Integrated Review Plan for the 

Primary National Ambient Air 

Quality Standard for Sulfur 

Dioxide 
EPA-452/R-14-007 

October 2014 

Integrated Review Plan for the 

Primary National Ambient Air Quality 

Standard for Sulfur Dioxide 

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 

October 2014
 ii October 2014 

DISCLAIMER 

This 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 plan may be modified based on 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. 
 iii October 2014 

TABLE OF CONTENTS 

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

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

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

1. INTRODUCTION .............................................................................................................. 1-8

1.1 LEGISLATIVE REQUIREMENTS ........................................................................ 1-8

1.2 OVERVIEW OF THE NAAQS REVIEW PROCESS .......................................... 1-10

1.3 HISTORY OF THE REVIEW OF AIR QUALITY CRITERIA FOR SULFUR 

OXIDES AND THE NAAQS FOR SULFUR DIOXIDE ................................... 1-14

1.4 SCOPE OF THE CURRENT REVIEW ................................................................ 1-17

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 ............................................................................. 4-2

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 .......................................................................................... 5-5

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

5.2 CONSIDERATION OF QUANTITATIVE ASSESSMENTS FOR THIS REVIEW

 5-7

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

5.2.2 Exposure Assessment......................................................................... 5-10

5.2.3 Risk Assessment ................................................................................ 5-11

5.2.4 Uncertainty and Variability ................................................................ 5-12

5.2.5 Presentation of Updated Exposure and Risk Information .................. 5-12

5.3 SCIENTIFIC AND PUBLIC 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 .... 6-2
 iv October 2014 

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

7.1 POLICY ASSESSMENT ........................................................................................ 7-1

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

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

APPENDIX A ............................................................................................................................. A-1
 v October 2014 

LIST OF FIGURES 

Figure 1-1 Overview of the NAAQS Review Process ........................................................... 1-11

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
 vi October 2014 

LIST OF TABLES 

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

dioxide since 1971 ..................................................................................................... 1-15

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

Table 5-1. Primary uncertainties associated with the air quality analysis in the previous 

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

..................................................................................................................................... .5-8

Table 5-2. The numbers of SO2 monitors 2003 to 2012 ........................................................ 5-10
 vii October 2014 

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 Core Based 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 

PWEI Population Weighted Exposure Index 

REA Risk and Exposure Assessment 

SES Socioeconomic status 

SLAMS State and local air monitoring stations 

SOx Sulfur oxides 

SO2 Sulfur dioxide 
 1-8 October 2014 

 

1. INTRODUCTION 

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

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

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

These elements will be considered collectively in evaluating the protection to public health 

afforded by the primary standard(s). 

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

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

scope of the current review, and an overview of past reviews of the primary SO2 NAAQS.5 

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

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

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

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

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

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

provided in chapter 8. 

1.1 LEGISLATIVE REQUIREMENTS 

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

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

pollutants and then to issue air quality criteria for those pollutants that are listed. The 

Administrator is to list those pollutants that in her “judgment, cause or contribute to air pollution 

which may reasonably be anticipated to endanger public health or welfare”; “the presence of 

 

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. 5

 The listed criteria pollutant is SOx (34 FR 1988), therefore in each NAAQS review EPA must evaluate health 

effects associated with all SOx species. In previous reviews, most all of the health information has been in terms of 

SO2, and therefore, SO2 has been used as the indicator for a NAAQS set to address the health effects associated with 

all gaseous SOx species (see section 3.1.2). In the current review, EPA will again evaluate health effects associated 

with all SOx species and then determine whether the indicator for the standard should be revised or retained. 
 1-9 October 2014 

 

which in the ambient air results from numerous or diverse mobile or stationary sources”; and for 

which she “plans to issue air quality criteria ....” Air quality criteria are intended to “accurately 

reflect the latest scientific knowledge useful in indicating the kind and extent of identifiable 

effects on public health or welfare which may be expected from the presence of [a] pollutant in 

ambient air . . . .” 42 U.S.C. § 7408(a)(2). 

 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.6

 42 

U.S.C. § 7409(a). Section 109(b)(1) defines a primary standard as one “the attainment and 

maintenance of which in the judgment of the Administrator, based on such criteria and allowing 

an adequate margin of safety, are requisite to protect the public health.”7 A secondary standard, 

as defined in section 109(b)(2), must “specify a level of air quality the attainment and 

maintenance of which, in the judgment of the Administrator, based on such criteria, is required to 

protect the public welfare from any known or anticipated adverse effects associated with the 

presence of [the] pollutant in the ambient air.”8

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

intended to address uncertainties associated with inconclusive scientific and technical 

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

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

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

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

U.S. 1034 (1982); Coalition of Battery Recyclers Ass'n v. EPA, 604 F.3d 613, 617-18 (D.C. Cir. 

2010). Both kinds of uncertainties are components of the risk associated with pollution at levels 

below those at which human health effects can be said to occur with reasonable scientific 

certainty. Thus, in selecting primary standards that include an adequate margin of safety, the 

Administrator is seeking not only to prevent pollution levels that have been demonstrated to be 

harmful but also to prevent lower pollutant levels that may pose an unacceptable risk of harm, 

even if the risk is not precisely identified as to nature or degree. The CAA does not require the 

Administrator to establish a primary NAAQS at a zero-risk level or at background concentration 

 

6

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

process, the secondary SO2 standard is being reviewed in conjunction with the review of the secondary NO2

standard. 

7

 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)]. 

8 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.” 
 1-10 October 2014 

 

levels, see Lead Industries v. EPA, 647 F.2d at 1156 n.51, Mississippi v. EPA, 723 F. 3d 246, 

255, 262-63 (D.C. Cir. 2013), but rather at a level that reduces risk sufficiently so as to protect 

public health with an adequate margin of safety. 

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

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

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

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

Administrator’s judgment. See Lead Industries Association v. EPA, supra, 647 F.2d at 1161-62; 

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

In setting primary and secondary standards that are “requisite” to protect public health 

and welfare, respectively, as provided in section 109(b), the EPA’s task is to establish standards 

that are neither more nor less stringent than necessary. In so doing, the EPA may not consider 

the costs of implementing the standards. See generally, Whitman v. American Trucking 

Associations, 531 U.S. 457, 465-472, 475-76 (2001). Likewise, “[a]ttainability and 

technological feasibility are not relevant considerations in the promulgation of national ambient 

air quality standards.” American Petroleum Institute v. Costle, 665 F. 2d at 1185. 

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

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

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

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

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

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

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

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

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

Committee (CASAC) of EPA’s Science Advisory Board. 9 

1.2 OVERVIEW OF THE NAAQS REVIEW PROCESS 

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

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

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

 

9 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. 
 1-11 October 2014 

below. 10

10 The EPA maintains a website on which key documents developed for NAAQS reviews are made available (http://www.epa.gov/ttn/n

NAAQS review process has evolved over time. Information on the current process is available at: http://www.epa.gov/ttn/naaqs/reviewsection 1.3 below, this process was generally followed in the primary SO2 NAAQS review completed in 2010 with the exception that th

Policy Assessment document issued; rather the Risk and Exposure Assessment (U.S. EPA 2009, ) included a policy assessment chapter 

Figure 1-1 Overview of the NAAQS Review Process
 1-12 October 2014 

 

The planning phase of the NAAQS review process begins with a science policy 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

and assessment approach for the ISA and its supporting materials. 

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

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

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

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

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

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

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

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

document will focus on consideration of the newly available data, methods and tools in light of 

areas of uncertainty in the assessments conducted for the last review and of the potential for new 

or updated assessments to provide notably different exposure and risk estimates with lower 

associated uncertainty. To the extent warranted, this document outlines a general plan, including 
 1-13 October 2014 

 

scope and methods, for conducting assessments. The REA Planning Document is generally 

prepared in conjunction with the first draft ISA and is presented for consultation with CASAC 

and for public comment. When an assessment is performed, one or more drafts of each risk and 

exposure assessment document (REA) undergoes CASAC and public review, with the initial 

draft REA generally being reviewed in conjunction with review of the second draft ISA, prior to 

completion of the final REA. The REA provides concise presentations of methods, key results, 

observations, and related uncertainties. Chapter 5 below discusses consideration of potential 

quantitative human health-related assessments for this review. 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

completion of the final PA. 

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

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

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

interagency review involving other federal agencies prior to publication.11 Materials upon 

 

11 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 law, is not considered in 

decisions regarding the review of the NAAQS. 
 1-14 October 2014 

 

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

public in the regulatory docket for the review.12 

A public comment period, during which public hearings are generally held, follows 

publication of the notice of proposed rulemaking. Taking into account comments received on 

the proposed rule,13 the Agency develops a final rule which undergoes interagency review prior 

to publication to complete the rulemaking process. Chapter 7 discusses the development of the 

PA and the rulemaking steps for this review. 

1.3 HISTORY OF THE REVIEW OF AIR QUALITY CRITERIA FOR 

SULFUR OXIDES AND THE NAAQS FOR SULFUR DIOXIDE 

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

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

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

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

0.030 ppm annual arithmetic mean.14 Since then, the Agency has completed multiple reviews of 

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

 

12 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. 

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

14 Note that 0.14 ppm is equivalent to 140 parts per billion (ppb) and 0.030 ppm is equivalent to 30 ppb. 
 1-15 October 2014 

 

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

dioxide since 197115

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 

ppb16

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 

years17

24-hour and annual SO2 standards revoked. 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

 

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

welfare effects. 

16 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. 17 The current 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. 
 1-16 October 2014 

 

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

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

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

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

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

peak concentrations of SO2. 

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

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

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

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

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

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

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

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

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

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

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

District of Columbia (“D.C. Circuit”) found that the EPA had failed to adequately explain its 

determination that no revision to the SO2 NAAQS was appropriate and remanded the decision 

back to EPA for further explanation. Specifically, the court required the EPA to provide 

additional rationale to support the Agency judgment that 5-minute peaks of SO2 do not pose a 

public health problem from a national perspective even though these peaks will likely cause 

adverse health impacts in a subset of asthmatics. Following the remand, the EPA and American 

Lung Association entered into negotiations which resulted in EPA requesting that states 

voluntarily submit 5-minute SO2 monitoring data. The Agency would then use this 5-minute 

monitoring data to conduct air quality analyses in order to gain a better understanding of the 

magnitude and frequency of high, 5-minute peak SO2 concentrations. The data submitted by 

states and the analyses based on this data are described in chapter 5 of this document. Moreover, 

the data and analyses described in chapter 5 helped inform the last review of the SO2 NAAQS, 

which ultimately addressed the issues raised in the 1998 remand. 

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

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

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

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 percentile of 1-hour daily 

maximum concentrations (see section 3.1.2). This standard was promulgated to provide 
 1-17 October 2014 

 

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

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

standard at 75 ppb would substantially limit exposures associated with the adverse respiratory 

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

asthmatics following 5-10 minute exposures in controlled human exposure studies, as well as the 

more serious health associations reported in epidemiologic studies of mostly 1- and 24-hours 

(e.g., respiratory-related emergency department visits and hospitalizations). In the last review, 

the EPA also revoked the then-existing 24-hour and annual primary standards based largely on 

the recognition that a 1-hour standard at 75 ppb would have the effect of maintaining 24-hour 

and annual SO2 concentrations generally well below the levels of the 24-hour and annual 

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

substantially limit exposure to 5-minute concentrations of SO2 resulting in adverse respiratory 

effects in exercising asthmatics, also satisfied the remand by the D.C. Circuit in 1998. 

As mentioned above, in the last review considerable weight was placed on substantially 

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

final rulemaking, the EPA for the first time required state reporting of 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 chapter 6). The rationale for this requirement was that this additional monitored data 

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

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

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

for review arguing that the EPA failed to follow notice-and-comment rulemaking procedures, 

and that the decision to establish the 1-hour SO2 NAAQS at 75 ppb was arbitrary and capricious 

because it was lower than statutorily authorized. The D.C. Circuit rejected these challenges, 

thereby upholding the standard in its entirety National Environmental Development 

Association’s Clean Air Project v. EPA, 686 F. 3d 803 (D.C. Cir. 2012). 

1.4 SCOPE OF THE CURRENT REVIEW 

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

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

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

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

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

2013; U.S. EPA 2009). 

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

standard and as such, will only consider relevant scientific information related to potential health 
 1-18 October 2014 

 

effects associated with exposure to sulfur oxides. In a separate process, the EPA is reviewing the 

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

53452, August 29, 2013).18

 

18 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. 
 2-1 October 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. 

 
 2-2 October 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 October 2014 

Integrated Science 

Assessment (ISA) 

First draft ISA February 2015 

CASAC/public review first draft ISA May 2015 

Second draft ISA November 2015 

CASAC/public review second draft ISA January 2015 

Final ISA June 2016 

Risk/Exposure 

Assessment (REA) 

REA Planning Document July 2015 

CASAC consultation/public review REA19

Planning Document 

If warranted: 

August 2015 

 First draft REA 20

 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 April 2016 

CASAC review/public review first draft PA May 2016 

Second Draft PA (if warranted) November 2016 

CASAC/public review second draft PA December 201621

Final PA May 2017 

Notice of proposed rulemaking October 2018 

Notice of final rulemaking July 2019 

 

19 If the REA planning document concludes that an REA is not required, the REA planning document will be 

submitted for CASAC review rather than for consultation. 20 An updated REA may not be warranted for this review of the SO2 primary NAAQS 21 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. 
 3-1 October 2014 

3. KEY POLICY-RELEVANT ISSUES 

The overarching question in each NAAQS review is: 

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

information support or call into question the adequacy of the protection 

afforded by the current standard(s)? 

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

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

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

for consideration? 

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

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

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

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

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

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

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

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

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

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

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

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

primary standard for SO2. 

3.1 CONSIDERATIONS AND CONCLUSIONS IN LAST REVIEW 

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

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

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

emerged since the last review was completed in 1996. 22 In addition, EPA also considered 

exposure and risk estimates regarding potential respiratory effects in exercising asthmatics 

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

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

 

22 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 
 3-2 October 2014 

increased protection for asthmatics and other at-risk populations23 against an array of adverse 

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

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

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

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

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

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

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

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

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

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

last review are noted in section 3.1.3. 

 

3.1.1 Need for Revision 

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

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

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

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

evidence assessed in the 2008 ISA for SOX – Health Criteria (U.S. EPA 2008), including the 

assessment of the policy-relevant aspects of that evidence, 24 quantitative exposure and risk 

analyses presented in the 2009 REA (U.S. EPA 2009), public comments, and the advice and 

recommendations of CASAC (Samet, 2009). 

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

judgment that the findings of controlled human exposure, epidemiologic, and animal 

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

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

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

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

 

23 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. 24 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. 
 3-3 October 2014 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Table 3–1). 

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

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

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

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

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

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

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

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

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

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

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

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

statistically significant at the group mean level 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 individuals.25 

 

25 200 ppb was also the lowest level tested in free-breathing controlled human exposure studies. Also note that very 

young children were not included in controlled human exposure studies and this absence of data on what is likely to 

be a sensitive lifestage was a source of uncertainty in the last review. 
 3-4 October 2014 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

In considering the epidemiologic evidence, the Administrator acknowledged uncertainties 

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

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

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

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

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

1-hour daily maximum and 24-hour average) SO2 concentrations and respiratory symptoms, 
 3-5 October 2014 

emergency department visits, and hospital admissions in locations meeting the then-existing 24-

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

were not adequately protecting public health. 

 The Administrator also agreed with CASAC advice when reaching the decision that the 

then-existing standards were not adequate to protect public health with an adequate margin of 

safety. Specifically, CASAC advised that: ‘‘the current 24-hour and annual standards are not 

adequate to protect public health, especially in relation to short-term exposures to SO2 (5–10 

minutes) by exercising asthmatics’’ (Samet, 2009, p. 15). 

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

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

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

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

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

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

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

3.1.2 Elements of a Revised Standard 

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

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 percentile of the yearly distribution of 1-hour daily 

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

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

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

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

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

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

Indicator 

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

oxides because the available scientific information regarding health effects was overwhelmingly 

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

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

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

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

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

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

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

to SO2, alone or in combination with other gaseous sulfur oxides (75 FR at 35536). In so doing, 
 3-6 October 2014 

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

likely reduce exposures to other sulfur oxides (75 FR at 35536).

Averaging Time 

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

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

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

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

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

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

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

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

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

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

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

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

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

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).26 

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

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

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

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

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

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

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

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

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

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 percentile 24-

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

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

 

26 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). 
 3-7 October 2014 

associations with ambient SO2 (75 FR at 35539 and U.S. EPA 2009, section 10.5.2.2). 27 

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

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

ranging from 5-minutes to 24-hours (75 FR at 35539). 

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

agreement with CASAC recommendations (75 FR at 35539). That is, CASAC stated that they 

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

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

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

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

favored. With respect to a 5-minute standard, there were concerns about standard stability (75 FR 

at 35539). Specific concerns related to the number of monitors needed and the placement of 

such monitors given the temporal and spatial heterogeneity of 5-minute SO2 concentrations. 

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

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

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

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

protection (75 FR at 35539). 

Form 

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

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

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

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

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

Administrator to be most appropriate (75 FR at 35541). This was because compared to an 

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

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

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

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

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

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

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

(Samet 2009, p. 16) 

 

27 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. 
 3-8 October 2014 

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

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

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

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

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

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

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 percentile form (at an appropriate level) 

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

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

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

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

controlled human exposure studies (75 FR at 35541). 

Level 

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

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

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

level of a new 1-hour standard. In particular, the Administrator concluded that the level of a 1-

hour standard should provide substantial protection against the 200 ppb and 400 ppb 5-minute 

benchmarks identified from these studies. As noted above (see section 3.1.1), these benchmark 

levels were highlighted because in free-breathing controlled human exposure studies of 

exercising asthmatics: (1) 400 ppb represented the lowest concentration where moderate or 

greater lung function decrements occurred which were often statistically significant at the group 

mean level 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.28

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

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

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

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

concentrations ≥ 200 or 400 ppb (75 FR at 35547). That is, the St. Louis exposure simulation 

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

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

 

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

studies. 
 3-9 October 2014 

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

from experiencing at least one exposure ≥ 200 ppb per year (75 FR at 35547). Moreover, the 

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

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

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

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

benchmark29 (75 FR at 35546). Furthermore, given a simulated 1-hour 100 ppb standard level, 

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

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

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

to exceed the 200 ppb benchmark (75 FR at 35546). 

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

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

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

studies generally reported positive, although not always statistically significant associations 

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

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

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

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

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

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

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

the appropriate level of a new 1-hour standard. 

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

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

reporting mostly positive and sometimes statistically significant associations between ambient 

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

99th percentile 1-hour daily maximum SO2 levels ranged from approximately 50–460 ppb (75 FR 

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 percentile of 

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

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

 

29 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). 
 3-10 October 2014 

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

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

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

99th percentile concentrations in the range of 78–150 ppb (75 FR at 35547). 

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

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

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

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

respiratory morbidity effects reported in these studies (75 FR at 35548). This judgement also 

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

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

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

not find that evidence strong enough to warrant a standard at that level or below (75 FR at 

35548). 

Revoking the Then-Existing 24-hour and Annual Standards 

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

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

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

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

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

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

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

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

3.1.3 Areas of Uncertainty 

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

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

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

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

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

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

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

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

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

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

epidemiologic studies are attributable to SO2; (4) the extent to which monitored ambient SO2
 3-11 October 2014 

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

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

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

3.2 GENERAL APPROACH FOR THE CURRENT REVIEW 

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

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

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

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

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

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

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

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

evidence- and exposure/risk-based considerations.30 

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

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

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

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

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

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

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

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

provisions of the CAA related to the review of NAAQS and with how the EPA and the courts 

have historically interpreted the CAA. As discussed in section 1.1 above, these provisions 

require the Administrator to establish primary standards that, in the Administrator’s judgment, 

are requisite (i.e., neither more nor less stringent than necessary) to protect public health with an 

adequate margin of safety. The CAA does not require that primary standards be set at a zero-risk 

level, but rather at a level that reduces risk sufficiently so as to protect public health with an 

adequate margin of safety. The four basic elements of the NAAQS (i.e., indicator, averaging 

time, form, and level) will be considered collectively in evaluating the health protection afforded 

by the current standard or any alternative standards considered. 

 

30 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. 
 3-12 October 2014 

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

appropriate, on any potential alternative standards, is largely a public health policy judgment to 

be made by the Administrator. Scientific information and analyses about health effects, 

population exposure and risks, as well as judgments about how to consider the range and 

magnitude of uncertainties that are inherent in the scientific evidence and analyses inform the 

Administrator’s final decision. As in the previous review as well as other recent NAAQS 

reviews, the EPA will consider the implications of placing more or less weight or emphasis on 

different aspects of the scientific evidence and exposure/risk-based information to inform the 

public health policy judgments that the Administrator will make in reaching final decisions on 

whether to retain or revise the current standard in this review. 

 
 3-13 October 2014 

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

 



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
 3-14 October 2014 

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

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

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

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

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

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

addressing a series of questions including the following: 

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

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

ambient air? 

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

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

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

outcomes? 

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

understanding of the health effects associated with various time periods of 

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

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

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

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

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

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

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

ozone, NO2)? 

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

evidence? 

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

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

to sulfur oxides? 

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

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

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

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

and lifestages should be given increased focus in this review? 

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

to SO2? 

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

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

of the day, or all twelve 5-minute concentrations for each hour of the day. To 
 3-15 October 2014 

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

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

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

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

protect against 5-minute peak concentrations of concern? 

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

exposures above benchmark levels) are likely to occur in the general population, or in atrisk groups or lifestages considering recent ambient SO2 concentrations or concentrations 

that just meet the current SO2 standard? 

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

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

from a public health perspective? 

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

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

and/or have new uncertainties emerged? 

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

basic elements of the current primary SO2 standard? For example, does newly available 

5-minute monitoring data and the air quality analyses based on this data call into question 

any of the basic elements of the current standard? 

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

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

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

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

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

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

elements include: 

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

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

addition to, or in place of SO2? 

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

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

provide support for considering any different averaging times? 

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

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

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

any different averaging times? 
 3-16 October 2014 

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

consideration of alternative standard forms? 

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

evidence evaluated in the ISA, air quality analyses and, if warranted, in the REA31 ? 

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

assessments and how might those uncertainties and limitations be taken into 

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

and/or levels?

 

31 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. 
 4-1 October 2014 

4. SCIENCE ASSESSMENT 

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

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.32 

 

4.1 SCOPE OF THE ISA 

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

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

human exposure, dosimetry, epidemiology, controlled human exposure, and toxicology, with 

consideration of effects in both the general population and at-risk lifestages and populations. 

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

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

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

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

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

questions described in Chapter 3. 

The current ISA will focus on literature published since the 2008 ISA for SOX – Health 

Criteria and integrate this newer evidence with evidence considered in the last review. Key 

findings, conclusions, and uncertainties from the 2008 ISA for SOX will be briefly summarized 

at the beginning of the ISA and individual sections. The results of recent studies will be 

integrated with previous findings. In evaluation of controlled human exposure and animal 

toxicological studies, emphasis will be placed on studies that examine health effects relevant to 

humans and on SOX concentrations that represent the range of human exposures across various 

ambient microenvironments. However, in recognition of the fact that controlled human exposure 

and animal toxicological studies do not necessarily reflect effects in the most sensitive 

populations, studies at higher exposure concentrations will be included when they provide 

information relevant to previously unreported effects, evidence of the potential biological 

mechanism for an observed effect, or information on exposure-response relationships. 

 

32Note that evidence related to environmental effects of SOX will be considered in the separate science assessment 

conducted as part of the review of the secondary NAAQS for NO2 and SO2. 
 4-2 October 2014 

4.2 ORGANIZATION OF THE ISA 

The organization of the ISA will be consistent with that used in the recent assessments 

for other criteria pollutants, e.g., the ISA for Ozone and Related Photochemical Oxidants (U.S. 

EPA, 2013b). The ISA will begin with a discussion of major legal and historical aspects of prior 

review documents as well as procedures for the assessment of scientific information. An 

integrative synthesis chapter will summarize the key information for each topic area, the causal 

determinations for relationships between exposure to SOX and health effects, information 

describing the extent to which health effects can be attributable specifically to SOX, and other 

uncertainties related to the interpretation of scientific information. The integrative synthesis 

chapter also will present a discussion of policy-relevant issues such as the exposure averaging 

times and lags associated with health effects, the concentration-response relationships including 

whether or not the evidence supports identification of a discernible threshold below which 

effects are not likely to occur, and the public health significance of health effects associated with 

exposure to SOX. Subsequent chapters are organized by subject area (see draft outline of the ISA 

in Appendix A) and contain the detailed evaluation of results of recent studies integrated with 

previous findings (see section 4.4 for specific issues to be addressed). Sections for each major 

health effect category (e.g., respiratory effects) conclude with a causal determination about the 

relationship with relevant exposures to SOX. The ISA will conclude with a chapter that 

examines exposure and health outcome data to draw conclusions about potential at-risk lifestages 

and populations. 

The ISA may be supplemented with additional materials if required to support 

information contained within the ISA. These supplementary materials may include more 

detailed and comprehensive coverage of relevant publications and may accompany the ISA or be 

available in electronic form as output from the Health and Environmental Research Online 

(HERO) database developed by EPA (http://hero.epa.gov/). Supplementary information 

available in the HERO database will be presented as electronic links in the ISA. 

4.3 ASSESSMENT APPROACH 

4.3.1 Introduction 

NCEA is responsible for preparing the ISA. In each NAAQS review, development of the 

science assessment begins with a “Call for Information” published in the Federal Register. This 

notice announces EPA’s initiation of activities in the preparation of the ISA for the specific 

NAAQS review and invites the public to assist through the submission of research studies in the 

identified subject areas. This and subsequent key components of the process currently followed 

for the development of an ISA (i.e., the development process) are presented in Figure 4.1 and are 

described in greater detail in the Preamble to the ISA for Lead (U.S. EPA, 2013a). How the ISA 
 4-3 October 2014 

fits into the larger NAAQS review process is briefly described in Section 1.2, the Overview of 

the Review Process. 

(Modified from Figure III of the Preamble to the ISA for Lead, U.S. EPA, 2013a) 

Figure 4-1. General Process for Development of Integrated Science Assessments (ISAs)
 4-4 October 2014 

Important aspects of the development of the ISA are described in the sections below, 

including the approach for searching the literature, identifying relevant publications, evaluating 

individual study quality, synthesizing and integrating the evidence, and developing scientific 

conclusions and causality determinations. These responsibilities are undertaken by expert 

authors of the ISA chapters which include EPA staff with extensive knowledge in their 

respective fields and extramural scientists solicited by EPA for their expertise in specific fields. 

This section of the IRP also presents specific policy-relevant questions developed from input 

received at the SOX kickoff workshop on science policy issues. These questions are intended to 

guide the development of the ISA. The process for scientific and public review of drafts of the 

ISA is described in Section 4.5. 

4.3.2 Literature Search and Selection of Relevant Studies 

NCEA uses a structured approach to identify relevant studies for consideration and 

inclusion in the ISA. A Federal Register notice is published to announce the initiation of a 

review and to request information, including relevant literature, from the public. The EPA 

maintains an ongoing, multi-tiered literature search process that includes extensive manual and 

computer-aided citation mining of databases on specific topics in a variety of disciplines. The 

search strategies are designed a priori and iteratively modified to optimize identification of 

pertinent publications. In addition, papers are identified for inclusion in several other ways: 

relational citation searches that identify recent publications that have cited references from 

previous assessments; specialized searches on specific topics; identification of relevant literature 

by external scientific experts; recommendations from the public and CASAC during the call for 

information and external review process; and review of citations in previous assessments. The 

studies identified will include research published or accepted for publication from January 2008, 

which slightly precedes the publication end date for studies reviewed in the 2008 ISA, through 

approximately two months before the release of the second external review draft of the ISA 

(target of November 2015, see Table 2-1). 

References identified through this multipronged search strategy are reviewed for 

relevance. Some publications are excluded based on screening of the title. Publications 

considered for inclusion in the ISA after reading the title are listed in the Health and 

Environmental Research Online (HERO) database (http://hero.epa.gov). Studies and reports that 

have undergone scientific peer review and have been published or accepted for publication are 

considered for inclusion in the ISA. 

From the group of considered references, references are selected for inclusion in the ISA 

based on review of the abstract and full text. The references cited in the ISA include a hyperlink 

to the HERO database. The selection process is based on the extent to which the study is 

potentially informative, pertinent, and policy-relevant. These studies include those that provide a 
 4-5 October 2014 

basis for or describe the relationship between the criteria pollutant and effects, in particular, 

those studies that offer innovation in method or design and studies that reduce uncertainty on 

critical issues. Uncertainty can be addressed, for example, by analyses of potential confounding 

or effect modification by copollutants or other factors, analyses of concentration-response or 

dose-response relationships, or analyses related to time between exposure and response. The 

ISA will include studies published since the 2008 ISA; however, evidence from previous studies 

will be included to integrate with results from recent studies and, in some cases, characterize the 

key policy-relevant information in a particular subject area. Analyses conducted by the EPA 

using publicly available data, for example, air quality and emissions data, also are considered for 

inclusion in the ISA. The combination of approaches described above is intended to produce the 

comprehensive collection of pertinent studies needed to address the key scientific issues that 

form the basis of the ISA. 

4.3.3 Evaluation of Individual Study Quality 

After selecting studies for inclusion, individual study quality is evaluated by considering 

the design, methods, conduct, and documentation of each study, but not the study results. This 

uniform approach aims to consider the strengths, limitations, and possible roles of chance, 

confounding, and other biases that may affect the interpretation of the results from individual 

studies. In general, in assessing the scientific quality of studies, the following parameters are 

considered: 

 How clearly were the study design, study groups, methods, data, and results presented to 

allow for study evaluation? 

 To what extent are the air quality data, exposure, or dose metrics of adequate quality to 

serve as credible exposure indicators? 

 Were the study populations, subjects, or animal models adequately selected, and are they 

sufficiently well-defined to allow for meaningful comparisons between study or exposure 

groups? 

 Are the statistical analyses appropriate, properly performed, and properly interpreted? 

 Are likely covariates (i.e., potential confounding factors, modifying factors) adequately 

controlled for or taken into account in the study design or statistical analyses? 

 Are the health endpoint measurements meaningful, valid, and reliable? 

Additional considerations specific to particular scientific disciplines are discussed below. 

Atmospheric Science and Exposure Assessment 

Atmospheric science and exposure assessment studies focus on measurement of, behavior 

of, and exposure to ambient air pollution using quality-assured field, experimental, and/or 

modeling techniques. The most informative measurement-based studies will include detailed 

descriptive statistics for high-quality measurements taken at varying spatial and temporal scales. 
 4-6 October 2014 

These studies will also include a clear and comprehensive description of measurement 

techniques and quality control procedures used. Quality control metrics (e.g., method detection 

limits) and quantitative relationships between and within pollutant measurements (e.g., 

regression model coefficients, intercepts, and fit statistics) should be provided when appropriate. 

Measurements including contrasting conditions for various time periods (e.g., weekday/weekend, 

season), populations, regions, and categories (e.g., urban/rural, proximity to various source 

sectors) are particularly useful. The most informative modeling-based studies will incorporate 

appropriate chemistry, transport, dispersion, and/or exposure modeling techniques with a clear 

and comprehensive description of model science, evaluation procedures, and metrics. 

Exposure measurement error, which refers to inaccuracies in the characterization of the 

exposures of study participants, can be an important contributor to uncertainty in air pollution 

epidemiologic study results. Exposure measurement error can influence observed epidemiologic 

associations between ambient pollutant concentrations and health outcomes by biasing effect 

estimates toward or away from the null and widening confidence intervals around those 

estimates (Zeger et al., 2000). Factors that could influence exposure estimates include, but are 

not limited to, nonambient sources of exposure, topography of the natural and built environment, 

meteorology, air quality measurement instrument or model uncertainties, time-activity patterns, 

and the infiltration into indoor environments. Additional information present in high-quality 

exposure studies includes location and activity information from diaries, questionnaires, global 

positioning system data, or other means, as well as information on commuting patterns. In 

general, atmospheric science and exposure studies focusing on the variety of locations pertinent 

to the range of exposures in the U.S. will have maximum value in informing review of the 

NAAQS. 

Epidemiology 

In evaluating quality of inference about health effects in epidemiologic studies, EPA 

additionally considers whether a given study: (1) presents quantitative information on 

associations of health effects with short- or long-term exposures that represent ambient 

concentrations of SOX across various microenvironments; (2) examines health effects of SOX; 

(3) assesses SOX as a component of a complex mixture of air pollutants by considering 

concentrations of copollutants, correlations of SOX with these copollutants, potential copollutant 

interactions (e.g., synergistic effects of SOX with other pollutants), potential copollutant 

confounding (e.g., bias of associations observed between SOX and health endpoints by the effects 

of copollutants), and other methods to assess the independent effect of SOX; (4) evaluates health 

endpoints not previously extensively researched; (5) evaluates lifestages and populations that 

potentially are at increased risk of health effects related to SOX; (6) examines other potential 

confounding factors or effect modifiers (e.g., socioeconomic status); and (7) examines important 
 4-7 October 2014 

methodological issues (e.g., lag or time period between exposure and effects, model 

specifications, thresholds, mortality displacement) related to the health effects of exposure to 

SOX. Among epidemiologic studies characterized as high quality by these parameters, emphasis 

will be given to multicity studies that employ standard methodological analyses for evaluating 

effects of SOX across cities, provide overall estimates for effects by pooling information across 

cities, and examine consistency of results across cities. To address specific issues relevant to 

standard setting in the U.S., such as regional heterogeneity in effects, emphasis will be placed on 

studies that involve exposures that are relevant to current U.S. populations (e.g., studies 

conducted in the U.S. or Canada). 

Controlled Human Exposure and Animal Toxicology 

Controlled human exposure and animal toxicological studies experimentally evaluate the 

health effects of administered exposures in human volunteers and animal models under highly 

controlled laboratory conditions. Controlled human exposure studies are also referred to as 

human clinical studies and, as noted above, provided the definitive evidence for a causal 

relationship between short-term exposure to SO2 and respiratory morbidity in the previous 

review. These experiments allow investigators to expose subjects to known concentrations of 

SOX under carefully regulated environmental conditions and activity levels. In addition to the 

general quality considerations discussed previously, evaluation of controlled human exposure 

and animal toxicological studies includes assessing the design and methodology of each study 

with focus on (1) characterization of the exposure concentration, dosing regimen (e.g., duration, 

activity level), and exposure route; (2) characterization of the pollutant(s); (3) sample size and 

statistical power to detect differences; and (4) control of other variables that could influence the 

occurrence of effects. The evaluation of study design generally includes consideration of factors 

that minimize bias in results such as randomization, blinding and allocation concealment of study 

subjects, investigators, and research staff, and unexplained loss of animals or 

withdrawal/exclusion of subjects. Additionally, studies must include appropriate control groups 

and exposures to allow for accurate interpretation of results relative to exposure. Emphasis is 

placed on studies that address concentration-dependent responses or time-course of responses 

and studies that investigate potentially at-risk lifestages and populations (e.g., with pre-existing 

disease), recognizing that controlled human exposure studies typically examine effects in groups 

of relatively healthy individuals, often adults, who do not represent the full range of 

susceptibilities in the general population. In addition, consideration will be given to studies that 

investigate exposure to SOX separately and in combination with other pollutants such as ozone 

and particulate matter. 

Controlled human exposure or animal toxicological studies that approximate expected 

human exposures in terms of concentration, duration, and route of exposure are of particular 
 4-8 October 2014 

interest. To best inform reviews of the NAAQS, evaluation of the evidence goes beyond a 

determination of causality at any dose or concentration to emphasize the relationship apparent at 

relevant pollutant exposures. Relevant pollutant exposures are considered to be those generally 

within two orders of magnitude of ambient concentrations measured across various 

microenvironments. Studies using higher concentration exposures or doses will be considered to 

the extent that they provide information relevant to understanding mode of action or 

mechanisms, interspecies variation, or at-risk human lifestages and populations. In vitro studies 

may be included if they provide mechanistic insight for effects examined in vivo or in 

epidemiologic studies. 

4.3.4 Integration of Evidence and Determination of Causality 

EPA has developed a consistent and transparent basis for integration of scientific evidence 

and evaluation of the causal nature of air pollution-related health or welfare effects for use in 

developing ISAs, as described in the online Preamble to the ISA for Lead (U.S. EPA, 2013a). 

Evidence from across scientific disciplines for related health effects is evaluated, synthesized, 

and integrated to develop conclusions and causality determinations. This includes consideration 

of strengths and weaknesses in the overall collection of studies across disciplines. Confidence in 

the collective body of evidence is based on evaluation of study design and quality. The relative 

importance of different types of evidence to the conclusions varies by pollutant or assessment, as 

does the availability of different types of evidence for causality determination. Consideration of 

human health effects is informed by controlled human exposure, epidemiologic, and 

toxicological studies. Other evidence including mechanistic evidence, toxicokinetics, and 

exposure assessment may be highlighted if it is relevant to the evaluation of health effects and if 

it is of sufficient importance to affect the overall evaluation. Causal inference can be 

strengthened by the integration of evidence across disciplines. A weak inference from one line of 

evidence can be bolstered by other lines of evidence and their coherence can add support to a 

cause-effect interpretation of the association. Scientists will also evaluate uncertainty in the 

scientific evidence, considering issues such as: generalizing results from a small number of 

controlled human exposure subjects to the broader population, including at-risk lifestages and 

populations; quantitative extrapolations of observed pollutant-induced pathophysiological 

alterations from laboratory animals to humans; confounding by co-exposure to other ambient 

pollutants or meteorological factors; the potential for effects due to exposure to air pollution 

mixtures; and the influence of exposure measurement error on epidemiologic study findings. 
 4-9 October 2014 

The ISA will evaluate the evidence for causal relationships between observed health 

outcomes and SOX exposures using a five-level hierarchy that classifies the weight of evidence 

for causation. Determination of causality involves the evaluation and integration of evidence 

across disciplines for major outcome categories (e.g., respiratory effects) or groups of related 

endpoints. Key considerations in drawing conclusions about causality include consistency of 

findings for an endpoint across studies, biological plausibility, and coherence of the evidence 

across disciplines and across related endpoints, including key events that inform modes of action 

(see Table I in Preamble to the ISA for Lead, U.S. EPA, 2013a). In discussing the causal 

determination, EPA characterizes the evidence on which the judgment is based, including 

strength of evidence for individual endpoints within the outcome category or group of related 

endpoints. The ISA will place emphasis on studies conducted with SOX exposure concentrations 

representative of those across various ambient microenvironments. In addition, EPA evaluates 

evidence relevant to understand the quantitative relationships between pollutant exposures and 

health effects. This includes evaluating the concentration-, exposure-, or dose-response 

relationships and, to the extent possible, drawing conclusions on the levels at which effects are 

observed. 

4.3.5 Quality Management 

NCEA participates in the Agency-wide Quality Management System, which requires the 

development of a Quality Management Plan (QMP; www.epa.gov/QUALITY/qmps.html). 

Implementation of the ORD-wide and NCEA QMP ensures that all data generated or used by 

NCEA scientists “have a degree of confidence in the quality of the data; and, are of the type and 

quality appropriate for their intended use” and that all information disseminated by NCEA 

adheres to a high standard for quality including objectivity, utility, and integrity. Quality 

assurance (QA) measures detailed in the QMP are being employed for the current SOX review, 

including the development of the ISA. The NCEA QA staff are responsible for the review and 

approval of quality-related documentation. NCEA scientists are responsible for the evaluation 

(and documentation) of all inputs to the ISA, including primary (new) and secondary (existing) 

data, to ensure their quality is appropriate for their intended purpose. NCEA adheres to the use 

of Data Quality Objectives, which clarify project objectives, define the appropriate type of data 

used in the project, and specify tolerable levels of confidence in the data and tolerable levels of 

potential decision errors that will be used as the basis for establishing the quality and quantity of 

data needed to identify the most appropriate inputs to the science assessment. The approaches 

utilized to search the literature and criteria for study selection and evaluation were detailed in the 
 4-10 October 2014 

two preceding subsections. Generally, NCEA scientists rely on scientific information found in 

peer-reviewed journal articles, books, and government reports. Where information is integrated, 

re-analyzed, modeled, or reduced from multiple sources to create new figures, tables, or 

summation, the data generated are considered to be new and are documented and subjected to 

rigorous quality assurance and quality control measures to ensure their accuracy, validity, and 

reproducibility. 

4.4 SPECIFIC ISSUES TO BE ADDRESSED IN THE ISA 

The organization of the ISA will be consistent with that used in the recent assessments 

for other criteria pollutants (e.g., ISA for O3, U.S. EPA, 2013b). Development of the ISA will be 

guided by policy-relevant questions that frame the entire review of the primary SO2 NAAQS. 

These policy-relevant questions are related to two overarching issues. The first issue is whether 

new evidence reinforces or calls into question the evidence presented and evaluated in the last 

NAAQS review with respect to factors such as the concentrations of SOX exposure associated 

with health effects and plausibility of health effects caused by SOX exposure. The second issue 

is whether uncertainties from the last review have been reduced and/or whether new 

uncertainties have emerged. This includes identifying research areas that lack adequate data. 

Specific questions that will be addressed in the ISA are listed subsequently by topic area. In the 

ISA, these topic areas will be discussed in separate chapters or sections. The beginning of the 

ISA will include an integrative synthesis chapter that summarizes the key information for each 

topic area and the causal determinations. The integrative synthesis chapter also presents a 

discussion of policy-relevant issues such as the exposure metrics, averaging times, and lags 

associated with health effects, the concentration-response relationship including threshold for 

effects, and public health significance of health effects associated with exposure to SOX (see 

Appendix). 

A. Air Quality and Atmospheric Chemistry: The ISA will present and evaluate data related 

to ambient concentrations of SOX; sources leading to the presence of SOX in the 

atmosphere; and chemical reactions that determine the formation, degradation, and 

lifetime of SOX in the atmosphere. The 2008 ISA concluded that most anthropogenic SO2

is emitted from elevated point sources such as the stacks of power plants and industrial 

facilities, many of which are located in the eastern U.S., leading to a strong east-west 
 4-11 October 2014 

gradient in SO2 concentrations. Non-anthropogenic sources, such as volcanoes, are 

important in some areas. SO2 is removed from the atmosphere both by deposition and by 

oxidation to sulfate, resulting in a typical atmospheric lifetime of <1 to 4 days, depending 

on local conditions. Mean U.S. daily 1-hour max SO2 concentrations in 2003-05 were 

approximately 13 ppb, with a 99th percentile value of 95 ppb and a maximum measured 

value of approximately 700 ppb. The large differences between 99th percentile and 

maximum values suggest that the maxima are strongly limited spatially and temporally 

and are not a major determinant of the mean values. At the time of the 2008 ISA, the very 

limited 5-minute SO2 data available showed that the median of the maximum 5-minute 

value in an hour ranged from 1-8 ppb, while the 99th percentile ranged from 21-184 ppb, 

depending on location (U.S. EPA, 2008, section 5.1). In the current ISA, description of 

the atmospheric chemistry of SOX will include both gaseous and particulate species in 

order to provide a complete analysis, although the health effects of particulate SOX are 

discussed in the review of the NAAQS for particulate matter (PM). SO2 is the most 

important of the gas-phase sulfur oxides for both atmospheric chemistry and health 

effects and is expected to be the focus of the ISA. SOX is usually defined to include sulfur 

trioxide (SO3) and gas-phase sulfuric acid (H2SO4) as well, but neither species is present 

in the atmosphere in concentrations significant for human exposures. In the current 

review, specific policy-relevant questions related to air quality and atmospheric 

chemistry that will be addressed include the following: 

 What are the main and emerging sources of ambient gas-phase SOX, and how have new 

fuels, emission standards, and technologies changed the magnitude and composition of 

SOX emissions? 

 What progress has been made in improving measurements and reducing interference 

problems in measuring SOX, particularly for concentrations near the method detection 

limit? What limitations still remain? 

 Based on recent air quality and emissions data, what are current emissions and 

concentrations of SOX? How have emissions and concentrations of SOX changed since 

the 2008 ISA? To what extent can other techniques, such as satellite data, photochemical 

modeling, and dispersion modeling, be used to improve the characterization of SOX

concentrations? 

 What spatial and temporal patterns can be seen in SOX concentrations? In particular, 

what patterns can be seen near point and other sources of SOX? What do monitoring, 
 4-12 October 2014 

satellite data, and dispersion and photochemical modeling results indicate regarding 

spatial patterns on neighborhood, urban, regional, and national scales? 

 What are the relationships among SOX concentrations measured with different averaging 

times (e.g., 5-minute, 1-hour, 24-hour)? 

 What are the relationships among SOX concentrations and concentrations of other 

pollutants, such as sulfate, other components of particulate matter, and gaseous 

pollutants? 

 What information is available regarding the capabilities of AERMOD and other air 

quality models for estimating SOX concentrations, particularly at the upper end of the air 

quality distribution? 

 Based on air quality and emissions data on SOX and atmospheric chemistry models, what 

are likely background concentrations of SOX in the absence of anthropogenic emissions? 

B. Human Exposure to Ambient SOX: The ISA will evaluate the factors that influence 

human exposure to ambient SOX and the uncertainties associated with extrapolation from 

ambient concentrations to personal exposures to SOX of ambient origin, particularly in 

the context of interpreting results from epidemiologic studies. As described in the 2008 

ISA, many exposure studies were unable to characterize the relationship between 

personal exposure and ambient SO2 due to indoor and outdoor concentrations that were 

below the detection limit of passive personal samplers. However, in studies with personal 

measurements above detection limits, a reasonably strong association was observed 

between personal SO2 exposure and ambient concentrations (U.S. EPA, 2008, section 

5.3). At the time of the 2008 ISA, no studies had evaluated the relationship between 

community average exposure and ambient concentrations, which is more directly relevant 

to many epidemiologic study designs, although the ISA concluded that intracommunity 

variations in the personal-ambient relationship would generally tend to widen the 

confidence interval rather than bias the effect estimate. Uncertainties differ according to 

the exposure period of interest as most short-term exposure studies (e.g., population-level 

studies using time-series analyses, field/panel studies) rely on temporal variation in 

exposure while long-term exposure studies (e.g., longitudinal cohort studies) rely on 

spatial variability of exposure. In the current review, specific policy-relevant questions 

related to exposure that will be addressed include the following: 

 What are the relationships between SOX measured at stationary monitoring sites and 

personal exposure to SOX over different time scales? What evidence is available 
 4-13 October 2014 

regarding these relationships in environments near point sources, ports, or other sources? 

What uncertainties remain regarding these exposures of interest? 

 What new information is available regarding microenvironmental SOX concentrations 

and personal exposures to SOX? What are the capabilities of currently available exposure 

measurement techniques? 

 What new information exists regarding characterization of error in SOX exposure 

assessment and how it influences personal-ambient exposure relationships? 

 What information is available regarding differences in SOX exposure patterns and 

personal-ambient exposure relationships among various lifestages and populations, 

particularly at-risk groups? 

 What new information exists regarding SOX measurements in a multipollutant context? 

What are the relationships between SOX exposures and exposures for other pollutants, 

such as sulfate, other components of particulate matter, and gaseous pollutants? 

 How does uncertainty in exposure estimates inform interpretation of epidemiologic, 

controlled human exposure, and toxicological studies? 

C. Dosimetry and Modes of Action: The ISA will evaluate literature focusing on dosimetry 

and modes of action that may underlie the health outcomes associated with exposure to 

SOX. These topic areas will be evaluated using both human and animal data. The 2008 

ISA concluded that SO2 is readily absorbed in the nasal passages due to its high water 

solubility; with increased ventilation rates during exercise, the pattern of SO2 absorption 

shifts from the upper airways to the tracheobronchial airways in conjunction with a shift 

from nasal to oronasal breathing (U.S. EPA, 2008, section 5.2). The compound most 

directly responsible for the health effects may be the inhaled SO2 and/or its chemical 

reaction products such as hydrogen ions, bisulfite anions and sulfite anions which are 

formed when SO2 contacts the fluids lining the airway. One of the principal effects of 

inhaled SO2 is bronchoconstriction, mediated by chemosensitive receptors that trigger 

nervous system reflexes. Preexisting inflammation may lead to enhanced sensitivity in 

asthmatics due to enhanced release of mediators, alterations in the autonomic nervous 

system, and/or sensitization of the chemosensitive receptors. In the current review, 

specific policy-relevant questions related to dosimetry and modes of action that will be 

addressed include the following: 

 What SOX reaction products can be found in the respiratory tract cells, tissues, or fluids 

that may serve as markers of SOX exposure and effect? 

 What information is available on the following dosimetric and mechanistic factors: 
 4-14 October 2014 

o The regional pattern of SOX-induced injury/perturbation in the respiratory 

tract? 

o Inter-individual variability of responses that may enhance the risk of an 

adverse health effect? 

o Homology of responses between animals and humans? 

 What are the potential biological mechanisms underlying responses to SOX at or near 

environmentally relevant exposures? 

 What new information is available related to the modes of action for health effects 

associated with exposure to SOX? 

 Do interactions between inhaled SOX and other inhaled pollutants influence the 

mechanisms underlying the toxic potential of SOX? 

 What are the effects of host factors such as lifestage, sex, pre-existing disease, genetic 

background, and physical activity on SOX uptake, cellular and tissue responses, and their 

underlying mechanisms? Are there critical windows of exposure (e.g., prenatal) that 

result in different effects and/or effects at lower exposures? 

 What information is available to discern the relative contribution of SOX derived 

exogenously from ambient exposures to endogenous SO2 and is there evidence for any 

alteration in function due to the former?

D. Health Effects: The 2008 ISA concluded that there is a causal relationship between 

respiratory morbidity and short-term exposure to SO2, based on consistent and coherent 

evidence from controlled human exposure, epidemiologic, and animal toxicological 

studies. The definitive evidence for the causal relationship came from controlled human 

exposure studies that reported respiratory symptoms and decreased lung function in 

exercising asthmatics following 5-10 minute exposures to SO2; in addition, numerous 

epidemiologic studies reported associations between short-term SO2 exposures and 

respiratory symptoms and hospitalizations (U.S. EPA, 2008, section 5.2). The ISA also 

concluded that the evidence is suggestive of a causal relationship between short-term 

exposure to SO2 and mortality, and that the evidence is inadequate to infer a causal 

relationship between short-term exposure to SO2 and cardiovascular effects or between 

long-term exposure to SO2 and morbidity and mortality. The current ISA will evaluate the 

literature related to respiratory, cardiovascular, reproductive and developmental health 

effects, mortality, and cancer associated with SOX exposure. Other health effects may also 

be evaluated, such as those related to the central nervous system. Health effects that occur 

following both short- and long-term exposures will be evaluated as examined in 
 4-15 October 2014 

epidemiologic, controlled human exposure, and animal toxicological studies, and causality 

determinations will be developed for each type of health effect. Efforts will be directed at 

identifying the lower concentrations at which effects are observed, including effects in 

populations and lifestages potentially at increased risk of SOX-induced health effects, and 

assessing the role of SOX within the broader mixture of ambient pollutants. Discussions 

about lack of associations at lower levels potentially due to insufficient statistical power 

will be included. The discussion of health effects also will be integrated with relevant 

information on dosimetry and modes of action. In the current review, specific policyrelevant questions related to health effects that will be addressed include the following: 

 What do controlled human exposure, animal toxicological, and epidemiologic studies 

indicate regarding the relationship between short-term (i.e., minutes to one month) 

exposures to SOX and health effects of concern, including the nature and time course, in 

healthy individuals and in those with pre-existing disease states (e.g., people with asthma 

or cardiovascular disease) or other factors (e.g., lifestage, genetic variants, nutritional 

deficiencies) that potentially modify the risk of SOX-induced health effects? What 

information is available that reduces uncertainties identified in the previous ISA, such as 

exposure measurement error and the potential for copollutant confounding? 

 How do results of recent studies expand current understanding of the relationships 

between long-term (i.e. more than one month to years) exposure to SOX and chronic 

respiratory effects manifested as permanent lung tissue damage, a reduction in baseline 

lung function, or a reduction in lung function growth? To what extent does long-term 

SOX exposure promote exacerbation and development of asthma or other chronic lung 

diseases, cardiovascular diseases, and other conditions? Are there certain lifestages that 

are especially vulnerable to the development of these chronic conditions? What is the 

relationship between SOX exposure and all-cause mortality and cause-specific mortality? 

 To what extent does the scientific evidence support the occurrence of health effects from 

long-term SOX exposure at ambient concentrations that are lower than those previously 

observed? If so, what uncertainties are related to these associations and are the health 

effects in question important from a public health perspective? 

 To what extent does short-term or long-term exposure to SOX contribute to health effects 

beyond the respiratory and cardiovascular systems (e.g., reproductive, developmental, 

cancer)? 

 What is the extent of coherence of findings for small changes in lung function, airway 

hyperresponsiveness, heart rate variability, and vasomotor function and changes in health 

effects such as hospital admissions, emergency department visits, and mortality? What 

other biomarkers of early effect may be used in the assessment of health effects? 

 What evidence is available regarding the shape of concentration-response relationships 

between short-term and long-term SOX exposure and health effects? 
 4-16 October 2014 

 What evidence is available regarding the nature of health effects from the combination of 

SOX and other ambient air pollutants in comparison to health effects following exposure 

to SOX alone? Does the evidence indicate differential effects of SOX from different 

source types? 

 What do results from studies conducted in environments near SOX sources indicate about 

the health effects of long-term or repeated SOX exposures? 

 To what extent does information across scientific disciplines on the pattern and/or 

exposure regime of SOX exposure (e.g., peak, repeated peak, average) provide 

understanding of the time course for changes in health effects? What information is 

available on time-activity patterns of study subjects such as time spent outdoors or 

activity levels that can aid in the understanding of the nature of exposure or dosimetry of 

ambient SOX concentrations that are associated with health effects?

 To what extent do data across scientific disciplines provide information on health effects 

related to various short-term SOX exposure indices or averaging times relevant to the 1-

hour standard? What data exist comparing associations of health effects among various 

short-term SOX exposure metrics (e.g., 1-hour versus 24-hour)? 

 What evidence is available regarding health effects related to long-term exposure 

windows other than annual or lifetime average (e.g., preconception, pregnancy average)? 

What data are available comparing associations of health effects among various longterm SOX exposure metrics (e.g., annual, seasonal, pregnancy average)? Are there critical 

windows of human development that are associated with the development of chronic 

respiratory disease? 

 To what extent are the observed epidemiologic health effect associations attributable to 

ambient SOX, another ambient pollutant, or to the pollutant mixtures that SOX may be 

representing? To what extent do findings from experimental studies provide biological 

plausibility? 

E. Populations and Lifestages Potentially at Increased Risk of SOX-Induced Health Effects: 

The 2008 ISA found substantial evidence from epidemiologic and controlled human 

exposure studies that asthmatic individuals are more susceptible to respiratory health 

effects from SO2 exposures than the general public (U.S. EPA, 2008, section 5.4). The 

ISA also presented limited evidence that children and older adults (≥ 65 years) are 

potentially at increased risk of SO2-induced respiratory effects. Since completion of the 

2008 ISA, EPA has developed an additional framework to provide a consistent and 

transparent basis for classifying the weight of evidence for populations and/or lifestages 

being at increased risk according to one of four levels: adequate evidence, suggestive 

evidence, inadequate evidence, and evidence of no effect (see Table 5-1 of ISA for Lead, 

U.S. EPA, 2013a). In the framework, key considerations in drawing such conclusions 

include consistency of findings for a factor within a discipline and coherence of the 
 4-17 October 2014 

evidence across disciplines. The current ISA will examine exposure and health outcome 

data to draw conclusions about specific populations or lifestages that are potentially at 

increased risk of SOX-induced health effects. Estimation of the sizes of potential 

populations and lifestages at increased risk and discussion of the public health 

significance of the health outcomes characterized to result from ambient SOX exposure 

may be included. Potential populations or lifestages at increased risk can be 

characterized by a variety of factors: intrinsic factors (biological factors such as age, 

genetic variants), extrinsic factors (nonbiological factors such as diet, lower 

socioeconomic status), and/or factors affecting dose or exposure (age, outdoor activity or 

work). It is important to note that some factors could be in more than one category and 

some factors are interconnected (e.g., low socioeconomic status [extrinsic] and 

comorbidities [intrinsic]). In the current review, specific policy-relevant questions related 

to populations and lifestages potentially at increased risk of SOX-induced health effects 

that will be addressed include: 

 Based on evidence integrated across studies and disciplines that examine factors which 

may increase exposure to or dose of SOX and/or risk of SOX-induced health effects, what 

conclusions can be drawn about the presence of at-risk lifestages (e.g., children, older 

adults) and/or populations? 

 Studies from which disciplines contribute information about particular at-risk lifestages 

and populations, and to what extent does limited or lack of information from specific 

disciplines produce uncertainty in conclusions about at-risk lifestages and populations? 

 How does new information augment that evaluated in the 2008 ISA regarding 

populations with pre-existing respiratory disease or genetic variants as well as lifestages 

potentially at increased risk of SOX-induced health effects? 

 What is the extent of the coherence of evidence regarding potential at-risk lifestages or 

populations for both short- and long-term exposures to SOX? 

 What quantitative information is available that characterizes the magnitude of greater 

biological response or risk of health effects in at-risk lifestages or populations? 

4.5 SCIENTIFIC AND PUBLIC REVIEW 

Drafts of the ISA will be made available for review by the CASAC SOX primary 

NAAQS review panel and the public as indicated in Figure 4-1 above; availability of draft 

documents will be announced in the Federal Register. The CASAC panel will review the draft 

ISA documents and discuss their comments in public meetings that will be announced in the 
 4-18 October 2014 

Federal Register. EPA will take into account comments, advice, and recommendations received 

from the CASAC panel and from the public in revising the ISA. EPA has established a public 

docket for the development of the ISA. After appropriate revision based on comments received 

from CASAC and the public, the final document will be made available on an EPA website and 

in hard copy. A notice announcing the availability of the final ISA will be published in the 

Federal Register. 
 5-1 October 2014 

5. QUANTITATIVE RISK AND EXPOSURE 

ASSESSMENTS 

In reviewing primary NAAQS, the EPA develops quantitative analyses to estimate the 

human exposures and/or health risks that are associated with just meeting existing standards and, 

when appropriate, with just meeting potential alternative standards. These analyses can inform 

conclusions on the adequacy of the public health protection provided by the existing primary 

standard(s), and conclusions on the alternative standard(s), if any, that are appropriate to 

consider. In determining the extent to which it is appropriate in this review of the primary SO2

standard to conduct new quantitative exposure and/or risk analyses, and in determining the scope 

of any such new analyses, the EPA staff will consider the updated scientific evidence, as 

assessed in the ISA; the updated air quality information now available; and updated tools and 

models available for assessing human exposures and health risks. Staff’s initial conclusions on 

the extent to which it is appropriate in this review to conduct new quantitative analyses, together 

with the aspects of the evidence and information supporting those initial conclusions, will be 

presented in the Risk and Exposure Assessment (REA) Planning Document. Staff’s final 

conclusions on the appropriateness of new quantitative analyses, and the scope of any such 

analyses, will consider CASAC advice, as well as public input, on that REA Planning Document. 

The REA Planning Document will present the EPA staff’s planned approach regarding 

the scope and the design of exposure and risk analyses. As a first step, the REA Planning 

Document will evaluate the exposure and risk analyses conducted as part of the previous review 

of the primary SO2 standard, and will highlight the important uncertainties identified in that 

review. Based on the newly available scientific evidence, air quality information, and/or 

exposure and risk tools and models, the REA planning document will then consider the extent to 

which updated analyses in the current review could reduce these uncertainties, and the extent to 

which such updated analyses could change our understanding of the SO2 exposures and risks 

associated with the current or alternative standards. With regard to the scientific evidence, the 

REA Planning Document will specifically consider (1) the extent to which the evidence for 

adverse health effects attributable to short- or long-term SO2 exposures has been strengthened in 

the current review, (2) the extent to which the evidence for particular populations and lifestages 

being at increased risk for SO2-attributable effects has been strengthened in the current review, 

and (3) the extent to which new evidence indicates SO2-attributable effects at lower ambient SO2

concentrations than in previous reviews. With regard to air quality information, the REA 

Planning Document will specifically consider the extent to which the information available in 

this review indicates important differences from the previous review in terms of (1) the ambient 
 5-2 October 2014 

SO2 concentrations present throughout the U.S., (2) the spatial and/or temporal patterns of 

ambient SO2, or (3) the relationships between SO2 concentrations based on various averaging 

times (e.g., 5-minute versus 1-hour, 24-hour). With regard to exposure tools and models, the 

REA Planning Document will consider the extent to which (1) new exposure tools or models 

exist, (2) existing tools or models have been updated or improved (e.g. expanded data in CHAD 

for at-risk lifestages), or (3) scientific review has strengthened the association between area-site 

monitored levels and personal exposures. 

Based on the considerations noted above, the REA Planning Document will reach 

conclusions on the extent to which the updated evidence and information supports new or 

updated exposure and/or risk analyses in the current review. These conclusions, together with 

consideration of the resources available, will inform the approach discussed in the REA Planning 

Document to presenting and assessing any new quantitative analyses (e.g., assessments presented 

in a separate REA document versus as part of the PA, as discussed in section 5.2.5 below), and 

the anticipated schedule for soliciting CASAC advice and public input on these analyses. The 

remainder of this chapter provides an overview of the risk and exposure assessment from the last 

review, including key observations and uncertainties from the 2009 REA (section 5.1); an 

overview of the types of newly available scientific evidence, air quality information, tools, and 

methodologies that could be considered in the REA Planning Document in this review and 

potential approaches for assessing and presenting any new exposure and risk analyses (section 

5.2); and an overview of the approach to obtaining CASAC advice and public input on the REA 

Planning Document (section 5.3). 

5.1 OVERVIEW OF RISK AND EXPOSURE ASSESSMENT FROM 

PRIOR REVIEW 

In the previous review of the primary SO2 NAAQS, the REA focused the quantitative 

exposure and risk analyses on 5-minute average concentrations of SO2 in excess of potential 

health effect benchmark levels derived from the controlled human exposure literature. These 

benchmark levels were not potential standards, but rather were concentrations which represented 

“exposures of potential concern” which were used in the analyses to estimate exposures and risks 

associated with 5-minute concentrations of SO2. The health effect benchmark levels used in the 

REA were derived primarily from the ISA’s evaluation of the 5 - 10 minute controlled human 

exposure literature. As noted above, the ISA concluded that moderate or greater decrements in 

lung function occurred in approximately 5 - 30% of exercising asthmatics following exposure to 

200 - 300 ppb SO2 for 5 - 10 minutes. In addition, the ISA concluded that moderate or greater 

decrements in lung function occurred in approximately 20 - 60% of exercising asthmatics 

following exposure to 400 - 600 ppb SO2 for 5 - 10 minutes. The ISA also concluded that at SO2
 5-3 October 2014 

concentrations ≥ 400 ppb, statistically significant moderate or greater decrements in lung 

function at the group mean level have often been reported and are frequently accompanied by 

respiratory symptoms. Moreover, small SO2-induced lung function decrements have been 

observed in exercising asthmatics at concentrations as low as 100 ppb when SO2 is administered 

via mouthpiece. Taken together, the REA concluded it was appropriate to examine potential 5-

minute benchmark levels in the range of 100 - 400 ppb. 

The purpose of the assessments in the SO2 REA was to characterize air quality, 

exposures, and health risks associated with recent ambient concentrations of SO2, with SO2

concentrations that could be associated with just meeting the then-existing SO2 standards (i.e., 30 

ppb annual average and 140 ppb daily average), and with SO2 levels that could be associated 

with just meeting alternative 1-hour daily maximum standards. The SO2 REA utilized three 

approaches, as described briefly below. 

In the first approach, measured 5-minute maximum SO2 concentrations (1997 - 2007) 

from 98 ambient monitors were evaluated for exceedances of the 5-minute potential health effect 

benchmark levels, counting the number of days (per monitor and per year) a particular 5-minute 

benchmark level was exceeded and considering unadjusted, as is annual average, daily average, 

and 1-hour daily maximum SO2 concentrations. In addition, 5-minute SO2 maximum 

concentrations were statistically estimated33 using all available monitors that measured 1-hour 

SO2 (1997 - 2006) to generate a similar output (i.e., the number of days per monitor per year a 

benchmark concentration was exceeded considering as is air quality). Then, 5-minute maximum 

concentrations were statistically estimated in 40 selected U.S. counties (2001 - 2006), though 

using 1-hour SO2 concentrations as is and, those adjusted to just meet the then-existing annual 

and daily standards, and concentrations adjusted to just meet potential 1-hour daily maximum 

alternative standards. In this analysis, all U.S. monitoring sites where SO2 data have been 

collected were included in this analysis and, as such, the results generated were considered a 

broad characterization of national air quality and potential human exposures that might be 

associated with these concentrations. 

In the second approach, the REA used EPA’s Air Pollutants Exposure (APEX) model 

(US EPA, 2012a,b), a Monte Carlo simulation model that can be used to simulate a large number 

of randomly sampled individuals within specified locations, generating estimates of population 

exposure. APEX simulates exposures in indoor, outdoor, and in-vehicle microenvironments 

 

33The 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 

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. 
 5-4 October 2014 

while taking into consideration the movement of individuals through time and space. APEX 

estimated 5-minute daily maximum exposures simulated asthmatics may experience while at 

moderate or greater exertion (e.g., while exercising) and compared these exposures to the same 

5-minute potential health effect benchmark levels. Two case study areas were selected for this 

exposure modeling: Greene County, Missouri, and three counties within the St. Louis 

Metropolitan Statistical Area (MSA). For these two case study areas, year 2002 census blocklevel hourly SO2 concentrations were estimated by EPA’s AERMOD (a dispersion model), input 

to APEX and combined with the same statistical model used for estimating 5-minute peaks 

described from the hourly SO2 concentrations above. Several modeled air quality scenarios were 

considered, including as is air quality, air quality adjusted to just meet the then-existing 

standards, and air quality adjusted to just meet potential alternative 1-hour daily maximum 

standards. Outputs from this exposure modeling were the number and percent of asthmatics in 

each study area experiencing at least one 5-minute daily maximum exposure at or above the 

potential health effect benchmark levels while at moderate or greater exertion. 

In the third approach, exposure-response relationships derived from controlled human 

exposure studies were used in conjunction with the outputs of the St. Louis and Greene County 

exposure analysis to estimate health impacts. More specifically, in each location the REA 

estimated the number and percent of all asthmatics or asthmatic children at moderate or greater 

exertion expected to experience moderate or greater decrements in lung function defined in terms 

of sRaw or FEV1 and considering the same air quality scenarios mentioned above. 

As mentioned above for each of these approaches, ambient SO2 concentrations and 

exposures were characterized by considering as is air quality (unadjusted concentrations) and 

several hypothetical air quality scenarios. Each of the hypothetical air quality scenarios had an 

ambient concentration target, derived from the form and level of the then-existing NAAQS or 

from potential alternative standards. Staff chose a proportional approach to adjust the SO2

concentrations to simulate each of the current and alternative air quality standard scenarios. A 

proportional approach was selected based on the mostly linear relationship between older high 

concentration years of air quality when compared with recent low concentration years at several 

locations (2009 SO2 REA, Section 7.4.2.5). 

The approach used to evaluate uncertainty was adapted from guidelines outlining how to 

conduct a qualitative uncertainty characterization (WHO, 2008), though staff also performed 

several quantitative sensitivity analyses to iteratively inform both model development and the 

qualitative uncertainty characterization, where possible. While it may be considered ideal to 

follow a tiered approach in the REA to quantitatively characterize all identified uncertainties, 

staff selected the mainly qualitative approach given the limited data available to inform 
 5-5 October 2014 

probabilistic analyses and time and resource constraints. Sections 5.1.1 and 5.12 identify the key 

observations and uncertainties from the prior SO2 REA. 

5.1.1 Key Observations 

Ambient Air Quality Characterization

 An increased probability of any 5-minute benchmark exceedance was consistently related 

to either increased 24-hour average or 1-hour daily maximum concentrations. 

 For any of the air quality scenarios considered, the probability of exceeding the 5-minute 

maximum benchmark levels was consistently greater at monitors sited in low-population 

density areas compared with high-population density areas. 

 Unadjusted as is air quality at ambient monitors measuring 5-minute maximum 

concentrations: 

o Measured daily and annual average concentrations were below that of the existing 

standards at all monitors, though measured 5-minute maximum ambient 

concentrations were present above the potential health effect benchmark levels. 

(2009 SO2 REA, Appendix A, Table A.5-1) 

 Nearly 70% of the monitor site-years analyzed had at least one daily 5-

minute maximum concentration above 100 ppb and over 20% had ≥ 25 

days with a daily 5-minute maximum concentration above 100 ppb. 

 About 44% of the monitor site-years analyzed had at least one 5-minute 

daily maximum concentration > 200 ppb, 25% had at least one > 300 ppb, 

and 17% had at least one > 400 ppb. 

 Air quality adjusted to simulate just meeting the then-existing annual standard in the 40 

selected U.S. counties 

o All counties evaluated were estimated to have multiple days per year where 5-

minute daily maximum ambient SO2 concentrations are > 100 ppb. For example, 

most counties are estimated to have, on average, 100 days or more per year with 

5-minute daily maximum SO2 concentrations > 100 ppb (2009 SO2 REA, Table 7-

11). 

o Fewer benchmark exceedances were estimated to occur with higher benchmark 

levels. For example, five of the forty counties were estimated to have 60 or more 

days per year with 5-minute maximum SO2 concentrations that exceed 300 ppb 

(2009 SO2 REA, Table 7-13). 

 Air quality adjusted to potential 1-hour daily maximum alternative standard levels: 

o Far fewer days per year with 5-minute maximum SO2 concentrations > 300 ppb 

and > 400 ppb (about 0 to 5 days/year) were estimated when adjusting air quality 

to just meet potential alternative standard levels of 100 and 150 ppb than 

compared with air quality adjusted to just meet the current standards (frequently 
 5-6 October 2014 

25 or more days/year) and the potential alternative standard levels of 200 and 250 

ppb (about 5 to 20 days/year) (2009 SO2 REA, Tables 7-13 and 7-14). 

Exposure Assessment 

 St. Louis had both a greater number and percent of asthmatic children and adults exposed 

above the benchmark levels than did Greene County for all air quality scenarios, largely a 

function of both the greater population density and the much greater SO2 emissions 

density in St. Louis (2009 SO2 REA, Section 8.9.2). 

 Estimated exposures above 5-minute potential health effect benchmark levels at moderate 

or greater exertion using APEX occurred most frequently outdoors (around 50 to > 90%, 

depending on the air quality scenario and modeling domain) (2009 SO2 REA, Figure 8-

21). 

 Simulating air quality that just meets the then-existing annual standard in either the 

Greene County or St. Louis Study areas resulted in the greatest number and percent of 

asthmatic persons exposed at all benchmark levels (2009 SO2 REA, Figures 8-16 and 8-

19). 

 The exposure results using as is air quality were similar to that estimated using air quality 

adjusted to a 99th percentile 1-hour daily maximum of 50 or 100 ppb in either study area 

(2009 SO2 REA, Figures 8-16 and 8-19). 

Health Risk Assessment 

 In terms of estimated percentage of all asthmatics or asthmatic children experiencing one 

or more lung function responses, estimated risks are greater for asthmatic children (2009 

SO2 REA, Tables 9-5 and 9-8, respectively), likely because they spend more time 

outdoors and at higher exertion levels than adults. 

o For example, approximately 13% of all asthmatics were estimated to experience 

at least one moderate lung function response (defined as an increase in sRaw ≥

100% (2009 SO2 REA, Table 9-5), while approximately 19% of asthmatic 

children experienced a similar response (2009 SO2 REA, Table 9-8). 

 A broad range of SO2 exposure concentration intervals selected, some as high as 500 ppb, 

contributes to the estimated risks of experiencing one or more lung function responses 

per year for some of the standards considered in the assessment. For potential alternative 

1-hour standards in the range of 100 to 150 ppb, SO2 exposure concentration intervals 

below 200 ppb contribute to most of the estimated risks of experiencing one or more lung 

function responses per year (2009 SO2 REA, Figures 9-7 and 9-8). 

5.1.2 Key Uncertainties 

 Uncertainty in the statistical model used to estimate 5-minute maximum SO2 

concentrations from 1-hour SO2 concentrations. 
 5-7 October 2014 

 Uncertainty in the spatial and temporal representativeness of the SO2 ambient monitoring 

network. 

 Uncertainties associated with the proportional air quality adjustment procedure that was 

used to simulate just meeting the then-existing standard and several alternative 1-hour 

daily maximum standards. 

 Uncertainties related to the exposure model inputs and exposure estimates which are an 

important input to the risk assessment. 

 Uncertainty about the shape of the exposure-response relationship for lung function 

responses at levels well below 200 ppb, the lowest level examined in free-breathing 

single-pollutant controlled human exposure studies. 

 Uncertainty with respect to how well the estimated exposure-response relationships 

reflect asthmatics with more severe disease than those tested in chamber studies. 

 Uncertainty about whether the presence of other pollutants in the ambient air would 

enhance the SO2-related responses observed in the controlled human exposure studies. 

 Uncertainty about the extent to which the risk estimates presented for the two modeled 

areas in Missouri are representative of other locations in the U.S. with significant SO2

point and area sources. 

5.2 CONSIDERATION OF QUANTITATIVE ASSESSMENTS FOR THIS 

REVIEW 

 As discussed above, the REA Planning Document will reach conclusions on the extent to 

which the updated scientific evidence, air quality information, or modeling tools and methods 

support new or updated exposure/risk analyses in the current review. These conclusions will 

reflect EPA staff consideration of the extent to which the newly available scientific evidence and 

technical information could reduce important uncertainties identified in the 2009 REA, and the 

extent to which updated analyses could lead to notably different conclusions than those reached 

in the previous review. Sections 5.2.1 to 5.2.3 below a more detailed discussion of important 

uncertainties associated with the air quality, exposure, and risk characterization from the last 

review, and the potential for newly available information to reduce those uncertainties. Section 

5.2.4 discusses how uncertainty and variability will be characterized in the current review. 

Section 5.2.5 discusses the potential options for presenting and assessing new or updated 

exposure/risk analyses. 

5.2.1 Ambient Air Quality Characterization 

In the last review, the SO2 ambient air quality characterization: (1) developed quantitative 

relationships between 5-minute peak concentrations and longer term average concentrations 

(e.g., 1-hour); (2) estimated 5-minute ambient SO2 concentrations, based on unadjusted air 

quality and air quality adjusted to just meet the then-existing SO2 standards and potential 
 5-8 October 2014 

alternative standards; and (3) identified key assumptions and uncertainties. The results of the air 

quality characterization were considered, along with the scientific evidence and exposure and 

risk analyses, to inform conclusions on the adequacy of the then current standards and on the 

range of potential alternative standards appropriate for consideration. 

Areas where additional information could reduce key uncertainties identified in the air 

quality assessment from the previous review, are presented in Table 5-1. For each component, 

the REA Planning Document will examine the extent to which newly available information 

could result in notably different air quality results than those reported in the 2009 REA and will 

use this information to help inform decisions on the extent to which new or updated air quality 

analyses are appropriate in this review. 

Table 5-1. Primary uncertainties associated with the air quality analysis in the 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 

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 substantially 

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 

levels34

The health effect benchmark 

levels used in the SO2 REA 

were derived from the ISA’s 

New estimates of benchmark 

exceedances could be 

developed if there are studies 

 

34 Note that the selection of health benchmark levels is also an uncertainty for the SO2 exposure analysis. 
 5-9 October 2014 

Component of 

Assessment 

Uncertainty/Limitation 

Remaining From Prior REA 

Consideration of Potential 

Utility of Information Newly 

Available in This Review 

For the Assessment 

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 

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. 

newly available in the ISA 

that indicate alternative 

benchmark levels exist outside 

of the range already 

considered in the 2009 SO2

REA. 

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. 

A key uncertainty, included in Table 5-1, with respect to the air quality characterization is 

the limited availability of 5-minute SO2 monitoring data. In the last review, 5-minute SO2 

concentrations were available through mid-2007 from a relatively small number of monitors (see 

Table 5-2)35. In the current review, there are far more monitors reporting 5-minute SO2

 

35 2006 was the most recent year with complete data at that time. 
 5-10 October 2014 

concentrations (see Table 5-2).36 It is possible that this additional 5-minute monitoring data could 

indicate relationships between 5-minute SO2 concentrations and 1-hour or 24-hour SO2

concentrations that are different from those reported in the last REA. The REA Planning 

document will discuss the extent to which air quality relationships based on additional 

monitoring data are notably different from those reported in the last review to help inform 

decisions on the extent to which new or updated analyses are appropriate in this review. In 

addition, a review of selected references on relationships between SO2 concentrations at different 

averaging times will also be performed and incorporated into this discussion (e.g., Gifford, 1960, 

1972; Hanna, 1984; Larsen, 1969; Montgomery and Coleman, 1975; Ramsdell and Hinos, 1971). 

Table 5-2. The numbers of SO2 monitors 2003 to 201237

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

 5-minute continuous monitors with at least 20,000 values/year (about 20% data 

 completeness). 

2

 5-minute maximum and hourly with at least 50% data completeness (4,380 values/year). 

5.2.2 Exposure Assessment 

In the last review, the SO2 exposure assessment: (1) estimated short-term exposures to 

ambient SO2 concentrations, based on unadjusted air quality and air quality adjusted to just meet 

the then-existing SO2 standards and potential alternative standards; (2) compared estimated 

exposures to potential health effect benchmark levels; and (3) identified key assumptions and 

uncertainties in the exposure assessment. The results of the exposure assessment were 

considered, along with the scientific evidence and the results of air quality and risk analyses, to 

 

36 As previously noted in section 3.1, the 2010 final rulemaking made it a requirement that states report for every 

hour of the day, all twelve 5-minute concentrations in an hour, or the highest 5-minute concentration in a given hour. 

37 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) 
 5-11 October 2014 

inform conclusions on the adequacy of the then current standards and on the range of potential 

alternative standards appropriate for consideration. 

In the last review, the following were identified as key areas of uncertainty in the 

exposure analysis: 

 Representativeness of the two study areas selected (i.e., St. Louis and Greene County, MO) 

 Estimates of the number of asthmatics and asthmatic children at elevated ventilation rates 

above potential health effect benchmarks in St. Louis and Greene County38 

 Factors that may contribute to greater personal exposures including the impacts of important 

sources of SO2 (e.g., outdoor point sources). 

 Factors that may contribute to lessened personal exposures including infiltration and the 

decay of SO2 indoors. 

 Impact of human behavior (e.g., time spent indoors or outdoors, averting behavior, time spent 

near sources, timing of exposure event, breathing rate) in influencing the magnitude and 

duration of exposures, and frequency of repeated short-term peak exposures. 

 Population living in close proximity to local sources or otherwise living in areas with 

elevated SO2 concentrations. 

 Frequency and (temporal and spatial) variability of peak air quality levels at concentrations 

and averaging times of significance. 

 Selection of potential health effect benchmark levels. 

The REA Planning Document will evaluate the extent to which new information or modeling 

approaches could reduce these uncertainties in exposure estimates. Decisions on whether to 

conduct new or updated exposure analyses in this review will be informed by consideration of 

the extent to which the updated evidence and information could impact exposure estimates in 

important ways (e.g., providing broader geographic coverage, improved characterization of 

exposures, improved basis for benchmarks), and by consideration of the extent to which updated 

exposure estimates would be expected to alter our understanding from the last review of SO2

exposures. 

5.2.3 Risk Assessment 

In the last review, the SO2 risk assessment: (1) estimated the number and percent of 

people at risk of adverse respiratory effects following exposure to SO2, based on unadjusted air 

quality and air quality adjusted to just meet the then-existing SO2 standards and potential 

alternative standards; (2) provided distributions of health risk estimates over a range of ambient 

SO2 concentrations; and (3) identified key assumptions and uncertainties in risk estimates. The 

 

38 For any exposure analyses done in the current review, it is likely that the latest version of the APEX model would 

be used to estimate 5-minute or longer-term SO2 exposures of interest (US EPA, 2012a; 2012b). 38 
 5-12 October 2014 

results of the risk assessment were considered, along with the scientific evidence and the results 

of air quality and exposure analyses, to inform conclusions on the adequacy of the then current 

standards and on the range of potential alternative standards appropriate for consideration. 

In the last review, the following were identified as key areas of uncertainty in the risk 

assessment: 

 The availability of exposure-response information for only a limited number of respiratory 

endpoints (i.e., sRaw and FEV1), likely not reflecting the full range of SO2-related health 

risks across the population. 

 The lack of sufficient information to support a risk assessment based on epidemiologic 

studies of the most serious SO2-related health outcomes (e.g., hospital admissions, 

emergency department visits). 

The REA Planning Document will evaluate the extent to which new evidence, information, 

or modeling approaches are available in the current review that could reduce these uncertainties 

in our understanding of SO2 health risks. As discussed above for air quality analyses and the 

exposure assessment, decisions on whether to conduct new or updated risk analyses in this 

review will be informed by consideration of the extent to which the evidence and information 

that has become available since the last review could impact SO2 risk estimates in important 

ways (e.g., quantitative changes in risk estimates, risks estimated for new populations or health 

endpoints), and consideration of the extent to which updated estimates would be expected to alter 

our understanding from the last review of SO2 health risks. 

5.2.4 Uncertainty and Variability 

Uncertainty reflects the degree of confidence in the representativeness of models or 

model components. Variability can be described in terms of empirical quantities that are 

inherently variable across time and space or between individuals (Cullen and Frey, 1999). 

Consistent with prior NAAQS REAs including the last SO2 REA, EPA would use the approach 

described in WHO (2008) to assess uncertainty and variability in any new or updated air quality, 

exposure, or risk analyses. A tiered approach to assessing uncertainty and variability in exposure 

and risk estimates will be employed, beginning with a qualitative analysis and progressing to a 

quantitative analysis only if warranted and if data are available to support such an analysis. 

5.2.5 Presentation of Updated Exposure and Risk Information 

As discussed above, the REA Planning Document will reach preliminary conclusions 

regarding the appropriate approach to presenting and assessing any new quantitative analyses 

that are judged appropriate. Specifically, such new analyses could be presented and assessed in a 

separate REA document or could be presented and assessed as part of the PA. Conclusions on 

whether to generate a new REA document, or to present exposure/risk results only as part of the 
 5-13 October 2014 

PA, will depend in part on the scope of any new analyses judged appropriate. For example, to the 

extent extensive new analyses of air quality, exposures, and health risks are conducted, it could 

be judged that the most effective way to facilitate CASAC advice and public input would be to 

generate a separate REA document that undergoes its own review process, independent of the 

PA. To the extent the new analyses will be more limited in scope (e.g., limited to only analyses 

of new air quality data), those analyses could potentially be included as part of the PA, rather 

than in a separate REA. The final decision on whether to generate a new REA, or to include 

quantitative analyses only as part of the PA, will also reflect staff’s consideration of CASAC 

advice and public input on the preliminary conclusions in the REA Planning Document. 

5.3 SCIENTIFIC AND PUBLIC REVIEW 

If the REA Planning Document concludes that an REA is not required, then the REA 

Planning Document will be subject to CASAC review and public comment. Similarly, draft 

versions of an REA, if one is generated, will be submitted for CASAC review and public 

comment. If an REA is not conducted, CASAC review of quantitative air quality, exposure, 

and/or risk analyses would occur as part of its review of the PA. As with all CASAC reviews, the 

SO2 panel will discuss their comments in public meetings that are announced in the Federal 

Register. Based on CASAC’s past practice, EPA expects that key CASAC advice and 

recommendations for revisions will be conveyed by the CASAC chair in a letter to the EPA 

Administrator. In revising the REA Planning Document or the draft REA, EPA will take into 

account any such advice and recommendations. EPA will also consider input from the public 

provided at the meeting itself, and any written public comments. If a first draft REA is prepared, 

EPA anticipates preparing a second draft of the REA for CASAC review and public comment. 

After appropriate revision, the final document will be made available on an EPA website and 

subsequently printed, with its public availability being announced in the Federal Register.
 6-1 October 2014 

6. AMBIENT AIR MONITORING 

 In the course of NAAQS reviews, aspects of the methods for measuring ambient levels of 

the NAAQS pollutant, as well as the current network of monitors, including their physical 

locations and monitoring objectives, are reviewed. The methods for sampling and analysis of 

each NAAQS pollutant are generally reviewed in conjunction with consideration of the indicator 

element for each NAAQS. Consideration of the ambient air monitoring network generally 

informs the interpretation of current data on ambient air concentrations and includes an 

assessment of the adequacy of the monitoring network for determining compliance with the 

existing or, as appropriate, a potentially revised NAAQS. This chapter describes plans for 

considering these aspects of the ambient air monitoring program for sulfur oxides which includes 

the indicator SO2. 

6.1 CONSIDERATION OF SAMPLING AND ANALYSIS METHODS 

In order for the data to be used to determine compliance, ambient SO2 concentration data 

must be obtained using Federal Reference Methods (FRMs) or Federal Equivalent Methods 

(FEMs) which are designated by the Agency in accordance with 40 CFR Part 50 and Part 53. 

As described earlier, SO2 is the indicator for the sulfur oxides NAAQS, and has been routinely 

measured by UV fluorescence methods since the 1980s. In the 2010 rulemaking the EPA 

promoted the automated federal equivalent UV fluorescence method to be a Federal Reference 

Method (FRM). This was done because of the need to update the cumbersome manual wetchemistry (pararosaniline) method to a continuous-type automated method that can readily 

provide 1-hour SO2 measurement capability. The UV fluorescence method was a clear and 

appropriate method to fulfill that need. The SO2 concentration data produced by modern UV 

fluorescence analyzers are routinely logged by state and local agencies who report the hourly 

average and either the maximum 5-minute value (one of twelve 5-minute periods) in the hour or 

all twelve 5-minute averages within the hour to EPA’s Air Quality System (AQS). 

The Agency is unaware of any recent technological advances in SO2 measurements 

beyond the current automated FRM or forthcoming modifications to existing methods that 

should be considered in this NAAQS review. Therefore, the EPA does not anticipate raising any 

specific sampling and analysis methods issues for consideration in this integrated review plan. 
 6-2 October 2014 

6.2 CONSIDERATION OF AIR MONITORING NETWORK 

REQUIREMENTS 

The ambient air quality monitoring networks for criteria pollutants support three major 

objectives: (1) to provide air pollution data to the general public in a timely manner; (2) to 

support compliance with NAAQS and emissions strategy development; and (3) to support air 

pollution research studies. A review of the available SO2 monitoring network and data was 

performed as part of the primary SO2 NAAQS review completed in 2010. Subsequent to that 

review, and in conjunction with revising the primary standards, the Agency promulgated 

minimum monitoring requirements to support the implementation of a new primary 1-hour SO2

standard. The 2010 action introduced minimum requirements based upon the use of a Population 

Weighted Emissions Index (PWEI). The PWEI utilizes both population and emissions data 

within Core Based Statistical Areas (CBSAs) to determine if monitoring is required in a CBSA 

and, if so, how many monitors are required. The intent of using the PWEI to require monitors is 

to focus monitoring into areas where there is a higher proximity of population and SO2

emissions. In effect, areas with a higher calculated PWEI value are expected to have higher 

potential for population exposure to peak, short-term SO2 emissions. 

The size of any ambient air monitoring network changes on an annual basis due to state, 

local, and tribal air agencies, plus industry-run monitors that report data to AQS being shutdown, relocated, or installed for a variety of reasons. As of July 2014, the ambient SO2

monitoring network is estimated to have 402 monitors in operation nationwide. This number far 

exceeds the approximately 129 required by PWEI-based requirements promulgated in 2010. 

Historically, the data used to determine compliance with the SO2 NAAQS have been 

largely based upon data obtained from ambient monitors operated by state, local, and tribal air 

monitoring agencies. These monitors are either required due to federal regulation contained in 

40 CFR Part 58, Appendix D, state implementation plans, industrial permits, or other state or 

local requirements or voluntary actions. While monitoring data are a mainstay in determining 

compliance for all other criteria pollutants, SO2 is unique in that there is a precedent to also use 

dispersion modeling in the implementation of its NAAQS. This is notable because the use of 

modeling in lieu of monitoring can potentially reduce the necessary size and distribution of a 

compliance monitoring network. As a result, the final monitoring requirements promulgated as 

part of the 2010 SO2 NAAQS revision reflected this potentiality. 
 6-3 October 2014 

More recently, in August 2013, EPA completed an initial round of nonattainment area 

designations for 29 areas having ambient monitoring data that exceeded the level of the 2010 

NAAQS, and EPA did not issue final designations for the rest of the country. For the portion of 

the country that remains undesignated, the EPA proposed the Data Requirements Rule for 1-hr 

SO2 Primary NAAQS (79 FR 27445) on April 17, 2014, which will direct the state and tribal air 

agencies to provide data to characterize current air quality in areas with large sources of SO2

emissions if such areas do not have sufficient air quality monitoring in place to identify 

maximum 1-hour SO2 concentrations. 

The proposed rule describes thresholds for identifying the sources around which air 

agencies would need to characterize SO2 air quality. It also describes a process and timetables by 

which air agencies would characterize air quality around sources through ambient monitoring 

and/or air quality modeling techniques and submit such data to the EPA. States would have the 

flexibility on an area by area basis whether to choose to deploy new ambient monitors or to 

conduct air quality modeling to characterize air quality. The air quality data developed by the 

states in accordance with this rule would be used by the EPA in future rounds of area 

designations for the 1-hour SO2 NAAQS in 2017 and 2020. The final rule is expected in 2015. 

The EPA also issued separate non-binding draft technical assistance documents (TADs) on 

monitoring and modeling issues to support this rule in December 2013. A main focus of the 

monitoring TAD is to describe analyses that can be done to identify potential monitoring site 

locations for monitoring maximum 1-hour SO2 concentrations. 
 7-1 October 2014 

7. POLICY ASSESSMENT/RULEMAKING 

7.1 POLICY ASSESSMENT 

The PA, like the previous OAQPS Staff Paper, is a document that provides a transparent 

OAQPS staff analysis and staff conclusions regarding the adequacy of the current standard and 

potential alternatives that are appropriate to consider prior to the issuance of proposed and final 

rules. The PA integrates and interprets the information from the ISA and REA(s) to frame policy 

options for consideration by the Administrator. The PA is also intended to facilitate CASAC’s 

advice to the Agency and recommendations to the Administrator on the adequacy of the existing 

standard or revisions that may be appropriate to consider. Staff conclusions in the PA are based 

on the information contained in the ISA and, as available, the REA, and any additional staff 

evaluations and assessments discussed in the PA. In so doing, the discussion in the PA is framed 

by consideration of a series of policy-relevant questions drawn from those outlined in chapter 3, 

including the fundamental questions associated with the adequacy of the current standard and, as 

appropriate, consideration of an alternative standard(s) in terms of the specific elements of the 

standard: indicator, averaging time, level, and form. 

The PA for the current review will identify conceptual evidence-based and risk/exposurebased approaches for reaching public health policy judgments. It will discuss the implications of 

the science and quantitative assessments for the adequacy of the current primary standard and for 

any alternative standards under consideration. The PA will also describe a broad range of policy 

options for standard setting, identifying the range for which the staff identifies support within the 

available information. In so doing, the PA will describe the underlying interpretations of the 

scientific evidence and risk/exposure information that might support such alternative policy 

options that could be considered by the Administrator in making decisions for the primary SO2

standard. Additionally, the PA will identify key uncertainties and limitations in the underlying 

scientific information and in our assessments. The PA will also highlight areas for future healthrelated research, model development, and data collection. 

In identifying a range of primary standard options for the Administrator to consider, it is 

recognized that the final decision will be largely a public health policy judgment. Scientific 

information and analyses about health effects and risks, as well as judgments about how to deal 

with the range of uncertainties that are inherent in the scientific evidence and analyses, inform a 

final decision. Staff’s approach to informing these judgments recognizes that the available 

health effects evidence generally reflects a continuum consisting of ambient concentrations at 

which scientists generally agree that health effects are likely to occur, through lower 

concentrations at which the likelihood and magnitude of the response become increasingly 
 7-2 October 2014 

uncertain. This approach is consistent with the requirements of the NAAQS provisions of the 

CAA and with how the EPA and the courts have historically interpreted the Act. 

In setting primary standards that are “requisite” to protect public health, as provided in 

section 109(b), the Administrator is to establish standards that are neither more nor less stringent 

than necessary. As discussed in section 1.1 above, the provisions do not require that primary 

standards be set at a zero-risk level, but rather at a level that reduces risk sufficiently so as to 

protect public health with an adequate margin of safety, including the health of at-risk 

populations.39 In so doing, the EPA may not consider the costs of implementing the standards 

and “[a]ttainability and technological feasibility are not relevant considerations in the 

promulgation of national ambient air quality standards.” 40 

Staff will prepare at least one draft of the PA document for CASAC review and public 

comment. The draft PA document will be distributed to the CASAC Sulfur Oxides Primary 

NAAQS Review Panel for their consideration and provided to the public for review and 

comment. Review by the CASAC Panel will be discussed at public meetings that will be 

announced in the Federal Register. Based on past practice by CASAC, the EPA expects that 

CASAC would summarize their key advice and recommendations for revision of the document 

in a letter to the EPA Administrator. In revising the draft PA document, OAQPS will take into 

account any such recommendations, and also consider comments received from CASAC and 

from the public, at the meeting itself, and any written comments received. The final document 

will be made available on an EPA website, with its public availability announced in the Federal 

Register41. 

7.2 RULEMAKING 

Following issuance of the final PA and the EPA management consideration of staff 

analyses and conclusions presented therein, and taking into consideration CASAC advice and 

recommendations, the Agency will develop a notice of proposed rulemaking. The notice of 

proposed rulemaking conveys the Administrator’s proposed conclusions regarding the adequacy 

of the current standard(s) and any revision that may be appropriate. A draft notice of proposed 

 

39 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 (as well as any other less sensitive 

population groups). 

40 See generally, Whitman v. American Trucking Associations, 531 U.S. 457, 465-472, 475-76 (2001) and American 

Petroleum Institute v. Costle, 665 F. 2d at 1185. 41 Note that the policy assessment/rulemaking process is also outlined in Figure 1-1. 
 7-3 October 2014 

rulemaking will be submitted to the Office of Management and Budget (OMB) for interagency 

review, in which OMB and other federal agencies are provided the opportunity for review and 

comment. After the completion of interagency review, the EPA will publish the notice in the 

Federal Register seeking comment on proposed agency action – namely whether or not to revise 

the current standard, and if so, how. Monitoring rule changes associated with review of the 

primary SO2 standard, and drawing from considerations outlined in Chapter 6 above, will be 

developed and proposed, as appropriate, in conjunction with this NAAQS rulemaking. 

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.42 Publication 

of the proposal notice is followed by a public comment period, generally lasting 60 to 90 days, 

during which time the public is invited to submit comments on the proposal to the rulemaking 

docket. EPA also will provide opportunity for a public hearing on any proposed action. Taking 

into account comments received on the proposed action, the Agency will then develop a notice of 

final rulemaking, which again undergoes OMB-coordinated interagency review prior to issuance 

by the EPA of the final rule. At the time of final rulemaking, the Agency responds to all 

significant comments on the proposed action.43 Publication of the final action in the Federal 

Register completes the process. 

 

42 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. 43 For example, Agency responses to all significant 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 
 8-1 October 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. Gifford, F.A. 1960. Peak-to-average concentration ratios according to a fluctuating plume model. Int. J. Air 

Poll. 3:253-260. 

3. Gifford, F.A. 1972. The form of the frequency distribution of air pollution concentrations. In Proceedings of 

Symposium on Statistical Aspects of Air Quality Data, Chapel Hill, NC, pp 3.1-3.17. 

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108(5):419-426. 
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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 No