Integrated Review Plan for the 

Primary National Ambient Air 

Quality Standard for Sulfur 

Dioxide 

External Review Draft
EPA-452/P-14-005 

March 2014 

Integrated Review Plan for the 

Primary National Ambient Air Quality 

Standard for Sulfur Dioxide 

External Review Draft

U. S. Environmental Protection Agency 

National Center for Environmental Assessment 

Office of Research and Development 

and 

Office of Air Quality Planning and Standards 

Office of Air and Radiation 

Research Triangle Park, North Carolina 

March 2014
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DISCLAIMER 

This draft integrated review plan serves as a public information document and as a 

management tool for the U.S. Environmental Protection Agency's National Center for 

Environmental Assessment and the Office of Air Quality Planning and Standards in conducting 

the review of the national ambient air quality standard for sulfur oxides. The approach described 

in this draft plan may be modified for presentation in the final plan to reflect consultation with 

the Clean Air Scientific Advisory Committee and public comments. Subsequent modifications 

to the plan may result from information developed during this review, and in consideration of 

advice and comments received from the Clean Air Scientific Advisory Committee and the public 

during the course of the review. Mention of trade names or commercial products does not 

constitute endorsement or recommendation for use. 
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TABLE OF CONTENTS 

LIST OF FIGURES ........................................................................................................................ v

LIST OF TABLES ......................................................................................................................... vi

LIST OF ACRONYMS/ABBREVIATIONS ............................................................................... vii

1. INTRODUCTION .............................................................................................................. 1-1

1.1 LEGISLATIVE REQUIREMENTS ........................................................................ 1-1

1.2 OVERVIEW OF THE NAAQS REVIEW PROCESS ............................................ 1-3

1.3 HISTORY OF THE REVIEW OF AIR QUALITY CRITERIA FOR SULFUR 

OXIDES AND THE NAAQS FOR SULFUR DIOXIDE ..................................... 1-7

1.4 SCOPE OF THE CURRENT REVIEW ................................................................ 1-10

2. STATUS AND SCHEDULE .............................................................................................. 2-1

3. KEY POLICY-RELEVANT ISSUES ................................................................................ 3-1

3.1 CONSIDERATIONS AND CONCLUSIONS IN LAST REVIEW ........................ 3-1

3.1.1 Need for Revision ................................................................................ 3-2

3.1.2 Elements of a Revised Standard .......................................................... 3-5

3.1.3 Areas of Uncertainty .......................................................................... 3-10

3.2 GENERAL APPROACH FOR THE CURRENT REVIEW ................................. 3-11

4. SCIENCE ASSESSMENT ................................................................................................. 4-1

4.1 SCOPE OF THE ISA ............................................................................................... 4-1

4.2 ORGANIZATION OF THE ISA ............................................................................. 4-1

4.3 ASSESSMENT APPROACH .................................................................................. 4-2

4.3.1 Introduction .......................................................................................... 4-2

4.3.2 Literature Search and Selection of Relevant Studies ........................... 4-4

4.3.3 Evaluation of Individual Study Quality ............................................... 4-5

4.3.4 Integration of Evidence and Determination of Causality .................... 4-8

4.3.5 Quality Management ............................................................................ 4-9

4.4 SPECIFIC ISSUES TO BE ADDRESSED IN THE ISA ...................................... 4-10

4.5 SCIENTIFIC AND PUBLIC REVIEW ................................................................. 4-17

5. QUANTITATIVE RISK AND EXPOSURE ASSESSMENTS ......................................... 5-1

5.1 OVERVIEW OF RISK AND EXPOSURE ASSESSMENT FROM PRIOR 

REVIEW ................................................................................................................ 5-2

5.1.1 Key Observations .......................................................................................... 5-4

5.1.2 Key Uncertainties.......................................................................................... 5-6

5.2 CONSIDERATION OF QUANTITATIVE ASSESSMENTS FOR THIS REVIEW

 5-6

5.2.1 Ambient Air Quality Characterization ................................................. 5-7

5.2.2 Exposure Assessment........................................................................... 5-8

5.2.3 Risk Assessment .................................................................................. 5-9

5.2.4 Uncertainty and Variability ................................................................ 5-13

5.3 PUBLIC AND SCIENTIFIC REVIEW ................................................................. 5-13

6. AMBIENT AIR MONITORING ........................................................................................ 6-1

6.1 CONSIDERATION OF SAMPLING AND ANALYSIS METHODS ................... 6-1

6.2 CONSIDERATION OF AIR MONITORING NETWORK REQUIREMENTS .... 6-1

7. POLICY ASSESSMENT/RULEMAKING........................................................................ 7-1
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7.1 POLICY ASSESSMENT ........................................................................................ 7-1

7.2 RULEMAKING ...................................................................................................... 7-2

8. REFERENCES ................................................................................................................... 8-1

APPENDIX A ............................................................................................................................. A-1
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LIST OF FIGURES 

Figure 1-1 Overview of the NAAQS Review Process ............................................................. 1-4

Figure 3-1 Overview of General Approach for Review of Primary SO2 Standard ........... 3-13

Figure 4.1. General Process for Development of Integrated Science Assessments (ISAs) .. 4-3
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LIST OF TABLES 

Table 1-1. History of the primary national ambient air quality standard(s) for sulfur 

dioxide since 1971 ....................................................................................................... 1-8

Table 2-1. Anticipated schedule for the SO2 NAAQS Review .............................................. 2-2

Table 5-1. The numbers of SO2 monitors 2003 to 2012 ......................................................... 5-8

Table 5-2. Primary uncertainties associated with the exposure and risk assessments in the 

previous review and the potential use of new information for reducing these 

uncertainties ............................................................................................................. 5-10
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LIST OF ACRONYMS/ABBREVIATIONS

AMMS Air Monitoring and Methods Subcommittee 

AQCD Air Quality Criteria Document 

AQS EPA’s Air Quality System 

CAA Clean Air Act 

CASAC Clean Air Scientific Advisory Committee 

CBSA Consolidated Business Statistical Area 

CFR Code of Federal Regulations 

C-R Concentration-response 

ED Emergency department 

EPA Environmental Protection Agency 

FEM Federal Equivalent Method 

FEV1 Forced expiratory volume in one second, volume of air exhaled in first 

second of exhalation 

FR Federal Register 

FRM Federal Reference Method 

HA Hospital admissions 

IRP Integrated Review Plan 

ISA Integrated Science Assessment 

Km Kilometer 

MSA Metropolitan Statistical Area 

NAAQS National Ambient Air Quality Standards 

NCEA National Center for Environmental Assessment 

NO2 Nitrogen dioxide 

O3 Ozone 

OAQPS Office of Air Quality Planning and Standards 

OAR Office of Air and Radiation 

OMB Office of Management and Budget 

ORD Office of Research and Development 

PA Policy Assessment 

PM Particulate matter 

ppb Parts per billion 

ppm Parts per million 

PRB Policy-relevant background 

REA Risk and Exposure Assessment 

SES Socioeconomic status 

SLAMS State and local air monitoring stations 

SO2 Sulfur dioxide 
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1 1. INTRODUCTION 

2 The U.S. Environmental Protection Agency (EPA) is conducting a review of the primary 

3 (health-based) national ambient air quality standard (NAAQS) for sulfur oxides (SOX). This 

4 draft Integrated Review Plan (IRP) presents the planned approach for the review. This review 

5 will provide an integrative assessment of relevant scientific information for SOX and will focus 

on the basic elements that define the NAAQS: the indicator,1 averaging time,2 form,3 and level.4 6 

7 The EPA Administrator will consider these elements collectively in evaluating the protection to 

8 public health afforded by the primary standard(s). 

9 This document is organized into eight chapters. Chapter 1 presents the legislative 

10 requirements for the review of the NAAQS, background information on the review process, 

11 scope of the current review, and an overview of past reviews of the primary SO2 NAAQS. 

12 Chapter 2 presents the status and schedule for the current review. Chapter 3 summarizes the 

13 approach in the last review and presents a set of policy-relevant questions that will serve to focus 

14 the current review on the critical scientific and policy issues. Chapters 4 through 7 discuss the 

15 planned scope and organization of key assessment documents, the planned approaches for 

16 preparing these documents, specific ambient air quality monitoring considerations, as well as 

17 plans for scientific and public review of these documents. Complete reference citations are 

18 provided in chapter 8. 

19 1.1 LEGISLATIVE REQUIREMENTS 

20 Two sections of the Clean Air Act (CAA) govern the establishment and revision of the 

21 NAAQS. Section 108 (42 U.S.C. 7408) directs the Administrator to identify and list “air 

22 pollutants” that “in his judgment, may reasonably be anticipated to endanger public health and 

23 welfare” and whose “presence . . . in the ambient air results from numerous or diverse mobile or 

24 stationary sources” and to issue air quality criteria for those that are listed. Air quality criteria 

25 are intended to “accurately reflect the latest scientific knowledge useful in indicating the kind 

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

27 presence of [a] pollutant in ambient air . . . .” 

 

1 The “indicator” of a standard defines the chemical species or mixture that is measured in determining whether an 

area attains the standard. 

2

 The “averaging time” defines the time period over which ambient measurements are averaged (e.g., 1-hour, 8-hour, 

24-hour, annual). 

3

 The “form” of a standard defines the air quality statistic that is compared to the level of the standard in determining 

whether an area attains the standard. For example, the form of the current 1-hour SO2 standard is the three-year 

average of the 99th percentile of the annual distribution of 1-hour daily maximum SO2 concentrations. 4

 The “level” defines the allowable concentration of the criteria pollutant in the ambient air. 
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1 Section 109 (42 U.S.C. 7409) directs the Administrator to propose and promulgate 

“primary” and “secondary” NAAQS for pollutants for which air quality criteria are issued.5 2 

3 Section 109(b)(1) defines a primary standard as one “the attainment and maintenance of which in 

4 the judgment of the Administrator, based on such criteria and allowing an adequate margin of 

safety, are requisite to protect the public health.”6 5 A secondary standard, as defined in section 

6 109(b)(2), must “specify a level of air quality the attainment and maintenance of which, in the 

7 judgment of the Administrator, based on such criteria, is required to protect the public welfare 

8 from any known or anticipated adverse effects associated with the presence of [the] pollutant in 

the ambient air.”7 9 

10 The requirement that primary standards provide an adequate margin of safety was 

11 intended to address uncertainties associated with inconclusive scientific and technical 

12 information available at the time of standard setting. It was also intended to provide a reasonable 

13 degree of protection against hazards that research has not yet identified. See Lead Industries 

14 Association v. EPA, 647 F.2d 1130, 1154 (D.C. Cir 1980), cert. denied, 449 U.S. 1042 (1980); 

15 American Petroleum Institute v. Costle, 665 F.2d 1176, 1186 (D.C. Cir. 1981), cert. denied, 455 

16 U.S. 1034 (1982). Both kinds of uncertainties are components of the risk associated with 

17 pollution at levels below those at which human health effects can be said to occur with 

18 reasonable scientific certainty. Thus, in selecting primary standards that include an adequate 

19 margin of safety, the Administrator is seeking not only to prevent pollution levels that have been 

20 demonstrated to be harmful but also to prevent lower pollutant levels that may pose an 

21 unacceptable risk of harm, even if the risk is not precisely identified as to nature or degree. The 

22 CAA does not require the Administrator to establish a primary NAAQS at a zero-risk level or at 

23 background concentration levels, see Lead Industries v. EPA, 647 F.2d at 1156 n.51, Mississippi 

24 v. EPA, 723 F. 3d 246, 255, 262-63 (D.C. Cir. 2013), but rather at a level that reduces risk 

25 sufficiently so as to protect public health with an adequate margin of safety. 

26 In addressing the requirement for an adequate margin of safety, the EPA considers such 

27 factors as the nature and severity of the health effects involved, the size of the sensitive 

28 population(s), and the kind and degree of uncertainties. The selection of any particular approach 

29 to providing an adequate margin of safety is a policy choice left specifically to the 

 

5

 As discussed in section 1.4 below, this document describes the review of the primary SO2 standard. The 

secondary SO2 standard will be separately reviewed in conjunction with review of the secondary NO2 standard. 6

 The legislative history of section 109 indicates that a primary standard is to be set at “the maximum permissible 

ambient air level . . . which will protect the health of any [sensitive] group of the population,” and that for this 

purpose “reference should be made to a representative sample of persons comprising the sensitive group rather than 

to a single person in such a group” [S. Rep. No. 91-1196, 91st Cong., 2d Sess. 10 (1970)]. 

7

 Welfare effects as defined in section 302(h) [42 U.S.C. 7602(h)] include, but are not limited to, “effects on soils, 

water, crops, vegetation, man-made materials, animals, wildlife, weather, visibility and climate, damage to and 

deterioration of property, and hazards to transportation, as well as effects on economic values and on personal 

comfort and well-being.” 
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1 Administrator’s judgment. See Lead Industries Association v. EPA, supra, 647 F.2d at 1161-62; 

2 Mississippi v. EPA, 723 F. 3d at 265. 

3 In setting standards that are “requisite” to protect public health and welfare, as provided 

4 in section 109(b), the EPA’s task is to establish standards that are neither more nor less stringent 

5 than necessary for these purposes. In so doing, the EPA may not consider the costs of 

6 implementing the standards. See generally, Whitman v. American Trucking Associations, 531 

7 U.S. 457, 465-472, 475-76 (2001). Likewise, “[a]ttainability and technological feasibility are not 

8 relevant considerations in the promulgation of national ambient air quality standards.” American 

9 Petroleum Institute v. Costle, 665 F. 2d at 1185. 

10 Section 109(d)(1) requires that “not later than December 31, 1980, and at 5-year 

11 intervals thereafter, the Administrator shall complete a thorough review of the criteria 

12 published under section 108 and the national ambient air quality standards . . . and shall make 

13 such revisions in such criteria and standards and promulgate such new standards as may be 

14 appropriate . . . .” Section 109(d)(2) requires that an independent scientific review committee 

15 “shall complete a review of the criteria . . . and the national primary and secondary ambient air 

16 quality standards . . . and shall recommend to the Administrator any new . . . standards and 

17 revisions of existing criteria and standards as may be appropriate . . . .” Since the early 1980s, 

18 this independent review function has been performed by the Clean Air Scientific Advisory 

Committee (CASAC) of EPA’s Science Advisory Board. 8 19 

20 1.2 OVERVIEW OF THE NAAQS REVIEW PROCESS 

21 The current process for reviewing the NAAQS includes four major phases: (1) planning, 

22 (2) science assessment, (3) risk/exposure assessment, and (4) policy assessment and rulemaking. 

23 Figure 1-1 provides an overview of this process, and each phase is described in more detail 

below. 9 24 

 

8 Lists of CASAC members and of members of the CASAC Sulfur Oxides Primary NAAQS Review Panel are 

available at: http://yosemite.epa.gov/sab/sabproduct.nsf/WebCASAC/CommitteesandMembership?OpenDocument. 

9 The EPA maintains a website on which key documents developed for NAAQS reviews are made available 

(http://www.epa.gov/ttn/naaqs/). The EPA’s NAAQS review process has evolved over time. Information on the 

current process is available at: http://www.epa.gov/ttn/naaqs/review.html. As discussed in section 1.3 below, this 

process was generally followed in the primary SO2 NAAQS review completed in 2010 with the exception that there 

was not a separate Policy Assessment document issued; rather the Risk and Exposure Assessment (U.S. EPA 2009, ) 

included a policy assessment chapter (i.e., Chapter 10). 
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1 

2 Figure 1-1 Overview of the NAAQS Review Process
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1 The planning phase of the NAAQS review process begins with a science policy 

2 workshop, which is intended to identify issues and questions to frame the review. Drawing from 

3 the workshop discussions, a draft IRP is prepared jointly by EPA’s National Center for 

4 Environmental Assessment (NCEA), within the Office of Research and Development (ORD), 

5 and EPA’s Office of Air Quality Planning and Standards (OAQPS), within the Office of Air and 

6 Radiation (OAR). The draft IRP is made available for CASAC review and for public comment. 

7 The final IRP is prepared in consideration of CASAC and public comments. This document 

8 presents the current plan and specifies the schedule for the entire review, the process for 

9 conducting the review, and the key policy-relevant science issues that will guide the review. 

10 The second phase of the review, the science assessment, involves the preparation of an 

11 Integrated Science Assessment (ISA) and supplementary materials. The ISA, prepared by 

12 NCEA, provides a concise review, synthesis, and evaluation of the most policy-relevant science, 

13 including key science judgments that are important to the design and scope of exposure and risk 

14 assessments, as well as other aspects of the NAAQS review. The ISA and its supplementary 

15 materials provide a comprehensive assessment of the current scientific literature pertaining to 

16 known and anticipated effects on public health and welfare associated with the presence of the 

17 pollutant in the ambient air, emphasizing information that has become available since the last air 

18 quality criteria review in order to reflect the current state of knowledge. As such, the ISA forms 

19 the scientific foundation for each NAAQS review and is intended to provide information useful 

20 in forming judgments about air quality indicator(s), form(s), averaging time(s) and level(s) for 

21 the NAAQS. The current review process generally includes production of a first and second 

22 draft ISA, both of which undergo CASAC and public review prior to completion of the final 

23 ISA. Chapter 4 below provides a more detailed description of the planned scope, organization 

24 and assessment approach for the ISA and its supporting materials. 

25 In the third phase, the risk/exposure assessment phase, OAQPS staff considers 

26 information and conclusions presented in the ISA, with regard to support provided for the 

27 development of quantitative assessments of the risks and/or exposures for health and/or welfare 

28 effects. As an initial step, staff prepare a planning document (REA Planning Document) that 

29 considers the extent to which newly available scientific evidence and tools/methodologies 

30 warrant the conduct of quantitative risk and exposure assessments. As discussed in Chapter 5 

31 below, the REA Planning Document focuses on the degree to which important uncertainties in 

32 the last review may be addressed by new information available in this review. Specifically, the 

33 document considers the extent to which newly available data, methods, and tools might be 

34 expected to appreciably affect the assessment results, or address important gaps in our 

35 understanding of the exposures and risks associated with SO2. To the extent warranted, this 

36 document outlines a general plan, including scope and methods, for conducting assessments. The 
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1 REA Planning Document is generally prepared in conjunction with the first draft ISA and is 

2 presented for consultation with CASAC and for public comment. When an assessment is 

3 performed, one or more drafts of each risk and exposure assessment document (REA) undergoes 

4 CASAC and public review, with the initial draft REA generally being reviewed in conjunction 

5 with review of the second draft ISA, prior to completion of the final REA. The REA provides 

6 concise presentations of methods, key results, observations, and related uncertainties. Chapter 5 

7 below discusses consideration of potential quantitative human health-related assessments for this 

8 review. 

9 The review process ends with the policy assessment and rulemaking phase. The Policy 

10 Assessment (PA) is a document, prepared prior to issuance of proposed and final rules, that 

11 provides a transparent presentation of OAQPS staff analysis and presents staff conclusions 

12 regarding the adequacy of the current standards and, if revision is considered, what revisions 

13 may be appropriate. The PA integrates and interprets the information from the ISA and REA to 

14 frame policy options for consideration by the Administrator. Such an evaluation of policy 

15 implications is intended to help ‘‘bridge the gap’’ between the Agency’s scientific assessments, 

16 presented in the ISA and REA, and the judgments required of the EPA Administrator in 

17 determining whether it is appropriate to retain or revise the NAAQS. In so doing, the PA is also 

18 intended to facilitate CASAC’s advice to the Agency and recommendations to the Administrator 

19 on the adequacy of the existing standards or revisions that may be appropriate to consider, as 

20 provided for in the CAA. In evaluating the adequacy of the current standards and, as 

21 appropriate, a range of alternative standards, the PA considers the available scientific evidence 

22 and, as available, quantitative risk-based analyses, together with related limitations and 

23 uncertainties. The PA focuses on the information that is most pertinent to evaluating the basic 

24 elements of national ambient air quality standards: indicator, averaging time, form, and level. 

25 One or more drafts of a PA are released for CASAC review and public comment prior to 

26 completion of the final PA. 

27 Following issuance of the final PA and consideration of conclusions presented therein, 

28 the Agency develops and publishes a notice of proposed rulemaking that communicates the 

29 Administrator’s proposed decisions regarding the standards review. A draft notice undergoes 

interagency review involving other federal agencies prior to publication.10 30 Materials upon 

31 which this decision is based, including the documents described above, are made available to the 

 

10 Where implementation of the proposed decision would have an annual effect on the economy of $100 million or 

more, e.g., by necessitating the implementation of emissions controls, the EPA develops and releases a draft 

regulatory impact analysis (RIA) concurrent with the notice of proposed rulemaking. This activity is conducted 

under Executive Order 12866. The RIA is conducted completely independent of and, by statute, is not considered in 

decisions regarding the review of the NAAQS. 
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public in the regulatory docket for the review.11 1 A public comment period, during which public 

2 hearings are generally held, follows publication of the notice of proposed rulemaking. Taking 

into account comments received on the proposed rule,12 3 the Agency develops a final rule which 

4 undergoes interagency review prior to publication to complete the rulemaking process. Chapter 

5 7 discusses the development of the PA and the rulemaking steps for this review. 

6 

7 1.3 HISTORY OF THE REVIEW OF AIR QUALITY CRITERIA FOR 

8 SULFUR OXIDES AND THE NAAQS FOR SULFUR DIOXIDE 

9 The EPA completed the initial review of the air quality criteria for sulfur oxides in 1969 

10 (34 FR 1988). Based on this review, the EPA in initially promulgating NAAQS for sulfur oxides 

11 in 1971, established the indicator as SO2. The 1971 primary standards were set at 0.14 parts per 

12 million (ppm) averaged over a 24-hour period, not to be exceeded more than once per year, and 

0.030 ppm annual arithmetic mean.13 13 Since then, the Agency has completed multiple reviews of 

14 the air quality criteria and standards, as summarized in Table 1-1. 

15 

 

11 All documents in the docket are listed in the www.regulations.gov index. Publicly available docket materials are 

available either electronically at www.regulations.gov or in hard copy at the Air and Radiation Docket and 

Information Center. The docket ID number for this review is EPA-HQ-OAR-2013-0566. 

12 When issuing the final rulemaking, the Agency responds to all significant comments on the proposed rule. 

13 Note that 0.14 ppm is equivalent to 140 parts per billion (ppb) and 0.030 ppm is equivalent to 30 ppb. 
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1 Table 1-1. History of the primary national ambient air quality standard(s) for sulfur 

dioxide since 197114 2 

Final 

Rule/Decision Indicator Averaging Time Level Form

1971 

36 FR at 8186 

Apr 30, 1971 

SO2

24-hour and 

Annual Avg 

24-hour: 140 ppb 

Annual Avg: 30 

ppb15

24-hour std: one 

allowable exceedance 

Annual std: Annual 

arithmetic average 

1996 

61 FR at 25566 

May 22, 1996 

Both the 24-hour and annual average standards retained without revision 

2010 

75 FR at 35520 

June 22, 2010 

SO2 1-hour 75 ppb 

99th percentile, 

averaged over 3 

years16

24-hour and annual SO2 standards revoked. 

3 

4 In 1982, the EPA published the Air Quality Criteria for Particulate Matter and Sulfur 

5 Oxides (U.S. EPA 1982) along with an addendum of newly published controlled human 

6 exposure studies, which updated the scientific criteria upon which the initial standards were 

7 based (U.S. EPA 1982). In 1986, a second addendum was published presenting newly available 

8 evidence from epidemiologic and controlled human exposure studies (U.S. EPA 1986). In 1988, 

9 the EPA published a proposed decision not to revise the existing standards (53 FR 14926). 

10 However, the EPA specifically requested public comment on the alternative of revising the 

11 current standards and adding a new 1-hour primary standard of 0.4 ppm to protect against short12 term peak exposures. 

13 As a result of public comments on the 1988 proposal and other post-proposal 

14 developments, the EPA published a second proposal on November 15, 1994 (59 FR 58958). The 

15 1994 re-proposal was based in part on a supplement to the second addendum of the criteria 

16 document, which evaluated new findings on short-term SO2 exposures in asthmatics (U.S. EPA 

17 1994). As in the 1988 proposal, the EPA proposed to retain the existing 24-hour and annual 

18 standards. The EPA also solicited comment on three regulatory alternatives to further reduce the 

19 health risk posed by exposure to high 5-minute peaks of SO2 if additional protection were judged 

 

14 In 1971 (36 FR 8186), a 3-hour secondary standard was set at 500 ppb to provide protection against adverse 

welfare effects. 

15 The initial level of the 24-hr SO2 standard was 0.140 ppm which is equal to 140 ppb. The initial level of the 

annual SO2 standard was 0.03 ppm which is equal to 30 ppb. 16 The form of the 1-hour standard is the 3-year average of the 99th percentile of the yearly distribution of 1-hour 

daily maximum SO2 concentrations. 
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1 to be necessary. The three alternatives were: 1) Revising the existing primary SO2 NAAQS by 

2 adding a new 5-minute standard of 0.60 ppm SO2; 2) establishing a new regulatory program 

3 under section 303 of the Act to supplement protection provided by the existing NAAQS, with a 

4 trigger level of 0.60 ppm SO2, one expected exceedance; and 3) augmenting implementation of 

5 existing standards by focusing on those sources or source types likely to produce high 5-minute 

6 peak concentrations of SO2. 

7 In assessing the regulatory options mentioned above, the Administrator concluded that 

8 the likely frequency of 5-minute concentrations of concern should also be a consideration in 

9 assessing the overall public health risks. Based upon an exposure analysis conducted by the 

10 EPA, the Administrator concluded that exposure of asthmatics to SO2 at levels that can reliably 

11 elicit adverse health effects was likely to be a rare event when viewed in the context of the entire 

12 population of asthmatics. As a result, the Administrator judged that 5-minute peak SO2 levels 

13 did not pose a broad public health problem when viewed from a national perspective, and a 5-

14 minute standard was not promulgated. In addition, no other regulatory alternative was finalized 

15 and the 24-hour and annual average primary SO2 standards were retained in 1996 (61 FR 25566). 

16 The American Lung Association and the Environmental Defense Fund challenged EPA’s 

17 decision not to establish a 5-minute standard. On January 30, 1998, the Court of Appeals for the 

18 District of Columbia found that the EPA had failed to adequately explain its determination that 

19 no revision to the SO2 NAAQS was appropriate and remanded the decision back to EPA for 

20 further explanation. Specifically, the court required the EPA to provide additional rationale to 

21 support the Agency judgment that 5-minute peaks of SO2 do not pose a public health problem 

22 from a national perspective even though these peaks will likely cause adverse health impacts in a 

23 subset of asthmatics. In response, the EPA collected and analyzed additional air quality data 

24 focused on 5-minute concentrations of SO2 and used this information to inform the last review of 

25 the SO2 NAAQS. 

26 On June 22, 2010, the EPA revised the primary SO2 NAAQS to provide requisite 

27 protection of public health with an adequate margin of safety. Specifically, after concluding that 

28 the then-existing 24-hour and annual standards were inadequate to protect public health with an 

29 adequate margin of safety (see section 3.1.1), the EPA established a new 1-hour SO2 standard at 

a level of 75 ppb, based on the 3-year average of the annual 99th 30 percentile of 1-hour daily 

31 maximum concentrations (see section 3.1.2). This standard was promulgated to provide 

32 substantial protection against SO2-related health effects associated with short-term exposures 

33 ranging from 5-minutes to 24-hours. More specifically, EPA concluded that a 1-hour SO2 

34 standard at 75 ppb would provide substantial protection against the adverse respiratory effects 

35 (e.g., decrements in lung function and/or respiratory symptoms) reported in exercising asthmatics 

36 following 5-10 minute exposures in controlled human exposure studies, as well as the more 
Do Not Quote or Cite 1-10 March 2013 

1 serious health associations reported in epidemiologic studies of mostly 1- and 24-hours (e.g., 

2 respiratory-related emergency department visits and hospitalizations). In the last review, the 

3 EPA also revoked the then-existing 24-hour and annual primary standards because neither of 

4 these standards would likely provide additional public health protection given a 1-hour standard 

5 at 75 ppb (see section 3.1.2). The decision to set a 1-hour standard at 75 ppb to in part, provide 

6 substantial protection against 5- minute concentrations of SO2 resulting in adverse respiratory 

7 effects in exercising asthmatics, also satisfied the DC Circuit Court remand of 1996. 

8 As mentioned above, in the last review substantial weight was placed on preventing 

9 health effects associated with 5-minute peak SO2 concentrations. Thus, as part of the final 

10 rulemaking, the EPA for the first time required state reporting of either the highest 5-minute 

11 concentration for each hour of the day, or all twelve 5-minute concentrations for each hour of the 

12 day (see chapter 6). The rationale for this requirement was that this additional monitored data 

13 could then be used in future reviews to evaluate the extent to which the 1-hour SO2 NAAQS at 

14 75 ppb provides protection against 5-minute peaks of concern. 

15 After publication of the final rule, a number of industry groups and states filed petitions 

16 for review maintaining that the 1-hour SO2 NAAQS at 75 ppb was overly stringent or otherwise 

17 arbitrary. The D.C. Circuit rejected these challenges, upholding the standard in its entirety. 

18 National Environmental Development Association’s Clean Air Project v. EPA, 686 F. 3d 803 

19 (D.C. Cir. 2012). 

20 

21 1.4 SCOPE OF THE CURRENT REVIEW 

22 Sulfur oxides include all forms of oxidized sulfur compounds including the gases SO2

23 and SO3 as well as their gaseous and particulate reaction products (e.g., sulfates; see 34 FR 

24 1988). As in previous reviews of the SO2 NAAQS, this review will focus on effects associated 

25 with the gaseous species only. Effects associated with the particulate species (e.g., sulfate) are 

26 addressed in the review of the NAAQS for particulate matter (PM) (78 FR 30866, January 15, 

27 2013; U.S. EPA 2009). 

28 Consistent with the review completed in 2010, this review is focused on the primary SO2

29 standard and as such, will only consider relevant scientific information related to potential health 

30 effects associated with exposure to sulfur oxides. The EPA is separately reviewing the 

31 secondary SO2 standard in conjunction with a review of the secondary NO2 standard (78 FR 

53452, August 29, 2013).17 32 

 

17 Additional information on the ongoing review of the secondary NO2 and SO2 standards is available at: 

http://www.epa.gov/ttn/naaqs/standards/no2so2sec/index.html. 
Do Not Quote or Cite 2-1 March 2014 

2. STATUS AND SCHEDULE 

In May of 2013, the EPA announced the initiation of the current periodic review of the 

air quality criteria for SOx and the primary SO2 NAAQS, and also issued a call for information 

in the Federal Register (78 FR 27387). Also, as an initial step in the NAAQS review process 

described in Section 1.1 above, EPA invited a wide range of external and internal EPA experts, 

representing a variety of areas of expertise (e.g., epidemiology, human and animal toxicology, 

statistics, risk/exposure analysis, atmospheric science), to participate in a workshop to discuss 

the policy-relevant science to inform development of this plan. This workshop was held June 

12-13, 2013, in Research Triangle Park, NC (78 FR 27387). This workshop provided an 

opportunity for the participants to broadly discuss the key policy-relevant issues around which 

EPA would structure the SO2 NAAQS review and to discuss the most meaningful new science 

that would be available to inform our understanding of these issues. Based in part on the 

workshop discussions, the EPA developed this draft IRP outlining the schedule, the process, and 

the policy-relevant science issues identified as key to guiding the evaluation of the air quality 

criteria for sulfur oxides and the review of the primary SO2 NAAQS. 

Table 2-1 outlines the schedule under which the Agency is currently conducting this 

review. The scope of the review and the key documents to be prepared during the review are 

discussed throughout the rest of this document. 

 
Do Not Quote or Cite 2-2 March 2014 

Table 2-1. Anticipated schedule for the SO2 NAAQS Review 

Stage of Review Major Milestone Draft Target Date 

Integrated Plan (IRP) Literature Search Ongoing 

Call for Information May 10, 2013 

Workshop on science/policy issues June 12-13 2013 

Draft IRP March 2014 

CASAC/public review on draft IRP April 22, 2014 

Final IRP July 2014 

Integrated Science 

Assessment (ISA) 

First draft ISA October 2014 

CASAC/public review first draft ISA January 2015 

Second draft ISA July 2015 

CASAC/public review second draft ISA October 2015 

Final ISA January 2016 

Risk/Exposure 

Assessment (REA) 

REA Planning Document February 2015 

CASAC consultation/public review REA 

Planning Document 

If warranted: 

March 2015 

 First draft REA 18

 CASAC/public review of first draft REA 

 Second draft REA 

 CASAC/public review of second draft REA 

 Final REA 

Policy Assessment 

(PA)/Rulemaking 

First Draft PA September 2015 

CASAC review/public review first draft PA October 2015 

Second Draft PA (if warranted) June 2016 

CASAC/public review second draft PA July 201619

Final PA December 2016 

Notice of proposed rulemaking May 2017 

Notice of final rulemaking February 2018 

 

18 An updated REA may not be warranted for the reviews of the SO2 primary NAAQS 19 The anticipated schedule presented in Table 2-1 includes preparation of two draft PAs for CASAC and public 

review. In NAAQS reviews in which the newly available information calls into question the adequacy of the current 

standard(s), a second draft PA is typically prepared to include staff consideration of potential alternative standards. 

However, in NAAQS reviews where a new REA is not developed and where staff preliminarily conclude in a first 

draft PA that it is appropriate to consider retaining the current standards without revision, the EPA may decide that 

there is no new substantive information that we would intend to add that would provide a basis for preparing a 

second draft PA. If the Agency determines that a second draft PA is not warranted, CASAC and public comments 

on the first draft PA will be considered in preparing the final PA and the schedule for the review will be revised 

accordingly. 
Do Not Quote or Cite 3-1 March 2014 

1 3. KEY POLICY-RELEVANT ISSUES 

2 The overarching question in each NAAQS review is: 

3  Does the currently available scientific evidence and exposure/risk-based 

4 information support or call into question the adequacy of the protection 

5 afforded by the current standard(s)? 

6 As appropriate, a review also addresses a second overarching question: 

7  What alternative standard(s), if any, are supported by the currently available 

8 scientific evidence and exposure/risk-based information and are appropriate 

9 for consideration? 

10 To inform our consideration of these overarching questions in the current review, we have 

11 identified key policy-relevant issues to be considered. These key issues reflect aspects of the 

12 health effects evidence, air quality information, and exposure/risk information that, in our 

13 judgment, are likely to be particularly important to informing the Administrator’s decisions. 

14 They build upon the key issues that were important in previous reviews. 

15 Section 3.1 below describes the key considerations and conclusions from the last review 

16 with regard to the adequacy of the then-current primary SO2 standards (section 3.1.1), and with 

17 regard to the elements for a revised standard judged in that review to provide requisite public 

18 health protection (section 3.1.2). Section 3.2 summarizes our general approach for reviewing the 

19 primary SO2 standard in the current review and outlines the key policy-relevant issues. These 

20 issues are presented as a series of questions that will frame our approach to considering the 

21 extent to which the available evidence and information support retaining or revising the current 

22 primary standard for SO2. 

23 

24 3.1 CONSIDERATIONS AND CONCLUSIONS IN LAST REVIEW 

25 The last review of the primary NAAQS for SO2 was completed in 2010 (75 FR at 35520, 

26 June 22, 2010). In that review, the EPA considered key controlled human exposure studies from 

27 previous reviews as well as the significantly expanded body of health effects evidence that had 

emerged since the last review was completed in 1996. 20 28 In addition, EPA also considered 

29 exposure and risk estimates regarding potential respiratory effects in exercising asthmatics 

30 following 5-10 minute exposures to SO2, as well as CASAC advice and public comments. 

31 Taking all this information together, the EPA established a new short-term standard to provide 

 

20 Documents related to the SO2 NAAQS reviews completed in 2010 and 1996 are available at: 

http://www.epa.gov/ttn/naaqs/standards/so2/s_so2_index.html 
Do Not Quote or Cite 3-2 March 2014 

increased protection for asthmatics and other at-risk populations21 1 against an array of adverse 

2 respiratory effects that have been linked to short-term SO2 exposures in both controlled human 

3 exposure and epidemiologic studies (75 FR at 35525 to 35527 and U.S. EPA 2008, section 5.5). 

Specifically, the EPA established a short-term standard defined by the 3-year average of the 99th 4 

5 percentile of the yearly distribution of 1-hour daily maximum SO2 concentrations, with a level of 

6 75 ppb. In addition to setting a new short-term standard, the then-existing 24-hour and annual 

7 standards were revoked based largely on the recognition that a 1-hour standard set at 75 ppb 

8 would have the effect of generally maintaining 24-hour and annual SO2 concentrations well 

9 below the levels of those standards (75 FR at 35550). 

10 Key policy-relevant aspects of the Administrator’s decisions with regard to the need to 

11 revise the primary SO2 NAAQS, and with regard to the elements of the revised standard, are 

12 described below in sections 3.1.1 and 3.1.2, respectively. Areas of uncertainty identified in the 

13 last review are noted in section 3.1.3. 

14 

15 3.1.1 Need for Revision 

16 The Administrator concluded in the last review that the then-existing 24-hour and annual 

17 SO2 standards were not adequate to protect public health, including the health of at-risk 

18 populations, from the effects associated with short-term exposures to SO2 (75 FR at 35520, June 

19 22, 2010). As described below, this conclusion was based on the extensive body of health 

20 evidence assessed in the 2008 ISA (U.S. EPA 2008), including the assessment of the policyrelevant aspects of that evidence, 22 21 quantitative exposure and risk analyses presented in the 2009 

22 REA (U.S. EPA 2009), public comments, and the advice and recommendations of CASAC 

23 (Samet, 2009). 

24 As an initial consideration in reaching this conclusion, the Administrator noted the ISA 

25 judgement that the findings of controlled human exposure, epidemiologic, and animal 

26 toxicological studies collectively provided evidence “sufficient to infer a causal relationship”

27 between short-term SO2 exposures ranging from 5-minutes to 24-hours and respiratory morbidity 

28 (75 FR at 35535). The ISA described the ‘‘definitive evidence’’ for this conclusion as being the 

29 results of 5–10 minute controlled human exposure studies demonstrating decrements in lung 

 

21 As used here and similarly throughout this document, the term population refers to persons having a quality or 

characteristic in common, such as a specific pre-existing illness or a specific age or lifestage. A lifestage refers to a 

distinguishable time frame in an individual’s life characterized by unique and relatively stable behavioral and/or 

physiological characteristics that are associated with development and growth. Identifying at-risk populations 

includes consideration of intrinsic (e.g., genetic or developmental aspects) or acquired (e.g., disease or smoking 

status) factors that increase the risk of health effects occurring with exposure to sulfur oxides as well as extrinsic, 

nonbiological factors such as those related to socioeconomic status, reduced access to health care, or exposure. 22 As noted in section 1.3 above, due to changes in the NAAQS process, the last review of the SO2 NAAQS did not 

include a separate Policy Assessment. Rather, the REA for that review included a Policy Assessment chapter. 
Do Not Quote or Cite 3-3 March 2014 

1 function and/or respiratory symptoms in exercising asthmatics (U.S. EPA 2008, section 5.2). In 

2 brief, the ISA examined numerous controlled human exposure studies and found that moderate 

3 or greater decrements in lung function (i.e., ≥ 15% decline in Forced Expiratory Volume (FEV1) 

4 and/or ≥ 100% increase in specific airway resistance (sRaw)) occurred in some exercising 

5 asthmatics exposed to SO2 concentrations as low as 200–300 ppb for 5–10 minutes. The ISA also 

6 found that among asthmatics, both the percentage of individuals affected, and the severity of the 

7 response increased with increasing SO2 concentrations. That is, at 5–10 minute concentrations 

8 ranging from 200–300 ppb, the lowest levels tested in free breathing chamber studies, 

9 approximately 5–30% percent of exercising asthmatics experienced moderate or greater 

10 decrements in lung function (U.S. EPA 2008, Table 3–1). At concentrations of 400–600 ppb, 

11 moderate or greater decrements in lung function occurred in approximately 20– 60% of 

12 exercising asthmatics, and compared to exposures at 200–300 ppb, a larger percentage of 

13 asthmatics experienced severe decrements in lung function (i.e., ≥ 20% decrease in FEV1 and/or 

14 ≥ 200% increase in sRaw; U.S. EPA 2008, Table 3–1). Moreover, at SO2 concentrations ≥ 400 

15 ppb, moderate or greater decrements in lung function were often statistically significant at the 

16 group mean level and were frequently accompanied by respiratory symptoms (U.S. EPA 2008, 

17 Table 3–1). 

18 In considering the controlled human exposure studies with respect to adequacy of the 

19 then-current standards, the Administrator first judged that 5–10 minute SO2 exposures ≥ 400 ppb 

20 and ≥ 200 ppb can result in adverse health effects in exercising asthmatics (75 FR at 35536). 

21 This judgment was based on ATS guidelines, explicit CASAC consensus written advice, as well 

22 as recommendations and judgments made by EPA in previous NAAQS reviews (see 75 FR at 

23 35526 and 75 FR at 35536). The Administrator therefore particularly noted analyses in the REA 

24 that utilized benchmark concentrations derived from the controlled human exposure evidence. In 

25 the REA, 5-minute benchmark concentrations ranged from 100 ppb to 400 ppb (see below, 

26 section 5.1), with 5-minute benchmark concentrations of 200 ppb and 400 ppb noted by the 

27 Administrator as being particularly important. These benchmark levels were highlighted because 

28 in free-breathing controlled human exposure studies: (1) 400 ppb represented the lowest 

29 concentration at which moderate or greater lung function decrements occurred which were often 

30 statistically significant at the group mean level and were frequently accompanied by respiratory 

31 symptoms; and (2) 200 ppb was the lowest level at which moderate or greater decrements in lung 

function were found in some individuals.23 32 

33 Given the emphasis on the 200 ppb and 400 ppb benchmarks, the Administrator 

34 particularly noted the modeled exposure analysis results for the St. Louis case study presented in 

 

23 200 ppb was also the lowest level tested in free-breathing controlled human exposure studies. 
Do Not Quote or Cite 3-4 March 2014 

1 the REA (see below, section 5.1). This analysis estimated that given air quality simulated to just 

2 meet the then-existing SO2 NAAQS, substantial percentages of asthmatic children at moderate or 

3 greater exertion would be exposed, at least once annually, to air quality exceeding the 200 ppb 

4 and 400 ppb 5-minute benchmarks (75 FR at 35536). The Administrator judged these 5-minute 

5 exposures to be significant from a public health perspective due to their estimated frequency: 

6 approximately 24% of asthmatic children at moderate or greater exertion in St. Louis were 

7 estimated to be exposed at least once per year to air quality exceeding the 5- minute 400 ppb 

8 benchmark. Additionally, approximately 73% of asthmatic children in St. Louis at moderate or 

9 greater exertion were estimated to be exposed at least once per year to air quality exceeding the 

10 5-minute 200 ppb benchmark (75 FR at 35536). 

11 With respect to the epidemiologic evidence, the ISA characterized epidemiologic studies 

12 of respiratory symptoms, emergency department visits and hospital admissions as providing 

13 “supporting evidence” for the causal relationship between short-term exposure to SO2 and 

14 respiratory morbidity. The ISA found that numerous epidemiologic studies reported positive 

15 associations between ambient SO2 concentrations and respiratory symptoms in children, as well 

16 as emergency department visits and hospitalizations for all respiratory causes and asthma across 

17 multiple age groups. The ISA concluded that these epidemiologic studies were consistent and 

18 coherent. This evidence was consistent in that associations were reported in studies conducted in 

19 numerous locations and with a variety of methodological approaches (U.S. EPA 2008, section 

20 5.2). It was coherent in that respiratory symptom results from epidemiologic studies of short21 term (predominantly 1-hour daily maximum or 24-hour average) SO2 concentrations were 

22 generally in agreement with respiratory symptom results from controlled human exposure studies 

23 of 5–10 minutes. Moreover, while recognizing the uncertainties associated with separating the 

24 effects of SO2 from those of co-occurring pollutants, the ISA concluded that ‘‘the limited 

25 available evidence indicates that the effect of SO2 on respiratory health outcomes appears to be 

26 generally robust and independent of the effects of gaseous co-pollutants, including NO2 and O3, 

27 as well as particulate copollutants, particularly PM2.5’’ (U.S. EPA 2008, section 5.3). 

28 In considering the epidemiologic evidence, the Administrator acknowledged uncertainties 

29 with these studies (e.g., potential confounding by co-pollutants), but agreed with judgments in 

30 the ISA that the epidemiologic evidence, supported by the controlled human exposure evidence, 

31 generally indicated that the effects seen in these studies were attributable to exposure to SO2, 

32 rather than co-pollutants. With respect to the adequacy of the SO2 NAAQS, the Administrator 

33 noted that many of these epidemiologic studies reported associations between short-term (mostly 

34 1-hour daily maximum and 24-hour average) SO2 concentrations and respiratory symptoms, 

35 emergency department visits, and hospital admissions in locations meeting the then-existing 24-
Do Not Quote or Cite 3-5 March 2014 

1 hour and annual standards (75 FR at 35535), thereby further indicating that the these standards 

2 were not adequately protecting public health. 

3 The Administrator also agreed with specific CASAC advice when reaching the decision 

4 that the then-existing standards were not adequate to protect public health with an adequate 

5 margin of safety. Specifically, CASAC advised that: ‘‘the current 24-hour and annual standards 

6 are not adequate to protect public health, especially in relation to short-term exposures to SO2

7 (5–10 minutes) by exercising asthmatics’’ (Samet, 2009, p. 15). 

8 Based on the considerations summarized above, the Administrator concluded that the 

9 then-existing 24-hour and annual primary SO2 NAAQS were not adequate to protect public 

10 health with an adequate margin of safety and that these standards should be revised in order to 

11 provide increased public health protection against respiratory effects associated with short-term 

12 exposures, particularly for susceptible populations such as asthmatics and children. Upon 

13 consideration of approaches to revising these standards, the Administrator concluded that it was 

14 appropriate to set a new short-term standard, as described below. 

15 3.1.2 Elements of a Revised Standard 

16 When considering alternative standards to provide requisite public health protection, the 

17 Administrator concluded it was appropriate to set a new 1-hour SO2 standard at a level of 75 ppb, 

based on the 3-year average of the 99th 18 percentile of the yearly distribution of 1-hour daily 

19 maximum concentrations. The rationale and approach for setting the 1-hour standard is 

20 presented below in terms of the individual elements of a NAAQS: indicator, averaging time, 

21 form, and level. Notably, given a new 1-hour standard at 75 ppb, the previous 24-hour and 

22 annual standards were revoked because neither of these standards was likely to provide 

23 additional public health protection (74 FR at 35550). 

24 Indicator 

25 In previous reviews, the EPA focused on SO2 as the most appropriate indicator for sulfur 

26 oxides because the available scientific information regarding health effects was overwhelmingly 

27 indexed by SO2. In the most recent review, this continued to be the case. Controlled human 

28 exposure studies and animal toxicological studies provided specific evidence for health effects 

29 following exposures to SO2. In addition, epidemiologic studies typically reported effects 

30 associated with SO2 concentrations. Thus, based on the information available in the last review 

31 and consistent with the views of CASAC that: ‘‘for indicator, SO2 is clearly the preferred 

32 choice’’ (Samet 2009, p. 14), the Administrator concluded it was appropriate to continue to use 

33 SO2 as the indicator for a standard that was intended to address effects associated with exposure 

34 to SO2, alone or in combination with other gaseous sulfur oxides (75 FR at 35536). In so doing, 

35 the EPA recognized that measures leading to reductions in population exposures to SO2 will also 

36 likely reduce exposures to other sulfur oxides (75 FR at 35536).
Do Not Quote or Cite 3-6 March 2014 

1 Averaging Time 

2 When considering the level of support available for specific averaging times, the 

3 Administrator first considered the strength of evidence from controlled human exposure and 

4 epidemiologic studies. As noted above (see section 3.1.1), controlled human exposure studies 

5 exposed exercising asthmatics to SO2 for 5 -10 minutes and consistently found decrements in 

6 lung function and/or respiratory symptoms. Importantly, the ISA described the controlled human 

7 exposure studies as being the “definitive evidence” for its conclusion that there existed a causal 

8 relationship between short-term (5-minutes to 24-hours) SO2 exposure and respiratory morbidity 

9 (U.S. EPA 2008, section 5.2). Supporting the controlled human exposure evidence were 

10 epidemiologic studies describing positive associations between short-term (e.g., 1-hour daily 

11 maximum and 24-hour average) SO2 levels and respiratory symptoms as well as hospital 

12 admissions and emergency department visits for all respiratory causes and asthma (U.S. EPA 

13 2008, Tables 5.4 and 5.5). Taken together, it was judged that controlled human exposure studies 

14 provided support for an averaging time that protected against 5-10 minute peak exposures, while 

15 epidemiologic evidence provided support for an averaging time that protected against both 1-

hour and 24-hour exposures (U.S. EPA 2009, section 10.5.2.1).24 16 

17 In further considering an appropriate averaging time, the Administrator took into account 

18 air quality analyses from the REA examining the potential for 24-hour and 1-hour averaging 

19 times to protect against 5-minute peak concentrations. Results of these analyses suggested that a 

20 standard based on 24-hour average SO2 concentrations would not likely be an effective or 

21 efficient approach for addressing 5-minute peak SO2 concentrations. That is, using a 24-hour 

22 average standard to address 5-minute peaks would likely result in over-controlling in some areas, 

23 while under-controlling in others (U.S. EPA 2009, section 10.5.2.2). In contrast, these analyses 

24 suggested that a standard with a 1-hour averaging time would be more efficient and effective at 

25 limiting 5-minute peaks of SO2 (U.S. EPA 2009, section 10.5.2.2). In additional air quality 

26 analyses, the REA suggested that a 1-hour standard (given an appropriate form and level) could 

likely provide protection against 99th percentile 1-hour daily maximum and 99th 27 percentile 24-

28 hour average SO2 concentrations found in locations where emergency department visit and 

29 hospital admission studies using multi-pollutant models with PM reported statistically significant 

associations with ambient SO2 (75 FR at 35539 and U.S. EPA 2009, section 10.5.2.2). 25 30 

31 Considering this information, the Administrator concluded that a 1-hour standard (given an 

 

24 The ISA did note that effects observed in epidemiologic studies also may have been due, at least in part, and 

especially in 24-hour epidemiologic studies, to shorter-term peaks of SO2 (see U.S. EPA 2008, section 5.2). More 

specifically, the ISA noted “that it is possible that these associations are determined in large part by peak exposures 

within a 24-hour period” (U.S. EPA 2008, section 5.2). 

25 Since SO2 is a pre-cursor to PM (e.g., sulfates), there was special consideration given to epidemiologic studies that 

used multipollutant models to separate the estimated SO2 associations from that of PM. 
Do Not Quote or Cite 3-7 March 2014 

1 appropriate form and level) was an appropriate means of controlling short-term exposures to SO2

2 ranging from 5-minutes to 24-hours (74 FR at 35539). 

3 The Administrator further noted that establishing a 1-hour averaging time was in 

4 agreement with CASAC recommendations (74 FR at 35539). That is, CASAC stated that they 

5 were ‘‘in agreement with having a short-term standard and finds that the REA supports a one6 hour standard as protective of public health’’ (Samet 2009, p. 1). CASAC also stated that a 

7 ‘‘one-hour standard is the preferred averaging time’’ (Samet 2009, p.15). 

8 Based solely on the controlled human exposure evidence, the Administrator also 

9 considered a 5-minute averaging time in the last review. However, such an approach was not 

10 favored. With respect to a 5-minute standard, there were concerns about standard stability. 

11 Specific concerns related to the number of monitors needed and the placement of such monitors 

12 given the temporal and spatial heterogeneity of 5-minute SO2 concentrations (74 FR at 35539). 

13 However, as noted above, the Administrator judged that a 1-hour averaging time, given an 

14 appropriate form and level, could adequately limit 5-minute SO2 exposures and provide a more 

15 stable regulatory target than setting a 5-minute standard. Consequently, the Administrator judged 

16 that a 5-minute averaging time was not the preferred approach to provide adequate public health 

17 protection (74 FR at 35539). 

18 Form 

19 The “form” of a standard defines the air quality statistic that is to be compared to the 

20 level of the standard in determining whether an area attains the NAAQS. In the last review, 

21 controlled human exposure evidence presented in the ISA indicated that the percentage of 

22 asthmatics affected and the severity of the response increased with increasing SO2

23 concentrations. Thus, a concentration-based form averaged over three years was judged by the 

24 Administrator to be most appropriate (74 FR at 35541). This was because compared to an 

25 exceedance-based form, a concentration-based form averaged over three years would give more 

26 weight to years when 1-hour SO2 concentrations are well above the level of the standard, than to 

27 years when 1- hour SO2 concentrations are just above the level of the standard. The 

28 Administrator also noted that a concentration-based form averaged over 3 years would likely be 

29 appreciably more stable than a no exceedance-based form (75 FR at 35541). Establishing a 

30 concentration-based form was also in agreement with specific CASAC advice stating that ‘‘there 

31 is adequate information to justify the use of a concentration-based form averaged over 3 years’’ 

32 (Samet 2009, p. 16) 

33 In selecting a specific concentration-based form, the Administrator considered health 

34 evidence from the ISA as well as air quality and exposure information from the REA. In the ISA, 

35 it was noted that a few epidemiologic studies reported an increase in SO2-related respiratory 

health effects at the upper end of the distribution of ambient SO2 concentrations (i.e., above 90th 36 
Do Not Quote or Cite 3-8 March 2014 

1 percentile SO2 concentrations; see U.S. EPA 2008, section 5.3). In the REA, air quality and 

exposure analyses suggested that a 99th 2 percentile form was likely to be appreciably more 

effective at limiting 5-minute peak exposures of concern than a 98th 3 percentile form (at a given 

4 standard level; U.S. EPA 2009, section 10.5.3, and U.S. EPA 2009, Figures 7–27 and 7–28). 

Taken together, the Administrator concluded that a 99th 5 percentile form (at an appropriate level) 

6 would limit both the upper end of the distribution of ambient SO2 concentrations reported in 

7 some epidemiologic studies to be associated with increased risk of SO2-related respiratory 

8 morbidity effects (e.g., emergency department visits), as well as 5-minute peak SO2

9 concentrations resulting in decrements in lung function and/or respiratory symptoms in 

10 controlled human exposure studies (75 FR at 35541). 

11 Level 

12 Controlled human exposure evidence was described in the ISA as providing the definitive 

13 evidence for a causal association between short-term exposure to SO2 and respiratory morbidity. 

14 The Administrator therefore placed considerable emphasis on these studies when selecting the 

15 level of a new 1-hour standard. In particular, the Administrator wanted the level of a 1-hour 

16 standard to provide substantial protection against the 200 ppb and 400 ppb 5-minute benchmarks 

17 identified from these studies. As noted above (see section 3.1.1), these benchmark levels were 

18 highlighted because in free-breathing controlled human exposure studies of exercising 

19 asthmatics: (1) 400 ppb represented the lowest concentration where moderate or greater lung 

20 function decrements occurred which were often statistically significant at the group mean level 

21 and were frequently accompanied by respiratory symptoms; and (2) 200 ppb was the lowest level 

at which moderate or greater decrements in lung function were found in some asthmatics.26 22 

23 Analyses in the REA described the varying degrees of protection different 1-hour 

24 standard levels could provide against 5-minute benchmark concentrations of 200 ppb and 400 

25 ppb (see below section 5.1). Considering these analyses, the Administrator judged that a 1-hour 

26 standard level of 100 ppb would appropriately limit the occurrence of 5-minute benchmark 

27 concentrations ≥ 200 or 400 ppb (74 FR at 35547). That is, the St. Louis exposure simulation 

28 estimated that a 1-hour standard at 100 ppb would likely protect > 99% of asthmatic children in 

29 that city at moderate or greater exertion from experiencing at least one 5-minute exposure ≥ 400 

30 ppb per year, and approximately 97% of those asthmatic children at moderate or greater exertion 

31 from experiencing at least one exposure ≥ 200 ppb per year (74 FR at 35547). Moreover, the 

32 40-county air quality analysis from the REA (see below section 5.1) estimated that a 100 ppb 1-

33 hour standard would allow at most 2 days per year on average in any county when estimated 5-

34 minute daily maximum SO2 concentrations exceed the 400 ppb benchmark, and at most 13 days 

 

26 As noted in section 3.1.1, 200 ppb was also the lowest level tested in free-breathing controlled human exposure 

studies. 
Do Not Quote or Cite 3-9 March 2014 

1 per year on average when 5-minute daily maximum SO2 concentrations exceed the 200 ppb 

benchmark27 2 (74 FR at 35546). Furthermore, given a simulated 1-hour 100 ppb standard level, 

3 most of the counties in that air quality analysis were estimated to experience 0 days per year on 

4 average when 5-minute daily maximum SO2 concentrations exceed the 400 ppb benchmark and 

5 ≤ 3 days per year on average when 5-minute daily maximum SO2 concentrations were estimated 

6 to exceed the 200 ppb benchmark (74 FR at 35546). 

7 In considering the epidemiologic evidence with respect to level, the Administrator noted 

8 that there were more than 50 peer-reviewed epidemiologic studies published worldwide 

9 evaluating SO2 since the prior review (75 FR at 35547). The Administrator also noted that these 

10 studies generally reported positive, although not always statistically significant associations 

11 between more serious health outcomes (i.e. respiratory-related emergency department visits and 

12 hospitalizations) and ambient SO2 concentrations (75 FR at 35547). She further agreed with the 

13 ISA finding that the controlled human exposure evidence lends biological plausibility to the 

14 effects reported in epidemiologic studies (75 FR at 35547), and that when evaluated as a whole, 

15 the results of epidemiologic studies were generally independent of the effects of gaseous and 

16 particulate co-pollutants (74 FR at 35544 and 75 FR 35547). Taken together, the Administrator 

17 judged it appropriate to place emphasis on the epidemiologic evidence when further considering 

18 the appropriate level of a new 1-hour standard. 

19 In considering the epidemiologic evidence with respect to level, the Administrator placed 

20 primary emphasis on ten U.S. epidemiologic studies (some conducted in multiple locations) 

21 reporting mostly positive and sometimes statistically significant associations between ambient 

22 SO2 concentrations and emergency department visit and hospital admissions in locations where 

99th 23 percentile 1-hour daily maximum SO2 levels ranged from approximately 50–460 ppb (74 FR 

24 at 35547). The Administrator further noted that within this broader range of SO2 concentrations 

there was a cluster of three epidemiologic studies between 78–150 ppb (for the 99th 25 percentile of 

26 the 1-hour daily maximum SO2 concentrations) where the SO2 effect estimate remained positive 

27 and statistically significant in multipollutant models with PM (NYDOH (2006), Ito et al., (2007), 

28 and Schwartz et al., (1995)). The Administrator judged these three studies were of particular 

29 relevance because they supported both the conclusion that SO2 effects were generally 

30 independent of PM and that these associations occurred in cities with 1-hour daily maximum, 

99th 31 percentile concentrations in the range of 78–150 ppb (74 FR at 35547). 

32 Weighing all of the evidence presented above, the Administrator concluded that the 

epidemiologic studies provided strong support for setting a standard that limited the 99th 33 

 

27 The REA considered 5-minute air quality data reported from the existing network of ambient monitors. However, 

since the number and geographic scope of monitors reporting 5-minute SO2 concentrations was very limited, the 

REA used statistically estimated 5-minute concentrations derived from measured 1-hour SO2 concentrations in the 

40 county air quality analysis (see below, section 5.1). 
Do Not Quote or Cite 3-10 March 2014 

1 percentile of the distribution of 1-hour daily maximum SO2 concentrations to 75 ppb. This 

2 judgment took into account the strong determinations in the ISA, based on a much broader body 

3 of evidence, that there is a causal relationship between exposure to SO2 and the types of 

4 respiratory morbidity effects reported in these studies (74 FR at 35548). This judgement also 

5 considered that a standard level of 75 ppb was consistent with the range of levels recommended 

6 by CASAC (75 FR at 35548). Finally, the Administrator acknowledged that there were some 

7 epidemiologic studies suggesting effects due to SO2 at concentrations as low as 50 ppb, but did 

8 not find that evidence strong enough to warrant a standard at that level or below (74 FR at 

9 35548). 

10 Revoking the Then-Existing 24-hour and Annual Standards 

11 In addition to setting a new 1-hour standard at 75 ppb, the then-current 24-hour and 

12 annual standards were revoked in the last review based largely on the recognition that a 1-hour 

13 standard set at 75 ppb would have the effect of generally maintaining 24-hour and annual SO2

14 concentrations well below the levels of those standards (75 FR at 35550). In addition, the annual 

15 standard was also revoked because of the lack of evidence supporting a relationship between 

16 long-term SO2 exposures and adverse health effects. That is, the ISA judged the health evidence 

17 linking long-term SO2 exposure to adverse health effects to be “inadequate” to infer the presence 

18 or absence of a causal relationship (75 FR at 35550 and U.S EPA 2008, section 5.5). 

19 3.1.3 Areas of Uncertainty 

20 While the available scientific information informing the review completed in 2010 was 

21 stronger and more consistent than in previous reviews and provided a strong basis for decisions 

22 made in that review, the Agency recognized that important uncertainties and limitations remain 

23 in our understanding of several policy-relevant issues. These uncertainties were generally 

24 related to: (1) statistical relationships between 5-minute concentrations and longer averaging 

25 times (e.g., 1-hour, 3-hour, 24-hour), including the extent to which these longer averaging times 

26 can limit 5-minute concentrations of concern (i.e., 5-minute benchmarks) identified from 

27 controlled human exposure studies; (2) understanding the role of SO2 within the complex 

28 ambient mixture of co-occurring pollutants (e.g., PM2.5, ozone, NO2); (3) understanding the 

29 range of ambient concentrations in which we have confidence that the health effects observed in 

30 epidemiologic studies are attributable to SO2; (4) the extent to which monitored ambient SO2

31 concentrations used in epidemiologic studies reflect exposures in study populations and; (5) 

32 characterization of SO2 exposures and risk including alternative approaches for estimating risks 

33 associated with air quality simulated to just meet current or alternative standards. 

34 
Do Not Quote or Cite 3-11 March 2014 

1 3.2 GENERAL APPROACH FOR THE CURRENT REVIEW 

2 The approach for this review builds on the substantial body of work done during the 

3 course of the last review, and will take into account the more recent scientific information and air 

4 quality data now available to inform our understanding of the key policy-relevant issues. The 

5 approach described below is most fundamentally based on using the EPA’s assessment of the 

6 current scientific evidence and associated quantitative analyses to inform the Administrator’s 

7 judgments regarding primary standards for sulfur oxides that are requisite to protect public health 

8 with an adequate margin of safety. This approach will involve translating scientific and technical 

9 information into the basis for addressing a series of key policy-relevant questions using both 

evidence- and exposure/risk-based considerations.28 10 

11 Figure 3-1 summarizes the general approach, including consideration of the policy12 relevant questions which will frame the current review. The ISA, REA (if warranted), and PA 

13 developed in this new review will provide the basis for addressing the key policy-relevant 

14 questions and will inform the Administrator’s judgment as to the adequacy of the current primary 

15 SO2 standard and decisions as to whether to retain or revise this standard. This approach 

16 recognizes that the available health effects evidence generally reflects a continuum, consisting of 

17 ambient concentrations at which scientists generally agree that health effects are likely to occur, 

18 through lower concentrations at which the likelihood and magnitude of the response become 

19 increasingly uncertain. Furthermore, this approach is consistent with the requirements of the 

20 NAAQS provisions of the CAA and with how the EPA and the courts have historically 

21 interpreted the CAA. As discussed in section 1.1 above, these provisions require the 

22 Administrator to establish primary standards that, in the Administrator’s judgment, are requisite 

23 to protect public health with an adequate margin of safety. In so doing, the Administrator seeks 

24 to establish standards that are neither more nor less stringent than necessary for this purpose. 

25 The CAA does not require that primary standards be set at a zero-risk level, but rather at a level 

26 that avoids unacceptable risks to public health. The four basic elements of the NAAQS (i.e., 

27 indicator, averaging time, form, and level) will be considered collectively in evaluating the 

28 health protection afforded by the current standard or any alternative standards considered. 

29 We note that the final decision on the adequacy of the current standard and, if 

30 appropriate, potential alternative standards, is largely a public health policy judgment to be made 

31 by the Administrator. The Administrator’s final decision must draw upon scientific information 

32 and analyses about health effects, population exposure and risks, as well as judgments about how 

33 to consider the range and magnitude of uncertainties that are inherent in the scientific evidence 

 

28 Evidence-based considerations include those related to the health effects evidence assessed and characterized in 

the ISA. Exposure/risk-based considerations draw from the results of the quantitative analyses. 
Do Not Quote or Cite 3-12 March 2014 

1 and analyses. As in the previous review as well as other recent NAAQS reviews, the EPA will 

2 consider the implications of placing more or less weight or emphasis on different aspects of the 

3 scientific evidence and exposure/risk-based information to inform the public health policy 

4 judgments that the Administrator will make in reaching final decisions on whether to retain or 

5 revise the current standard in this review. 

6 
Do Not Quote or Cite 3-13 March 2014 

1 

2 Figure 3-1 Overview of General Approach for Review of Primary SO2 Standard 

3 

4 



related uncertainties

question prior conclusions?



question any of the basic elements of the

standard?

hour standard and

minute peaks/24-hour average concentrations?

Importance of remaining risks from public 

Adequacy of the Current 1- Hour SO2 Standard?

Evidence-based Considerations

Does currently available evidence and

strengthen or call into

 Evidence of health effects not

previously identified?

Evidence of effects at lower

concentrations than previously observed or

in areas that would have likely met current 

standard?

Expanded understanding of at-risk

populations and lifestages?

Does newly available information call into 

Risk/Exposure -based Considerations

 Nature, magnitude, and uncertainties of

estimated exposures and risks remaining 

upon just meeting the current 1-hour

standard?

 Relationship between 1 - 5-



health perspective?

Uncertainties in the exposure and risk

estimates?

Consideration of Potential Alternative Standard(s)

Elements of Potential Alternative Standard(s)

 Indicator

 Averaging times

Forms

Levels

Consider

retaining

current 1-

hour SO2

standard

YES

Does information NO

call into question

adequacy of current

1-hour SO2

standard?

Potential alternative standard(s) for consideration
Do Not Quote or Cite 3-14 March 2014 

1 The initial overarching question in reviewing the adequacy of the current primary SO2

2 NAAQS is whether the available body of scientific evidence, assessed in the ISA and used as a 

3 basis for developing or interpreting risk/exposure analyses, supports or calls into question the 

4 scientific conclusions reached in the last review regarding health effects related to exposures to 

5 sulfur oxides. The evaluation of the available scientific evidence and risk/exposure information 

6 with regard to adequacy of the current standard will focus on key policy-relevant issues by 

7 addressing a series of questions including the following: 

8  To what extent has new information altered the scientific support for the occurrence of 

9 health effects as a result of short- and/or long-term exposure to sulfur oxides in the 

10 ambient air? 

11 o What evidence is available from recent studies focused on specific chemical 

12 components within the broader group of sulfur oxides (e.g., SO2, SO3) to inform 

13 our understanding of the nature of exposures that are linked to various health 

14 outcomes? 

15 o To what extent is key scientific evidence becoming available to improve our 

16 understanding of the health effects associated with various time periods of 

17 exposures, including short-term (e.g., 5-minute, 1-hour, 24-hour) and chronic 

18 exposures (e.g., months to years)? 

19 o At what pollutant concentrations do these health effects occur? Is there evidence 

20 of effects at exposure concentrations lower than have been previously observed or 

21 in areas that would likely meet the current SO2 primary standard? 

22 o To what extent are health effects associated with exposures to sulfur oxides, 

23 including SO2, as opposed to one or more co-occurring pollutants (e.g., PM2.5, 

24 ozone, NO2)? 

25 o What are the important uncertainties and limitations associated with the scientific 

26 evidence? 

27  Has new information altered our understanding of human lifestages and populations that 

28 are particularly at increased risk for experiencing health effects associated with exposure 

29 to sulfur oxides? 

30 o Is there new information to shed light on the nature of the exposure-response 

31 relationship in different at-risk lifestages and/or populations? 

32 o Is there new or emerging evidence on health effects beyond respiratory effects in 

33 asthmatics, children, and the elderly that suggest additional at-risk populations 

34 and lifestages should be given increased focus in this review? 

35  What are the air quality relationships between short-term and longer-term exposures 

36 to SO2? 

37 o As noted in section 1.3, as part of the final rulemaking the EPA for the first time 

38 required state reporting of either the highest 5-minute concentration for each hour 

39 of the day, or all twelve 5-minute concentrations for each hour of the day. To 
Do Not Quote or Cite 3-15 March 2014 

1 what extent can this 5-minute monitoring data collected since the last review be 

2 used to further characterize the relationship between 5-minute peaks and longer 

3 term (e.g., 1-hour, 3-hour, 24-hour) average concentrations? 

4 o What are the important uncertainties associated with using a 1-hour NAAQS to 

5 protect against 5-minute peak concentrations of concern? 

6  To what extent does risk or exposure information suggest that exposures of concern (i.e., 

7 exposures above benchmark levels) are likely to occur with recent ambient SO2

8 concentrations or with concentrations that just meet the current SO2 standard? 

9 o Are the estimated risks/exposures considered in this review of sufficient 

10 magnitude such that the health effects might reasonably be judged to be important 

11 from a public health perspective? 

12 o What are the important uncertainties associated with any risk/exposure estimates? 

13  To what extent have important uncertainties identified in the last review been reduced 

14 and/or have new uncertainties emerged? 

15  To what extent does newly available information reinforce or call into question any of the 

16 basic elements of the current primary SO2 standard? 

17 If the evidence suggests that revision of the current standard might be appropriate, the 

18 EPA will evaluate how the standard might be revised. Specifically, we will evaluate how the 

19 scientific information and assessments inform decisions regarding the basic elements of the 

20 primary SO2 NAAQS: indicator, averaging time, form and level. These elements will be 

21 considered collectively in evaluating the health protection afforded by the current or any 

22 alternative standard(s) considered. Specific policy-relevant questions related to these standard 

23 elements include: 

24  To what extent does any new information provide support for the continued use of SO2 as 

25 the indicator for sulfur oxides? Is there evidence to support using an indicator in 

26 addition to, or in place of SO2? 

27  To what extent does the health effects evidence evaluated in the ISA continue to provide 

28 support for the existing 1-hour averaging time? Does the currently available information 

29 provide support for considering any different averaging times? 

30  To what extent do air quality analyses conducted since the last review suggest a standard 

31 with an averaging time of 1-hour or longer can protect against 5-minute and/or 24-hour 

32 concentrations of concern? Do these air quality analyses provide support for considering 

33 any different averaging times? 

34  To what extent do the ISA, air quality analyses, and other information provide support for 

35 consideration of alternative standard forms? 
Do Not Quote or Cite 3-16 March 2014 

1  What range of alternative standard levels should be considered based on the scientific 

evidence evaluated in the ISA, air quality analyses and, if available, in the REA29 2 ? 

3  What are the important uncertainties and limitations in the available evidence and 

4 assessments and how might those uncertainties and limitations be taken into 

5 consideration in identifying alternative standard indicators, averaging times, forms, 

6 and/or levels?

 

29 As outlined in Table 2-1 and discussed in Chapter 5 below, the REA Planning Document will consider the extent 

to which newly available scientific evidence and tools/methodologies warrant the conduct of new quantitative risk 

and exposure assessments. To the extent completely new assessments are not developed for this review, assessments 

from the last review may be interpreted in light of the newly available information in addressing the key policy 

questions for the review. 
Do Not Quote or Cite 4-1 March 2014 

1 4. SCIENCE ASSESSMENT 

2 The ISA comprises the science assessment phase of the SO2 NAAQS review. As 

3 described in section 1.4 above, this assessment focuses on updating the air quality criteria 

associated with health evidence to inform the review of the primary SO2 standard only.30 4 

5 

6 4.1 SCOPE OF THE ISA 

7 The ISA will critically evaluate and integrate the scientific information on exposure and 

8 health effects associated with SOX in ambient air in the discipline areas of atmospheric science, 

9 human exposure, dosimetry, epidemiology, controlled human exposure, and toxicology. The 

10 purpose of the discussions within the ISA is not to provide a detailed literature review but to 

11 draw upon the existing body of evidence to synthesize the current state of knowledge on the most 

12 relevant issues pertinent to the review of the NAAQS for SO2, to identify changes in the 

13 scientific evidence base since the previous review, and to describe remaining or newly identified 

14 uncertainties. The ISA discussions will be designed to focus on the key policy-relevant 

15 questions described in Section 3.4. 

16 The current ISA will focus on literature published since the 2008 SOX ISA and integrate 

17 this newer evidence with evidence considered in the last review. Key findings, conclusions, and 

18 uncertainties from the 2008 ISA for SOX will be briefly summarized at the beginning of the ISA 

19 and individual sections. The results of recent studies will be integrated with previous findings. 

20 In evaluation of controlled human exposure and animal toxicological studies, emphasis will be 

21 placed on studies that examine health effects relevant to humans and on SOX concentrations that 

22 represent the range of human exposures across various ambient microenvironments. However, 

23 in recognition of the fact that controlled human exposure and animal toxicological studies do not 

24 necessarily reflect effects in the most sensitive populations, studies at higher exposure 

25 concentrations will be included when they provide information relevant to previously unreported 

26 effects, evidence of the potential biological mechanism for an observed effect, or information on 

27 exposure-response relationships. 

28 4.2 ORGANIZATION OF THE ISA 

29 The organization of the ISA for health criteria of SOX will be consistent with that used in 

30 the recent assessments for other criteria pollutants, e.g., the ISA for Ozone and Related 

 

30Note that evidence related to environmental effects of SOX will be considered separately in the science assessment 

conducted as part of the review of the secondary NAAQS for NO2 and SO2. 
Do Not Quote or Cite 4-2 March 2014 

1 Photochemical Oxidants (U.S. EPA, 2013b). The ISA will begin with a discussion of major legal 

2 and historical aspects of prior review documents as well as procedures for the assessment of 

3 scientific information. An integrative synthesis chapter will summarize the key information for 

4 each topic area, the causal determinations for relationships between exposure to SOX and health 

5 effects, information describing the extent to which health effects can be attributable specifically 

6 to SOX, and other uncertainties related to the interpretation of scientific information. The 

7 integrative synthesis chapter also will present a discussion of policy-relevant issues such as the 

8 exposure averaging times and lags associated with health effects, the concentration-response 

9 relationships including whether or not the evidence supports identification of a discernible 

10 threshold below which effects are not likely to occur, and the public health significance of health 

11 effects associated with exposure to SOX. Subsequent chapters are organized by subject area (see 

12 draft outline of the ISA in Appendix A) and contain the detailed evaluation of results of recent 

13 studies integrated with previous findings (see section 4.4 for specific issues to be addressed). 

14 Sections for each major health effect category (e.g., respiratory effects) conclude with a causal 

15 determination about the relationship with relevant exposures to SOX. The ISA will conclude 

16 with a chapter that examines exposure and health outcome data to draw conclusions about 

17 potential at-risk lifestages and populations. 

18 The ISA may be supplemented with additional materials if required to support 

19 information contained within the ISA. These supplementary materials may include more 

20 detailed and comprehensive coverage of relevant publications and may accompany the ISA or be 

21 available in electronic form as output from the Health and Environmental Research Online 

22 (HERO) database developed by EPA (http://hero.epa.gov/). Supplementary information 

23 available in the HERO database will be presented as electronic links in the ISA. 

24 4.3 ASSESSMENT APPROACH 

25 4.3.1 Introduction 

26 The NCEA-RTP is responsible for preparing the ISA for SOX health criteria. In each 

27 NAAQS review, development of the science assessment begins with a “Call for Information” 

28 published in the Federal Register. This notice announces EPA’s initiation of activities in the 

29 preparation of the ISA for the specific NAAQS review and invites the public to assist through the 

30 submission of research studies in the identified subject areas. This and subsequent key 

31 components of the process currently followed for the development of an ISA (i.e., the 

32 development process) are presented in Figure 3.1 and are described in greater detail in the 

33 Preamble to the ISA for Lead (U.S. EPA, 2013a). How the ISA fits into the larger NAAQS 

34 review process is briefly described in Section 1.2, the Overview of the Review Process. 

35 
Do Not Quote or Cite 4-3 March 2014 

1 

2 

3 (Modified from Figure III of the Preamble to the ISA for Lead, U.S. EPA, 2013a) 

4 Important aspects of the development of the ISA are described in the sections below, 

5 including the approach for searching the literature, identifying relevant publications, evaluating 

Literature Search and

Study Selection

Develop Initial Sections

Review and summarize new study results and 

findings and conclusions from previous 

assessments by category of outcome/effect and 

by discipline, e.g., toxicological studies of lung 

function. 

Development of Scientific Conclusions and Causal Determinations

Characterize weight of evidence and develop judgments regarding causality for health or welfare effect categories. 

Develop conclusions regarding concentration- or dose-response relationships, potentially at-risk populations, 

lifestages, or ecosystems.

Draft Integrated Science Assessment

Evaluation and integration of newly published studies after each draft

Clean Air Scientific Advisory Committee

Independent review of draft documents for scientific 

quality and sound implementation of causal 

framework; anticipated review of two drafts of ISA in 

public meetings.

Final Integrated Science Assessment

Evaluation, Synthesis and Integration of Evidence 

Integrate evidence from scientific disciplines – for example, toxicological, controlled human exposure and 

epidemiologic study findings for particular health outcome. Evaluate evidence for related groups of endpoints or 

outcomes to draw conclusions regarding health or welfare effect categories, integrating health or welfare effects 

evidence with information on mode of action and exposure assessment.

Public Comments

Comments on draft ISA solicited by EPA

Evaluation of Individual Study Quality

After study selection, the quality of individual studies is evaluated by EPA or outside experts in the fields of 

atmospheric science, exposure assessment, dosimetry, animal toxicology, controlled human exposure studies, 

epidemiology, ecology and other welfare effects, considering the design, methods, conduct, and documentation of 

each study. Strengths and limitations of individual studies that may affect the interpretation of the study are 

considered. 

Peer Input Consultation

Review of initial draft materials by scientists 

from both outside and within EPA in public 

meeting or public teleconference.

Figure 4.1. General Process for Development of Integrated Science Assessments (ISAs)
Do Not Quote or Cite 4-4 March 2014 

1 individual study quality, synthesizing and integrating the evidence, and developing scientific 

2 conclusions and causality determinations. These responsibilities are undertaken by expert 

3 authors of the ISA chapters which include EPA staff with extensive knowledge in their 

4 respective fields and extramural scientists solicited by EPA for their expertise in specific fields. 

5 This section of the IRP also presents specific policy-relevant questions developed from input 

6 received at the SOX kickoff workshop. These questions are intended to guide the development of 

7 the ISA. The process for scientific and public review of drafts of the ISA is described in Section 

8 4.3. 

9 4.3.2 Literature Search and Selection of Relevant Studies 

10 The NCEA-RTP uses a structured approach to identify relevant studies for consideration 

11 and inclusion in the ISA. A Federal Register notice is published to announce the initiation of a 

12 review and to request information, including relevant literature, from the public. The EPA 

13 maintains an ongoing, multi-tiered literature search process that includes extensive manual and 

14 computer-aided citation mining of databases on specific topics in a variety of disciplines using as 

15 keywords terms such as SOX, SO2, sulfur oxide(s), or sulfur dioxide. The search strategies are 

16 designed a priori and iteratively modified to optimize identification of pertinent publications. In 

17 addition, papers are identified for inclusion in several other ways: specialized searches on 

18 specific topics; relational searches that identify recent publications that have cited references 

19 from previous assessments; identification of relevant literature by external scientific experts; 

20 recommendations from the public and CASAC during the call for information and external 

21 review process; and review of citations in previous assessments. The studies identified will 

22 include research published or accepted for publication from January 2008, which slightly 

23 precedes the publication end date for studies reviewed in the 2008 SOX ISA, through 

24 approximately two months before the release of the second external review draft of the ISA 

25 (target of June 2015, see Table 2-1). 

26 References identified through this multipronged search strategy are reviewed for 

27 relevance. Some publications are excluded based on screening of the title. Publications 

28 considered for inclusion in the ISA after reading the title are listed in the Health and 

29 Environmental Research Online (HERO) database (http://hero.epa.gov). Studies and reports that 

30 have undergone scientific peer review and have been published or accepted for publication are 

31 considered for inclusion in the ISA. 

32 From the group of considered references, references are selected for inclusion in the ISA 

33 based on review of the abstract and full text. The references cited in the ISA include a hyperlink 

34 to the HERO database. The selection process is based on the extent to which the study is 

35 potentially informative and policy-relevant. Potentially policy-relevant and informative studies 

36 include those that provide a basis for or describe the relationship between the criteria pollutant 
Do Not Quote or Cite 4-5 March 2014 

1 and effects, in particular, those studies that offer innovation in method or design and studies that 

2 reduce uncertainty on critical issues. Uncertainty can be addressed, for example, by analyses of 

3 potential confounding or effect modification by copollutants or other factors, analyses of 

4 concentration-response or dose-response relationships, or analyses related to time between 

5 exposure and response. The ISA will generally emphasize studies published since the 2008 SOX

6 ISA; however, evidence from previous studies will be included to integrate with results from 

7 recent studies and, in some cases, characterize the key policy-relevant information in a particular 

8 subject area. Analyses conducted by the EPA using publicly available data, for example, air 

9 quality and emissions data, also are considered for inclusion in the ISA. The combination of 

10 approaches described above is intended to produce the comprehensive collection of pertinent 

11 studies needed to address the key scientific issues that form the basis of the ISA. 

12 4.3.3 Evaluation of Individual Study Quality 

13 After selecting studies for inclusion, individual study quality is evaluated by considering 

14 the design, methods, conduct, and documentation of each study, but not whether the results are 

15 positive, negative, or null. This uniform approach aims to consider the strengths, limitations, and 

16 possible roles of chance, confounding, and other biases that may affect the interpretation of the 

17 results from individual studies. In assessing the scientific quality of studies, the following 

18 parameters are considered: 

19  How clearly were the study design, study groups, methods, data, and results presented to 

20 allow for study evaluation? 

21  To what extent are the air quality data, exposure, or dose metrics of adequate quality to 

22 serve as credible exposure indicators? 

23  Were the study populations, subjects, or animal models adequately selected, and are they 

24 sufficiently well defined to allow for meaningful comparisons between study or exposure 

25 groups? 

26  Are the statistical analyses appropriate, properly performed, and properly interpreted? 

27  Are likely covariates (i.e., potential confounding factors, modifying factors) adequately 

28 controlled for or taken into account in the study design or statistical analyses? 

29  Are the health endpoint measurements meaningful, valid, and reliable? 

30 Additional considerations specific to particular scientific disciplines are discussed below. 

31 Atmospheric Science and Exposure Assessment

32 Atmospheric science and exposure assessment studies focus on measurement of, behavior 

33 of, and exposure to ambient air pollution using quality-assured field, experimental, and/or 

34 modeling techniques. The most informative measurement-based studies will include detailed 

35 descriptive statistics for high-quality measurements taken at varying spatial and temporal scales. 

36 These studies will also include a clear and comprehensive description of measurement 
Do Not Quote or Cite 4-6 March 2014 

1 techniques and quality control procedures used. Quality control metrics (e.g., method detection 

2 limits) and quantitative relationships between and within pollutant measurements (e.g., 

3 regression model coefficients, intercepts, and fit statistics) should be provided when appropriate. 

4 Measurements including contrasting conditions for various time periods (e.g., weekday/weekend, 

5 season), populations, regions, and categories (e.g., urban/rural, proximity to various source 

6 sectors) are particularly useful. The most informative modeling-based studies will incorporate 

7 appropriate chemistry, transport, dispersion, and/or exposure modeling techniques with a clear 

8 and comprehensive description of model science, evaluation procedures, and metrics. 

9 Exposure measurement error, which refers to the uncertainty associated with the exposure 

10 metrics used to represent exposure of an individual or population, can be an important 

11 contributor to uncertainty in air pollution epidemiologic study results. Exposure measurement 

12 error can influence observed epidemiologic associations between ambient pollutant 

13 concentrations and health outcomes by biasing effect estimates toward or away from the null and 

14 widening confidence intervals around those estimates (Zeger et al., 2000). Factors that could 

15 influence exposure estimates include, but are not limited to, nonambient sources of exposure, 

16 topography of the natural and built environment, meteorology, air quality measurement 

17 instrument or model uncertainties, time-activity patterns, and the infiltration into indoor 

18 environments. Additional information present in high-quality exposure studies includes location 

19 and activity information from diaries, questionnaires, global positioning system data, or other 

20 means, as well as information on commuting patterns. In general, atmospheric science and 

21 exposure studies focusing on the variety of locations pertinent to the range of exposures in the 

22 U.S. will have maximum value in informing review of the NAAQS. 

23 Epidemiology 

24 In evaluating quality of epidemiologic studies, EPA additionally considers whether a 

25 given study: (1) presents quantitative information on associations of health effects with short- or 

26 long-term exposures that represent ambient concentrations of SOX across various 

27 microenvironments; (2) examines health effects of SOX; (3) assesses SOX as a component of a 

28 complex mixture of air pollutants by considering concentrations of copollutants, correlations of 

29 SOX with these copollutants, potential copollutant interactions (e.g., synergistic effects of SOX

30 with other pollutants), potential copollutant confounding (e.g., bias of associations observed 

31 between SOX and health endpoints by the effects of copollutants), and other methods to assess 

32 the independent effect of SOX; (4) evaluates health endpoints not previously extensively 

33 researched; (5) evaluates lifestages and populations that potentially are at increased risk of health 

34 effects related to SOX; (6) examines other potential confounding factors or effect modifiers (e.g., 

35 socioeconomic status); and (7) examines important methodological issues (e.g., lag or time 

36 period between exposure and effects, model specifications, thresholds, mortality displacement) 
Do Not Quote or Cite 4-7 March 2014 

1 related to the health effects of exposure to SOX. Among epidemiologic studies characterized as 

2 high quality by these parameters, emphasis will be given to multicity studies that employ 

3 standard methodological analyses for evaluating effects of SOX across cities, provide overall 

4 estimates for effects by pooling information across cities, and examine consistency of results 

5 across cities. To address specific issues relevant to standard setting in the U.S., such as regional 

6 heterogeneity in effects, emphasis will be placed on studies that involve exposures that are 

7 relevant to current U.S. populations (e.g., studies conducted in the U.S. or Canada). 

8 Controlled Human Exposure and Animal Toxicology 

9 Controlled human exposure and animal toxicological studies experimentally evaluate the 

10 health effects of administered exposures in human volunteers and animal models under highly 

11 controlled laboratory conditions. Controlled human exposure studies are also referred to as 

12 human clinical studies and, as noted above, provided the definitive evidence for a causal 

13 relationship between short-term exposure to SO2 and respiratory morbidity in the previous 

14 review. These experiments allow investigators to expose subjects to known concentrations of 

15 SOX under carefully regulated environmental conditions and activity levels. In addition to the 

16 general quality considerations discussed previously, evaluation of controlled human exposure 

17 and animal toxicological studies includes assessing the design and methodology of each study 

18 with focus on (1) characterization of the intake dose, dosing regimen (e.g., duration, activity 

19 level), and exposure route; (2) characterization of the pollutant(s); (3) sample size and statistical 

20 power to detect differences; and (4) control of other variables that could influence the occurrence 

21 of effects. The evaluation of study design generally includes consideration of factors that 

22 minimize bias in results such as randomization, blinding and allocation concealment of study 

23 subjects, investigators, and research staff, and unexplained loss of animals or 

24 withdrawal/exclusion of subjects. Additionally, studies must include appropriate control groups 

25 and exposures to allow for accurate interpretation of results relative to exposure. Emphasis is 

26 placed on studies that address concentration-dependent responses or time-course of responses 

27 and studies that investigate potentially at-risk lifestages and populations (e.g., with pre-existing 

28 disease), recognizing that controlled human exposure studies typically examine effects in groups 

29 of relatively healthy individuals, often adults, who do not represent the full range of 

30 susceptibilities in the general population. In addition, consideration will be given to studies that 

31 investigate exposure to SOX separately and in combination with other pollutants such as ozone 

32 and particulate matter. 

33 Controlled human exposure or animal toxicological studies that approximate expected 

34 human exposures in terms of concentration, duration, and route of exposure are of particular 

35 interest. Relevant pollutant exposures are considered to be those generally within two orders of 

36 magnitude of ambient concentrations measured across various microenvironments. Studies using 
Do Not Quote or Cite 4-8 March 2014 

1 higher concentration exposures or doses will be considered to the extent that they provide 

2 information relevant to understanding mode of action or mechanisms, interspecies variation, or 

3 at-risk human lifestages and populations. In vitro studies may be included if they provide 

4 mechanistic insight or support results demonstrated in vivo. 

5 4.3.4 Integration of Evidence and Determination of Causality 

6 EPA has developed a consistent and transparent basis for integration of scientific evidence 

7 and evaluation of the causal nature of air pollution-related health or welfare effects for use in 

8 developing ISAs, as described in the online Preamble to the ISA for Lead (U.S. EPA, 2013a). 

9 Evidence from across scientific disciplines for related health effects is evaluated, synthesized, 

10 and integrated to develop conclusions and causality determinations. This includes consideration 

11 of strengths and weaknesses in the overall collection of studies across disciplines. Confidence in 

12 the body of evidence is based on evaluation of study design and quality. The relative importance 

13 of different types of evidence to the conclusions varies by pollutant or assessment, as does the 

14 availability of different types of evidence for causality determination. Consideration of human 

15 health effects is informed by controlled human exposure, epidemiologic, and toxicological 

16 studies. Other evidence including mechanistic evidence, toxicokinetics, and exposure assessment 

17 may be highlighted if it is relevant to the evaluation of health effects and if it is of sufficient 

18 importance to affect the overall evaluation. Scientists will also evaluate uncertainty in the 

19 scientific evidence, considering issues such as generalizing results from a small number of 

20 controlled human exposure subjects to the broader population, quantitative extrapolations of 

21 observed pollutant-induced pathophysiological alterations from laboratory animals to humans, 

22 confounding by co-exposure to other ambient pollutants or meteorological factors, the potential 

23 for effects due to exposure to air pollution mixtures, and the influence of exposure measurement 

24 error on epidemiologic study findings. 

25 The ISA will evaluate the evidence for causal relationships between observed health 

26 outcomes and SOX exposures using a five-level hierarchy that classifies the weight of evidence 

27 for causation. Determination of causality involves the evaluation and integration of evidence 

28 across disciplines for major outcome categories (e.g., respiratory effects) or groups of related 

29 endpoints. Key considerations in drawing conclusions about causality include consistency of 

30 findings for an endpoint across studies, biological plausibility, and coherence of the evidence 

31 across disciplines and across related endpoints, including key events that inform modes of action 

32 (see Table I in Preamble to the ISA for Lead, U.S. EPA, 2013a). In discussing the causal 

33 determination, EPA characterizes the evidence on which the judgment is based, including 
Do Not Quote or Cite 4-9 March 2014 

1 strength of evidence for individual endpoints within the outcome category or group of related 

2 endpoints. The ISA will place emphasis on studies conducted with SOX exposure concentrations 

3 representative of those across various ambient microenvironments. However, studies that provide 

4 evidence for biological plausibility and modes of action, which are conducted at higher exposure 

5 concentrations than those typically associated with health effects in humans, may be included in 

6 the ISA. In addition, EPA evaluates evidence relevant to understand the quantitative 

7 relationships between pollutant exposures and health effects. This includes evaluating the 

8 concentration-response or dose-response relationships and, to the extent possible, drawing 

9 conclusions on the levels at which effects are observed. 

10 4.3.5 Quality Management 

11 NCEA participates in the Agency-wide Quality Management System, which requires the 

12 development of a Quality Management Plan (QMP). Implementation of the ORD-wide and 

13 NCEA QMP ensures that all data generated or used by NCEA scientists “have a degree of 

14 confidence in the quality of the data; and, are of the type and quality appropriate for their 

15 intended use” and that all information disseminated by NCEA adheres to a high standard for 

16 quality including objectivity, utility, and integrity. Quality assurance (QA) measures detailed in 

17 the QMP are being employed for the current SOX review, including the development of the ISA 

18 for health criteria of SOX. The NCEA QA staff are responsible for the review and approval of 

19 quality-related documentation. NCEA scientists are responsible for the evaluation (and 

20 documentation) of all inputs to the ISA, including primary (new) and secondary (existing) data, 

21 to ensure their quality is appropriate for their intended purpose. NCEA adheres to the use of 

22 Data Quality Objectives, which clarify project objectives, define the appropriate type of data 

23 used in the project, and specify tolerable levels of confidence in the data and tolerable levels of 

24 potential decision errors that will be used as the basis for establishing the quality and quantity of 

25 data needed to identify the most appropriate inputs to the science assessment. The approaches 

26 utilized to search the literature and criteria for study selection and evaluation were detailed in the 

27 two preceding subsections. Generally, NCEA scientists rely on scientific information found in 

28 peer-reviewed journal articles, books, and government reports. Where information is integrated, 

29 re-analyzed, modeled, or reduced from multiple sources to create new figures, tables, or 

30 summation, the data generated are considered to be new and are documented and subjected to 

31 rigorous quality assurance and quality control measures to ensure their accuracy, validity, and 

32 reproducibility. 
Do Not Quote or Cite 4-10 March 2014 

1 4.4 SPECIFIC ISSUES TO BE ADDRESSED IN THE ISA 

2 The organization of the ISA for SOX health criteria will be consistent with that used in 

3 the recent assessments for other criteria pollutants (e.g., ISA for O3, U.S. EPA, 2013b). 

4 Development of the ISA will be guided by policy-relevant questions that frame the entire review 

5 of the primary SO2 NAAQS. These policy-relevant questions are related to two overarching 

6 issues. The first issue is whether new evidence reinforces or calls into question the evidence 

7 presented and evaluated in the last NAAQS review with respect to factors such as the 

8 concentrations of SOX exposure associated with health effects and plausibility of health effects 

9 caused by SOX exposure. The second issue is whether uncertainties from the last review have 

10 been reduced and/or whether new uncertainties have emerged. Specific questions that will be 

11 addressed in the ISA are listed subsequently by topic area. In the ISA, these topic areas will be 

12 discussed in separate chapters or sections. The beginning of the ISA will include an integrative 

13 synthesis chapter that summarizes the key information for each topic area and the causal 

14 determinations. The integrative synthesis chapter also presents a discussion of policy-relevant 

15 issues such as the exposure metrics, averaging times, and lags associated with health effects, the 

16 concentration-response relationship including threshold for effects, and public health 

17 significance of health effects associated with exposure to SOX (see Appendix). 

18 

19 A. Air Quality and Atmospheric Chemistry: The ISA will present and evaluate data related 

20 to ambient concentrations of SOX; sources leading to the presence of SOX in the 

21 atmosphere; and chemical reactions that determine the formation, degradation, and 

22 lifetime of SOX in the atmosphere. The 2008 SOX ISA concluded that most SO2 is 

23 emitted from elevated point sources such as the stacks of power plants and industrial 

24 facilities, many of which are located in the eastern U.S., leading to a strong east-west 

25 gradient in SO2 concentrations. SO2 is removed from the atmosphere both by deposition 

26 and by oxidation to sulfate, resulting in a typical atmospheric lifetime of <1 to 4 days, 

27 depending on local conditions. Mean U.S. daily 1-hour max SO2 concentrations in 2003-

05 were approximately 13 ppb, with a 99th 28 percentile value of 95 ppb and a maximum 

value of approximately 700 ppb. The large differences between 99th 29 percentile and 

30 maximum values suggest that the maxima are strongly limited spatially and temporally 

31 and are not a major determinant of the mean values. At the time of the 2008 SOX ISA, the 
Do Not Quote or Cite 4-11 March 2014 

1 very limited 5-minute SO2 data available showed that the median hourly maximum 5-

minute average ranged from 1-8 ppb, while the 99th 2 percentile value ranged from 21-184 

3 ppb, depending on location (U.S. EPA, 2008, section 5.1). In the current ISA, description 

4 of the atmospheric chemistry of SOX will include both gaseous and particulate species in 

5 order to provide a complete analysis, although the health effects of particulate SOX are 

6 discussed in the review of the NAAQS for particulate matter (PM). SO2 is the most 

7 important of the gas-phase sulfur oxides for both atmospheric chemistry and health 

8 effects and is expected to be the focus of the ISA. SOX is usually defined to include sulfur 

9 trioxide (SO3) and gas-phase sulfuric acid (H2SO4) as well, but neither species is present 

10 in the atmosphere in concentrations significant for human exposures. In the current 

11 review, specific policy-relevant questions related to air quality and atmospheric 

12 chemistry that will be addressed include the following: 

13  What are the main and emerging sources of ambient gas-phase SOX, and how have new 

14 fuels, emission standards, and technologies changed the magnitude and composition of 

15 SOX emissions? 

16  What progress has been made in improving measurements and reducing interference 

17 problems in measuring SOX, particularly for concentrations near the method detection 

18 limit? What limitations still remain? 

19  Based on recent air quality and emissions data, what are current emissions and 

20 concentrations of SOX? How have emissions and concentrations of SOX changed since 

21 the 2008 SOX ISA? To what extent can other techniques, such as satellite data and 

22 dispersion modeling, be used to improve the characterization of SOX concentrations? 

23  What spatial and temporal patterns can be seen in SOX concentrations? In particular, 

24 what patterns can be seen near point and other sources of SOX? What do monitoring, 

25 satellite data, and dispersion modeling results indicate regarding spatial patterns on 

26 neighborhood, urban, regional, and national scales? 

27  What are the relationships among SOX concentrations measured with different averaging 

28 times (e.g., 5-minute, 1-hour, 24-hour)? How well do 1-hour or longer averaging time 

29 concentrations represent peak exposures to SOX? 

30  What are the relationships among SOX concentrations and concentrations of other 

31 pollutants, such as sulfate, other components of particulate matter, and gaseous 

32 pollutants? 

33  What are the capabilities of air quality models for estimating SOX concentrations, 

34 particularly at the upper end of the air quality distribution? 

35  Based on air quality and emissions data on SOX and atmospheric chemistry models, what 

36 are likely background concentrations of SOX in the absence of anthropogenic emissions? 
Do Not Quote or Cite 4-12 March 2014 

1 B. Human Exposure to Ambient SOX: The ISA will evaluate the factors that influence 

2 human exposure to ambient SOX and the uncertainties associated with extrapolation from 

3 ambient concentrations to personal exposures to SOX of ambient origin, particularly in 

4 the context of interpreting results from epidemiologic studies. As described in the 2008 

5 SOX ISA, many exposure studies were unable to characterize the relationship between 

6 personal exposure and ambient SO2 due to indoor and outdoor concentrations that were 

7 below the detection limit of passive personal samplers. However, in studies with personal 

8 measurements above detection limits, a reasonably strong association was observed 

9 between personal SO2 exposure and ambient concentrations (U.S. EPA, 2008, section 

10 5.3). At the time of the 2008 SOX ISA, no studies had evaluated the relationship between 

11 community average exposure and ambient concentrations, which is more directly relevant 

12 to many epidemiologic study designs, although the ISA concluded that intracommunity 

13 variations in the personal-ambient relationship would generally tend to widen the 

14 confidence interval rather than bias the effect estimate. Uncertainties differ according to 

15 the exposure period of interest as most short-term exposure studies (e.g., population-level 

16 studies using time-series analyses, field/panel studies) rely on temporal variation in 

17 exposure while long-term exposure studies (e.g., longitudinal cohort studies) rely on 

18 spatial variability of exposure. In the current review, specific policy-relevant questions 

19 related to exposure that will be addressed include the following: 

20  What are the relationships between SOX measured at stationary monitoring sites and 

21 personal exposure to SOX over different time scales? What evidence is available 

22 regarding these relationships in environments near point sources, ports, or other sources? 

23 What uncertainties remain regarding these exposures of interest? 

24  What new information is available regarding microenvironmental SOX concentrations 

25 and personal exposures to SOX? What are the capabilities of currently available exposure 

26 measurement techniques? 

27  What new information exists regarding characterization of error in SOX exposure 

28 assessment and how it influences personal-ambient exposure relationships? 

29  What information is available regarding differences in SOX exposure patterns and 

30 personal-ambient exposure relationships among various lifestages and populations, 

31 particularly at-risk groups? 

32  What new information exists regarding SOX measurements in a multipollutant context? 

33 What are the relationships between SOX exposures and exposures for other pollutants, 

34 such as sulfate, other components of particulate matter, and gaseous pollutants? 
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1  How does uncertainty in exposure estimates inform interpretation of epidemiologic, 

2 controlled human exposure, and toxicological studies? 

3 C. Dosimetry and Modes of Action: The ISA will evaluate literature focusing on dosimetry 

4 and modes of action that may underlie the health outcomes associated with exposure to 

5 SOX. These topic areas will be evaluated using both human and animal data. The 2008 

6 SOX ISA concluded that SO2 is readily absorbed in the nasal passages due to its high 

7 water solubility; with increased ventilation rates during exercise, the pattern of SO2

8 absorption shifts from the upper airways to the tracheobronchial airways in conjunction 

9 with a shift from nasal to oronasal breathing (U.S. EPA, 2008, section 5.2). The 

10 compound most directly responsible for the health effects may be the inhaled SO2 and/or 

11 its chemical reaction products such as hydrogen ions, bisulfite anions and sulfite anions 

12 which are formed when SO2 contacts the fluids lining the airway. One of the principal 

13 effects of inhaled SO2 is bronchoconstriction, mediated by chemosensitive receptors that 

14 trigger nervous system reflexes. Preexisting inflammation may lead to enhanced 

15 sensitivity in asthmatics due to enhanced release of mediators, alterations in the 

16 autonomic nervous system, and/or sensitization of the chemosensitive receptors. In the 

17 current review, specific policy-relevant questions related to dosimetry and modes of 

18 action that will be addressed include the following: 

19  What SOX reaction products can be found in the respiratory tract cells, tissues, or fluids 

20 that may serve as markers of SOX exposure and effect? 

21  What information is available on the following dosimetric and mechanistic factors: 

22 o The regional pattern of SOX-induced injury/perturbation in the respiratory 

23 tract? 

24 o Inter-individual variability of responses that may enhance the risk of an 

25 adverse health effect? 

26 o Homology of responses between animals and humans? 

27  What are the potential biological mechanisms underlying responses to SOX at or near 

28 environmentally relevant exposures? 

29  What new information is available related to the modes of action for health effects 

30 associated with exposure to SOX? 

31  Do interactions between inhaled SOX and other inhaled pollutants influence the 

32 mechanisms underlying the toxic potential of SOX? 
Do Not Quote or Cite 4-14 March 2014 

1  What are the effects of host factors such as lifestage, sex, pre-existing disease, genetic 

2 background, and physical activity on SOX uptake, cellular and tissue responses, and their 

3 underlying mechanisms? Are there critical windows of exposure (e.g. prenatal) that result 

4 in different effects and/or effects at lower exposures? 

5  What information is available to discern the relative contributions to internal SOX

6 compounds of SOX derived exogenously from ambient exposures and SOX derived from 

7 endogenous biological processes? 

8 D. Health Effects: The 2008 SOX ISA concluded that there is a causal relationship between 

9 respiratory morbidity and short-term exposure to SO2, based on consistent and coherent 

10 evidence from controlled human exposure, epidemiologic, and animal toxicological 

11 studies. The definitive evidence for the causal relationship came from controlled human 

12 exposure studies that reported respiratory symptoms and decreased lung function in 

13 exercising asthmatics following 5-10 minute exposures to SO2; in addition, numerous 

14 epidemiologic studies reported associations between short-term SO2 exposures and 

15 respiratory symptoms and hospitalizations (U.S. EPA, 2008, section 5.2). The ISA also 

16 concluded that the evidence is suggestive of a causal relationship between short-term 

17 exposure to SO2 and mortality, and that the evidence is inadequate to infer a causal 

18 relationship between short-term exposure to SO2 and cardiovascular effects or between 

19 long-term exposure to SO2 and morbidity and mortality. The current ISA will evaluate the 

20 literature related to respiratory, cardiovascular, reproductive and developmental health 

21 effects, mortality, and cancer associated with SOX exposure. Other health effects may also 

22 be evaluated, such as those related to the central nervous system. Health effects that occur 

23 following both short- and long-term exposures will be evaluated as examined in 

24 epidemiologic, controlled human exposure, and animal toxicological studies, and causality 

25 determinations will be developed for each type of health effect. Efforts will be directed at 

26 identifying the lower concentrations at which effects are observed, including effects in 

27 populations and lifestages potentially at increased risk of SOX -induced health effects, and 

28 assessing the role of SOX within the broader mixture of ambient pollutants. The discussion 

29 of health effects also will be integrated with relevant information on dosimetry and modes 

30 of action. In the current review, specific policy-relevant questions related to health effects 

31 that will be addressed include the following: 

32  What do controlled human exposure, animal toxicological, and epidemiologic studies 

33 indicate regarding the relationship between short-term (i.e., minutes to one month) 
Do Not Quote or Cite 4-15 March 2014 

1 exposures to SOX and health effects of concern, including the nature and time course, in 

2 healthy individuals and in those with pre-existing disease states (e.g., people with asthma 

3 or cardiovascular disease) or other factors (e.g., lifestage, genetic variants, nutritional 

4 deficiencies) that potentially modify the risk of SOX-induced health effects? What 

5 information is available that reduces uncertainties identified in the previous ISA, such as 

6 exposure measurement error and the potential for copollutant confounding? 

7  How do results of recent studies expand current understanding of the relationships 

8 between long-term (i.e. more than one month to years) exposure to SOX and chronic 

9 respiratory effects manifested as permanent lung tissue damage, a reduction in baseline 

10 lung function, or a reduction in lung function growth? To what extent does long-term 

11 SOX exposure promote exacerbation and development of asthma or other chronic lung 

12 diseases, cardiovascular diseases, and other conditions? Are there certain lifestages that 

13 are especially vulnerable to the development of these chronic conditions? What is the 

14 relationship between SOX exposure and all-cause mortality and cause-specific mortality? 

15  To what extent does the scientific evidence support the occurrence of health effects from 

16 long-term SOX exposure at ambient concentrations that are lower than those previously 

17 observed? If so, what uncertainties are related to these associations and are the health 

18 effects in question important from a public health perspective? 

19  To what extent does short-term or long-term exposure to SOX contribute to health effects 

20 beyond the respiratory and cardiovascular systems (e.g., reproductive, developmental, 

21 cancer)? 

22  What is the extent of coherence of findings for small changes in lung function, airway 

23 hyperresponsiveness, heart rate variability, and vasomotor function and changes in health 

24 effects such as hospital admissions, emergency department visits, and mortality? What 

25 other biomarkers of early effect may be used in the assessment of health effects? 

26  What evidence is available regarding the shape of concentration-response relationships 

27 between short-term and long-term SOX exposure and health effects? 

28  What evidence is available regarding the nature of health effects from the combination of 

29 SOX and other ambient air pollutants in comparison to health effects following exposure 

30 to SOX alone? 

31  What do results from studies conducted in environments near SOX sources indicate about 

32 the health effects of long-term or repeated SOX exposures? 

33  To what extent does information across scientific disciplines on the pattern of SOX

34 exposure (e.g., peak, repeated peak, average) provide understanding of the time course 

35 for changes in health effects? What information is available on time-activity patterns of 

36 study subjects such as time spent outdoors or activity levels that can aid in the 

37 understanding of the nature of exposure or dosimetry of ambient SOX concentrations that 

38 are associated with health effects? 

39  To what extent do data across scientific disciplines provide information on health effects 

40 related to various short-term SOX exposure indices or averaging times relevant to the 1-

41 hour standard? What data exist comparing associations of health effects among various 

42 short-term SOX exposure metrics (e.g., 1-hour versus 24-hour)? 
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1  What information is available regarding the effect of long-term, low-concentration 

2 exposure to SOX on an individual’s sensitivity to short-term but higher concentration 

3 exposures? 

4  What evidence is available regarding health effects related to long-term exposure 

5 windows other than annual or lifetime average (e.g., preconception, pregnancy average)? 

6 What data are available comparing associations of health effects among various long7 term SOX exposure metrics (e.g., annual, seasonal, pregnancy average)? Are there critical 

8 windows of human development that are associated with the development of chronic 

9 respiratory disease? 

10  To what extent are the observed epidemiologic health effect associations attributable to 

11 ambient SOX, another ambient pollutant, or to the pollutant mixtures that SOX may be 

12 representing? To what extent do findings from experimental studies provide biological 

13 plausibility? 

14 E. Populations and Lifestages Potentially at Increased Risk of SOX-Induced Health Effects: 

15 The 2008 SOX ISA found substantial evidence from epidemiologic and controlled human 

16 exposure studies that asthmatic individuals are more susceptible to respiratory health 

17 effects from SO2 exposures than the general public (U.S. EPA, 2008, section 5.4). The 

18 ISA also presented limited evidence that children and older adults (≥ 65 years) are 

19 potentially at increased risk of SO2-induced respiratory effects. Since completion of the 

20 2008 ISA, EPA has developed a framework to provide a consistent and transparent basis 

21 for classifying the weight of evidence about whether populations and/or lifestages are at 

22 increased risk according to one of four levels: adequate evidence, suggestive evidence, 

23 inadequate evidence, and evidence of no effect (see Table 5-1 of ISA for Lead, U.S. EPA, 

24 2013a). In the framework, key considerations in drawing such conclusions include 

25 consistency of findings for a factor within a discipline and coherence of the evidence 

26 across disciplines. The current ISA will examine exposure and health outcome data to 

27 draw conclusions about specific populations or lifestages that are potentially at increased 

28 risk of SOX-induced health effects. Estimation of the sizes of potential populations and 

29 lifestages at increased risk and discussion of the public health significance of the health 

30 outcomes characterized to result from ambient SOX exposure may be included. Potential 

31 populations or lifestages at increased risk can be characterized by a variety of factors: 

32 intrinsic factors (biological factors such as age, genetic variants), extrinsic factors 

33 (nonbiological factors such as diet, lower socioeconomic status), and/or factors affecting 

34 dose or exposure (age, outdoor activity or work). It is important to note that some factors 
Do Not Quote or Cite 4-17 March 2014 

1 (e.g., age) are interconnected and may influence risk through multiple avenues. In the 

2 current review, specific policy-relevant questions related to populations and lifestages 

3 potentially at increased risk of SOX-induced health effects that will be addressed include: 

4  Based on evidence integrated across studies and disciplines that examine factors which 

5 may increase exposure to SOX and/or risk of SOX-induced health effects, what 

6 conclusions can be drawn about the presence of at-risk lifestages (e.g., fetuses, children, 

7 older adults) and/or populations? 

8  Studies from which disciplines contribute information about particular at-risk lifestages 

9 and populations, and to what extent does limited or lack of information from specific 

10 disciplines produce uncertainty in conclusions about at-risk lifestages and populations? 

11  How does new information augment that evaluated in the 2008 SOX ISA regarding 

12 populations with pre-existing respiratory disease or genetic variants as well as lifestages 

13 potentially at increased risk of SOX-induced health effects? 

14  What information is available that provides insight as to whether an at-risk lifestage or 

15 population has higher exposure or dose of SOX and/or has a greater biological response to 

16 a given exposure? 

17  What is the extent of the coherence of evidence regarding potential at-risk lifestages or 

18 populations for both short- and long-term exposures to SOX? 

19  What quantitative information is available that characterizes the magnitude of greater 

20 biological response or risk of health effects in at-risk lifestages or populations? 

21 

22 4.5 SCIENTIFIC AND PUBLIC REVIEW 

23 Drafts of the ISA will be made available for review by the CASAC SOX primary 

24 NAAQS review panel and public as indicated in Figure 4-1 above; availability of draft 

25 documents will be announced in the Federal Register. The CASAC panel will review the draft 

26 ISA documents and discuss their comments in public meetings that will be announced in the 

27 Federal Register. EPA will take into account comments, advice, and recommendations received 

28 from the CASAC panel and from the public in revising draft ISA documents. EPA has 

29 established a public docket for the development of the ISA. After appropriate revision based on 

30 comments received from CASAC and the public, the final document will be made available on 

31 an EPA website and in hard copy. A notice announcing the availability of the final ISA will be 

32 published in the Federal Register. 
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1 5. QUANTITATIVE RISK AND EXPOSURE 

2 ASSESSMENTS 

3 Within the context of NAAQS reviews, quantitative risk and exposure assessments 

4 (REAs) are designed to estimate human exposure and health risks associated with existing and 

5 potential alternative standards. The appropriate scope of any REA will be informed by the 

6 availability of scientific information from the ISA as well as air quality information and 

7 information on data and models that may help to address important uncertainties or provide 

8 additional insights beyond those provided by previous REAs. As a result, the first step in the 

9 REA planning process is an assessment of the appropriate scope of the REA, which includes a 

10 determination of whether a distinct REA document is needed. As part of this planning process, 

11 we evaluate the REA for the previous SO2 NAAQS review in the context of the extent to which 

12 important uncertainties may be addressed by new information available since the previous 

13 review and the extent to which new information may change results of the REA in important 

14 ways or may allow for additional analyses that can address important gaps in our understanding 

15 of the exposures and risks associated with SO2. 

16 This phase of the NAAQS review begins with the preparation of a REA Planning 

17 Document and considers the extent to which newly available scientific evidence and 

18 tools/methodologies provide support for conducting quantitative risk and exposure assessments. 

19 To the extent warranted, the scope and methods for components of exposure/risk assessments 

20 will be described. As outlined in Table 2-1 above, the EPA plans to issue this REA Planning 

21 Document in February 2015. This document will be the subject of a CASAC consultation and 

22 will be made available to the public for review and comment. CASAC advice and public 

23 comments on this draft IRP will be considered in developing the REA Planning Document. If 

24 warranted, one or more drafts of an REA will then be prepared and released for CASAC review 

25 and public comment prior to completion of a final REA. 

26 The information newly available in this review will be considered in light of the 

27 comprehensive, complex and resource-intensive quantitative assessments of human exposure and 

28 health risks documented in the 2009 REA as discussed in section 5.1 below. As discussed in 

29 section 5.2 below, the REA Planning Document will consider the available scientific evidence, 

30 tools and methodologies in light of areas of uncertainty identified in the 2009 REA and the 

31 potential for new analyses to provide notably different exposure and risk estimates, with lower 

32 associated uncertainty. CASAC advice and comments from the public on this draft IRP, as well 

33 as the availability of resources, will also inform development of the REA Planning Document. 
Do Not Quote or Cite 5-2 March 2014 

1 5.1 OVERVIEW OF RISK AND EXPOSURE ASSESSMENT FROM 

2 PRIOR REVIEW 

3 In the previous review of the primary SO2 NAAQS, the REA focused the quantitative 

4 exposure and risk analyses on 5-minute levels of SO2 in excess of potential health effect 

5 benchmark values derived from the controlled human exposure literature. These benchmark 

6 levels are not potential standards, but rather are concentrations which represent “exposures of 

7 potential concern” which are used in the analyses to estimate potential exposures and risks 

8 associated with 5-minute concentrations of SO2. The health effect benchmark values used in the 

9 REA were derived primarily from the ISA’s evaluation of the 5 - 10 minute controlled human 

10 exposure literature. As noted above, the ISA concluded that moderate or greater decrements in 

11 lung function occurred in approximately 5 - 30% of exercising asthmatics following exposure to 

12 200 - 300 ppb SO2 for 5 - 10 minutes. In addition, the ISA concluded that moderate or greater 

13 decrements in lung function occurred in approximately 20 - 60% of exercising asthmatics 

14 following exposure to 400 - 600 ppb SO2 for 5 - 10 minutes. The ISA also concluded that at SO2

15 concentrations ≥ 400 ppb, statistically significant moderate or greater decrements in lung 

16 function at the group mean level have often been reported and are frequently accompanied by 

17 respiratory symptoms. Moreover, small SO2-induced lung function decrements have been 

18 observed in exercising asthmatics at concentrations as low as 100 ppb when SO2 is administered 

19 via mouthpiece. Taken together, the REA concluded it was appropriate to examine potential 5-

20 minute benchmark values in the range of 100 - 400 ppb. 

21 The purpose of the assessments in the SO2 REA was to characterize air quality, 

22 exposures, and health risks associated with recent ambient levels of SO2, with SO2 levels that 

23 could be associated with just meeting the then-existing SO2 standards (i.e., 30 ppb annual 

24 average and 140 ppb daily average) and with SO2 levels that could be associated with just 

25 meeting alternative 1-hour daily maximum standards. The SO2 REA utilized three approaches to 

26 characterize health risks and are briefly described with the following. 

27 In the first approach, measured 5-minute maximum SO2 concentrations (1997 - 2007) 

28 from 98 ambient monitors were evaluated for exceedances of the 5-minute potential health effect 

29 benchmark levels, counting the number of days (per monitor and per year) a particular 5-minute 

30 benchmark concentration was exceeded and considering unadjusted, as is annual average, daily 

31 average, and 1-hour daily maximum SO2 concentrations. In addition, 5-minute SO2 maximum 

concentrations were statistically estimated31 32 using all available monitors that measured 1-hour 

 

31The approach for statistically estimating 5-minute maximum concentrations from 1-hour concentrations was based 

on a characterization of ratios of measured 5-minute maximum concentrations to measured 1-hour average 
Do Not Quote or Cite 5-3 March 2014 

1 SO2 (1997 - 2006) to generate a similar output (i.e., the number of days per monitor per year a 

2 benchmark concentration was exceeded considering as is air quality). Then, 5-minute maximum 

3 concentrations were statistically estimated in 40 selected U.S. counties (2001 - 2006), though 

4 using 1-hour SO2 concentrations as is and, those adjusted to just meet the then-existing annual 

5 and daily standards, and concentrations adjusted to just meet potential 1-hour daily maximum 

6 alternative standards. In this analysis, all U.S. monitoring sites where SO2 data have been 

7 collected were included in this analysis and, as such, the results generated were considered a 

8 broad characterization of national air quality and potential human exposures that might be 

9 associated with these concentrations. 

10 In the second approach, we used EPA’s Air Pollutants Exposure (APEX) model (US 

11 EPA, 2012a,b), a Monte Carlo simulation model that can be used to simulate a large number of 

12 randomly sampled individuals within specified locations, generating estimates of population 

13 exposure. APEX simulates exposures in indoor, outdoor, and in-vehicle microenvironments 

14 while taking into consideration the movement of individuals through time and space. APEX 

15 estimated 5-minute daily maximum exposures simulated asthmatics may experience while at 

16 moderate or greater exertion (e.g., while exercising) and compared these exposures to the same 

17 5-minute potential health effect benchmark levels. Two case study areas were selected for this 

18 exposure modeling: Greene County, Missouri, and three counties within the St. Louis 

19 Metropolitan Statistical Area (MSA). For these two case study areas, year 2002 census block20 level hourly SO2 concentrations were estimated by EPA’s AERMOD (a dispersion model), input 

21 to APEX and combined with the same statistical model used for estimating 5-minute peaks 

22 described from the hourly SO2 concentrations above. Several modeled air quality scenarios were 

23 considered, including as is air quality, air quality adjusted to just meet the then-existing 

24 standards, and air quality adjusted to just meet potential alternative 1-hour daily maximum 

25 standards. Output from this exposure modeling were the number and percent of asthmatics in 

26 each study area experiencing at least one 5-minute daily maximum exposure at or above the 

27 potential health effect benchmark levels while at moderate or greater exertion. 

28 In the third approach, exposure-response relationships derived from controlled human 

29 exposure studies were used in conjunction with the outputs of the St. Louis and Greene County 

30 exposure analysis to estimate health impacts. More specifically, in each location we estimated 

31 the number and percent of all asthmatics or asthmatic children at moderate or greater exertion 

32 expected to experience moderate or greater decrements in lung function defined in terms of sRaw 

33 or FEV1 and considering the same air quality scenarios mentioned above. 

 concentrations (Section 7.2.3 of the 2009 SO2 REA). Nineteen separate ratio distributions were developed from the 

measurement data, stratified by seven 1-hour concentration levels and three concentration variability levels. 
Do Not Quote or Cite 5-4 March 2014 

1 As mentioned above for each of these approaches, ambient SO2 concentrations and 

2 exposures were characterized by considering as is air quality (unadjusted concentrations) and 

3 several hypothetical air quality scenarios. Each of the hypothetical air quality scenarios had an 

4 ambient concentration target, derived from the form and level of the then-existing NAAQS or 

5 from potential alternative standards. Staff chose a proportional approach to adjust the SO2

6 concentrations to simulate each of the current and alternative air quality standard scenarios. A 

7 proportional approach was selected based on the mostly linear relationship between older high 

8 concentration years of air quality when compared with recent low concentration years at several 

9 locations (2009 SO2 REA, Section 7.4.2.5). 

10 The approach used to evaluate uncertainty was adapted from guidelines outlining how to 

11 conduct a qualitative uncertainty characterization (WHO, 2008), though staff also performed 

12 several quantitative sensitivity analyses to iteratively inform both model development and the 

13 qualitative uncertainty characterization, where possible. While it may be considered ideal to 

14 follow a tiered approach in the REA to quantitatively characterize all identified uncertainties, 

15 staff selected the mainly qualitative approach given the limited data available to inform 

16 probabilistic analyses and time and resource constraints. 

17 The following identifies the key observations and uncertainties from the prior SO2 REA. 

18 

19 5.1.1 Key Observations 

20 

21 Ambient Air Quality Characterization

22  An increased probability of any 5-minute benchmark exceedance was consistently related 

23 to either increased 24-hour average or 1-hour daily maximum concentrations. 

24  For any of the air quality scenarios considered, the probability of exceeding the 5-minute 

25 maximum benchmark levels was consistently greater at monitors sited in low-population 

26 density areas compared with high-population density areas. 

27  Unadjusted as is air quality at ambient monitors measuring 5-minute maximum 

28 concentrations: 

29 o Measured daily and annual average concentrations were below that of the existing 

30 standards at all monitors, though measured 5-minute maximum ambient 

31 concentrations were present above the potential health effect benchmark levels. 

32 (2009 SO2 REA, Appendix A, Table A.5-1) 

33  Nearly 70% of the monitor site-years analyzed had at least one daily 5-

34 minute maximum concentration above 100 ppb and over 20% had ≥ 25 

35 days with a daily 5-minute maximum concentration above 100 ppb. 

36  About 44% of the monitor site-years analyzed had at least one 5-minute 

37 daily maximum concentration > 200 ppb, 25% had at least one > 300 ppb, 

38 and 17% had at least one > 400 ppb. 
Do Not Quote or Cite 5-5 March 2014 

1  Air quality adjusted to simulate just meeting the then-existing annual standard in the 40 

2 selected U.S. counties 

3 o All counties evaluated were estimated to have multiple days per year where 5-

4 minute daily maximum ambient SO2 concentrations are > 100 ppb. For example, 

5 most counties are estimated to have, on average, 100 days or more per year with 

6 5-minute daily maximum SO2 concentrations > 100 ppb (2009 SO2 REA, Table 7-

7 11). 

8 o Fewer benchmark exceedances were estimated to occur with higher benchmark 

9 levels. For example, five of the forty counties were estimated to have 60 or more 

10 days per year with 5-minute maximum SO2 concentrations that exceed 300 ppb 

11 (2009 SO2 REA, Table 7-13). 

12  Air quality adjusted to potential 1-hour daily maximum alternative standard levels: 

13 o Far fewer days per year with 5-minute maximum SO2 concentrations > 300 ppb 

14 and > 400 ppb (about 0 to 5 days/year) were estimated when adjusting air quality 

15 to just meet potential alternative standard levels of 100 and 150 ppb than 

16 compared with air quality adjusted to just meet the current standards (frequently 

17 25 or more days/year) and the potential alternative standard levels of 200 and 250 

18 ppb (about 5 to 20 days/year) (2009 SO2 REA, Tables 7-13 and 7-14). 

19 Exposure Assessment 

20  St. Louis had both a greater number and percent of asthmatic children and adults exposed 

21 above the benchmark levels than did Greene County for all air quality scenarios, largely a 

22 function of both the greater population density and the much greater SO2 emissions 

23 density in St. Louis (2009 SO2 REA, Section 8.9.2). 

24  Estimated exposures above 5-minute potential health effect benchmark levels at moderate 

25 or greater exertion using APEX occurred most frequently outdoors (around 50 to > 90%, 

26 depending on the air quality scenario and modeling domain) (2009 SO2 REA, Figure 8-

27 21). 

28  Simulating air quality that just meets the then-existing annual standard in either the 

29 Greene County or St. Louis Study areas resulted in the greatest number and percent of 

30 asthmatic persons exposed at all benchmark levels (2009 SO2 REA, Figures 8-16 and 8-

31 19). 

32  The exposure results using as is air quality were similar to that estimated using air quality 

adjusted to a 99th 33 percentile 1-hour daily maximum of 50 or 100 ppb in either study area 

34 (2009 SO2 REA, Figures 8-16 and 8-19). 

35 Health Risk Assessment 

36  In terms of estimated percentage of all asthmatics or asthmatic children experiencing one 

37 or more lung function responses, estimated risks are greater for asthmatic children (2009 

38 SO2 REA, Tables 9-5 and 9-8, respectively), likely because they spend more time 

39 outdoors and at higher exertion levels than adults. 

40 o For example, approximately 13% of all asthmatics were estimated to experience 

41 at least one moderate lung function response (defined as an increase in sRaw ≥
Do Not Quote or Cite 5-6 March 2014 

1 100% (2009 SO2 REA, Table 9-5), while approximately 19% of asthmatic 

2 children experienced a similar response (2009 SO2 REA, Table 9-8). 

3  A broad range of SO2 exposure concentration intervals selected, some as high as 500 ppb, 

4 contributes to the estimated risks of experiencing one or more lung function responses 

5 per year for some of the standards considered in the assessment. For potential alternative 

6 1-hour standards in the range of 100 to 150 ppb, SO2 exposure concentration intervals 

7 below 200 ppb contribute to most of the estimated risks of experiencing one or more lung 

8 function responses per year (2009 SO2 REA, Figures 9-7 and 9-8). 

9 

10 5.1.2 Key Uncertainties 

11  Uncertainty in the statistical model used to estimate 5-minute maximum SO2 

12 concentrations from 1-hour SO2 concentrations. 

13  Uncertainty in the spatial and temporal representativeness of the SO2 ambient monitoring 

14 network. 

15  Uncertainties associated with the proportional air quality adjustment procedure that was 

16 used to simulate just meeting the then-existing standard and several alternative 1-hour 

17 daily maximum standards. 

18  Uncertainties related to the exposure model inputs and exposure estimates which are an 

19 important input to the risk assessment. 

20  Uncertainty about the shape of the exposure-response relationship for lung function 

21 responses at levels well below 200 ppb, the lowest level examined in free-breathing 

22 single-pollutant controlled human exposure studies. 

23  Uncertainty with respect to how well the estimated exposure-response relationships 

24 reflect asthmatics with more severe disease than those tested in chamber studies. 

25  Uncertainty about whether the presence of other pollutants in the ambient air would 

26 enhance the SO2-related responses observed in the controlled human exposure studies. 

27  Uncertainty about the extent to which the risk estimates presented for the two modeled 

28 areas in Missouri are representative of other locations in the U.S. with significant SO2

29 point and area sources. 

30 

31 5.2 CONSIDERATION OF QUANTITATIVE ASSESSMENTS FOR THIS 

32 REVIEW 

33 This discussion is focused particularly on considering the extent to which newly available 

34 scientific evidence and tools/methodologies are available to inform our understanding of the key 

35 areas of uncertainty identified in the 2009 REA. As outlined in Table 2-1 above, the EPA plans 

36 to release an REA Planning Document for consultation with CASAC and for public comments in 

37 February 2015 that will consider the extent to which new quantitative risk and exposure 

38 assessments would be appropriate to conduct in the current review. CASAC review and public 

39 comments on this draft IRP will be considered in developing the REA Planning Document. 
Do Not Quote or Cite 5-7 March 2014 

1 Some key areas being considered by staff, including types of data, methodologies and 

2 tools, are identified and summarized below, with a focus on the three approaches used to 

3 estimate exposure and health risk: an air quality characterization, an exposure assessment, and a 

4 health risk assessment. 

5 5.2.1 Ambient Air Quality Characterization 

6 The goals of an SO2 ambient air quality characterization in a new quantitative risk and 

7 exposure assessment would be (1) to estimate short- and long-term ambient concentration levels 

8 that consider unadjusted SO2 air quality and air quality adjusted to just meeting the existing and 

9 any potential alternative SO2 standards; (2) to develop quantitative relationships between short10 term peak concentrations and time-averaged concentrations; and (3) to identify key assumptions 

11 and uncertainties. 

12 For the analyses conducted during the last review, ambient SO2 monitoring data were 

13 available up to mid-2007 (2006 was the most recent year with complete data at that time). Since 

14 that review, additional 5-minute data have become available (Table 5-1), particularly during the 

15 most recent years (2010-2012). Ambient monitors reporting all twelve 5-minute values per hour 

are tabulated in the 2nd 16 column; monitors which report one maximum 5-minute value per hour 

are in the 3rd 17 column; and hourly average monitors not included in the two preceding columns 

18 are counted in the last column. Given the greatly expanded number of monitors, it is possible 

19 that we could develop a new statistical model to estimate 5-minute concentrations from hourly 

20 concentrations. Additional ambient monitoring attributes (e.g., proximity to selected emission 

21 sources) could be considered in its design. Output from this new model could be compared with 

22 that generated using the statistical model used in the prior air quality characterization. In 

23 addition, relationships between 5-minute peak concentrations and longer averaging times (e.g., 

24 greater than 1-hour but less than 24-hour) would be considered. And finally, new completeness 

25 criteria could be proposed in development of this new statistical model to potentially ensure the 

26 quality and representativeness of available measurements that are used. 

27 Table 5-2 summarizes the potential areas where additional information, if available, 

28 would provide reasonable substance to address key uncertainties identified in the previous 

29 review. These will be considered, in addition to the above factors, in deciding the extent to 

30 which new quantitative risk and exposure assessments would be appropriate to conduct in the 

31 current review. 
Do Not Quote or Cite 5-8 March 2014 

Table 5-1. The numbers of SO2 monitors 2003 to 201232 1 

Year Monitors Reporting 5-

Minute Continuous 

Concentrations1

Monitors Reporting 5-

Minute Maximum 

Concentrations2

Monitors Reporting 

1-Hour 

Concentrations2

2003 6 40 528 

2004 6 32 524 

2005 6 24 510 

2006 4 24 498 

2007 4 22 499 

2008 3 20 471 

2009 2 20 440 

2010 149 31 435 

2011 194 183 435 

2012 195 185 450 

1 2 5-minute continuous monitors with at least 20,000 values/year (about 20% data 

3 completeness). 

2 4 5-minute maximum and hourly with at least 50% data completeness (4,380 values/year). 

5 

6 5.2.2 Exposure Assessment 

7 The goals of an SO2 exposure assessment in a new quantitative risk and exposure 

8 assessment would be (1) to estimate short- and long-term exposures to ambient concentrations 

9 through air quality and modeling analyses considering current air quality for SO2 and air quality 

10 levels just meeting the current and any potential alternative SO2 standards; (2) compare 

11 estimated exposures to potential health effect benchmark levels; and (3) to identify key 

12 assumptions and uncertainties. Our assessment of uncertainties in the prior SO2 REA and the 

13 potential utility and impact of newly available information regarding the conduct of a new 

14 exposure assessment could consider the following: 

15  Factors that may contribute to greater personal exposures including the impacts of important 

16 sources of SO2 (e.g., outdoor point sources). 

17  Factors that may contribute to lessened personal exposures including infiltration and the 

18 decay of SO2 indoors. 

19  Impact of human behavior (e.g., time spent indoors or outdoors, time spent near sources, 

20 timing of exposure event, breathing rate) in influencing the magnitude and duration of 

21 exposures, and frequency of repeated short-term peak exposures. 

22  Population living in close proximity to local sources or otherwise living in areas with 

23 elevated SO2 concentrations. 

24  Frequency and (temporal and spatial) variability of peak air quality levels at concentrations 

25 and averaging times of significance. 

 

32 In the last review, the final rulemaking required States to report either the highest 5-minute concentration for each 

hour of the day, or all twelve 5-minute concentrations for each hour of the day (see section 1.3) 
Do Not Quote or Cite 5-9 March 2014 

1 As done was done previously, APEX could be used though we would employ the latest 

version the model33 2 (US EPA, 2012a; 2012b) to estimate 5-minute or long-term exposures of 

3 interest. Table 5-2 summarizes the potential areas where additional information regarding the 

4 assessment of exposure, if available, would provide reasonable substance to address key 

5 uncertainties identified in the previous review. These will be considered, in addition to the 

6 above factors, in deciding the extent to which new quantitative risk and exposure assessments 

7 would be appropriate to conduct in the current review. 

8 5.2.3 Risk Assessment 

9 The goals of a SO2 risk assessment in a new quantitative risk and exposure assessment 

10 would be (1) to estimate the number/percent of people at risk of adverse health effects following 

11 exposure to SO2 concentrations considering current air quality for SO2 and air quality levels just 

12 meeting the current and any potential alternative SO2 standards; (2) to provide distributions of 

13 health risk estimates over a range of ambient SO2 concentrations; and (3) to identify key 

14 assumptions and uncertainties. Our assessment of uncertainties in the prior SO2 REA and the 

15 potential utility and impact of newly available information regarding the conduct of a new risk 

16 assessment could consider the following: 

17  The level and averaging time associated with potential health effect benchmark levels, 

18 particularly if there are newly identified at-risk study groups. 

19  New controlled human exposure studies having the same responses reported in the last 

20 review (i.e., sRaw and FEV1) or newly identified adverse responses that could form the basis 

21 for the development of exposure-response (E-R) relationships. 

22  New epidemiologic study(s) that provide(s) concentration-response (C-R) relationships based 

23 on data collected in environmentally-relevant settings. Depending on the type of health 

24 response function(s) available, ambient SO2 concentration data would be used for 

25 characterizing risks and would be most appropriately applied in areas where the 

26 epidemiologic study was performed. 

27 

28 Table 5-2 summarizes the potential areas where additional information regarding the 

29 assessment of risk, if available, would provide reasonable substance to address key uncertainties 

30 identified in the previous review. These will be considered, in addition to the above factors, in 

31 deciding the extent to which new quantitative risk and exposure assessments would be 

32 appropriate to conduct in the current review. 

 

33 APEX is also referred to as the Total Risk Integrated Methodology/Exposure (TRIM.Expo) model (see 

http://www.epa.gov/ttn/fera/trim_gen.html for general details on TRIM). 
Do Not Quote or Cite 5-10 March 2014 

1 Table 5-2. Primary uncertainties associated with the exposure and risk assessments in the 

2 previous review and the potential use of new information for reducing these uncertainties 

Component of 

Assessment 

Uncertainty/Limitation 

Remaining From Prior REA 

Consideration of Potential 

Utility of Information Newly 

Available in This Review 

For the Assessment 

Air quality characterization

Characterize relationships 

between 5-minute peak 

concentrations and longer 

averaging times. 

Ambient monitor spatial and 

temporal representativeness 

regarding the limited number 

of monitors reporting 5-minute 

SO2 concentrations. 

There are now more monitors 

reporting 5-minute 

concentrations compared with 

that used in the last review. 

A new characterization of 

monitor site attributes and 

emissions sources influencing 

both 5-minute and hourly SO2

ambient monitoring 

concentrations could be 

performed. 

Develop predictive 

relationships to 

approximate the probability 

of occurrence of 5-minute 

peak concentrations given 

hourly average 

concentrations and site 

specific data for use in 

locations without 5-minute 

ambient monitors. 

Uncertainty of the statistical 

model used to estimate 5-

minute maximum SO2

concentrations at monitors that 

reported only 1-hour SO2

concentrations. 

The estimated number of 

exceedances of potential 

health effect benchmark 

levels occurring at 

monitors located across the 

U.S. 

Ambient monitor spatial and 

temporal representativeness 

Selection of potential 

health effect benchmark 

levels 

The health effect benchmark 

levels used in the SO2 REA 

were derived from the ISA’s 

evaluation of the 5 - 10 minute 

controlled human exposure 

literature. 

The subjects participating in 

these human exposure studies 

were exercising asthmatics and 

do not include individuals who 

may be most susceptible to the 

respiratory effects of SO2 (e.g., 

the most severe asthmatics). 

Since the majority of controlled 

human exposure studies 

investigating lung function 

New estimates of benchmark 

exceedances could be 

developed if there are studies 

newly available that indicate 

alternative benchmark levels 

exist outside of the range 

already considered in the 2009 

SO2 REA. 
Do Not Quote or Cite 5-11 March 2014 

Component of 

Assessment 

Uncertainty/Limitation 

Remaining From Prior REA 

Consideration of Potential 

Utility of Information Newly 

Available in This Review 

For the Assessment 

responses to SO2 were 

conducted with adult subjects, 

the risk assessment relies on 

data from adult asthmatic 

subjects to estimate exposureresponse relationships that have 

been applied to all asthmatic 

individuals, including children. 

Approach used to simulate 

just meeting potential air 

quality standard scenarios 

The proportional adjustment 

factors derived from an area’s 

design monitor are applied to 

adjust all ambient monitors 

within the given study area. 

Deviation from proportionality 

at any monitor could result in 

either over or under-estimation 

of concentrations. 

A different methodology 

could be used if there are 

studies newly available that 

indicate an improved 

alternative approach to 

adjusting air quality. 

Exposure assessment

The estimated number of 

people with exposures 

above the potential health 

effect benchmarks in 

different locations 

Uncertainty in some of the 

exposure model input data 

(e.g., activity patterns, indoor 

decay rates, air exchange rates) 

It is possible that there could 

be additional data and/or 

analyses that could be reduce 

this uncertainty to some 

extent. 

Representativeness of 

study areas 

The modeling approach used in 

the prior REA to assessing 

exposures was resource 

intensive; therefore, the 

geographic scope of this 

analysis was limited to two 

study areas, albeit having two 

differing emissions and 

population densities. 

The availability of recently 

collected 5-minute ambient 

monitor concentrations and 

consideration of other air 

quality input data sources 

(e.g., dispersion model) could 

allow for exposure estimates 

to be developed in other study 

areas. 

Risk assessment based on clinical exposure studies

Probabilistic exposureresponse relationships A generally common and 

important uncertainty in human 

exposure studies is the limited 

number of study subjects as 

well as limits to the type of preexisting health conditions 

subjects may have, particularly 

if the health condition affords 

the subject with heightened 

The availability of new 

clinical studies could reduce 

the uncertainty associated 

with probabilistic exposureresponse relationships. 
Do Not Quote or Cite 5-12 March 2014 

Component of 

Assessment 

Uncertainty/Limitation 

Remaining From Prior REA 

Consideration of Potential 

Utility of Information Newly 

Available in This Review 

For the Assessment 

effects sensitivity to the 

pollutant exposure. 

There remains greater 

uncertainty in responses below 

200 ppb because of the lack of 

experimental data. 

Risk assessment based on epidemiologic studies

City-specific 

concentration-response 

relationships

In the last SO2 NAAQS review, 

the REA concluded that the 

epidemiologic evidence was 

not appropriate for use in 

quantitative risk analyses. 

The ability to conduct an 

epidemiology-based risk 

assessment for SO2 would 

depend on the availability of 

concentration-response 

relationships from new 

epidemiologic studies 

sufficient to reduce the 

uncertainty to an acceptable 

level. 

A risk characterization based 

on epidemiologic studies also 

requires baseline incidence 

rates and population data for 

the risk assessment locations. 
Do Not Quote or Cite 5-13 March 2014 

1 

2 5.2.4 Uncertainty and Variability 

3 The uncertainty and variability inherent in characterizing ambient air quality and in 

4 estimating exposure and risk would also be evaluated in a new quantitative risk and exposure 

5 assessment. Uncertainty reflects the degree of confidence in the representativeness of models or 

6 model components. Variability can be described in terms of empirical quantities that are 

7 inherently variable across time and space or between individuals (Cullen and Frey, 1999). 

8 Consistent with prior NAAQS REAs including the last SO2 REA, EPA would consider using the 

9 approach described in WHO (2008), whereas a tiered approach to assessing uncertainty and 

10 variability in exposure and risk estimates will be employed, beginning with a qualitative analysis 

11 and progressing to a quantitative analysis only if warranted and if data are available to support 

12 such an analysis. 

13 5.3 PUBLIC AND SCIENTIFIC REVIEW 

14 The CASAC review panel on the SO2 primary NAAQS will be consulted on the 

15 risk/exposure assessment REA Planning Document at a public meeting. The panel will also 

16 review drafts of the risk/exposure assessment. The panel will review the draft document and 

17 discuss their comments in a public meeting announced in the Federal Register. Based on 

18 CASAC’s past practice, EPA expects that key CASAC advice and recommendations for revision 

19 of the document will be conveyed by the CASAC chair in a letter to the EPA Administrator. In 

20 revising the draft risk/exposure assessment for SO2, EPA will take into account any such advice 

21 and recommendations. EPA will also consider comments received from CASAC or from the 

22 public at the meeting itself and any written public comments. EPA anticipates preparing a 

23 second draft of the risk/exposure assessment for CASAC review and public comment. After 

24 appropriate revision, the final document will be made available on an EPA website and 

25 subsequently printed, with its public availability being announced in the Federal Register.
Do Not Quote or Cite 6-1 March 2014 

1 6. AMBIENT AIR MONITORING 

2 In the course of NAAQS reviews, aspects of the methods for measuring ambient levels of 

3 the NAAQS pollutant, as well as the current network of monitors, including their physical 

4 locations and monitoring objectives, are reviewed. The methods for sampling and analysis of 

5 each NAAQS pollutant are generally reviewed in conjunction with consideration of the indicator 

6 element for each NAAQS. Consideration of the ambient air monitoring network generally 

7 informs the interpretation of current data on ambient air concentrations and includes an 

8 assessment of the adequacy of the monitoring network for determining compliance with the 

9 existing or, as appropriate, a potentially revised NAAQS. This chapter describes plans for 

10 considering these aspects of the ambient air monitoring program for sulfur oxides which includes 

11 the indicator SO2. 

12 

13 6.1 CONSIDERATION OF SAMPLING AND ANALYSIS METHODS 

14 In order for the data to be used to determine compliance, ambient SO2 concentration data 

15 must be obtained using Federal Reference Methods (FRMs) or Federal Equivalent Methods 

16 (FEMs) which are designated by the Agency in accordance with 40 CFR Part 50 and Part 53. 

17 As described earlier, SO2 is the indicator for the sulfur oxides NAAQS, and has been routinely 

18 measured by UV fluorescence FEMs since the 1980s. The SO2 concentration data produced by 

19 modern FEM analyzers are routinely logged by state and local agencies whom report the hourly 

20 average and either the maximum 5-minute value (one of twelve 5-minute periods) in the hour or 

21 all twelve 5-minute averages within the hour to EPA’s Air Quality System (AQS). 

22 The Agency is unaware of any recent technological advances in SO2 measurements or 

23 forthcoming modifications to existing methods that should be considered in this NAAQS review. 

24 Therefore, the EPA does not anticipate raising any specific sampling and analysis methods issues 

25 for consideration in this integrated review plan. 

26 6.2 CONSIDERATION OF AIR MONITORING NETWORK 

27 REQUIREMENTS 

28 The ambient air quality monitoring networks for criteria pollutants support three major 

29 objectives: (1) to provide air pollution data to the general public in a timely manner; (2) to 
Do Not Quote or Cite 6-2 March 2014 

1 support compliance with NAAQS and emissions strategy development; and (3) to support air 

2 pollution research studies. A review of the available SO2 monitoring network and data was 

3 performed as part of the primary SO2 NAAQS review completed in 2010. Subsequent to that 

4 review, and in conjunction with revising the primary standards, the Agency promulgated 

5 minimum monitoring requirements to support the implementation of a new primary 1-hour SO2

6 standard. The 2010 action introduced minimum requirements based upon the use of a Population 

7 Weighted Emissions Index (PWEI). The PWEI utilizes both population and emissions data 

8 within Core Based Statistical Areas (CBSAs) to determine if monitoring is required in a CBSA 

9 and, if so, how many monitors are required. The intent of using the PWEI to require monitors is 

10 to focus monitoring into areas where there is a higher proximity of population and SO2

11 emissions. In effect, areas with a higher calculated PWEI value are expected to have higher 

12 potential for population exposure to peak, short-term SO2 emissions. 

13 Historically, the data used to determine compliance with the SO2 NAAQS have been 

14 largely based upon data obtained from ambient monitors operated by state, local, and tribal air 

15 monitoring agencies. These monitors are either required due to federal regulation contained in 

16 40 CFR Part 58, Appendix D, state implementation plans, industrial permits, or other state or 

17 local requirements or voluntary actions. While monitoring data are a mainstay in determining 

18 compliance for all other criteria pollutants, SO2 is unique in that there is a precedent to also use 

19 dispersion modeling in the implementation of its NAAQS. This is notable because the use of 

20 modeling in lieu of monitoring can potentially reduce the necessary size and distribution of a 

21 compliance monitoring network. As a result, the final monitoring requirements promulgated as 

part of the 2010 SO2 NAAQS revision reflected this potentiality.34 22 

23 As of December 2013, the ambient SO2 monitoring network is estimated to have 431 

24 monitors in operation nationwide. This number far exceeds the approximate 129 required by 

25 PWEI. 

 

34 The best available rationale and description of the Agency’s current thinking on the SO2 implementation is “Next 

Steps for Area Designations and Implementation of the Sulfur Dioxide National Ambient Air Quality Standard,” 

also known as the “strategy paper,” which was released in February of 2013 

(http://www.epa.gov/airquality/sulfurdioxide/pdfs/20130207SO2StrategyPaper.pdf). 
Do Not Quote or Cite 7-1 March 2014 

1 7. POLICY ASSESSMENT/RULEMAKING 

2 7.1 POLICY ASSESSMENT 

3 The PA, like the previous OAQPS Staff Paper, is a document that provides a transparent 

4 OAQPS staff analysis and staff conclusions regarding the adequacy of the current standard and 

5 potential alternatives that are appropriate to consider prior to the issuance of proposed and final 

6 rules. The PA integrates and interprets the information from the ISA and REA(s) to frame policy 

7 options for consideration by the Administrator. The PA is also intended to facilitate CASAC’s 

8 advice to the Agency and recommendations to the Administrator on the adequacy of the existing 

9 standard or revisions that may be appropriate to consider. Staff conclusions in the PA are based 

10 on the information contained in the ISA and, as available, the REA, and any additional staff 

11 evaluations and assessments discussed in the PA. In so doing, the discussion in the PA is framed 

12 by consideration of a series of policy-relevant questions drawn from those outlined in chapter 3, 

13 including the fundamental questions associated with the adequacy of the current standard and, as 

14 appropriate, consideration of an alternative standard(s) in terms of the specific elements of the 

15 standard: indicator, averaging time, level, and form. 

16 The PA for the current review will identify conceptual evidence-based and risk/exposure17 based approaches for reaching public health policy judgments. It will discuss the implications of 

18 the science and quantitative assessments for the adequacy of the current primary standard and for 

19 any alternative standards under consideration. The PA will also describe a broad range of policy 

20 options for standard setting, identifying the range for which the staff identifies support within the 

21 available information. In so doing, the PA will describe the underlying interpretations of the 

22 scientific evidence and risk/exposure information that might support such alternative policy 

23 options that could be considered by the Administrator in making decisions for the primary SO2

24 standard. Additionally, the PA will identify key uncertainties and limitations in the underlying 

25 scientific information and in our assessments. The PA will also highlight areas for future health26 related research, model development, and data collection. 

27 In identifying a range of primary standard options for the Administrator to consider, it is 

28 recognized that the final decision will be largely a public health policy judgment. A final 

29 decision must draw upon scientific information and analyses about health effects and risks, as 

30 well as judgments about how to deal with the range of uncertainties that are inherent in the 

31 scientific evidence and analyses. Staff’s approach to informing these judgments recognizes that 

32 the available health effects evidence generally reflects a continuum consisting of ambient 

33 concentrations at which scientists generally agree that health effects are likely to occur, through 

34 lower concentrations at which the likelihood and magnitude of the response become increasingly 
Do Not Quote or Cite 7-2 March 2014 

1 uncertain. This approach is consistent with the requirements of the NAAQS provisions of the 

2 CAA and with how the EPA and the courts have historically interpreted the Act. These 

3 provisions require the Administrator to establish primary standards that are requisite to protect 

4 public health and are neither more nor less stringent than necessary for this purpose. As 

5 discussed in section 1.1 above, the provisions do not require that primary standards be set at a 

6 zero-risk level, but rather at a level that avoids unacceptable risks to public health, including the 

health of at-risk populations35 7 . 

8 Staff will prepare at least one draft of the PA document for CASAC review and public 

9 comment. The draft PA document will be distributed to the CASAC Sulfur Oxides Primary 

10 NAAQS Review Panel for their consideration and provided to the public for review and 

11 comment. Review by the CASAC Panel will be discussed at public meetings that will be 

12 announced in the Federal Register. Based on past practice by CASAC, the EPA expects that 

13 CASAC would summarize their key advice and recommendations for revision of the document 

14 in a letter to the EPA Administrator. In revising the draft PA document, OAQPS will take into 

15 account any such recommendations, and also consider comments received from CASAC and 

16 from the public, at the meeting itself, and any written comments received. The final document 

17 will be made available on an EPA website, with its public availability announced in the Federal 

18 Register. 

19 

20 7.2 RULEMAKING 

21 Following issuance of the final PA and the EPA management consideration of staff 

22 analyses and conclusions presented therein, and taking into consideration CASAC advice and 

23 recommendations, the Agency will develop a notice of proposed rulemaking. The proposed 

24 rulemaking notice conveys the Administrator’s proposed conclusions regarding the adequacy of 

25 the current standard(s) and any revision that may be appropriate. A draft notice of proposed 

26 rulemaking will be submitted to the Office of Management and Budget (OMB) for interagency 

27 review, in which OMB and other federal agencies are provided the opportunity for review and 

28 comment. After the completion of interagency review, the EPA will publish the notice in the 

29 Federal Register seeking comment on proposed agency action – namely whether or not to revise 

30 the current standard, and if so, how. Monitoring rule changes associated with review of the 

 

35 The at-risk population groups identified in a NAAQS review may include low income or minority groups. Where 

low income/minority groups are among the at-risk populations, the rulemaking decision will be based on providing 

protection for these and other at-risk populations and lifestages (e.g., children, older adults, persons with preexisting heart and lung disease). To the extent that low income/minority groups are not among the at-risk 

populations identified in the ISA, a decision based on providing protection of the at-risk lifestages and populations 

would be expected to provide protection for the low income/minority groups. 
Do Not Quote or Cite 7-3 March 2014 

1 primary SO2 standard, and drawing from considerations outlined in Chapter 6 above, will be 

2 developed and proposed, as appropriate, in conjunction with this NAAQS rulemaking. 

3 At the time of publication of the notice of proposed rulemaking, all materials on which 

the proposal is based are made available in the public docket for the rulemaking.36 4 Publication 

5 of the proposal notice is followed by a public comment period, generally lasting 60 to 90 days, 

6 during which the public is invited to submit comments on the proposal to the rulemaking docket. 

7 EPA also will provide opportunity for a public hearing on any proposed action. Taking into 

8 account comments received on the proposed action, the Agency will then develop a notice of 

9 final rulemaking, which again undergoes OMB-coordinated interagency review prior to issuance 

10 by the EPA of the final rule. At the time of final rulemaking, the Agency responds to all 

significant comments on the proposed action.37 11 Publication of the final action in the Federal 

12 Register completes the process. 

13 

14 

15 

16 

17 

 

36 The rulemaking docket for the current primary SO2 NAAQS review is identified as EPA-HQ-OAR-2013-0566. 

This docket has incorporated the ISA docket (EPA–HQ–ORD–2013-0357) by reference. Both dockets are publicly 

accessible at www.regulations.gov. 37 For example, Agency responses to all substantive comments on the 2009 notice of proposed rulemaking in the last 

review were provided in the preamble to the final rule and in a document titled Responses to Significant Comments 

on the 2009 Proposed Rule on the Primary National Ambient Air Quality Standards for Sulfur Dioxide, available at:

http://www.epa.gov/ttn/naaqs/standards/so2/s_so2_cr_rc.html 
Do Not Quote or Cite 8-1 March 2014 

8. REFERENCES 

1. Cullen AC and Frey HC (1999). Probabilistic Techniques in Exposure Assessment. A handbook for dealing 

with variability and uncertainty in models and inputs. New York, NY. Plenum Press. 

2. McCurdy, T., Glen, G., Smith, L., Lakkadi, Y. (2000). The National Exposure Research Laboratory's 

Consolidated Human Activity Database. J Expo Anal Environ Epidemiol. 10: 566-578. 

3. Morgan M.G.; Henrion M. (1990). Uncertainty: A Guide To Dealing with Uncertainty in Qualitative Risk and 

Policy Analysis. Cambridge University Press. 

4. Samet JM. (2009). Letter to EPA Administrator Lisa P. Jackson: Clean Air Scientific Advisory Committee’s 

(CASAC) Review of EPA’s Risk and Exposure Assessment to Support the Review of the SO2 Primary National 

Ambient Air Quality Standards: Second Draft. EPA–CASAC–09–007, May 18, 2009. Sulfur Dioxide Review 

Docket. Docket ID No. EPA–HQ–OAR–2007– 0352–0035. Available at http://www.regulations.gov. 

5. EPA. (1982). Air Quality Criteria for Particulate Matter and Sulfur Oxides. US EPA, Research Triangle Park, 

NC: Office of Health and Environmental Assessment. 

6. EPA. (1986). Second Addendum to Air Quality Criteria for Particulate Matter and Sulfur Oxides (1982): 

Assessment of Newly Available Health Effects Information. US EPA, Research Triangle Park, NC: Office of 

Health and Environmental Assessment. 

7. U.S. EPA (1994). Supplement to the Second Addendum (1986) to Air Quality Criteria for Particulate Matter 

and Sulfur Oxides (1982): Assessment of New Findings on Sulfur Dioxide and Acute Exposure Health Effects 

in Asthmatic Individuals EPA/600/FP-93/002. 

8. U.S. EPA (2004). AERMOD: Description of Model Formulation. Office of Air Quality Planning and 

Standards. EPA-454/R-03-004. Available at: http://www.epa.gov/scram001/7thconf/aermod/aermod_mfd.pdf. 

9. U.S. EPA (2007). Green Book Nonattainment Areas for Criteria Pollutants. Available at: 

http://www.epa.gov/air/oaqps/greenbk/index.html. 

10. U.S. EPA (2008). Integrated Science Assessment (ISA) for Sulfur Oxides – Health Criteria (Final Report). 

EPA/600/R-08/047F. Available at: http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=198843. 

11. U.S. EPA (2009). Risk and Exposure Assessment to Support the Review of the SO2 Primary National Ambient 

Air Quality Standard. EPA-452/P-09-007. July 2009. Available at: 

http://www.epa.gov/ttn/naaqs/standards/so2/s_so2_cr_rea.html. 

12. U.S. Environmental Protection Agency (2012a). Total Risk Integrated Methodology (TRIM) - Air Pollutants 

Exposure Model Documentation (TRIM.Expo / APEX, Version 4.4) Volume I: User’s Guide. Office of Air 

Quality Planning and Standards, U.S. Environmental Protection Agency, Research Triangle Park, NC. EPA452/B-12-001a. Available at: http://www.epa.gov/ttn/fera/human_apex.html

13. U.S. Environmental Protection Agency (2012b). Total Risk Integrated Methodology (TRIM) - Air Pollutants 

Exposure Model Documentation (TRIM.Expo / APEX, Version 4.4) Volume II: Technical Support Document. 

Office of Air Quality Planning and Standards, U.S. Environmental Protection Agency, Research Triangle Park, 

NC. EPA-452/B-12-001b. Available at: http://www.epa.gov/ttn/fera/human_apex.html 

14. U.S. Environmental Protection Agency. (2013a) Integrated Science Assessment for Lead (Final Report). U.S. 

Environmental Protection Agency, Washington, DC, EPA/600/R-10/075F... Available at: 

http://www.epa.gov/ttn/naaqs/standards/pb/s_pb_2010_isa.html. 
Do Not Quote or Cite 8-2 March 2014 

15. U.S. Environmental Protection Agency (2013b). Integrated Science Assessment of Ozone and Related 

Photochemical Oxidants (Final Report). U.S. Environmental Protection Agency, Washington, DC. EPA/600/R10/076F. Available at: http://www.epa.gov/ttn/naaqs/standards/ozone/s_o3_2008_isa.html 

16. WHO (2006). Air Quality Guidelines. Global Update 2005. Particulate matter, ozone, nitrogen dioxide and 

sulfur dioxide Summary of Risk Assessment. World Health Organization. Available at, 

http://www.euro.who.int/InformationSources/Publications/Catalogue/20070323_1

17. WHO. (2008). WHO/IPCS Harmonization Project Document No. 6. Part 1: Guidance Document on 

Characterizing and Communicating Uncertainty in Exposure Assessment. Geneva, World Health Organization, 

International Programme on Chemical Safety. Available at: 

http://www.who.int/ipcs/methods/harmonization/areas/exposure/en 
Do Not Quote or Cite A-1 March 2014 

APPENDIX A 

DRAFT OUTLINE FOR INTEGRATED SCIENCE ASSESSMENT FOR 

SULFUR OXIDES – HEALTH CRITERIA 

Preamble Process of ISA Development 

(will be available online) EPA Framework for Causal Determination 

 Public Health Impact 

 Concepts in Evaluating Adversity of Health Effects 

Preface Legislative Requirements for the NAAQS Review 

 History of the Primary NAAQS for Sulfur Dioxide 

Executive Summary 

Chapter 1 Integrative Summary 

1.1 Policy-relevant Questions for Sulfur Dioxide NAAQS Review 

1.2 ISA Development and Scope 

1.3 Sulfur Oxides Sources, Ambient Concentrations, Exposure 

1.4 Health Effects Evidence 

 Exposure, Dosimetry, and Modes of Action 

 Comparison of 2008 ISA and Current Conclusions 

 Key Evidence for Evaluated Health Effects 

1.5 Policy-Relevant Considerations 

 Concentration-Response and Thresholds 

 Exposure Averaging Times and Lags 

 At-risk Populations 

 Adverse Health Effects, Public Health Significance 

1.6 Summary 

Chapter 2 Atmospheric Behavior of Sulfur Oxides 

2.1 Introduction 

2.2 Sources 

2.3 Atmospheric Chemistry and Fate 

2.4 Monitoring 

2.5 Atmospheric Concentrations of Sulfur Oxides 

2.6 Modeling 

2.7 Summary and Conclusions 

Chapter 3 Exposure to Ambient Sulfur Oxides 

3.1 Introduction 

3.2 General Considerations 

3.3 Exposure Measurement 

3.4 Exposure-related Metrics 
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3.5 Exposure Modeling 

3.6 Implications for Epidemiologic Studies 

3.7 Summary and Conclusions 

Chapter 4 Integrated Health Effects Exposure to Sulfur Oxides 

4.1 Introduction 

4.2 Dosimetry and Mode of Action 

4.3 Respiratory Morbidity 

 Peak (5-10 min) and Short-Term (1+ hr) Exposure 

 Long-Term Exposure 

4.4 Cardiovascular Morbidity (Short-Term and Long-Term) 

4.5 Other Morbidity 

 Reproductive and Developmental 

 Cancer 

 Neurological/Other Emerging Outcomes 

4.6 Mortality (Short-Term and Long-Term Exposure) 

4.7 Summary and Conclusions 

Chapter 5 Potential At-risk Lifestages and Populations 

 Introduction and Summary of 2008 ISA Key Findings 

 Review of Evidence for Specific Lifestages or Factors 

 Influencing Health Effects of Sulfur Oxides such as: 

 Children, Older Adults, Socioeconomic Status, Diet, Sex, 

 Pre-existing Disease, Genetic Variants 

 Summary and Conclusions 
 

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United States 

Environmental Protection Agency

Office of Air Quality Planning and Standards 

Health and Environmental Impacts Division 

Research Triangle Park, NC 

Publication N