latitudes. Ozone in the troposphere provides supp lemental 

### 12

shielding of radiation in the wavelength band from 280

- 315 nm, referred to as UV

- B 

### 13Draft

– Do Not Cite or Quote 2

- 48 September 2011 radiation. UV

- B radiation has important effects on human health and ecosystems, and is 

### 1

associated with materials damage. 

### 2

Adverse human health effects associated wit h solar UV

- B radiation exposure include 

### 3

erythema, skin cancer, ocular damage, and immune system suppression. A potential 

### 4

human health benefit of increased UV

- B exposure involves the UV

- induced production 

### 5

of vitamin D which may help reduce the risk of metab olic bone disease, type I diabetes, 

### 6

mellitus, and rheumatoid arthritis, and may provide beneficial immunomodulatory effects 

### 7

on multiple sclerosis, insulin

- dependent diabetes mellitus, and rheumatoid arthritis. 

### 8

Adverse ecosystem and materials damage effects associated with solar UV

- B radiation 

### 9

exposure include terrestrial and aquatic ecosystem impacts, alteration of biogeochemical 

### 10

cycles, and degradation of man

- made materials. Terrestrial ecosystem effects from 

### 11

increased UV

- B radiation include reduced plant productivity and plant cover, changes in 

### 12

biodiversity, susceptibility to infection, and increases in natural UV protective responses. 

### 13

In general, however, these effects are small for moderate UV

- B increases at mid



### 14

latitudes. Aquatic ecosystem effects from increased UV

- B radiation include sensitivity in 

### 15

growth, immune response, and behavioral patterns of aquatic organisms and the potential 

### 16

for increased catalysis and mobility of trace metals. Biogeochemical cycles, particularly 

### 17

the carbon cycle, can also be influenced by increased UV

- B radiation with effects ranging 

### 18

from UV

- induced increases in CO 2 uptake through soil respiration to UV

- induced release 

### 19

of CO 2 through photodegradation of above

- ground plant litter. Changes in solar UV 

### 20

radiation may also have eff ects on carbon cycling and CO 2 uptake in the oceans as well 

### 21

as release of dissolved organic matter from sediment and algae. Finally, materials damage 

### 22

from increased UV

- B radiation includes UV

- induced photodegradation of wood and 

### 23

plastics. 

### 24

There is a lack o f published studies that critically examine the incremental health or 

### 25

welfare effects (adverse or beneficial) attributable specifically to changes in UV

- B 

### 26

exposure resulting from perturbations in tropospheric O 3 concentrations. The effects are 

### 27

expected to be small and they cannot yet be critically assessed within reasonable 

### 28

uncertainty. Overall, the evidence is inadequate to determine if a causal relationship 

### 29

exists between tropospheric O 3 and UV

- B related health and welfare effects. 

### 30Draft

– Do Not Cite or Quote 2

- 49 September 2011 

## 2.9 Summary of Causal Determinations for Health Effects and

Welfare Effects

This chapter has provided an overview of the underlying evidence used in making the 

### 1

causal determinations for the health and welfare effects of O 3 . This review builds upon 

### 2

the conclusions of the previo us AQCDs for O 3

. 

### 3

The evaluation of the epidemiologic, toxicological, and controlled human exposure 

### 4

studies published since the completion of the 2006 O 3 AQCD have provided additional 

### 5

evidence for O 3 - related health outcomes. Table 2

- 3 provides an overview of the causal 

### 6

determinations for all of the health outcomes evaluated. Causal determinations for O 3 and 

### 7

welfare effects are included in Table 2

- 4 , while causal determinations for climate change 

### 8

and UV

- B effects are in Table 2

- 5 . Detailed discussions of the scientific evidence and 

### 9

rationale for these causal determinations are provided in subsequent chapters of this ISA. 

### 10

Table 2

- 3 Summary of ozone caus al determinations by exposure duration

and health outcome

Health Outcome Conclusions from 2006 O 3 AQCD Conclusions from

2011 1st Draft ISA

Short

- Term Exposure to O 3

Respiratory effects The overall evidence supports a causal relationship between acute ambient O 3 exposures and increased respiratory morbidity outcomes. Causal Relationship

Cardiovascular effects The limited evidence is highly suggestive that O 3 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 O 3 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

M ortality The evidence is highly suggestive that O 3 directl y or indirectly contributes to non

accidental and cardiopulmonary

- related mortality. Likely to be a Causal Relationship

Long

- term Exposure to O 3

Respiratory effects The current evidence is suggestive but inconclusive for respiratory health effects from long

- term O 3 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 O 3 effects. Suggestive of a Causal Relationship

Central nervous system

effects Evidence regarding chronic expo sure and neurobehavioral effects was not available. Suggestive of a Causal Relationship

Cancer Little evidence for a relationship between chronic O 3 exposure and increased risk of lung cancer. Inadequate to infer a Causal Relationship

Mortality There is little evidence to suggest a causal relationship between chronic O 3 exposure and increased risk for mortality in humans. Suggestive of a Causal RelationshipDraft

– Do Not Cite or Quote 2

- 50 September 2011 

### Table 2

- 4 Summary of ozone causal determination for welfare effects

Vegetation and Ecosystem Effects Conclusions from 2006 O 3 AQCD Conclusions from

2011 2nd Draft ISA

Visible Foliar Injury Effects on Vegetation Data published since the 1996 O 3 AQCD strengthen previous conclusions that there is strong evidence that current ambient O 3 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 O 3 AQCD strengthen previous conclusions that there is strong evidence that current ambient O 3 concentrations cause decreased growth and biomass accumulation in annual, perennial and woody plants, including agronomic crops, annuals, shrubs, grasses, and trees. Causal Relationship

Red uced Productivity in Terrestrial Ecosystems There is evidence that O 3 is an important stressor of ecosystems and that the

effects of O 3 on individual plants and processes are scaled up through the ecosystem, affecting net primary productivity. Causal Relat ionship

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 O 3 AQCD strengthen previous conclusio ns that there is strong evidence that current ambient O 3 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 q uantity may be affected by O 3 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 O 3 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 disso lved 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

co mmunity composition resulting directly from O 3 exposure have been

demonstrated. Likely to be a Causal Relationship



### Table 2

- 5 Summary of ozone causal determination for climate change and

UV

- B effects

Effects Conclusions from 2006 O 3 AQCD Conclusions from

2011 1st Draft ISA

Radiative Forcing Climate forcing by O 3 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 O 3 await further advances in monitoring and chemical transport modeling, the overall body of scientific evidence suggests that high concentrations of O 3 on the regional scale could have a discernable influence on climate, leading to surface temperature and hydrological cycle changes. Likely to be a Causal Relationship

UV

- B Related Health and

Welfare Effects UV

- B has not been studied in sufficient detail to allow for a credible health benefits assessment. In conclusion, the effect of changes in surface

- level O 3 concentrations on

UV

- induced health outcomes cannot yet be critically assessed within reasonable uncertainty. Inadequate to Determine if

a Causal Relationship

Exists



### 1Draft

– Do Not Cite or Quote 2

- 51 September 2011 

## 2.10 References

CAA. (Air quality criteria and control techniques, Section 108 of the Clean Air Act). 42. § 7408, (1990a).

U.S. EPA. (U.S. Environmental Protection Agency). (1978a). Air quality criteria for ozone and other
photochemical oxidants. (EPA/600/8

- 78/004). Washington, DC.

U.S. EPA. (U.S. Environmental Protection Agency). (1984). Air quality criteria for ozone and other
photochemical oxidants, Vol. 3. (EPA/600/8

- 84/020A). Research Triangle Par k, NC.
http://nepis.epa.gov/Exe/ZyPURL.cgi?Dockey=2000AVEV.txt

. U.S. EPA. (U.S. Environm ental Protection Agency). (1996a). Air quality criteria for ozone and related
photochemical oxidants. (EPA/600/P

- 93/004AF). Research Triangle Park, NC.

U.S. EPA. (U.S. Environmental Protection Agency). (1996b). Air quality criteria for ozone and related
photochemical oxidants, Vol. II of III. (EPA/600/P

- 93/004BF). Research Triangle Park, NC.

U.S. EPA. (U.S. Environmental Protection Agency). (2006b). Air quality criteria for ozone and related
photochemical oxidants. (EPA/600/R

- 05/004AF). Research Triangle Park, NC: U.S. Environmental
Protection Agency, Office of Rese arch and Development.
http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=149923

. U.S. EPA. (U.S. Environmental Protection Agency). (2008f). Notice of workshop and call for information on
integrated science assessment for ozone. Fed Reg 73: 56581

- 56583.

U.S. EPA. (U.S. Environmental Protection Agency). (2009c). Integrated review plan for the ozone National
Ambient Air Quality Standards review (external review draft). (EPA 452/D

- 09

- 001). Washington, DC.
http://www.epa.gov/ttnnaaqs/standards/ozone/data/externalreviewdraftO3IRP093009.pdf

. U.S. EPA. (U.S. Environmental Protection Agency). (2010e). Our nation's air: Status and trends through 2008.
(EPA

- 454/R

- 09

- 002). Research Triangle Park, NC.
http://www.epa.gov /airtrends/2010/report/fullreport.pdf

. Zhang, L; Jacob, DJ; Downey, NV; Wood, DA; Blewitt, D; Carouge, CC; Van donkelaar, A; Jones, DBA; Murray,
LT; Wang, Y. (In Press) Improved estimate of the policy

- relevant background ozone in the United States
using the GEOS

- Chem global model with 1/2° × 2/3° horizontal resolution over North America. Atmos

Environ. http://dx.doi.org/10.1016/j.atmosenv.2011.07.054

.