vvEPA
United States                             September 2007
|ng™mental Protection	EPA/600/R-07/108A
            Annexes for the
            Integrated Science Assessment
            for Sulfur Oxides -
            Health Criteria
            (First External Review Draft)

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                                            EPA/600/R-07/108A
                                              September 2007
           Annexes for the
 Integrated Science Assessment
for Sulfur Oxides - Health Criteria
 National Center for Environmental Assessment-RTF Division
         Office of Research and Development
         U.S. Environmental Protection Agency
            Research Triangle Park, NC

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                                     DISCLAIMER

       This document is a first external review draft being released for review purposes only and
does not constitute U.S. Environmental Protection Agency policy. Mention of trade names or
commercial products does not constitute endorsement or recommendation for use.

                                       PREFACE

Legislative Requirements
       Two sections of the Clean Air Act (CAA) govern the establishment and revision of the
national ambient air quality standards (NAAQS).  Section 108 (U.S. Code, 2003a) directs the
Administrator to identify and list "air pollutants" that "in his judgment, may reasonably be
anticipated to endanger public health and welfare" and whose "presence ... in the ambient air
results from numerous or diverse mobile or stationary sources" and to issue air quality criteria
for those that are listed. 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 ...."
       Section 109 (U.S. Code, 2003b) directs the Administrator to propose and promulgate
"primary" and "secondary" NAAQS for pollutants listed under section 108. Section 109(b)(l)
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."1  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."2
 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" [U.S. Senate (1970)].
 Welfare effects as defined in section 302(h) [U.S. Code, 2005] include, but are not limited to, "effects on soils,
 water, crops, vegetation, man-made materials, animals, wildlife, weather, visibility and climate, damage to and
 deterioration of property, and hazards to transportation, as well as effects on economic values and on personal
 comfort and well-being."
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       The requirement that primary standards include 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).  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.
       In selecting a margin of safety, the U.S. Environmental Protection Agency (EPA)
considers such factors as the nature and severity of the health effects involved, the size of
sensitive population(s) at risk, and the kind and degree of the uncertainties that must be
addressed.  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.
       In setting standards that are "requisite" to protect public  health and welfare,  as provided
in section 109(b), EPA's task is to establish standards that are neither more nor less stringent
than necessary for  these purposes. In so doing, 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).
       Section 109(d)(l) 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

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independent review function has been performed by the Clean Air Scientific Advisory
Committee (CASAC) of EPA's Science Advisory Board.

History of Reviews of the Primary NAAQS for Sulfur Dioxide
       On April 30, 1971, the EPA promulgated primary NAAQS for sulfur dioxide (SO2).
These primary standards, which were based on the findings outlined in the original 1969 Air
Quality Criteria (hereafter "AQCD") for Sulfur Oxides (U.S. DHEW, 1969), 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.  In 1982, EPA published the AQCD for
Particulate Matter (PM) and Sulfur Oxides along with an addendum of newly published
controlled human exposure studies (U.S. Environmental Protection Agency, 1982), which
updated the scientific  criteria upon which the initial standards were based. In 1986, a second
addendum was published presenting newly available evidence from epidemiologic and
controlled human exposure studies (U.S. Environmental Protection Agency, 1986). In 1988,
EPA reviewed and revised the health criteria upon which the SO2 standards were based. As a
result of that review, EPA published a proposed decision not to revise the existing standards
(Federal Register,  1988). However,  EPA specifically requested public comment  on the
alternative of revising the current standards and adding a new 1-h primary standard of 0.4 ppm.
       As a result of public comments on the 1988 proposal and other post-proposal
developments, EPA published a second proposal on November 15,  1994 (Federal Register,
1994). 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. Environmental Protection Agency, 1994). As in the 1988 proposal, EPA proposed to
retain the existing 24-h and annual standards.  The EPA also solicited comment on three
regulatory alternatives to further reduce the health risk posed by exposure to high 5-min peaks of
SO2 if additional protection were judged to be necessary. The three alternatives included (1)
revising the existing primary SO2 NAAQS by adding a new 5-min 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; and (3) augmenting
implementation of existing standards by focusing on those sources or source types likely to
produce high 5-min peak concentrations of SO2.  On May 22, 1996, EPA's final decision, that
revisions of the NAAQS for sulfur oxides were not appropriate at that time, was announced in

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the Federal Register (Federal Register, 1996).  In that decision, EPA announced an intention to
propose guidance, under section 303 of the Act, to assist states in responding to short-term peak
levels of SO2.
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          Annexes for the Integrated Science Assessment
                 for Sulfur Oxides - Health Criteria
                       ANNEX CHAPTERS
AXl.   CHAPTER 1 ANNEX-INTRODUCTION	AX1-1

AX2.   CHAPTER 2 ANNEX - ATMOSPHERIC CHEMISTRY OF
      NITROGEN AND SULFUR OXIDES	AX2-1

AX3.   CHAPTER 3 ANNEX - A FRAMEWORK FOR MODELING HUMAN
      EXPOSURES TO SO2 AND RELATED AIR POLLUTANTS	AX3-1

AX4.   CHAPTER 4 ANNEX - TOXICOLOGICAL STUDIES OF THE
      HEALTH EFFECTS OF SULFUR OXIDES	AX4-1

AX5.   CHAPTER 5 ANNEX - EPIDEMIOLOGICAL STUDIES OF HUMAN
      HEALTH EFFECTS ASSOCIATED WITH EXPOSURE TO AMBIENT
      SULFUR OXIDES	AX5-1
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                     ANNEX TABLE OF CONTENTS
                                                                      Page
List of Tables	ix
List of Figures	xi
Authors, Contributors, and Reviewers	xiii
U.S. Environmental Protection Agency Project Team	xviii
U.S. Environmental Protection Agency Science Advisory Board (SAB)
   Staff Office Clean Air Scientific Advisory Committee (CASAC)	xxi
Abbreviations and Acronyms	xxiv

AX1.  CHAPTER 1 ANNEX-INTRODUCTION	AX1-1
      AX1.1   LEGISLATIVE REQUIREMENTS	AX1-2
      AX1.2   HISTORY OF REVIEWS OF THE PRIMARY NAAQS
              FORSO2	AX1-3

AX2.  CHAPTER 2 ANNEX - ATMOSPHERIC CHEMISTRY OF
      NITROGEN AND SULFUR OXIDES	AX2-1
      AX2.1   INTRODUCTION	AX2-1
      AX2.2   CHEMISTRY OF NITROGEN OXIDES IN THE
              TROPOSPHERE	AX2-2
              AX2.2.1   Basic Chemistry	AX2-2
              AX2.2.2  Nonlinear Relations between Nitrogen Oxide
                       Concentrations and Ozone Formation	AX2-9
              AX2.2.3   Multiphase Chemistry Involving NOX	AX2-12
      AX2.3   CHEMISTRY OF SULFUR OXIDES IN THE
              TROPOSPHERE	AX2-24
      AX2.4   MECHANISMS FOR THE AQUEOUS PHASE
              FORMATION OF SULFATE AND NITRATE	AX2-28
      AX2.5   TRANSPORT OF NITROGEN AND SULFUR OXIDES IN
              THE ATMOSPHERE	AX2-31
      AX2.6   SOURCES AND EMISSIONS OF NITROGEN OXIDES,
              AMMONIA, AND SULFUR DIOXIDE	AX2-35
              AX2.6.1   Interactions of Nitrogen Oxides with
                       the Biosphere	AX2-35
              AX2.6.2  Emissions of NOX, NH3, and SO2	AX2-48
              AX2.6.3   Field Studies Evaluating Emissions Inventories	AX2-56
      AX2.7   METHODS USED TO CALCULATE CONCENTRATIONS
              OF NITROGEN OXIDES AND THEIR CHEMICAL
              INTERACTIONS IN THE ATMOSPHERE	AX2-58
              AX2.7.1   Chemistry-Transport Models	AX2-59
              AX2.7.2  CTM Evaluation	AX2-73
      AX2.8   SAMPLING AND ANALYSIS OF NITROGEN
              AND SULFUR OXIDES	AX2-86
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                    ANNEX TABLE OF CONTENTS
                                 (cont'd)
                                                                    rage
              AX2.8.1  Availability and Accuracy of Ambient
                      Measurements forNOy	AX2-86
              AX2.8.2  Measurements of HNO3	AX2-93
              AX2.8.3  Techniques for Measuring Other NOy Species	AX2-95
              AX2.8.4  Remote Sensing of Tropospheric NO2 Columns
                      for Surface NOX Emissions and Surface NO2
                      Concentrations	AX2-96
              AX2.8.5  SAMPLING AND ANALYSIS FOR SO2	AX2-98
              AX2.8.6  Sampling and Analysis for Sulfate, Nitrate,
                      and Ammonium	AX2-101
      AX2.9   POLICY RELEVANT BACKGROUND CONCENTRATIONS
              OF NITROGEN AND SULFUR OXIDES	AX2-110
      AX2.10  REFERENCES	AX2-129

AX3.   CHAPTER 3 ANNEX - A FRAMEWORK FOR MODELING HUMAN
      EXPOSURES TO SO2 AND RELATED AIR POLLUTANTS	AX3-1
      AX3.1   INTRODUCTION: CONCEPTS,  TERMINOLOGY,
              AND OVERALL  SUMMARY	AX3-1
      AX3.2   POPULATION EXPOSURE MODELS:  THEIR
              EVOLUTION AND CURRENT STATUS	AX3-7
      AX3.3   CHARACTERIZATION OF AMBIENT CONCENTRATIONS
              OF SO2 AND RELATED AIR POLLUTANTS	AX3-10
      AX3.4   CHARACTERIZATION OF MICROENVIRONMENTAL
              CONCENTRATIONS	AX3-11
              AX3.4.1  Characterization of Activity Events	AX3-13
              AX3.4.2  Characterization of Inhalation Intake and Uptake	AX3-13
      AX3.5   CONCLUDING COMMENTS	AX3-14
      AX3.6   REFERENCES	AX3-17

AX4.   CHAPTER 4 ANNEX - TOXICOLOGICAL STUDIES OF THE
      HEALTH EFFECTS OF SULFUR OXIDES	AX4-1
      AX4.1   REFERENCES	AX4-66

AX5.   CHAPTER 5 ANNEX - EPIDEMIOLOGICAL STUDIES OF HUMAN
      HEALTH EFFECTS ASSOCIATED WITH EXPOSURE TO AMBIENT
      SULFUR OXIDES	AX5-1
      AX5.1   REFERENCES	AX5-236
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                           ANNEX LIST OF TABLES
                                                                                Page
AX2.3-1.     Atmospheric Lifetimes of Sulfur Dioxide and Reduced Sulfur Species
             With Respect to Reaction With OH, NO3, and Cl Radicals	AX2-119
AX2.4-la.    Relative Contributions of Various Reactions to the Total S(IV)
             Oxidation Rate within a Sunlit Cloud, 10 Minutes after
             Cloud Formation	AX2-120
AX2.4-lb.    Relative Contributions of Various Gas and Aqueous Phase Reactions
             to Aqueous Nitrate Formation within a Sunlit Cloud, 10 Minutes
             after Cloud Formation	AX2-121
AX2.6-1.     Emissions  of Nitrogen Oxides, Ammonia, and Sulfur Dioxide
             in the United States in 2002	AX2-122
AX2.8-1.     Satellite Instruments Used to Retrieve Tropospheric NO2 Columns	AX2-128
AX3.2-1.     The Essential Attributes of the pNEM, HAPEM, APEX, SHEDS,
             andMENTOR-lA	AX3-16
AX4-1.       Physiological Effects of SO2 Exposure	AX4-2
AX4-2.       Inflammatory Responses Following SO2 Exposure	AX4-4
AX4-3.       Effects of SO2 Exposure on Hypersensitivity/Allergic Reactions	AX4-5
AX4-4.       Effects of SO2 Exposure on Host Lung Defenses	AX4-7
AX4-5.       Effects of SO2 Exposure on Cardiovascular Endpoints	AX4-8
AX4-6.       Nervous System—Neurophysiology and Biochemistry Effects of
             SO2 and Derivatives	AX4-11
AX4-7.       Reproductive and Developmental Effects of SO2	AX4-18
AX4-8.       Hematological Effects of SO2	AX4-20
AX4-9.       Endocrine  System Effects of SO2	AX4-22
AX4-10.      Effects of SO2 Exposure on Respiratory System Morphology	AX4-23
AX4-11.      Carcinogenic Effects  of SO2	AX4-24
AX4-12.      Respiratory System Biochemistry Effects of SO2	AX4-27
AX4-13.      Respiratory System Effects of SO2 in Disease Models	AX4-31
AX4-14.      Effects of Mixtures Containing SO2 and Ozone	AX4-32
AX4-15.      Effects of SO2 Layered on Metallic or Carbonaceous Particles	AX4-3 5
AX4-16.      Effects of SO2 and Sulfate Mixtures	AX4-45
AX4-17.      Effects of Actual or Simulated Air Pollution Mixtures	AX4-48
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                           ANNEX LIST OF TABLES
                                       (cont'd)

                                                                                 Page
AX4-18.      Effects of Meteorological Conditions on SO2 Effects	AX4-52
AX4-19.      In Vitro or Ex Vivo Respiratory System Effects of SO2 and
             Metabolites	AX4-55
AX4-20.      Genotoxic Effects of SO2 and Metabolite	AX4-57
AX4-21.      Liver and Gastrointestinal Effects of SO2	AX4-61
AX4-22.      Renal Effects of SO2	AX4-64
AX4-23.      Lymphatic System Effects of SO2 and SO2 Mixture	AX4-65
AX5-1.       Associations of Short-term Exposure to Sulfur Dioxide with
             Respiratory Morbidity in Field/Panel Studies	AX5-2
AX5.2.       Associations of Short-Term Exposure to Sulfur Dioxide with
             Emergency Department Visits and Hospital Admissions
             for Respiratory Diseases	AX5-45
AX5.3.       Associations of Short-Term Exposure to Sulfur Dioxide with
             Cardiovascular Morbidity in Field/Panel Studies	AX5-134
AX5.4.       Associations of Short-Term Exposure to Sulfur Dioxide with
             Emergency Department Visits and Hospital Admissions
             for Cardiovascular Diseases	AX5-146
AX5.5.       Associations of Short-Term Exposure to Sulfur Dioxide on Mortality	AX5-174
AX5.6.       Associations of Long-Term Exposure to Sulfur Dioxide with
             Respiratory Morbidity	AX5-197
AX5.7.       Associations of Long-Term Exposure to Sulfur Dioxide with
             Incidence of Cancer	AX5-214
AX5.8.       Associations of Long-Term Exposure to Sulfur Dioxide with
             Prenatal and Neonatal Outcomes	AX5-216
AX5.9.       Associations of Long-Term Exposure to Sulfur Dioxide
             with Mortality	AX5-229
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                           ANNEX LIST OF FIGURES
                                                                                 Page
AX2.1-1.     Schematic diagram of the cycle of reactive nitrogen species in
             the atmosphere	AX2-3
AX2.2-1.     Measured values of 63 and NOZ (NOy-NOx) during the afternoon at rural
             sites in the eastern United States (gray circles) and in urban areas and
             urban plumes associated with Nashville, TN (gray dashes), Paris, FR
             (black diamonds) and Los Angeles, CA (X's)	AX2-12
AX2.2-2.     Structures of nitro-polycyclic aromatic hydrocarbons	AX2-16
AX2.2-3.     Formation of 2-nitropyrene (2NP) from the reaction of OH with
             gaseous pyrene (PY)	AX2-17
AX2.3-1.     Transformations of sulfur compounds in the atmosphere	AX2-26
AX2.4-1.     Comparison of aqueous-phase oxidation paths	AX2-29
AX2.6-1.     Diel cycles of median concentrations (upper panels) and fluxes
             (lower panels) for the Northwest clean sector, left panels) and Southwest
             (polluted sector, right panels) wind sectors at Harvard Forest,
             April-November, 2000, for NO, NO2, and O3/10. NO and O3 were
             sampled at a height of 29m, andNO2at22m	AX2-43
AX2.6-2.     Simple NOX photochemical canopy model outputs	AX2-44
AX2.6-3.     Hourly (dots) and median nightly (pluses) NO2 flux vs. concentration,
             with results of least-squares fit on the hourly data (curve)	AX2-45
AX2.6-4.     Averaged profiles at Harvard Forest give some evidence of some
             NO2 input near the canopy top from light-mediated ambient reactions,
             or emission from open stomates	AX2-46
AX2.6-5.     Summer (June-August) 2000 median concentrations (upper panels),
             fractions of NOy (middle panels), and fluxes (lower panels) of NOy
             and component species separated by wind direction (Northwest on the
             left and Southwest on the right)	AX2-47
AX2.7-1.     Scatter plot of total nitrate (HNOs plus aerosol nitrate) wet deposition
             (mg(N)m 2yr^) of the mean model versus measurements for the
             North American Deposition Program (NADP) network	AX2-70
AX2.7-2.     Same as Figure AX2.7-1 but for sulfate wet deposition (mg(S)m"2yr-1).... AX2-71
AX2.7-3a,b.  Impact of model uncertainty on control strategy predictions for
             O3 for two days (August 1 Oa and 1 Ib, 1992) in Atlanta, GA	AX2-76
AX2.7-4.     Ozone isopleths (ppb) as a function of the average emission rate for
             NOX and VOC (1012 molec. cm"2 s"1) in zero dimensional box
             model calculations	AX2-77
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                          ANNEX LIST OF FIGURES
                                       (cont'd)
                                                                                 age
AX2.7-5a.    Time series for measured gas-phase species in comparison with results
             from a photochemical model	AX2-78
AX2.7-5b.    Time series for measured gas-phase species in comparison with results
             from a photochemical model	AX2-79
AX2.7-6.     Correlations for O3 versus NOZ (NOy-NOx) in ppb from chemical
             transport models for the northeast corridor, Lake Michigan, Nashville,
             the San Joaquin Valley, and Los Angeles	AX2-81
AX2.7-7a,b.  Evaluation of model versus measured O3 versus NOy for two model
             scenarios for Atlanta	AX2-83
AX2.7-8a,b.  Evaluation of model versus: (a) measured O3 versus NOZ and (b) O3
             versus the sum 2H2O2 + NOZ for Nashville, TN	AX2-84
AX2.7-9.     Time series of concentrations of RO2, HO2, and OH radicals, local O3
             photochemical  production rate and concentrations of NOX from
             measurements made during BERLIOZ	AX2-85
AX2.8-1.     Tropospheric NO2 columns (molecules NO2/ cm2) retrieved from the
             SCIAMACHY satellite instrument for 2004-2005	AX2-97
AX2.9-1.     Annual mean concentrations of NO2 (ppbv) in surface air over the
             United States in the present-day (upper panel)  and policy relevant
             background (middle panel) MOZART-2 simulations	AX2-112
AX2.9-2.     Same as Figure AX2.9-1 but for SO2 concentrations	AX2-113
AX2.9-3.     Same as for Figure AX2.9-1 but for wet and dry deposition of
             HNO3, NH4NO3, NOX, HO2NO2, and organic nitrates (mg N m~V ^	AX2-114
AX2.9-4.     Same as Figure AX2.9-1 but for SOX deposition (SO2 + SO4)
             (mgSnrV1)	AX2-115

AX2.9-5.     July mean soil NO emissions (upper panels; 1  x 10 9 molecules cm"2 s1)
             and surface PRB NOX concentrations (lower panels; pptv) over the
             United States from MOZART-2 (left) and GEOS-Chem (right) model
             simulations in which anthropogenic O3 precursor emissions were
             set to zero in North America	AX2-116
AX3.1-1.     Schematic description of a general framework identifying the processes
             (steps or components) involved in assessing inhalation exposures and
             doses for individuals and populations	AX3-4
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                     Authors, Contributors, and Reviewers
Authors

Dr. Jee Young Kim (SOX Team Leader)—National Center for Environmental Assessment (B243-
01), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Jeffrey Arnold—National Center for Environmental Assessment (B243-01), U.S.
Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. James S. Brown—National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Douglas Bryant—Intrinsik Science, 1900 Minnesota Court, Mississauga, Ontario L8S IPS

Dr. Ila Cote—National Center for Environmental Assessment (B243-01), U.S. Environmental
Protection Agency, Research Triangle Park, NC 27711

Dr. Arlene Fiore—Geophysical Fluid Dynamics Laboratory/National Oceanographic &
Atmospheric Administration, 201 Forrestal Rd., Princeton, NJ 08542-0308

Dr. Panos Georgopoulos—Computational Chemodynamics Laboratory, EOHSI Room 308, 170
Frelinghuysen Road, Piscataway, New Jersey 08854

Dr. Brett Grover—National Exposure Research Laboratory (D205-03), U.S. Environmental
Protection Agency, Research Triangle Park, NC 27711

Dr. Vic Hasselblad—Duke University Medical Center, Box 17969, Durham, NC 27715

Dr. Larry Horowitz—Geophysical Fluid Dynamics Lab oratory/National Oceanographic &
Atmospheric Administration, Princeton University Forrestal Campus, 201 Forrestal Road,
Princeton, NJ 08540-5063

Dr. Annette lanucci—Sciences International, 1800 Diagonal Road, Suite 500, Alexandria, VA
22314

Dr. Kazuhiko Ito—New York  University School of Medicine, 57 Old Forge Road, Tuxedo, NY
10987

Dr. Doug Johns—National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Ellen Kirrane—National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
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                     Authors, Contributors, and Reviewers
                                      (cont'd)
Authors
Dr. Jane Koenig—University of Washington, Department of Environmental and Occupational
Health Sciences, Box 357234, Seattle, WA 98195-7234

Dr. Thomas Long—National Center for Environmental Assessment (B243-01), U.S.
Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Thomas Luben—National Center for Environmental Assessment (B243-01), U.S.
Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Therese Mar—University of Washington, Department of Environmental and Occupational
Health Sciences, Box 357234, Seattle, WA 98195-7234

Dr. Qingyu Meng—National Center for Environmental Assessment (B243-01), U.S.
Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Anu Mudipalli—National Center for Environmental Assessment (B243-01), U.S.
Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Joseph Pinto—National Center for Environmental Assessment (B243-01), U.S.
Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Mary Ross—National Center for Environmental Assessment (B243-01), U.S. Environmental
Protection Agency, Research Triangle Park, NC 27711

Dr. David Svendsgaard—National Center for Environmental Assessment (B243-01), U.S.
Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Lori White—National Center for Environmental Assessment (B243-01), U.S. Environmental
Protection Agency, Research Triangle Park, NC 27711

Dr. William Wilson—National Center for Environmental Assessment (B243-01), U.S.
Environmental Protection Agency, Research Triangle Park, NC 27711
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                     Authors, Contributors, and Reviewers
                                      (cont'd)
Contributors
Dr. Dale Allen, University of Maryland, College Park, MD

Ms. Louise Camalier, U.S. EPA, OAQPS, Research Triangle Park, NC

Dr. Russell Dickerson, University of Maryland, College Park, MD

Dr. Tina Fan, EOHSI/UMDNJ, Piscataway, NJ

Dr. William Keene, University of Virginia, Charlottesville, VA

Dr. Randall Martin, Dalhousie University, Halifax, Nova Scotia

Dr. Maria Morandi, University of Texas, Houston, TX

Dr. William Munger, Harvard University, Cambridge, MA

Mr. Charles Piety, University of Maryland, College Park, MD

Dr. Sandy  Sillman, University of Michigan, Ann Arbor, MI

Dr. Helen Suh, Harvard University, Boston, MA

Dr. Charles Wechsler, EOHSI/UMDNJ, Piscataway, NJ

Dr. Clifford Weisel, EOHSI/UMDNJ, Piscataway, NJ

Dr. Jim Zhang, EOHSI/UMDNJ, Piscataway, NJ


Reviewers

Dr. Tina Bahadori—American Chemistry Council, 1300 Wilson Boulevard, Arlington, VA
22209

Dr. Tim Benner—Office of Science Policy, Office of Research and Development, Washington,
DC 20004

Dr. Daniel Costa—National Program Director for Air, Office of Research and Development,
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711



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                      Authors, Contributors, and Reviewers
                                       (cont'd)
Reviewers
Dr. Robert Devlin—National Health and Environmental Effects Research Laboratory, Office of
Research and Development, U.S. Environmental Protection Agency, Chapel Hill, NC

Dr. Judy Graham—American Chemistry Council, LRI, 1300 Wilson Boulevard, Arlington, VA
22209

Dr. Stephen Graham—Office of Air Quality Planning and Standards (C504-06), Office of Air
and Radiation, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Ms. Beth Hassett-Sipple—Office of Air Quality Planning and Standards (C504-06), Office of
Air and Radiation, U.S. Environmental Protection Agency (C504-06), Research Triangle Park,
NC27711

Dr. Gary Hatch—National Health and Environmental Effects Research Laboratory, Office of
Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC
27711

Dr. Scott Jenkins—Office of Air Quality Planning and Standards (C504-06), Office of Air and
Radiation, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. David Kryak—National Exposure Research Laboratory, Office of Research and
Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Mr. John Langstaff—Office of Air Quality Planning and Standards (C504-06), Office  of Air and
Radiation, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Morton Lippmann—NYU School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987

Dr. Karen Martin—Office of Air Quality Planning and Standards (C504-06), Office of Air and
Radiation, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. William McDonnell—William F. McDonnell Consulting,  1207 Hillview Road, Chapel Hill,
NC27514

Dr. Dave McKee—Office of Air Quality Planning and Standards (C504-06), Office of Air and
Radiation, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Lucas Neas—National Health and Environmental Effects Research Laboratory, Office of
Research and Development, U.S. Environmental Protection Agency, Chapel Hill, NC 27711
September 2007                           xvi        DRAFT-DO NOT QUOTE OR CITE

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                      Authors, Contributors, and Reviewers
                                       (cont'd)
Reviewers

Dr. Russell Owen—National Health and Environmental Effects Research Laboratory, Office of
Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC
27711

Dr. Haluk Ozkaynak—National Exposure Research Laboratory, Office of Research and
Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Jennifer Peel—Colorado State University, 1681 Campus Delivery, Fort Collins, CO 80523-
1681

Mr. Harvey Richmond—Office of Air Quality Planning and Standards (C504-06), Office of Air
and Radiation, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Mr. Steven Silverman—Office of General Counsel, U.S. Environmental Protection Agency,
Washington, DC 20460

Dr. Michael Stewart—Office of Air Quality Planning and Standards (C504-06), Office of Air
and Radiation, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Ms. Susan Stone—Office of Air Quality Planning and Standards (C504-06), Office of Air and
Radiation, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Ms. Chris Trent—Office of Air Quality Planning and Standards (C504-06), Office  of Air and
Radiation, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. John Vandenberg—National Center for Environmental Assessment (B243-01), Office of
Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC
27711

Dr. Alan Vette—National Exposure Research Laboratory, Office of Research and Development,
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Mr. Ron Williams—National Exposure Research Laboratory, Office of Research and
Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
September 2007                           xvii        DRAFT-DO NOT QUOTE OR CITE

-------
             U.S. Environmental Protection Agency Project Team
              for Development of Integrated Scientific Assessment
                                 for Sulfur Oxide
Executive Direction

Dr. Ila Cote (Acting Director)—National Center for Environmental Assessment-RTF Division,
(B243-01), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
Scientific Staff

Dr. Jee Young Kim (SOX Team Leader)—National Center for Environmental Assessment
(B243-01), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Jeff Arnold—National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. James S. Brown—National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Ellen Kirrane—National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Dennis Kotchmar—National  Center for Environmental Assessment (B243-01),
Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Tom Long—National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Thomas Luben—National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Quingyu Meng—National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Joseph Pinto—National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Paul Reinhart—National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
September 2007                          xviii        DRAFT-DO NOT QUOTE OR CITE

-------
             U.S. Environmental Protection Agency Project Team
              for Development of Integrated Scientific Assessment
                                 for Sulfur Oxide
                                      (cont'd)
Scientific Staff
(cont'd)

Dr. Mary Ross—National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. David Svendsgaard—National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Lori White—National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. William Wilson—National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
Technical Support Staff

Ms. Emily R. Lee—Management Analyst, National Center for Environmental Assessment
(B243-01), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Ms. Christine Searles—Management Analyst, National Center for Environmental Assessment
(B243-01), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Ms. Debra Walsh—Program Analyst, National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Mr. Richard Wilson—Clerk, National Center for Environmental Assessment (B243-01),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
Document Production Staff

Ms. Barbra H. Schwartz—Task Order Manager, Computer Sciences Corporation,
2803 Slater Road, Suite 220, Morrisville, NC 27560

Mr. John A. Bennett—Technical Information Specialist, Library Associates of Maryland,
11820 Parklawn Drive, Suite 400, Rockville, MD 20852
September 2007                          xix        DRAFT-DO NOT QUOTE OR CITE

-------
             U.S. Environmental Protection Agency Project Team
              for Development of Integrated Scientific Assessment
                                 for Sulfur Oxide
                                      (cont'd)
Document Production Staff
(cont'd)

Mrs. Melissa Cesar—Publication/Graphics Specialist, Computer Sciences Corporation,
2803 Slater Road, Suite 220, Morrisville, NC 27560

Mrs. Rebecca Early—Publication/Graphics Specialist, TekSystems, 1201 Edwards Mill Road,
Suite 201, Raleigh, NC 27607

Mr. Eric Ellis—Records Management Technician, InfoPro, Inc., 8200 Greensboro Drive, Suite
1450, McLean, VA 22102

Ms. Stephanie Harper—Publication/Graphics Specialist, TekSystems, 1201 Edwards Mill Road,
Suite 201, Raleigh, NC 27607

Ms. Sandra L. Hughey—Technical Information Specialist, Library Associates of Maryland,
11820 Parklawn Drive, Suite 400, Rockville, MD 20852

Dr. Barbara Liljequist—Technical Editor, Computer Sciences Corporation, 2803 Slater Road,
Suite 220, Morrisville, NC 27560

Ms. Molly Windsor—Graphic Artist, Computer Sciences Corporation, 2803 Slater Road,
Suite 220, Morrisville, NC 27560
September 2007                           xx        DRAFT-DO NOT QUOTE OR CITE

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                     U.S. Environmental Protection Agency
                         Science Advisory Board (SAB)
        Staff Office Clean Air Scientific Advisory Committee (CASAC)
             CASAC NOX and SOX Primary NAAQS Review Panel
Chair
Dr. Rogene Henderson*, Scientist Emeritus, Lovelace Respiratory Research Institute,
Albuquerque, NM

Members

Mr. Ed Avol, Professor, Preventive Medicine, Keck School of Medicine, University of Southern
California, Los Angeles, CA

Dr. John R. Balmes, Professor, Department of Medicine, Division of Occupational and
Environmental Medicine, University of California, San Francisco, CA

Dr. Ellis Cowling*, University Distinguished Professor At-Large, North Carolina State
University, Colleges of Natural Resources and Agriculture and Life Sciences, North Carolina
State University, Raleigh, NC

Dr. James D. Crapo [M.D.]*, Professor, Department of Medicine, National Jewish Medical and
Research Center, Denver, CO

Dr. Douglas Crawford-Brown*, Director, Carolina Environmental Program; Professor,
Environmental Sciences and Engineering;  and Professor, Public Policy, Department of
Environmental Sciences and Engineering,  University of North Carolina at Chapel Hill, Chapel
Hill, NC

Dr. Terry Gordon, Professor, Environmental Medicine, NYU School of Medicine, Tuxedo, NY

Dr. Dale Hattis, Research Professor, Center for Technology, Environment, and Development,
George Perkins Marsh Institute, Clark University, Worcester, MA

Dr. Patrick Kinney, Associate Professor,  Department of Environmental Health Sciences,
Mailman School of Public Health, Columbia University, New York, NY

Dr. Steven Kleeberger, Professor, Laboratory Chief, Laboratory of Respiratory Biology,
NIH/NIEHS, Research Triangle Park, NC

Dr Timothy Larson, Professor, Department of Civil and Environmental Engineering, University
of Washington, Seattle, WA
September 2007                          xxi        DRAFT-DO NOT QUOTE OR CITE

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                     U.S. Environmental Protection Agency
                         Science Advisory Board (SAB)
        Staff Office Clean Air Scientific Advisory Committee (CASAC)
             CASAC NOX and SOX Primary NAAQS Review Panel
                                      (cont'd)

Members
(cont'd)

Dr. Kent Pinkerton, Professor, Regents of the University of California, Center for Health and
the Environment, University of California, Davis, CA

Mr. Richard L. Poirot*, Environmental Analyst, Air Pollution Control Division, Department of
Environmental Conservation, Vermont Agency of Natural Resources, Waterbury, VT

Dr. Edward Postlethwait, Professor and Chair, Department of Environmental Health Sciences,
School of Public Health, University of Alabama at Birmingham, Birmingham, AL

Dr. Armistead (Ted) Russell*, Georgia Power Distinguished Professor of Environmental
Engineering, Environmental Engineering Group, School of Civil and Environmental
Engineering, Georgia Institute  of Technology, Atlanta, GA

Dr. Richard Schlesinger, Associate Dean, Department of Biology, Dyson College, Pace
University, New York, NY

Dr. Christian Seigneur, Vice  President, Atmospheric and Environmental Research, Inc., San
Ramon, CA

Dr. Elizabeth A. (Lianne) Sheppard, Research Professor, Biostatistics and Environmental &
Occupational Health Sciences, Public Health and Community Medicine, University of
Washington, Seattle, WA

Dr. Frank Speizer [M.D.]*, Edward Kass Professor of Medicine, Channing Laboratory,
Harvard Medical School, Boston, MA

Dr. George Thurston, Associate Professor, Environmental Medicine, NYU School of Medicine,
New York University, Tuxedo, NY

Dr. James Ultman, Professor, Chemical Engineering, Bioengineering Program, Pennsylvania
State University, University Park, PA

Dr. Ronald Wyzga, Technical Executive, Air Quality Health and Risk, Electric Power Research
Institute, P.O. Box 10412, Palo Alto, CA
September 2007                          xxii        DRAFT-DO NOT QUOTE OR CITE

-------
                    U.S. Environmental Protection Agency
                        Science Advisory Board (SAB)
        Staff Office Clean Air Scientific Advisory Committee (CASAC)
             CASAC NOX and SOX Primary NAAQS Review Panel
                                    (cont'd)


SCIENCE ADVISORY BOARD STAFF

Mr. Fred Butterfield, CASAC Designated Federal Officer, 1200 Pennsylvania Avenue, N.W.,
Washington, DC, 20460, Phone: 202-343-9994, Fax: 202-233-0643 fbutterfield.fred@epa.gov)
(Physical/Courier/FedEx Address: Fred A. Butterfield, III, EPA Science Advisory Board Staff
Office (Mail Code 1400F), Woodies Building,  1025 F Street, N.W., Room 3604, Washington,
DC 20004, Telephone: 202-343-9994)

* Members of the statutory Clean Air Scientific Advisory Committee (CASAC) appointed by the EPA
 Administrator
September 2007                         xxiii       DRAFT-DO NOT QUOTE OR CITE

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 ACCENT

 ADS
 AHH
 AHR
 AIRPEX
 AIRQUIS
 ALT
 AM
 AMF
 AMI
 AMMN
 ANOVA
 AP
 API
 AOR
 APEX
 APHEA
 APIMS
 AQCD
 AQEG
 ARIC
 ARIMA
 ARR
 ATP
 ATTILA
 asl
 AST
 P
 BAL
 B[or]P
 BC
 BERLIOZ
 BHPN
 BHR
 BME
 BMI
    Abbreviations and Acronyms
European Union project Atmospheric Composition Change: the
European Network of Excellence
annular denuder system
aryl hydrocarbon hydroxylase
airways hyperreactiveness
Air Pollution Exposure (model)
Air Quality Information System (model)
alanine-amino-transferase
alveolar or pulmonary macrophages
air mass factor
acute myocardial infarction
7V-nitroso-acetoxymethylmethylamine
analysis of variance
alkaline phosphatase
air pollution index
adjusted odds ratio
Air Pollution Exposure (model)
Air Pollution on Health: a European Approach (study)
atmospheric pressure ionization mass spectrometer
Air Quality Criteria Document
Air Quality Expert Group
Atherosclerosis Risk in Communities (study)
Autoregressive Integrated Moving Average (model)
arrhythmia
adenosine triphosphate
type of Lagrangian model
above sea level
aspartate-amino-transferase
beta; slope
bronchoalveolar lavage
benzo[a]pyrene
black carbon
Berlin Ozone Experiment
7V-bis(2-hydroxypropyl)nitrosamine
bronchial hyperresponsiveness
Bayesian  Maxim Eutropy
body mass index
September 2007
                 xxiv
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-------
 bpm
 Br
 Br
 BrO
 bw
 C
 CA
 CAMP
 CAMx
 CAT
 CB4, CB-IV
 CCN
 CD
 Cd
 CEPEX
 CFD
 CG
 CH4
 C5H8
 CHAD
 CH3-CHO
 CH3CH(O)OONO2
 CH3C(O)O
 CH3-C(0)02,
 CH3-C(O)OO
 CHF
 CH2I2
 Choi
 CH3OOH
 (CH3)2S, CH3.S-CH3
 CH3-S-H
 (CH3)2SO
 CH3SO3H
 CH3-S-S-CH3
 CI
 CIMS
beats per minute
bromine
bromine ion
bromine oxide
body weight
carbon or carbon black particles
chromosome aberrations
Childhood Asthma Management Program
Comprehensive Air-Quality Model
catalase
Carbon Bond 4 (chemical mechanism)
cyanomethylidyne radical
criteria document
cadmium
Central Equatorial Pacific Experiment
Computational Fluid Dynamics
cloud-to-ground (flash)
methane
ethene
ethane
isoprene
Consolidated Human Activities Database
acetaldehyde
peroxyacetyl nitrate
peroxyacetyl radical
acetyl peroxy, peroxyacetyl

congestive heart failure
diiodomethane
cholesterol
methyl hydroperoxide
dimethylsulfide
methyl mercaptan
dimethylsulfoxide
methanesulfonic acid
dimethyl disulfide
confidence interval
chemical ionization mass spectroscopy
September 2007
                  xxv
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 CL
 Cl
 cr
 CLRD
 CMAQ
 CMD
 CO
 CoH
 COPD
 CP
 Cr
 CS2
 CTM
 Cu
 CVD
 CYP
 Dae
 DEcCBP
 DEN
 DEP
 DEP+C
 dG
 DL
 DMBA
 DMS
 DMSO
 DNA
 DNS
 DOAS
 EC
 ECG
 ED
 EDMAS
 EDXRF
 EE
 EIB
 EMECAM
 EPA
chemiluminescence
chorine
chorine ion
chronic lower respiratory disease
Community Multiscale Air Quality (model)
count median diameter
carbon monoxide
coefficient of haze
chronic obstructive pulmonary disease
coarse paniculate
chromium
carbon disulfide
chemistry transport model
copper
cardiovascular disease
cytochrome P450
aerodynamic diameter
diesel exhaust particulates extract-coated carbon black particles
diethylnitrosamine
diesel exhaust particles
diesel exhaust particle extract adsorbed to C
2'-deoxyguanosine
detection limit
7, 12-dimethylbenzanthracene
dimethylsulfide
dimethylsulfoxide
deoxyribonucleic acid
Direct Numerical Simulation
differential optical absorption spectroscopy
elemental carbon
el ectrocardi ogram
emergency department
Exposure and Dose Modeling and Analysis System
energy dispersive X-ray fluorescence
energy expenditure
exercise-linked bronchial reactivity
Spanish Multicentre Study on Air Pollution
U.S. Environmental Protection Agency
September 2007
                  xxvi
DRAFT-DO NOT QUOTE OR CITE

-------
 ER
 ESR
 F344
 Fe
 FEM
 FEVi
 FHLC
 FL
 FLEXPART
 FP
 FPD
 FRM
 FTIR
 FVC
 FW2
 yN205
 GAM
 GCE
 GC/ECD
 GCS
 GEE
 GEOS-Chem

 GEOS-1 DAS
 GFED
 GIS
 GLM
 GMP
 GOME
 GP
 GPx
 GRed
 GSD
 GSH
 GSH-Px
 GSSG
 GSSO3H
emergency room
electron spin resonance (spectroscopy)
Fischer 344 (rat)
iron
forced expiratory flow between 25 and 75% of vital capacity
Federal Equivalent Method
forced expiratory volume in 1 second
fetal hamster lung cells
fluoranthene
type of Lagrangian model
fine paniculate
flame photometric detection
Federal Reference Method
Fourier Transform Infrared Spectroscopy
forced vital capacity
black carbon soot model
uptake coefficient for N2O5
Generalized Additive Model(s)
Goddard Cumulus Ensemble (model)
gas chromatography-electron capture detection
y-glutamylcysteine synthetase
Generalized Estimating Equations
three-dimensional model of atmospheric composition driven by
assimilated Goddard  Earth Orbiting System observations
NASA Goddard Earth Orbiting System Data Assimilation System
Global Fire Emissions Database
Geographic Information System
Generalized Linear Model(s)
guanosine-3',5'-monophosphate
Global Ozone Monitoring Instrument
general practitioner physician
glutathione peroxidase
glutathione reductase
geometric standard deviation
glutathione
glutathione peroxidase
oxidized glutathione; glutathione disulfide
glutathione S-sulfonate
September 2007
                 xxvn
DRAFT-DO NOT QUOTE OR CITE

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 GST
 GT
 3H
 H+
 HA
 HAPEM
 HCHO
 HC1
 HC
 HCOO
 HEADS
 HEI
 HES
 HF
 Hg
 HNO3
 HNO4
 HO2
 H202
 HOBr
 HOC1
 HONO, HNO2
 H02N02
 HOONO
 HOX
 HOX
 HP
 HRV
 HS
 H2S
 HSO3
 H2S04
 hv
 HVA-/Ca
 I
 IARC
 fflEM
 1C
glutathione S-transferase (e.g., GSTM1, GSTP1, GSTT1)
y-glutamyltransferase
hydrogen-3 radionuclide; tritium
hydrogen ion
hospital admissions
Hazardous Air Pollutant Exposure Model
formaldehyde
hydrochloric acid
hydrocarbon
formate
Harvard-EPA Annular Denuder System
Health Effects Institute
hospital episode statistics
high frequency
mercury
nitric acid
pernitric acid
hydroperoxyl; hydroperoxy radical
hydrogen peroxide
hypobromous acid
hypochlorous acid
nitrous acid
peroxynitric acid
pernitrous acid
hypohalous acid
oxides of hydrogen
hydrolyzed protein
heart rate variability
hemorrhagic stroke
hydrogen sulfide
hydrogen sulfite
sulfuric acid
solar ultraviolet photon
high-voltage activated calcium currents
iodine
International Agency for Research on Cancer
Individual Based Exposure Models
intracloud (flash);  ion chromatography
September 2007
                 xxvin
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 ICARTT

 ICD, ICD9
 Ig
 fflD
 IIASA
 IMPROVE
 INDOEX
 INO3
 INTEX-NA

 IO
 IPCC-AR4

 IPCC-TAR
 IQR
 IS
 IUGR
 JPL
 Ka
 KH
 85Kr
 Kw
 LEW
 LDH
 LES
 LF
 LFHFR
 LIF
 LOESS
 LP
 LRD
 LRI
 LRS
 LWC
 M
 MAD
 MAP
 MAQSIP
International Consortium for Atmospheric Research on Transport and
Transformation
International Classification of Disease, 9th Revision
immunoglobulin (e.g., IgA, IgE, IgG)
ischemic heart disease
International Institute for Applied Systems Analysis
Interagency Monitoring of Protected Visual Environments
Indian Ocean Experiment
iodine nitrate
NASA Intercontinental Chemical Transport Experiment - North
America
iodine oxide
Intergovernmental Panel on Climate Change-Fourth Assessment
Report
Intergovernmental Panel on Climate Change-Third Assessment Report
interquartile range
ischemic stroke
intrauterine growth retardation
Jet Propulsion Laboratory
acid dissociation constant in M
Henry's Law constant in M atm"1
krypton-85 radionuclide
ion product of water
low birth weight
lacticate dehydrogenase
Large Eddy Simulation
low frequency
low frequency/high frequency ratio
laser-induced fluorescence
locally estimated smoothing splines
long-path
lower respiratory disease
lower respiratory illness
lower respiratory symptoms
liquid water content
air molecule
median aerodynamic diameter
mean arterial pressure
Multiscale Air Quality Simulation Platform
September 2007
                  XXIX
DRAFT-DO NOT QUOTE OR CITE

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 MAX
 MBL
 MCM
 MDA
 MEF50
 MEM
 MENTOR-1A
 MET
 MgO
 MI
 MIESR
 MM5

 MMAD
 MMEF
 MN
 MNPCE
 Mo
 MOBILE6
 MONICA

 MOZART-2
 MPAN
 MPP
 mRNA
 MSA
 15N
 N
 N, n
 N2
 NA
 NAAQS
 NaCl
 Na2CO3
 NADP
 NaHCO3
 NARSTO
 NASA
 NBS
multi axis
marine boundary layer
master chemical mechanism
malondialdehyde
maximal midexpiratory flow at 50% of forced vital capacity
model ensemble mean
Modeling Environment for Total Risk for One-Atmosphere studies
metabolic equivalent of work
magnesium oxide
myocardial infarction
matrix isolation electron spin resonance (spectroscopy)
National Center for Atmospheric Research/Penn State Mesoscale
Model
mass median aerodynamic diameter
maximal midexpiratory flow
micronuclei
micrenucleated polychromatic erythrocytes
molybdenum
Highway Vehicle Emission Factor Model
Monitoring Trend and Determinants in Cardiovascular Disease
(registry)
(model)
peroxymethacryloyl nitrate; peroxy-methacrylic nitric anhydride
multi-phase process
messenger ribonucleic acid
metropolitan statistical area
nitrogen-15 radionuclide
nitrogen
number of observations
molecular nitrogen, nitrogen gas
not available
National Ambient Air Quality Standards
sodium chloride
sodium carbonate
National Atmospheric Deposition Program
sodium bicarbonate
North American Regional Strategy for Atmospheric Ozone
National Aeronautics and Space Administration
National Bureau of Standards
September 2007
                  XXX
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 NCAR
 NCICAS
 NDMA
 NDMA-D
 NMBzA
 NEM
 NEM/pNEM

 NERL
 NF
 NH2
 NH3
 NH4+
 NH4C1
 NH4NO3
 (NH4)2SO4
 NIST
 NMHC
 NMOC
 NN
 NO
 NO2
 NO2+
 NO2
 N03
 NO3
 N205
 NOX
 NOy
 NOZ
 NP
 NPAHs
 NR
 NRC
 NS
 NSA
 nss
 NTRMs
National Center for Atmospheric Research
National Cooperative Inner-City Asthma Study
7V-nitrosodimethylamine
7V-nitrosodimethylamine demethylase
7V-nitrosomethylbenzylamine
National Ambient Exposure Model
National Ambient Exposure Model and Probabilistic National
Exposure Model
National Exposure Research Laboratory
nitrofluoranthene (e.g., 3- or 8-nitrofluoranthene)
amino
ammonia
ammonium ion
ammonium chloride
ammonium nitrate?
ammonium sulfate
National Institute of Standards and Technology
nonmethane hydrocarbon
nonmethane organic compound
nitronaphthalene (e.g., 1- or 2-nitronaphthalene)
nitric oxide
nitrogen dioxide
nitronium ion
nitrite
nitrate (radical)
nitrate
dinitrogen pentoxide
nitrogen oxides; oxides of nitrogen
sum of NOX and NOZ; odd nitrogen species
oxides of nitrogen and nitrates; difference between NOy and NOX
nitropyrene (e.g., 1- or 2-nitropyrene)
nitro polycyclic aromatic hydrocarbons
not reported; data not relevant
National Research Council
nonsignificant
nitrosating agent
non-sea-salt
NIST Traceable Reference Materials
September 2007
                  XXXI
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 16Q
 02
 03
 OAQPS
 OC
 OCS
 OC'D)
 OH
 OHC
 8-OHdG
 OMI
 0(3P)
 OPE
 OPSIS
 OR
 OSPM
 P,P
 PAHs
 PAMS, PAMs
 PAN
 Pb
 PBEM
 PCA
 PCE
 PE
 PEC
 PEF
 PEFR
 PERI
 P(HN03)
 PIH
 PIXE
 PKA
 PKI
 PL
 PM
 PM2.5
oxygen-16 radionuclide
molecular oxygen
ozone
Office of Air Quality Planning and Standards
organic carbon
carbonyl  sulfide
electronically excited oxygen atom
hydroxyl radical
oxygenated hydrocarbons
8-hydroxy-2'-deoxyguanosine
Ozone Monitoring Instrument
ground-state oxygen atom
ozone production efficiency
Open Path Ambient Air Monitoring Systems for SO2
odds ratio
Danish Operational Street Pollution Model
probability value
polycyclic aromatic hydrocarbons
Photochemical Aerometric Monitoring System
peroxyacetyl nitrate; peroxyacyl nitrate
lead
Population Based Exposure Models
principal  component analysis
polychromatic erythrocytes
parameter estimates
pulmonary endocrine cells
peak expiratory flow
peak expiratory flow rate
peripheral vascular and cerebrovascular disease
particulate nitrate
primary intracerebral hemorrhage
particle induced X-ray emission
cyclic AMP-dependent protein kinase A
synthetic peptide inhibitor of PKA
phospholipids
particulate matter
particulate matter with 50% upper cut point aerodynamic diameter of
2.5 jim for sample collection; surrogate for fine PM
September 2007
                 xxxn
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 PMiQ-2.5
 PM13

 PM-CAMx
 PMN
 PNC
 PNN50
 PMT
 pNEM
 P(03)
 POM
 ppb
 ppbv
 ppm
 PPN
 ppt
 pptv
 PRB
 Pt
 PSA
 psi
 PTEP
 PTFE
 PY
 r
 R2
 RACM
 RADM
 RANS
 RBC
 RDBMS
 REHEX
 RH
 RMR
 r-MSSD
particulate matter with 50% upper cut point aerodynamic diameter of
10 |im for sample collection
particulate matter with 10 |im as upper cut point aerodynamic diameter
and 2.5 jim as lower cut point for sample collection; surrogate for
thoracic coarse PM (does not include fine PM)
particulate matter with 50% upper cut point aerodynamic diameter of
13 jim for sample collection
Particulate Matter Comprehensive Air Quality Model with Extensions
polymorphonuclear leukocytes
particle number concentration
percentage of differences between adjacent NN intervals
photomultiplier tube
Probabilistic National Exposure Model
ozone precursor
particulate organic matter
parts per billion
parts per billion by volume
parts per million
peroxypropionyl nitrate; peroxypropionic nitric anhydride
parts per trillion
parts per trillion by volume
policy relevant background
platinum
particle strong acidity
pounds per square inch
PMio Technical Enhancement Program
polytetrafluoroethylene (Teflon)
pyrene
correlation coefficient
coefficient of determination
Regional Air Chemistry Mechanism
Regional Acid Deposition Model
Reynolds Averaged Numerical Simulation
red blood cell or erythrocyte
Relational Database Management Systems
Regional Human Exposure Model
relative humidity
resting metabolic rate
root mean square of successive differences in R-R intervals.
September 2007
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 RO2
 RONO2
 ROONO2, RO2NO2
 RR
 34
 S2*
 S20
 SCAQS
 SCE
 SCIAMACHY

 SCOS97
 SD
 SDNN
 SE
 SEPs
 SGV
 SHEDS
 SHS
 SIDS
 SMOKE
 SO
 SO2
 S02*
 SO3
 SO32
 SO42
 SOD
 SONEX
 SOX
 SPF
 SPM
 SQCA
 SRM
 SSO
 STE
organic peroxyl; organic peroxy
organic nitrate
peroxy nitrate
relative risk
sulfur-34 radionuclide
sulfur
sulfide
electronically excited sulfur molecules
disulfur monoxide
Southern California Air Quality Study
sister chromatid exchange
Scanning Imaging Absorption Spectrometer for Atmospheric
Chartography
1997 Southern California Ozone Study
standard deviation
standard deviation of normal R-R intervals
standard error
somatosensory-evoked potentials
subgrid variability
Simulation of Human Exposure and Dose System
sub arachnoid hemorrhagic stroke
sudden infant death syndrome
Spare-Matrix Operator Kernel Emissions (system)
sulfur monoxide
sulfur dioxide
electronically excited sulfur dioxide molecules
sulfur trioxide
sulfite ion
sulfate ion
superoxide dismutase
Subsonic Assessment Ozone and Nitrogen Oxides Experiment
oxides of sulfur
specific pathogen free
suspended particulate matter
squamous cell carcinoma
standard reference material; suspended particulate matter extract
seabuckthorn seed oil
stratospheric-tropospheric exchange
September 2007
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 STEP
 STN
 STPD
 STRF
 SV40
 T
 t
 TEARS
 TC
 TOLAS
 Tg
 TIA
 TOC
 TOR
 TP
 TPLIF
 TRS
 TSDS
 TSP
 TSPM
 TTFMS
 TTX
 TTX-R
 TTX-S
 UBRE
 U-EPX
 UMD-CTM
 URD
 URI
 URS
 UV
 V
 vd
 VE
 VEPs
 VOC
 W
 WHO
Stratospheric-Tropospheric-Exchange Proj ect
Speciation Trends Network
standard temperature and pressure, dry
Spatio-Temporal Random Field (theory)
simian virus 40
tau; atmospheric lifetime
t statistic
thiobarbituric acid-reactive substances
total carbon
tunable-diode laser absorption spectroscopy
teragram
transient ischemic attack
potassium channel transient outward currents
thermal-optical reflectance
total paniculate
two-photon laser-induced fluorescence
total reduced sulfur
treatment, storage, or disposal facilities
total suspended particles
total suspended paniculate matter
two-tone frequency-modulated spectroscopy
tetrodotoxin
tetrodotoxin-resi stant
tetrodotoxin-sensitive
unbiased risk estimator
urinary eosinophil protein
University of Maryland Chemical Transport Model
upper respiratory disease
upper respiratory illness
upper respiratory symptoms
ultraviolet
vanadium
deposition velocity
total ventilation rate
visual-evoked potentials
volatile organic compound
tungsten
World Health Organization
September 2007
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 XRF                 X-ray fluorescence
 Zn                  zinc
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 i            AX1.  CHAPTER 1 ANNEX-INTRODUCTION
 2
 O
 4          The draft Annexes are prepared in support of the draft Integrated Science Assessment for
 5    Sulfur Oxides - Health Criteria (EPA/600/R-07/108).  The Integrated Science Assessment (ISA)
 6    presents a concise synthesis of the most policy-relevant science to form the scientific foundation
 7    for the review of the primary (health-based) national ambient air quality standards (NAAQS) for
 8    sulfur dioxide (802). This series of Annexes provide more extensive and detailed summaries of
 9    the most pertinent scientific literature.  The Annexes identify, evaluate, and summarize scientific
10    research in the areas of atmospheric sciences, air quality analyses, exposure assessment,
11    dosimetry, controlled human exposure studies, toxicology, and epidemiology, focusing on
12    studies relevant to the review of the primary NAAQS.
13          These draft Annexes are organized by scientific study areas and include research that is
14    relevant to the key policy questions discussed previously to provide an evidence base supporting
15    the development of the ISA, risk, and exposure assessments.  In this Annex 1, we provide
16    legislative background and history of previous reviews of the NAAQS for sulfur oxides.  In
17    Annex 2, we present evidence related to the physical and chemical processes controlling the
18    production, destruction, and levels of sulfur oxides in the atmosphere, including both oxidized
19    and reduced species. Annex 3 presents information on environmental concentrations, patterns,
20    and human exposure to ambient sulfur oxides; however, most information relates to SC>2. Annex
21    4 presents results from toxicological  studies as well as information on dosimetry of sulfur oxides.
22    Annex 5 discusses evidence from epidemiologic studies. These Annexes include more detailed
23    information on  health or exposure studies that is summarized in tabular form, as well as more
24    extensive discussion of atmospheric chemistry, source, exposure, and dosimetry information.
25    Annex tables for health studies are generally organized to include information about
26    (1) concentrations of sulfur oxides levels or doses and exposure times, (2) description of study
27    methods employed, (3) results and comments, and (4) quantitative outcomes for sulfur oxides
28    measures.
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 1    AX1.1   LEGISLATIVE REQUIREMENTS
 2           Two sections of the Clean Air Act (CAA) govern the establishment and revision of the
 3    NAAQS.  Section 108 (42 U.S.C. 7408) directs the Administrator to identify and list "air
 4    pollutants" that "in his judgment, may reasonably be anticipated to endanger public health and
 5    welfare" and whose "presence ... in the ambient air results from numerous or diverse mobile or
 6    stationary sources" and to issue air quality criteria for those that are listed. Air quality criteria
 7    are intended to "accurately reflect the latest scientific knowledge useful in indicating the kind
 8    and extent of identifiable effects on public health or welfare which may be expected from the
 9    presence of [a] pollutant in ambient air ... ."
10           Section 109 (42 U.S.C. 7409) directs the Administrator to propose and promulgate
11    "primary" and "secondary" NAAQS for pollutants listed under section 108.  Section 109(b)(l)
12    defines a primary standard as one "the attainment and maintenance of which in the judgment of
13    the Administrator, based on such criteria and allowing an adequate margin of safety, are requisite
14    to protect the public health."1  A secondary standard, as defined in section 109(b)(2), must
15    "specify a level of air quality the attainment and maintenance of which, in the judgment of the
16    Administrator, based on such criteria, is required to protect the public welfare from any known
17    or anticipated adverse effects associated with the presence of [the] pollutant in the ambient air."2
18           The requirement that primary standards include an adequate margin of safety was
19    intended to address uncertainties associated with inconclusive scientific and technical
20    information available at the time of standard setting. It was also intended to provide a reasonable
21    degree of protection against hazards that research has not yet identified.  See Lead Industries
22    Association v. EPA, 647 F.2d 1130,  1154  (D.C. Cir 1980), cert, denied, 449 U.S. 1042 (1980);
23    American Petroleum Institute v.  Costle, 665 F.2d 1176,  1186 (D.C.  Cir. 1981), cert, denied,  455
24    U.S. 1034(1982). Both kinds of uncertainties are  components of the risk associated with
              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)].
             2
              Welfare effects as defined in section 302(h) [42 U.S.C. 7602(h)] include, but are not limited to, "effects
      on soils, water, crops, vegetation, man-made materials, animals, wildlife, weather, visibility and climate, damage to
      and deterioration of property, and hazards to transportation, as well as effects on economic values and on personal
      comfort and well-being."
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 1    pollution at levels below those at which human health effects can be said to occur with
 2    reasonable scientific certainty. Thus, in selecting primary standards that include an adequate
 3    margin of safety, the Administrator is seeking not only to prevent pollution levels that have been
 4    demonstrated to be harmful but also to prevent lower pollutant levels that may pose an
 5    unacceptable risk of harm, even if the risk is not precisely identified as to nature or degree.
 6          In selecting a margin of safety, the EPA considers such factors as the nature and severity
 7    of the health  effects involved, the size of sensitive population(s) at risk, and the kind and degree
 8    of the uncertainties that must be addressed. The selection of any particular approach to
 9    providing an adequate margin of safety is a policy choice left specifically to the Administrator's
10    judgment.  See Lead Industries Association v. EPA, supra, 647 F.2d at 1161-62.
11          In setting standards that are "requisite" to protect public health and welfare, as provided
12    in section 109(b), EPA's task is to establish standards that are neither more nor less stringent
13    than necessary for these purposes. In so doing, EPA may not consider the costs of implementing
14    the standards. See generally Whitman v. American Trucking Associations, 531 U.S. 457,  465-
15    472,475-76(2001).
16          Section 109(d)(l) requires that "not later than December 31, 1980, and at 5-year
17    intervals thereafter, the Administrator shall complete a thorough review of the criteria
18    published under section 108 and the national ambient air quality standards . . . and shall make
19    such revisions in such criteria and standards and promulgate such new standards as may be
20    appropriate .  . . ." Section 109(d)(2) requires that an independent scientific review committee
21    "shall complete a review of the criteria . . . and the  national primary and secondary ambient air
22    quality standards . .  . and shall recommend to the Administrator any new . . . standards and
23    revisions of existing criteria and standards as may be appropriate .  . . ." Since the early 1980s,
24    this independent review function has been performed by the Clean Air Scientific Advisory
25    Committee (CASAC) of EPA's Science Advisory Board.
26
27
28    AX1.2    HISTORY OF REVIEWS OF THE PRIMARY NAAQS FOR SO2
29          On April 30, 1971, the EPA promulgated primary NAAQS for SO2. These primary
30    standards, which were based on the findings outlined in the original 1969 Air Quality Criteria for
31    Sulfur Oxides, were set at 0.14 parts per million (ppm) averaged over a 24-hour period, not to be
32    exceeded more than once per year, and 0.030 ppm annual arithmetic mean. In 1982, EPA

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 1    published the Air Quality Criteria for Particulate Matter and Sulfur Oxides along with an
 2    addendum of newly published controlled human exposure studies, which updated the scientific
 3    criteria upon which the initial standards were based (EPA, 1982).  In 1986, a second addendum
 4    was published presenting newly available evidence from epidemiologic and controlled human
 5    exposure studies (EPA, 1986).  In 1988,  EPA reviewed and revised the health criteria upon
 6    which the SC>2 standards were based. As a result of that review, EPA published a proposed
 7    decision not to revise the existing standards (53 FR 14926). However, EPA specifically
 8    requested public comment on the alternative of revising the current standards and adding a new
 9    1 -hour primary standard of 0.4 ppm.
10          As a result of public comments on the 1988 proposal and other post-proposal
11    developments, EPA published a second proposal on November 15, 1994 (59 FR 58958).  The
12    1994 re-proposal was based in part on a  supplement to the second addendum of the criteria
13    document, which evaluated new findings on short-term SC>2 exposures in asthmatics (EPA,
14    1994a). As in the 1988 proposal, EPA proposed to retain the existing 24-hour and annual
15    standards.  The EPA also solicited comment on three regulatory alternatives to further reduce the
16    health risk posed by exposure to high 5-minute peaks of 862 if additional protection were judged
17    to be necessary. The three alternatives included: 1) Revising the existing primary 862 NAAQS
18    by adding a new 5-minute standard of 0.60 ppm 862; 2) establishing a new regulatory program
19    under section 303 of the Act to supplement protection provided by the existing NAAQS,  with a
20    trigger level of 0.60 ppm SO2, one expected exceedance; and 3) augmenting implementation of
21    existing standards by focusing on those sources or source types likely to produce high 5-minute
22    peak  concentrations of SC>2.  On May 22, 1996, EPA's final decision, that revisions of the
23    NAAQS for sulfur oxides were not appropriate at that time, was announced in the Federal
24    Register.  In that decision, EPA announced an intention to propose guidance, under section
25    303 of the Act, to assist states in responding to short-term peak levels of 862. The basis for the
26    decision, and subsequent litigation, is discussed below in Chapter 3.
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 i            AX2.  CHAPTER 2 ANNEX-ATMOSPHERIC
 2      CHEMISTRY OF NITROGEN AND SULFUR OXIDES
 3
 4
 5   AX2.1   INTRODUCTION
 6          Nitrogen oxides (NOX) along with volatile organic compounds (VOCs) including
 7   anthropogenic and biogenic hydrocarbons, aldehydes, etc. and carbon monoxide (CO) serve as
 8   precursors in the formation of ozone (03) and other elements of photochemical smog. Nitrogen
 9   oxides are defined here as nitric oxide (NO) and nitrogen dioxide (NO2), the latter of which is a
10   U.S. Environmental Protection Agency (EPA) Criteria Air Pollutant; similarly, oxides of sulfur
11   (SOX) are defined here to be sulfur monoxide  (SO), sulfur dioxide (S02), the largest component
12   of SOX and also a EPA Criteria Air Pollutant,  and sulfur trioxide (SO3).  S03 rapidly reacts with
13   water vapor to form H2S04, and only S02 is present in the atmosphere at detectable levels.
14          Nitrogen dioxide is an oxidant and can further react to form other photochemical
15   oxidants, in particular the organic nitrates, including peroxy acetyl nitrates (PAN)  and higher
16   PAN analogues. It can also react with toxic compounds such as polycyclic aromatic
17   hydrocarbons (PAHs) to form nitro-PAHs, which may be even more toxic than the precursors.
18   Nitrogen dioxide together with sulfur dioxide (S02), another EPA criteria air pollutant, can be
19   oxidized to the strong mineral acids, nitric acid (HN03) and sulfuric acid (H2S04), which
20   contribute to the acidity of cloud, fog, and rainwater, and can form ambient particles.
21          The role of NOX in 03 formation was reviewed in Chapter 2 (Section 2.2) of the latest
22   AQCD for Ozone and Other Photochemical Oxidants (U.S. Environmental Protection Agency,
23   2006 CD06), and in numerous texts (e.g., Seinfeld and Pandis, 1998; Jacob, 2000; Jacobson,
24   2002). Mechanisms for transporting 03 precursors, the factors controlling the efficiency of 03
25   production from NOX, methods for calculating 03 from its precursors, and methods for
26   measuring NOX were all reviewed in Section 2.6 of CD06.  The main points from those
27   discussions in CD06 and updates, based on new materials will be presented here.  Ammonia
28   (NH3) is included here because its oxidation can be a source of NOX, and it is a precursor for
29   ammonium ions (NH4+), which play a key role in neutralizing acidity in ambient particles and in
30   cloud, fog, and rain water. Ammonia is also involved in the ternary nucleation of  new particles,
31   and it reacts with gaseous HN03 to form ammonium nitrate (NH4N03),  which is a major
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 1   constituent of ambient Particulate Matter (PM) in many areas. Ammonia is also involved in over
 2   nitrification of aqueous and terrestrial ecosystems and participates in the N cascade (Galloway
 3   et al., 2003)
 4          The atmospheric chemistry of NOX is discussed in Section AX2.2, and of SOz in Section
 5   AX2.3. Mechanisms for the formation of aqueous-phase sulfate (S042~) and nitrate (N(V) are
 6   reviewed in Section AX2.4.  Sources and emissions of NOX, NHs, and SOz are discussed in
 7   Section AX2.5. Modeling methods used to calculate the atmospheric chemistry, transport, and
 8   fate of NOX and S02 and their oxidation products are presented in Section AX2.6. Measurement
 9   techniques for the nitrogen-containing compounds and for SOz, nitrates, sulfates, and ammonium
10   ion are discussed in Section AX2.8. Estimates of policy-relevant background concentrations of
11   NOX and SOX are given in Section AX2.9. An overall review of key points in this chapter is
12   given in Section AX2.11.
13          The overall chemistry of reactive nitrogen compounds in the atmosphere is summarized
14   in Figure AX2.1-1 and is described in greater detail in the following sections. Nitrogen oxides
15   are emitted primarily as NO with smaller quantities of N02. Emissions of NOX are spatially
16   distributed vertically with some occurring at  or near ground level and others aloft as indicated  in
17   Figure AX2.1-1. Because of atmospheric chemical reactions, the relative abundance of different
18   compounds contributed by different sources varies with location.  Both anthropogenic and
19   natural (biogenic) processes emit NOX. In addition to gas phase reactions, multiphase processes
20   are important for forming aerosol-phase pollutants, including aerosol N0s~.
21
22
23   AX2.2   CHEMISTRY OF NITROGEN OXIDES IN THE TROPOSPHERE
24
25   AX2.2.1  Basic Chemistry
26          There is a rapid photochemical cycle  in the troposphere that involves photolysis of N02
27   by solar UV-A radiation to yield NO and a ground-state oxygen atom, 0(3P):
28
                                         hv ^N0 + 0(3P),
29   This ground-state oxygen atom can then combine with molecular oxygen (Oz) to form Os; and,
30   colliding with any molecule from the surrounding air (M = Nz, Oz, etc), the newly formed Os
31   molecule, transfers excess energy and is stabilized:

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                                                Long range transport to remote
                                                regions at low  temperatures
              V
                     HMO
NH
                                                                nitro-PAHs
                                                           Urt  R-C=C-RW
                                                           NO,	—^ RONC)
                                                             nitrosamines,
                                                             nitro-phenols,
                                                             quinones, etc.
                                                                 deposition
                                           emissions
Figure AX2.1-1.
                       Schematic diagram of the cycle of reactive nitrogen species in the
                       atmosphere. MPP refers to multi-phase process; hv  to a photon of
                       solar energy.
2
3
4
6
7
8
9
                                0(3P)
                                              03 + M,
                                                                           (AX2 2)
where M = Nz, Oz. Reaction AX2-2 is the only significant reaction forming Os in the
troposphere.
      NO and 03 react to reform N02:
                                                  ,                       (AX23)

Reaction AX2-3 is responsible for 03 decreases and N02 increases found near sources of NO
(e.g., highways) , especially at night when the actinic flux is 0. Oxidation of reactive VOCs leads
to the formation of reactive radical species that allow the conversion of NO to N02 without the
participation of Os (as in Reaction AX2-3):
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                                     ,.„  HO,,RO,
 1                                   N0     *    * >    2'                        (AX2-4)
 2          Ozone, therefore, can accumulate as N02 photolyzes as in Reaction AX2-1, followed by
 3   Reaction AX2-2. Specific mechanisms for the oxidation of a number of VOCs were discussed in
 4   the 03 AQCD (U.S. Environmental Protection Agency, 2006).
 5          It is often convenient to speak about families of chemical species defined in terms of
 6   members that interconvert rapidly among themselves on time scales that are shorter than those
 7   for formation or destruction of the family as a whole. For example, an "odd oxygen" (Ox) family
 8   can be defined as

 9                            0, = I(0(JP) + OC D) + 03 + NO y)
10   In much the same way, NOX is sometimes referred to as  "odd nitrogen". Hence, we see that
1 1   production of Ox occurs by the schematic Reaction AX2-4, and that the sequence of reactions
12   given by reactions AX2-1 through AX2-3 represents no  net production of Ox.  Definitions of
13   species families and methods for constructing families are discussed in Jacobson (1999) and
14   references therein. Other families that include nitrogen- containing species (and which will be
1 5   referred to later in this chapter) include:
24
16
17   One can then see that production of Ox occurs by the schematic Reaction AX2-4, and that the
18   sequence of reactions given by reactions AX2-1 through AX2-3 represents no net production of
19   Ox. Definitions of species families and methods for constructing families are discussed in
20   Jacobson (1999) and references therein. Other families that include nitrogen- containing species,
21   and which will be referred to later in this chapter, are: (which is the sum of the products of the
22   oxidation of NOX)

        NOZ = X (HNO3 + HNO4  + NO3 + 2NO2O5 + PAN(CH3CHO - OO - NO2) + other
23      organic ni trades + halogen nitrates + particulate nitrate)',
                                 NOy = NOX + NOZ + HONO;
                                   andNHx ^
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            The reaction of N02 with 03 leads to the formation of N03~ radical,
N03 + hv ^N0 + 02(}0%}
 2
 3   However, because the NOs radical photolyzes rapidly (lifetime of ~ 5 s during the
 4   photochemically most active period of the day around local solar noon (Atkinson et al., 1992a),

                                                                                  (AX2 6a)

 6                                        2         (90%}                         (AX2-6b)
 7   its concentration remains low during daylight hours, but can increase after sunset to nighttime
 8   concentrations of <5 x  107 to 1 x 1010 molecules cm"3 (<2 to 430 parts per trillion (ppt)) over
 9   continental areas influenced by anthropogenic emissions of NOX (Atkinson et al., 1986). At
10   night, NOs, rather than the hydroxyl radical (OH), is the primary oxidant in the system.
1 1          Nitrate radicals can combine with N02 to form dinitrogen pentoxide (N20s):
12
13   and N20s both photolyzes and thermally decomposes back to N02 and N03 during the day;
14   however, N205 concentrations ([N205]) can accumulate during the night to parts per billion (ppb)
1 5   levels in polluted urban atmospheres.
16          The tropospheric chemical removal processes for NOX include reaction of N02 with the
17   OH radical and hydrolysis of N20s in aqueous aerosol solutions if there is no organic coating.
18   Both of these reactions produce HNOs.
19                                          23                       (AX2.8)
20                                     2s—
21          The gas-phase reaction of the OH radical with N02 (Reaction AX2-8) initiates one of the
22   major and ultimate removal processes for NOX in the troposphere. This reaction removes OH
23   and N02 radicals and competes with hydrocarbons for OH radicals in areas characterized by high
24   NOX concentrations, such as urban centers (see Section AX2.2.2). The timescale (T) for
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 1   conversion of NOX to HN03 in the planetary boundary layer at 40 N latitude ranges from about
 2   4 hours in July to about 16 hours in January. The corresponding range in T at 25 N latitude is
 3   between 4 and 5 hours, while at 50 N latitude, HN03 T ranges from about 4 to 20 hours (Martin
 4   et al., 2003). In addition to gas-phase HNOs, Golden and Smith (2000) have shown on the basis
 5   of theoretical studies that pernitrous acid (HOONO) is also produced by the reaction of NOz and
 6   OH radicals. However, this channel of production most likely represents a minor yield
 7   (approximately 15% at the surface) (Jet Propulsion Laboratory, 2003).  Pernitrous acid will also
 8   thermally decompose and can photolyze. Gas-phase HNOs formed from Reaction AX2-8
 9   undergoes wet and dry deposition to the surface, and uptake by ambient aerosol particles.
10   Reaction AX2-8 limits NOX T to a range of hours to days.
1 1         In addition to the uptake of HN03 on particles and in cloud drops, it photolyzes and
1 2   reacts with OH radicals via
13                                      3                 2                     (AX2_1Q)
14   and
15                                HN03 + OH^NOi + H20.                    (AX2 n)

16   The lifetime of HNOs with respect to these two reactions  is long enough for HNOs to act as a
17   reservoir species for NOX during long-range transport, contributing in this way to N02 levels and
18   to Os formation in areas remote from the source region of the NOX that formed this HNOs.
19          Geyer and Platt (2002) concluded that Reaction AX2-9 constituted about 10% of the
20   removal of NOX at a site near Berlin, Germany during spring and summer. However, other
21   studies found a larger contribution to HNOs production from Reaction AX2-9. Dentener and
22   Crutzen (1993) estimated 20% in summer and 80% of HNOs production in winter is from
23   Reaction AX2-9.  Tonnesen and Dennis (2000) found between 16 to 31% of summer HNOs
24   production was from Reaction AX2-9. The contribution of Reaction AX2-9 to HNOs formation
25   is highly uncertain during both winter and summer. The importance of Reaction AX2-9 could be
26   much higher during winter than during summer because of the much lower concentration of OH
27   radicals and the enhanced stability of N20s due to lower temperatures and less sunlight. Note
28   that Reaction AX2-9 proceeds as a heterogeneous reaction.  Recent work in the northeastern
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 1   United States indicates that this reaction is proceeds at a faster rate in power plant plumes than in
 2   urban plumes (Brown et al., 2006a,b; Frost et al., 2006).
 3          OH radicals also can react with NO to produce nitrous acid (HONO or HN02) :
 4                                                       ,_                      (AX212)

 5   In the daytime, HN02 is rapidly photolyzed back to the original reactants:
 6                                       2                 .                       (AX2_13)

 7   Reaction AX2-12 is, however, a negligible source of HONO, which is formed mainly by
 8   multiphase processes (see Section AX2.2.3). At night, heterogeneous reactions of N02 in
 9   aerosols or at the earth's surface result in accumulation of HONO (Lammel and Cape, 1996;
10   Jacob, 2000; Sakamaki et al., 1983; Pitts et al., 1984; Svensson et al., 1987; Jenkin et al., 1988;
1 1   Lammel and Perner, 1988; Notholt et al., 1992a,b).  Harris et al. (1982) and Zhang et al. (2006)
1 2   (e.g.) suggested that photolysis of this HN02 at sunrise could provide an important early-
13   morning source of OH radicals to drive Os formation
14          Hydroperoxy (H02) radicals can react with N02 to produce pernitric acid  (HN04):
15                               H02 + N02+M^HNO^M                   (AX2.M)

16   which then can thermally decompose and photolyze back to its original reactants. The acids
17   formed in these gas-phase reactions are all water soluble. Hence, they can be incorporated into
18   cloud drops and in the aqueous phase of particles.
19          Although the lifetimes of HN04 and N20s are short (minutes to hours) during typical
20   summer conditions, they can be much longer at the lower temperatures and darkness found
21   during the polar night.  Under these conditions, species such as PAN, HN03, HN04, and N20s
22   serve as NOX reservoirs that can liberate N02 upon the return of sunlight during the polar spring.
23   A broad range of organic nitrogen compounds can be directly emitted by combustion sources or
24   formed in the atmosphere from NOX emissions. Organic nitrogen compounds include the PANs,
25   nitrosamines, nitro-PAHs, and the more recently identified nitrated organics in the quinone
26   family.  Oxidation of VOCs produces organic peroxy radicals (R02), as discussed in the latest
27   AQCD for Ozone and Other Photochemical Oxidants (U.S. Environmental Protection Agency,
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 1   2006). Reaction of R02 radicals with NO and N02 produces organic nitrates (RON02) and
 2   peroxynitrates (R02N02):
                                                                             (AX2-15)
                                DD _i_ KID    M  i P/O  A//O
 4                              ^+ N°2 	>R02N02                   (AX2-16)
 5         Reaction (AX2-15) is a minor branch for the reaction of R02 with NO. The major branch
 6   produces RO and N02, as discussed in the next section; however, the organic nitrate yield
 7   increases with carbon number (Atkinson, 2000).
 8         The most important of these organic nitrates is PAN, the dominant member of the
 9   broader family of peroxyacylnitrates which includes peroxypropionyl nitrate (PPN) of
10   anthropogenic origin and peroxymethacrylic nitrate (MPAN) produced from isoprene oxidation.
11   The PANs are formed by the combination reaction of acetyl peroxy radicals with N02:

12                       CH3C(O)-OO + NO2 -> CH3C(O}OONO2

13   where the acetyl peroxy radicals are formed mainly during the oxidation of ethane (C2H6).
14   Acetaldehyde (CH3CHO) is formed as an intermediate species during the oxidation of ethane.
15   Acetaldehyde can be photolyzed or react with OH radicals to yield acetyl radicals:

16                          CH3-C(0)H + hv -> CH3-C(0) + H               (AX2-18)
17                        CH3-C(0)H + OH^ CH3-C(0) + H2O             (AX2-19)
18   Acetyl radicals then react with 02 to yield acetyl peroxy radicals

19                       CHr-C(0) + 02 + M -> CH3C(0)-00 + M            (AX2-20)
20   However, acetyl peroxy radicals will react with NO in areas of high NO concentrations

2i                       CH3(CO)-OO + NO^ CH3(CO)-O + NO2

22   and the acetyl-oxy radicals will then decompose

23                              CH3(CO)-0 -> CH3 + C02

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 1   Thus, the formation of PAN is favored at conditions of high ratios of NOz to NO, which are most
 2   typically found under low NOX conditions. The PANs both thermally decompose and photolyze
 3   back to their reactants on timescales of a few hours during warm sunlit conditions, with lifetimes
 4   with respect to thermal decomposition ranging from ~1 hour at 298 K to -2.5 days at 273 K, up
 5   to several weeks at 250 K. Thus, they can provide an effective sink of NOX at cold temperatures
 6   and high solar zenith angles, allowing release of NOz as air masses warm, in particular by
 7   subsidence.  The PANs are also removed by uptake to vegetation (Sparks et al., 2003;
 8   Teklemariam and Sparks, 2004).
 9          The organic nitrates may react further, depending on the functionality of the R group, but
10   they will typically not return NOX and can therefore be viewed mainly as a permanent sink for
11   NOX, as alkyl nitrates are sparingly soluble and will photolyze. This sink is usually small
12   compared to HNOs formation, but the formation of isoprene nitrates may be a significant sink for
13   NOX in the United States in summer (Liang et al.,  1998).
14          The peroxynitrates produced by (1-16) are thermally unstable and most have very short
15   lifetimes (less than a few minutes) owing to thermal decomposition back to the original
16   reactants. They are thus not effective sinks of NOX.
17
18   AX2.2.2    Nonlinear Relations between Nitrogen Oxide Concentrations and
19                Ozone Formation
20          Ozone is unlike some other species whose rates of formation vary directly with the
21   emissions of their precursors in that Os production (P(0s)) changes nonlinearly with the
22   concentrations of its precursors. At the low NOX concentrations found in most environments,
23   ranging from remote continental areas to rural and suburban areas downwind of urban centers,
24   the net production of Os increases with increasing NOX. At the high NOX concentrations found in
25   downtown metropolitan areas, especially near busy streets and roadways, and in power plant
26   plumes, there is net destruction of 03 by (titration) reaction with  NO. Between these two
27   regimes is a transition stage in which Os shows only a weak dependence on NOX concentrations.
28   In the high NOX regime, N02 scavenges OH radicals which would otherwise oxidize VOCs to
29   produce peroxy radicals, which in turn would oxidize NO to NOz. In the low NOX regime, VOV
30   (VOC) oxidation generates, or at least does not consume, free radicals, and Os production varies
31   directly with NOX. Sometimes the terms 'VOC-limited' and 'N0x-limited' are used to describe
32   these two regimes. However,  there are difficulties with this usage because:  (1) VOC

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 1   measurements are not as abundant as they are for NOX, (2) rate coefficients for reaction of
 2   individual VOCs with free radicals vary over an extremely wide range, and (3) consideration is
 3   not given to CO nor to reactions that can produce free radicals without invoking VOCs.  The
 4   terms N0x-limited and N0x-saturated (used by, e.g., Jaegle et al., 2001) will be used wherever
 5   possible to describe  these two regimes more adequately. However, the terminology used in
 6   original articles will also be kept.  The chemistry of OH radicals, which are responsible for
 7   initiating the oxidation of hydrocarbons, shows behavior similar to that for Os with respect to
 8   NOX concentrations  (Hameed et al., 1979; Pinto et al., 1993; Poppe et al., 1993; Zimmerman and
 9   Poppe, 1993).  These considerations introduce a high degree of uncertainty into attempts to relate
10   changes in 03 concentrations to emissions of precursors.  It should also be noted at the outset that
11   in a N0x-limited (or N0x-sensitive) regime, Os formation is not insensitive to radical production
12   or the flux of solar UV photons, just that Os formation is more sensitive to NOX. For example,
13   global tropospheric Os is sensitive to the concentration of CH4 even though the troposphere is
14   predominantly N0x-limited.
15          Various analytical techniques have been proposed that use ambient NOX and VOC
16   measurements to derive information about 03 production and 03-NOX-VOC sensitivity.
17   Previously (e.g., National Research Council, 1991), it was suggested that 03 formation in
18   individual urban areas could be understood in terms of measurements of ambient NOX and VOC
19   concentrations during the early morning. In this approach, the ratio  of summed (unweighted by
20   chemical reactivity)  VOC to NOX  concentrations is used to determine whether conditions are
21   N0x-sensitive or VOC sensitive.  This technique is inadequate to characterize Os formation
22   because it omits many factors recognized as important for P(0s), including:  the effect of
23   biogenic VOCs (which are not present in urban centers during early morning); important
24   individual differences in the ability of VOCs to generate free radicals, rather than just from total
25   VOC concentration and other differences in Os-forming potential for individual VOCs (Carter,
26   1995); the effect of multiday transport;  and general changes in photochemistry as air moves
27   downwind from urban areas (Milford et al., 1994).
28          Jacob et al. (1995) used a combination of field measurements and a chemical transport
29   model (CTM) to show that the formation of Os changed from N0x-limited to N0x-saturated as
30   the season changed from summer  to fall at a monitoring site in Shenandoah National Park, VA.
31   Photochemical production of Os generally occurs together with production of various  other

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 1   species including HN03, organic nitrates, and hydrogen peroxide (H202). The relative rates of
 2   P(03) and the production of other species varies depending on photochemical conditions, and can
 3   be used to provide information about 03-precursor sensitivity.
 4          There are no hard and fast rules governing the levels of NOX at which the transition from
 5   NOx-limited to N0x-saturated conditions occurs. The transition between these two regimes is
 6   highly spatially and temporally dependent. In the upper troposphere, responses to NOX additions
 7   from commercial aircraft have been found which are very similar to these in the lower
 8   troposphere (Bruhl et al., 2000).  Bruhl et al.  (2000) found that the NOX levels for 03 production
 9   versus loss are highly sensitive to the radical  sources included in model calculations.  They found
10   that inclusion of only CH4 and CO oxidation  leads to a decrease in net 03 production in the
11   North Atlantic flight corridor due to NO emissions from aircraft.  However, the additional
12   inclusion of acetone photolysis was found to  shift the maximum in 03 production to higher NOX
13   mixing ratios, thereby reducing or eliminating areas in which 03 production rates decreased due
14   to aircraft emissions.
15          Trainer et al. (1993)  suggested that the slope of the regression line between 03 and
16   summed NOX oxidation products (NOZ, equal to the difference between measured total reactive
17   nitrogen, N0y, and NOX) can be used to estimate the rate of P(03) per NOX (also known as the 03
18   production efficiency, or OPE). Ryerson et al.  (1998, 2001) used measured correlations between
19   03 and NOZ to identify different rates of 03 production in plumes from large point sources.
20          Sillman (1995) and Sillman and He (2002)  identified several secondary reaction products
21   that show different correlation patterns for N0x-limited conditions and N0x-saturated conditions.
22   The most important correlations are for 03 versus N0y, 03 versus NOZ, 03 versus HN03, and
23   H202 versus HN03. The correlations between 03 and N0y, and 03 and NOZ are especially
24   important because measurements of N0y and NOX are widely available. Measured 03 versus
25   NOZ (Figure AX2.2-1) shows distinctly different patterns in different locations.  In rural areas
26   and in urban areas such as Nashville, TN, 03 shows a strong correlation with NOZ and a
27   relatively steep slope to the regression line. By contrast, in Los Angeles 03 also increases with
28   NOZ, but the rate of increase of 03 with NOZ  is lower and the 03 concentrations for a given NOZ
29   value are generally lower.
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 1          The difference between N0x-limited and N0x-saturated regimes is also reflected in
 2   measurements of H202.  Formation of H202 takes place by self-reaction of photochemically-
 3   generated H02 radicals, so that there is large seasonal variation of H202 concentrations, and
                    250 -i	
Q.
Q.
£   100
     Figure AX2.2-1.
                                                 x
                                                        X
                                                               X
                                                               X
                                                      X X
10           20
        NOZ {ppb)
                                                                         X
                                                                            XX ^
                                                                              ' .
                                                                30
                                                              40
          Measured values of O3 and NOZ (NOy-NOx) during the afternoon at
          rural sites in the eastern United States (gray circles) and in urban
          areas and urban plumes associated with Nashville, TN (gray dashes),
          Paris, FR (black diamonds) and Los Angeles, CA (X's)
 4   values in excess of 1 ppb are mainly limited to the summer months when photochemistry is more
 5   active (Kleinman,  1991). Hydrogen peroxide is produced in abundance only when Os is
 6   produced under N0x-limited conditions. When the photochemistry is N0x-saturated, much less
 7   H202 is produced.  In addition, increasing NOX tends to slow the formation of H202 under NOX-
 8   limited conditions.  Differences between these two regimes are also related to the preferential
 9   formation of sulfate during summer and to the inhibition of sulfate and hydrogen peroxide during
10   winter (Stein and Lamb, 2003). Measurements  in the rural eastern United States (Jacob et al.,
11   1995), at Nashville (Sillman et al., 1998), and at Los Angeles (Sakugawa and Kaplan, 1989)
12   show large differences in H202 concentrations likely due to differences in NOX availability at
13   these locations.
14
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 1   AX2.2.3    Multiphase Chemistry Involving NOX
 2          Recent laboratory studies on sulfate and organic aerosols indicate that the reaction
 3   probability yN205 is in the range of 0.01 to 0.05 (Kane et al., 2001; Hallquist et al., 2003;
 4   Thornton et al., 2003). Tie et al. (2003) found that a value of 0.04 in their global model gave the
 5   best simulation of observed NOX concentrations over the Arctic in winter.
 6          Using aircraft measurements over the northeastern United States., Brown et al. (2006b)
 7   found that the uptake coefficient for NzOs, yNzOs, on the  surfaces of particles depends strongly
 8   on their sulfate content.  They found that yNzOs was highest (0.017) in regions where the aerosol
 9   sulfate concentration was highest and lower elsewhere  (<0.0016). This result contrasts with that
10   of Dentener and Crutzen (1993) who concluded that yN2Os would be independent of aerosol
11   composition,  based on a value for yN2Os of 0.1, implying that the heterogeneous hydrolysis of
12   N205 would be saturated for typical ambient aerosol surface areas. The importance of this
13   reaction to tropospheric chemistry depends on the value of yNzOs. If it is 0.01 or lower, there
14   may be difficulty in explaining the loss of N0y and  the formation of aerosol nitrate, especially
15   during winter. A decrease in NzOs slows down the  removal of NOX by leaving more NOz
16   available for reaction and thus increases Os production. Based on the consistency between
17   measurements of N0y partitioning and gas-phase models, Jacob (2000) considers it unlikely that
18   HNOs is recycled to NOX in the lower troposphere in significant concentrations. However, only
19   one of the reviewed studies  (Schultz et al., 2000) was conducted in the marine troposphere and
20   none was conducted in the MBL. An investigation  over the equatorial Pacific reported
21   discrepancies between observations and theory (Singh et al., 1996) which might be explained by
22   HNOs recycling. It is important to recognize that both  Schultz et al. (2000) and Singh et al.
23   (1996) involved aircraft sampling at altitude which, in the MBL, can significantly under-
24   represent sea  salt aerosols and thus most total  NOs (defined to be HNOs + NOs") and large
25   fractions of N0y in marine air (e.g., Huebert et al., 1996).  Consequently, some caution is
26   warranted when interpreting constituent ratios and N0y budgets based on such data.
27          Recent work in the Arctic has quantified significant photochemical recycling of NOs" to
28   NOX and attendant perturbations of OH chemistry in snow (Honrath et al., 2000; Dibb et al.,
29   2002; Domine and Shepson, 2002) which suggest the possibility that similar multiphase
30   pathways could occur in aerosols. As mentioned above, NOs" is photolytically reduced to NOz
31   (Zafiriou and True, 1979) in acidic sea salt solutions (Anastasio et al., 1999).  Further photolytic

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 1   reduction of N02  to NO (Zafariou and True, 1979) could provide a possible mechanism for
 2   HNOs recycling. Early experiments reported production of NOX during the irradiation of
 3   artificial seawater concentrates containing N03~ (Petriconi and Papee, 1972). Based on the
 4   above, HNOs recycling in sea salt aerosols is potentially important and warrants further
 5   investigation. Other possible recycling pathways involving highly acidic aerosol solutions and
 6   soot are reviewed by Jacob (2000).
 7          Stemmler et al. (2006) studied the photosensitized reduction of N02 to HONO on humic
 8   acid films using radiation in the UV-A through the visible spectral regions. They also found
 9   evidence for reduction occurring in the dark, reactions which may occur involving surfaces
10   containing partly oxidized aromatic structures.  For example, Simpson et al. (2006) found that
11   aromatic compounds constituted -20% of organic films coating windows in downtown Toronto.
12   They  calculated production rates of HONO that are compatible with observations of high HONO
13   levels in a variety of environments. The photolysis of HONO formed this way could account for
14   up to  60% of the integrated source of OH radicals in the inner planetary boundary layer. A
15   combination of high N02 levels and surfaces of soil and buildings and other man-made structures
16   exposed to diesel exhaust would then be conducive to HONO formation and, hence, to high
17   [OH]  (Xuetal., 2006).
18          Ammann et al. (1998)  reported the efficient conversion of N02 to HONO on fresh soot
19   particles in the presence of water. They suggest that interaction between N02 and soot particles
20   may account for high mixing ratios of HONO observed in urban environments.  Conversion of
21   N02 to HONO and subsequent photolysis and HONO to NO + OH would constitute a NOX-
22   catalyzed Os sink involving snow. High concentrations of HONO can lead to the rapid growth in
23   OH concentrations shortly after sunrise, giving a "jump start" to photochemical smog formation.
24   Prolonged exposure to ambient oxidizing agents appears to deactivate this process. Broske et al.
25   (2003) studied the interaction  of N02 on secondary organic aerosols and concluded that the
26   uptake coefficients were too low for this reaction to be an important source of HONO in the
27   troposphere.
28          Choi and Leu (1998) evaluated the interactions of HN03 on model black carbon soot
29   (FW2), graphite, hexane, and kerosene soot.  They found that HNOs decomposed to N02 and
30   H20 at higher HNOs surface coverages, i.e., P(HNOs) > =  10~4 Torr.  None of the soot models
31   used were reactive at low HNOs coverages, at P(HNOs) = 5 x 10~7 Torr or at temperatures below

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 1   220 K. They conclude that it is unlikely that aircraft soot in the upper troposphere/lower
 2   stratosphere reduces HN03.
 3          Heterogeneous production on soot at night is believed to be the mechanism by which
 4   HONO accumulates to provide an early morning source of HOX in high NOX environments
 5   (Harrison et al., 1996; Jacob, 2000). HONO has been frequently observed to accumulate to
 6   levels of several ppb overnight, and this has been attributed to soot chemistry (Harris et al., 1982;
 7   Calvert et al., 1994; Jacob, 2000).
 8          Longfellow et al. (1999) observed the formation of HONO when methane, propane,
 9   hexane, and kerosene  soots were  exposed to N02. They suggested that this reaction may account
10   for some part of the unexplained high levels of HONO observed in urban areas. They comment
11   that without details about the surface area, porosity, and amount of soot available for this
12   reaction, reactive uptake values cannot be estimated reliably. They comment that soot and N02
13   are produced in close  proximity during combustion, and that large quantities of HONO have
14   been observed in aircraft plumes.
15          Saathoff et al.  (2001) studied the heterogeneous loss of N02, HN03, N03/N205,
16   H02/H02N02 on soot aerosol using a large aerosol chamber. Reaction periods of up to several
17   days were monitored and results used to fit a detailed model. Saathoff et al. derived reaction
18   probabilities at 294 K and 50% RH for N02, N03, H02, and H02N02 deposition to soot; HN03
19   reduction to N02; and N20s hydrolysis. When these probabilities were included in
20   photochemical box model calculations  of a 4-day smog event, the only noteworthy influence of
21   soot was a 10% reduction in the second day 03 maximum,  for a soot loading of 20 pg rrf3, i.e.,
22   roughly a factor of 10 times observed black carbon loadings seen in United States urban areas,
23   even during air pollution episodes.
24          Munoz and Rossi (2002) conducted Knudsen cell studies of HN03 uptake  on black and
25   grey decane soot produced in lean and rich flames, respectively. They observed HONO as the
26   main species released following HN03 uptake on grey soot, and NO and traces of N02 from
27   black soot.  They conclude that these reactions would only have relevance in special situations in
28   urban settings where soot and HN03 are present in high concentrations simultaneously.
29
30   Formation ofNitro PAHs
31          Nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) (see Figure AX2.2-2 for some
32   example nitro-PAHs)  are generated from incomplete combustion processes through electrophilic

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     2-nitronaphthalene   9-nitroanthracene     2-nitrofluoranthene   6-nitrobenzo(a)pyrene
     Figure AX2.2-2.     Structures of nitro-polycyclic aromatic hydrocarbons.
 1   reactions of poly cyclic aromatic hydrocarbons (PAHs) in the presence of NO 2 (International
 2   Agency for Research on Cancer [IARC] ,1989; World Health Organization [WHO], 2003).
 3   Among combustion sources, diesel emissions have been identified as the major source of nitro-
 4   PAHs in ambient air (Bezabeh et al, 2003; Gibson, 1983; Schuetzle, 1983; Tokiwa and Ohnishi,
 5   1986).  Direct emissions of NPAHs in PM vary with type of fuel, vehicle maintenance, and
 6   ambient conditions (Zielinska et al., 2004).
 7          In addition to being directly emitted, nitro-PAHs can also be formed from both gaseous
 8   and heterogeneous reactions of PAHs with gaseous nitrogenous pollutants in the atmosphere
 9   (Arey et al., 1986; Arey et al.,  1989, Arey, 1998; Perrini, 2005; Pitts, 1987; Sasaki et al., 1997;
10   Zielinska et al., 1989). Different isomers of nitro-PAHs are formed through different formation
11   processes.  For example, the most abundant nitro-PAH in diesel particles is 1-nitropyene (1NP),
12   followed by 3-nitrofluoranthene (3NF) and 8-nitrofluoranthene (8NF) (Bezabeh et al., 2003;
13   Gibson, 1983; Schuetzle, 1983; Tokiwa and Ohnishi, 1986). However, in ambient particulate
14   organic matter (POM), 2-nitrofluoranthene (2NF) is the dominant compound, followed by 1NP
15   and 2-nitropyrene (2NP) (Arey et al., 1989; Bamford et al., 2003; Reisen and Arey, 2005;
16   Zielinska et al., 1989), although 2NF and 2NP are not directly emitted from primary combustion
17   emissions.  The reaction mechanisms for the different nitro-PAH formation processes have been
18   well documented and are presented in Figure AX2.2-2.
19          The dominant process for the formation of nitro-PAHs in the atmosphere is gas-phase
20   reaction of PAHs with OH radicals in the presence of NOX (Arey et al., 1986, Arey, 1998;
21   Atkinson and Arey, 1994; Ramdahl et al.,  1986; Sasaki et al., 1997). Hydroxyl radicals can be
22   generated photochemically or at night through ozone-alkene reactions, (Finlayson-Pitts and Pitts,
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 1   2000).  The postulated reaction mechanism of OH with PAHs involves the addition of OH at the
 2   site of highest electron density of the aromatic ring, for example, the 1-position for pyrene (PY)
 3   and the 3-position for fluoranthene (FL). This reaction is followed by the addition of N02 to the
 4   OH-PAH adduct and elimination of water to form the nitroarenes (Figure AX2.2-3, Arey et al.,
 5   1986; Aktinson et al., 1990; Pitts, 1987). After formation, nitro-PAHs with low vapor pressures
 6   (such as 2NF and 2NP) immediately migrate to particles under ambient conditions (Fan et al.,
 7   1995; Feilberg et al., 1999). The second order rate-constants for the reactions of OH with most
 8   PAHs range from 10~10 to 10~12 cm3moleonVy * at 298 K with the yields ranging from -0.06 to
 9   -5% (Atkinson and Arey, 1994).  2NF and 2NP have been found as the most abundant nitro-
10   PAHs formed via reactions of OH with gaseous PY and FL, respectively in ambient air.
     Figure AX2.2-3.
                                            OH
                                                        |NO£
                             2NP
Formation of 2-nitropyrene (2NP) from the reaction of OH with
gaseous pyrene (PY).
11          The second important process for the formation of nitro-PAHs in the atmosphere is the
12   nitration of PAHs by N0s~ in the presence of NOX at night (Atkinson et al., 1990; Atkinson and
13   Arey, 1994; Sasaki et al., 1997). Nitrate radicals can be generated by reaction of ozone (03) with
14   NOz in the atmosphere by Reaction AX2-5:
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                                                                                  (AX2-5)
 2          Similar to the mechanism of OH reactions with PAHs, N03 initially adds to the PAH ring
 3   to form an N03-PAH adduct, followed by loss of HN03 to form nitro-PAHs (Atkinson et al.,
 4   1990; Atkinson and Arey, 1994; Sasaki et al., 1997). For example, in the mixture of naphthalene
 5   and NzOs-NOs-NOz, the major products formed through the N03 reaction are 1- and 2-nitro-
 6   naphthalene (INN and 2NN) (Atkinson et al., 1990; Feilberg et al., 1999; Sasaki et al., 1997).
 7   2NF and 4NP were reported as the primary products of the gas-phase reactions of FL and PY
 8   with N03 radical, respectively (Atkinson et al.,  1990; Atkinson and Arey, 1994).
 9          The reaction with N03 is of minor importance in the daytime because N03 radical is not
10   stable in sunlight.  In addition, given the rapid reactions of NO with N03 and with 03 in the
11   atmosphere (Finlayson-Pitts and Pitts 2000), concentrations  of N03 at ground level are low
12   during daytime. However, at night, concentrations of N03 radicals formed in polluted ambient
13   air are expected to increase. According to Atkinson et al. (1991), the average N03 concentration
14   is about 20 ppt in the lower troposphere at night and can be as high as 430 ppt. It is also worth
15   noting that significant N03 radical concentrations are found at elevated altitudes where 03 is
16   high but NO is low (Reissell and Arey, 2001; Stutz et al., 2004).  When N03 reaches high
17   concentrations, the formation of nitro-PAHs by the reaction  of gaseous PAHs with N03 may be
18   of environmental significance. At 10~17 - 10~18 cm3 molecule" V1, the rate constants of N03
19   with most PAHs are several orders of magnitude lower than those of OH with the same PAHs;
20   however, the yields of nitro-PAHs from N03 reactions are generally much higher than those of
21   OH reactions.  For example, the  yields of 1-NN and 2NF are 0.3% and 3%, respectively from
22   OH reactions, but the yields are  17% and 24% for these two compounds generated from the N03
23   radical reactions (Atkinson and Arey, 1994).  Therefore, formation of nitro-PAHs via reactions
24   of N03 at nighttime under certain circumstances can be significant.
25          The third process of nitro-PAH formation in the atmosphere is nitration of PAHs by
26   N02/N205 in the presence of trace amounts of HN03 (HN03) in both gas and particle phases.
27   This mechanism could be operative throughout the day and night (Pitts et al., 1983, 1985a,b;
28   Grosjean et al., 1983; Ramdahl et al., 1984; Kamens et al., 1990).  The formation of nitro-
29   fluoranthenes was observed when adsorbed FL was exposed to gaseous NzOs, and the
30   distribution of product NF isomers was 3- > 8- > 7- > 1- NF (Pitts et al., 1985a,b). The proposed


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 1   mechanism for this reaction was an ionic electrophilic nitration by nitronium ion (N02+).  It was
 2   speculated that N20s became ionized prior to the reaction with FL (Zielinska et al, 1986). Only
 3   1NP was observed for the reaction of PY with N205 on filters (Pitts et al., 1985b).  Compared to
 4   the reactions of OH and NOs, nitration of PAHs by NOz/NzOs is less important.
 5          Measurements of nitro-PAHs in ambient air provide evidence for the proposed reaction
 6   mechanism, i.e. the reactions of OH and NOs radicals with PAHs are the major sources of
 7   nitro-PAHs (Bamford and Baker, 2003; Reisen and Arey, 2005; and references therein). 2NF is
 8   a ubiquitous component of ambient POM, much higher than 1NP, itself a marker of combustion
 9   sources.  Nitro-PAH isomer ratios show strong seasonality. For instance, the mean ratios of
10   2NF/1NP were higher in summer than in winter (Bamford et al., 2003; Reisen and Arey, 2005),
11   indicating that reactions of OH and NOs with FL are the major sources of nitro-PAHs in ambient
12   air in summer. The ratio of 2NF/1NP was lower in winter than in summer because of lower OH
13   concentrations and, therefore, less production of 2NF via atmospheric reactions. A ratio of
14   1NP/2NF greater than 1 was observed in locations with major contributions from vehicle
15   emissions (Dimashki et al., 2000; Feilberg et al., 2001). In addition, the ratio of 2NF/2NP was
16   also used to evaluate the contribution of OH and N03 initiated reactions to the  ambient nitro-
17   PAHs (Bamford et al.,  2003; Reisen and Arey, 2005).
18          The concentrations for most nitro-PAHs found in ambient air are much lower than
19   1 pg/m3, except NNs, 1NP, and 2NF, which can be present at several pg/m3.  These levels are
20   much lower (~2 to -1000 times lower) than their parent PAHs.  However, nitro-PAHs are much
21   more toxic than PAHs  (Durant et al., 1996; Grosovsky et al., 1999; Salmeen et al., 1982; Tokiwa
22   et al., 1998; Tokiwa and Ohnishi, 1986). Moreover, most nitro-PAHs are present in particles
23   with a mass median diameter <0.1 pm.
24          Esteve et al. (2006) examined the reaction of gas-phase N02 and OH radicals with
25   various PAHs adsorbed onto model diesel particulate matter (SRM 1650a, NIST).  Using pseudo
26   second order rate coefficients, they derived lifetimes for conversion of the particle-bound PAHs
27   to nitro-PAHs of a few days  (for typical urban N02 levels of 20 ppb). They also found that the
28   rates of reaction of OH with the PAHs were about four orders of magnitude larger than for the
29   reactions involving NOz. However, since the concentrations of NOz used above are more than
30   four  orders  of magnitude larger than those for OH (106-107/cm3), they concluded that the
31   pathway involving NOz is expected to be favored over that involving OH radicals. Consistent

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 1   with the importance of the gas-phase formation of NPAHS, both the mutagenic potency of PM
 2   and the content of NPAHs in PM vary by particle size, and are higher in the submicron size
 3   range (Xu and Lee, 2000; Kawanaka et al, 2004).
 4          The major loss process of nitro-PAHs is photodecomposition (Fan et al., 1996; Feilberg
 5   et al., 1999; Feilberg and Nielsen, 2001), with lifetimes on the order of hours.  However, lacking
 6   direct UV light sources indoors, nitro-PAHs are expected have a longer lifetimes (days) indoors
 7   than outdoors; and may therefore pose increased health risks. Many nitro-PAHs are semi- or
 8   nonvolatile organic compounds.  As stated above, indoor environments have much greater
 9   surface areas than outdoors. Thus, it is expected that gas/particle distribution of nitro-PAHs
10   indoors will be different from those in ambient air. A significant portion of nitro-PAHs will
11   probably be adsorbed by indoor surfaces, such as carpets, leading to different potential  exposure
12   pathways to nitro-PAHs in indoor environments.  The special characteristics of indoor
13   environments, which can affect the indoor chemistry and potential exposure pathways
14   significantly, should be taken into consideration when conducting exposure studies of nitro-
15   PAHs.
16          Reaction with OH and NOs radicals is a major mechanism for removing gas-phase PAHs,
17   with OH radical initiated reactions predominating depending on season (Vione et al., 2004;
18   Bamford et al., 2003).  Particle-bound PAH reactions occur but tend to be slower.
19   Nitronaphthalenes tend to remain in the vapor phase, but because phase partitioning depends on
20   ambient temperature, in very cold regions these species can condense (Castells et al., 2003)
21   while the higher molecular weight PAHs such as the  nitroanthracenes, nitrophenantrenes and
22   nitrofluoranthenes condense in and on PM (Ciganek et al., 2004; Cecinato, 2003).
23
24   Multiphase Chemical Processes Involving Nitrogen Oxides and Halogens
25          Four decades of observational data on Os in the  troposphere have revealed numerous
26   anomalies not easily explained by gas-phase HOX-NOX photochemistry.  The best-known
27   example  is the dramatic depletion of ground-level 03 during polar sunrise due to multiphase
28   catalytic  cycles involving inorganic Br and Cl radicals (Barrie et al., 1988; Martinez et  al., 1999;
29   Foster et al., 2001).  Other examples of anomalies in  tropospheric 03 at lower  latitudes  include
30   low levels of 03 (<10 ppbv) in the marine boundary layer (MBL) and overlying free troposphere
31   (FT) at times over large portions of the tropical Pacific  (Kley et al., 1996), as well as post-sunrise
32   Os depletions over the western subtropical Pacific Ocean (Nagao et al., 1999), the temperate

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15
 1   Southern Ocean (Galbally et al, 2000), and the tropical Indian Ocean (Dickerson et al, 1999).
 2   The observed Os depletions in near-surface marine air are generally consistent with the model-
 3   predicted volatilization of Br2, BrCl, and C12 from sea salt aerosols through autocatalytic halogen
 4   "activation" mechanisms (e.g., Vogt et al., 1996; von Glasow et al., 2002a) involving these
 5   aqueous phase reactions.

 6                              HOBr +  Br- + H+ -> Br2 + H2O

 7                            HOCL + Br~ + //+-» BrCl + H2O

 8                             HOC1 +  Cl- + H* -> C12 + H20                  (AX2_25)
 9   In polluted marine regions at night, the heterogeneous reaction

1Q                              N205+C1-^C1N02+N03-                   (AX2_26)

1 1   may also be important (Finlayson-Pitts et al., 1989;  Behnke et al., 1997; Erickson et al., 1999).
12   Diatomic bromine, BrCl, Clz, and CINOz volatilize and photolyze in sunlight to produce atomic
13   Br and Cl.  The acidification of sea salt aerosol via incorporation of HN03 (and other acids)
14   leads to the volatilization of HC1 (Erickson et al., 1999), e.g.
                                HN03+C1-->HCH-N03
1 6   and the corresponding shift in phase partitioning can accelerate the deposition flux to the surface
17   of total N03 (Russell et al., 2003; Fischer et al., 2006). However, Pryor and Sorensen (2000)
18   have shown that the dominant form of nitrate deposition is a complex function of wind speed. In
19   polluted coastal regions where HC1 from Reaction 35 often exceeds 1 ppbv, significant
20   additional atomic Cl~ is produced via:
21                                 ffCl + OH -> Cl + H20                      (AX2_28)
22    (Singh and Kasting, 1988; Keene et al., 2007).  Following production, Br and Cl atoms
23    catalytically destroy Os via:
24                                    X + O3^>XO + O2                        (AX2-29)

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                                                                                  (AX2_3Q)

                                                                                  (AX2_31)
 3   where (X = Br and Cl).
 4   Formation of Br and Cl nitrates via
 5                                             2-3                         (AX2.32)
 6   and the subsequent reaction of XNOs with sea salt and sulfate aerosols via

 7                            XNO3 + H2O -» HOX +H+ + NO3-

 8   and:
 9                                      1                                         (AX2_34)

10    (where Y = Cl, Br, or I) accelerates the conversion of NOX to particulate N0s~ and thereby
1 1    contributes indirectly to net Os destruction (Sander et al., 1999; Vogt et al., 1999, Pszenny et al.,
1 2    2004) .  Most XNOs reacts via reaction 34 on sea salt whereas reaction 33 is more important on
13    sulfate aerosols. Partitioning of HC1 on sulfate aerosols following Henry's Law provides Cl~ for
14    reaction 34 to form BrCl.  Product N03~ from both reactions AX2-33 and AX2-34 partitions
15    with the gas-phase HNOs following Henry's Law. Because most aerosol size fractions in the
16    MBL are near equilibrium with respect to HN03 (Erickson et al., 1999; Keene et al., 2004), both
17    sulfate and sea salt aerosol can sustain the catalytic removal of NOX and re-activation of Cl and
18    Br with no detectable change in composition. The photolytic reduction of N0s~ in sea salt
19    aerosol solutions recycles  NOX to the gas phase  (Pszenny et al., 2004). Halogen chemistry also
20    impacts 03 indirectly by altering OH/H02 ratios (XO + H02 -> HOX + 02 -> OH + X)  (e.g.,
21    Stutz et al., 1999; Bloss et al., 2005).
22          In addition to Os destruction via reaction AX2-37, atomic Cl oxidizes hydrocarbons
23    (HCs) primarily via hydrogen abstraction to form HC1 vapor and organz products (Jobson et al.,
24    1994; Pszenny et al., 2006).  The enhanced supply of odd-H radicals from  HC oxidation leads to
25    net Os production in the presence of sufficient NOX (Pszenny et al., 1993). Available evidence
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 1   suggests that Cl  radical chemistry may be a significant net source for 03 in polluted
 2   coastal/urban air (e.g., Tanaka et al., 2003; Finley and Saltzman, 2006).
 3          An analogous autocatalyic 03 destruction cycle involving multiphase iodine chemistry
 4   also operates in the marine atmosphere (Alicke et al., 1999, Vogt et al., 1999; McFiggans et al.,
 5   2000; Ashworth et al., 2002).  In this case, the primary source of I is believed to be either
 6   photolysis of ClH^Iz, other I-containing gases (Carpenter et al., 1999; Carpenter, 2003), and/or
 7   perhaps lz (McFiggans et al., 2004;  Saiz-Lopez and Plane, 2004; McFiggans, 2005) emitted by
 8   micro-and macro flora. Sea salt and sulfate aerosols provide substrates for multiphase reactions
 9   that sustain the catalytic I-IO cycle.  The 10  radical has been measured by long-path (LP) and/or
10   multi axis (MAX) differential optical absorption spectroscopy (DOAS)  at Mace Head, Ireland;
11   Tenerife, Canary Islands; Cape Grim, Tasmania;  and coastal New England, USA; having
12   average daytime levels of about 1 ppt with maxima up to 7 ppt (e.g., Allan  et al., 2000; Pikelnaya
13   et al., 2006).  Modeling suggests that up to 13% per day of Os in marine air may be destroyed via
14   multiphase iodine chemistry (McFiggans et al., 2000).  The reaction of 10 with NOz followed by
15   uptake of INOs into aerosols (analogous to Reactions AX2-9 through AX2-11)  accelerates the
16   conversion of NOX to participate N03~  and thereby contributes to net 03 destruction. The
17   reaction  10 + NO —»• I + N02 also influences NOX cycling.
18          Most of the above studies have  focused on halogen-radical chemistry and related
19   influences on NOX cycling in coastal and urban air. However, available evidence suggests that
20   similar chemical transformations proceed in  other halogen-rich tropospheric regimes.  For
21   example, Cl,  Br, and/or I oxides have been measured at significant concentrations in near-surface
22   air over the Dead Sea, Israel, the Great Salt Lake, Utah  (e.g., Hebestreit et al., 1999; Stutz et al.,
23   1999, 2002; Zingler and Platt, 2005), and the Salar de Uyuni salt pan in the Andes mountains
24   (U. Platt, unpublished data, 2006); high column densities of halogenated compounds have also
25   been observed from satellites over the northern Caspian Sea (Wagner et al., 2001; Hollwedel
26   et al., 2004).  The primary source of reactive halogens in these regions is thought to be from
27   activation along the lives of that in reactions in AX2-23 through AX2-25 involving concentrated
28   salt deposits on surface evaporite pans. High concentrations of BrO have also been measured in
29   volcanic plumes (Bobrowski et al.,  2003, Gerlach, 2004).  Although virtually unexplored, the
30   substantial emissions of inorganic halogens during biomass burning (Lobert et al., 1999; Keene
31   et al., 2006) and in association with crustal dust (Keene et al., 1999; Sander et al., 2003) may

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 1   also support active halogen-radical chemistry and related transformations involving NOX
 2   downwind of sources.  Finally, observations from satellites, balloons, and aircraft indicate that
 3   BrO is present in the free troposphere at levels sufficient to significantly influence
 4   photochemistry (e.g., von Glasow et al., 2004).
 5
 6
 7   AX2.3    CHEMISTRY OF SULFUR OXIDES IN THE TROPOSPHERE
 8          The four known monomeric sulfur oxides are sulfur monoxide (SO), sulfur dioxide
 9   (S02), sulfur trioxide (S03), and disulfur monoxide (S20). SO can be formed by photolysis of
10   S02 at wavelengths less than 220 nm, and so could only be found in the middle and upper
11   stratosphere (Pinto et al.,  1989). SOs can be emitted from the stacks of power plants and
1 2   factories however, it reacts  extremely rapidly with H20 in the stacks or immediately after release
13   into the atmosphere to form H2S04.  Of the four species, only S02 is present at concentrations
14   significant for atmospheric  chemistry and human exposures.
1 5          Sulfur dioxide can be oxidized either in the gas phase, or, because it is soluble, in the
16   aqueous phase in cloud drops.  The gas-phase oxidation  of S02 proceeds through the reaction
1 7                                SO2 + OH+M^ HSO3 + M

18   followed by
19                                      3    23      2                      (AX2_36)

20                                   SO 3 + H20 -> H2S04                        (AX2-37)
21   Since H2S04 is extremely soluble, it will be removed rapidly by transfer to the aqueous phase of
22   aerosol particles and cloud drops.  Rate coefficients for reaction of S02 with H02 or N03 are too
23   low to be significant (JPL, 2003) .
24          S02 is chiefly but not exclusively primary in origin; it is also produced by the
25   photochemical oxidation of reduced sulfur compounds such as dimethyl sulfide (CH3-S-CH3) ,
26   hydrogen sulfide (H2S), carbon disulfide (CS2), carbonyl sulfide (OCS), methyl mercaptan
27   (CHs-S-H), and dimethyl disulfide (CHs-S-S-CHs) which are all mainly biogenic in origin.
28   Their sources are discussed in Section AX2.5. Table AX2.3-1 lists the atmospheric lifetimes of
29   reduced sulfur species with respect to reaction with various oxidants.  Except for OCS, which is

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 1   lost mainly by photolysis (x~6 months), all of these species are lost mainly by reaction with OH
 2   and N03 radicals. Because OCS is relatively long-lived in the troposphere, it can be transported
 3   upwards into the stratosphere. Crutzen (1976) proposed that its oxidation serves as the major
 4   source of sulfate in the stratospheric aerosol layer sometimes referred to the "Junge layer,"
 5   (Junge et al., 1961) during periods when volcanic plumes do not reach the stratosphere.
 6   However, the flux of OCS into the stratosphere is probably not sufficient to maintain this
 7   stratospheric aerosol layer. Myhre et al. (2004) propose instead that S02 transported upwards
 8   from the troposphere is the most likely source, have become the upward flux of OCS is too small
 9   to sustain observed sulfate loadings in the Junge layer.  In addition, insitu measurements of the
10   isotopic composition of sulfur do not match those of OCS (Leung et al., 2002).  Reaction with
11   NOs radicals at night most likely represents the major loss process for dimethyl sulfide and
12   methyl mercaptan.  The mechanisms for the oxidation of DMS are still  not completely
13   understood. Initial attack by NOs and OH radicals involves H atom abstraction, with a smaller
14   branch leading to OH addition to the S atom. The OH addition branch increases in importance as
15   temperatures decrease and becoming the major pathway below temperatures  of 285 K
16   (Ravishankara, 1997). The adduct may either decompose to form methane sulfonic acid (MSA),
17   or undergo further reactions in the main pathway, to yield dimethyl sulfoxide (Barnes et al.,
18   1991). Following H atom abstraction from DMS, the main reaction products include MSA and
19   S02.  The ratio of MSA to S02 is strongly temperature dependent, varying from about 0.1 in
20   tropical waters to about 0.4 in Antarctic waters (Seinfeld and Pandis, 1998).  Excess sulfate (over
21   that expected from the sulfate in seawater) in marine aerosol is related mainly to the production
22   of SOz from the oxidation of DMS.  Transformations among atmospheric sulfur compounds are
23   summarized in Figure AX2.3-1.
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                      hv, O
                                           so
           OH
                     Tropopause
    Figure AX2.3-1.    Transformations of sulfur compounds in the atmosphere.
    Source:  Adapted from Berresheim et al. (1995).
1   Multiphase Chemical Processes Involving Sulfur Oxides and Halogens
2          Chemical transformations involving inorganic halogenated compounds effect changes in
3   the multiphase cycling of sulfur oxides in ways analogous to their effects on NOX. Oxidation of
4   dimethylsulfide (CH3)2S by BrO produces dimethylsulfoxide (CH3)2SO (Barnes et al.,  1991 ;
5   Toumi, 1994), and oxidation by atomic chloride leads to formation of SOz (Keene et al., 1996).
6   (CHs^SO and SOz are precursors for methanesulfonic acid (CHsSOsH) and IH^SCM.  In the MBL,
7   virtually all IH^SCM and CHsSOsH vapor condenses onto existing aerosols or cloud droplet, which
8   subsequently evaporate, thereby contributing to aerosol growth and acidification.  Unlike
9   CH3S03H, H2S04 also has the potential to produce new particles (Korhonen et al., 1999; Kumala
    September 2007
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 1    et al., 2000), which in marine regions is thought to occur primarily in the free troposphere. Saiz-
 2    Lopez et al. (2004) estimated that observed levels of BrO at Mace Head would oxidize (CH3)2S
 3    about six times faster than OH and thereby substantially increase production rates of H2S04 and
 4    other condensible S species in the MBL. Sulfur dioxide is also scavenged by deliquesced
 5    aerosols and oxidized to H2S04 in the aqueous phase by several strongly pH-dependent pathways
 6    (Chameides and Stelson, 1992; Vogt et al., 1996; Keene et al., 1998). Model calculations
 7    indicate that oxidation of S(IV) by Os dominates in fresh, alkaline sea salt aerosols, whereas
 8    oxidation by hypohalous acids (primarily HOC1) dominates in moderately acidic solutions.
 9    Additional particulate non-sea salt (nss) S042~ is generated by S02 oxidation in cloud droplets
10    (Clegg and Toumi, 1998). Ion-balance calculations indicate that most nss S042~ in short-lived
11    (two to 48 hours) sea salt size fractions accumulates in acidic aerosol solutions and/or in acidic
12    aerosols processed through clouds (e.g., Keene et al., 2004). The production, cycling, and
13    associated radiative effects of S-containing aerosols in marine and coastal air are regulated in
14    part by chemical transformations involving inorganic halogens (von  Glasow et al., 2002b).
15    These  transformations include: dry-deposition fluxes of nss S042~ in marine air dominated,
16    naturally, by the sea salt size fractions (Huebert et al., 1996; Turekian et al., 2001); HC1 phase
17    partitioning that regulates sea salt pH and associated pH-dependent pathways for S(IV) oxidation
18    (Keene et al., 2002; Pszenny et al., 2004); and potentially important oxidative reactions with
19    reactive halogens for (CH3)2S and S(IV). However, both  the absolute magnitudes and relative
20    importance of these processes in MBL S cycling are poorly understood.
21           Iodine chemistry has been linked to ultrafine particle bursts at Mace Head (O'Dowd
22    et al., 1999, 2002). Observed bursts coincide with the elevated concentrations of 10 and are
23    characterized by particle concentrations increasing from background levels to up to
24    300,000 cm"3 on a time scale of seconds to minutes.  This newly identified source of marine
25    aerosol would provide additional aerosol surface area for  condensation of sulfur oxides and
26    thereby presumably diminish the potential for nucleation pathways involving H2S04. However,
27    a subsequent investigation in polluted air along the New England, USA coast found no
28    correlation between periods of nanoparticle growth and corresponding concentrations of I oxides
29    (Russell et al., 2006). The potential importance of I chemistry in aerosol nucleation and its
30    associated influence on sulfur cycling remain highly uncertain.
31

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 1   AX2.4    MECHANISMS FOR THE AQUEOUS PHASE FORMATION OF
 2              SULFATE AND NITRATE
 3          The major species containing sulfur in clouds are HS03~ and S032~, which are derived
 4   from the dissolution of S02 in water and are referred to as S(IV); and HSO,f and S042~, which
 5   are referred to as S(VI). The major species capable of oxidizing S(IV) to S(VI) in cloud water
 6   are 03, peroxides  (either H202 or organic peroxides), OH radicals, and ions of transition metals
 7   such as Fe and Cu that can catalyze the oxidation of S(IV) to S(VI) by 02.
 8          The basic mechanism of the aqueous phase oxidation of S02 has long been studied and
 9   can be found in numerous texts on atmospheric chemistry, e.g., Seinfeld and Pandis (1998),
10   Jacob (2000), and Jacobson (2002). The steps involved in the aqueous phase oxidation of S02
11   can be summarized as follows (Jacobson, 2002):
12          Dissolution of S02

13                                   SO2(g) <=> SO2(aq)                         (AX2-38)
14          The formation and dissociation of H2S03

15              SO2(aq) + H2O(aq) <^ H2SO3  <^> H++ HSOf O 2H+

16   In the pH range commonly found in rainwater (2 to 6), the most important reaction converting
17   S (IV) to S (VI) is
lg                      HSO3~ + H2O2 + //+<=> SO/' + H2O + 2H+

19   as S032~ is much less abundant than HS03~.
20         Major pathways for the aqueous phase oxidation of S(IV) to S(VI) as a function of pH are
21   shown in Figure AX2.4-1.  For pH up to about 5.3, H202 is seen to be the dominant oxidant;
22   above 5.3, 03, followed by Fe(III) becomes dominant. Higher pHs are expected to be found
23   mainly in marine aerosols.  However, in marine aerosols, the chloride-catalyzed oxidation of
24   S(IV) may be more important (Zhang and Millero, 1991; Hoppel and Caffrey, 2005). Because
25   NH4+ is so effective in controlling acidity, it affects the rate of oxidation of S(IV) to S(VI) and
26   the rate of dissolution of S02 in particles and cloud drops.
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    Figure AX2.4-1.
                        (A
                             10-'
                            10
                             ,-10
                        t3
                        \
                        53  io-12
                            10
                             ,-14
                            10
                              -16
                            10
                             ,-18
                                       I      I
                                                          I      I
                                                  H2°2

                                0     1
                    234
                          PH
Comparison of aqueous-phase oxidation paths.  The rate of
conversion of S(IV) to S(VI) is shown as a function of pH. Conditions
assumed are:  [SO2(g)] = 5 ppb; [NO2(g)]  = 1 ppb; [H2O2(g)] = 1 ppb;
[O3(g>] = 50 ppb; [Fe(III)(aq)] = 0.3 uM;  [Mn(II)(aq)] = 0.3 uM.
    Source: Seinfeld and Pandis (1998).
1          Nitrogen dioxide is also taken up in cloud drops and can be oxidized to N0s~, although it
2   is much less soluble than SOz and this pathway is of minor importance.  Instead, the uptake of
3   more highly soluble nitrogen- containing acids initiates aqueous-phase chemistry of NOs
4   formation.
5          Warneck (1999) constructed a box model describing the chemistry of the oxidation of
6   S02 and N02 including the interactions  of N and S species and minor processes in sunlit cumulus
7   clouds.  The relative contributions of different reactions to the oxidation of S(IV) species to
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 1   S(VI) and N02 to N03  10 minutes after cloud formation are given in Tables AX2.4-la and
 2   AX2.4-lb. The two columns show the relative contributions with and without transition metal
 3   ions.  As can be seen from Table AX2.4-la, S02 within a cloud (gas + cloud drops) is oxidized
 4   mainly by H202 in the aqueous phase, while and the gas-phase oxidation by OH radicals is small
 5   by comparison.  A much smaller contribution in the aqueous phase is made by methyl
 6   hydroperoxide (CH3OOH) because it is formed mainly in the gas phase and its Henry's Law
 7   constant is several orders of magnitude smaller that of H202. After H202, HN04 is the major
 8   contributor to S(IV) oxidation. The contribution from the gas phase oxidation of S02 to be small
 9   by comparison to the aqueous -phase reactions given above.
10          In contrast to the oxidation of S02, Table AX2.4-lb shows that the oxidation  of N02
11   occurs mainly in the gas phase within clouds, implying that the gas phase oxidation of N02 by
12   OH radicals predominates.  Clouds occupy about 15%, on average, of the volume of the
13   troposphere.
14          The values shown in Tables AX2.4-la and AX2.4-lb indicate that only about 20% of
15   S02 is oxidized in the gas phase, but about 90% of N02 is oxidized in the gas phase.  Thus, S02
16   is oxidized mainly by aqueous-phase reactions, but N02 is oxidized mainly by gas phase
17   reactions.

18   Multiphase Chemical Processes Involving Sulfur Oxides and Ammonia
19          The phase partitioning of NH3 with deliquesced aerosol solutions is controlled primarily
20   by the thermodynamic properties of the system expressed as follows:

                                        KH        Kb
2!                          NH3g <-> [NH3aq] <-> [NH4+] + K

22
23   where KH and Kb are the temperature-dependent Henry's Law and dissociation constants
24   (62 M atrrf1)  (1.8 x 10~5 M), respectively, for NH3, and Kw is the ion product of water (1.0 x
25   10~14  M) (Chameides, 1984).  It is evident that for a given amount of NHX (NH3 + particulate
26   NH4+) in the system, increasing aqueous concentrations of particulate H+ will shift the
27   partitioning of NH3 towards the condensed phase.  Consequently, under the more polluted
28   conditions characterized by higher concentrations of acidic sulfate aerosol, ratios of gaseous NH3
29   to particulate  NH4+ decrease (Smith et al., 2007).  It also follows that in marine air, where

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 1    aerosol acidity varies substantially as a function of particle size, NH3 partitions preferentially to
 2    the more acidic sub-pm size fractions (e.g., Keene et al., 2004; Smith et al., 2007).
 3          Because the dry-deposition velocity of gaseous NH3 to the surface is substantially greater
 4    than that for the sub-pm, sulfate aerosol size factions with which most particulate NH4+ is
 5    associated, dry-deposition fluxes of total NH3 are dominated by the gas phase fraction (Russell
 6    et al., 2003; Smith et al., 2007). Consequently, partitioning with highly acidic sulfate aerosols
 7    effectively increases the atmospheric lifetime of total NH3 against dry deposition.  This shift has
 8    important consequences for NH3 cycling and potential ecological effects. In coastal New
 9    England during summer, air transported from rural eastern Canada contains relatively low
10    concentrations of particulate non-sea salt (nss) S042~ and total NH3 (Smith et al., 2007). Under
11    these conditions, the roughly equal partitioning of total NH3 between the gas and particulate
12    phases sustains substantial dry-deposition fluxes of total NH3 to the coastal ocean (median of
13    10.7 pmol rrf2 day"1).  In contrast, heavily polluted air transported from the industrialized
14    midwestern United States contains concentrations of nss S042~ and total NH3 that are, about a
15    factory of 3 greater, based on median values. Under these conditions, most total NH3 (>85%)
16    partitions to the highly acidic sulfate aerosol size fractions and, consequently, the median dry-
17    deposition flux of total NH3 is 30% lower than that under the cleaner northerly flow regime. The
18    relatively longer atmospheric lifetime of total NH3 against dry deposition under more polluted
19    conditions implies that, on average, total NH3 would accumulate to higher atmospheric
20    concentrations under these conditions and also be subject to atmospheric transport over longer
21    distances. Consequently, the importance NHX of removal via wet deposition would also increase.
22    Because of the inherently sporadic character of precipitation, we might expect by greater
23    heterogeneity in NH3 deposition fields and any potential responses by sensitive ecosystems
24    downwind of major S-emission regions.
25
26
27    AX2.5  TRANSPORT OF NITROGEN AND SULFUR OXIDES IN
28             THE ATMOSPHERE
29          Major episodes of high 03 concentrations in the eastern United Sates and in Europe are
30    associated with slow moving high-pressure systems. High-pressure systems during the warmer
31    seasons are associated with subsidence, resulting in warm, generally cloudless conditions with
32    light winds. The subsidence results in stable conditions near the surface, which inhibit or reduce

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 1   the vertical mixing of 03 precursors (NOX, VOCs, and CO). Photochemical activity is enhanced
 2   because of higher temperatures and the availability of sunlight. However, it is becoming
 3   increasingly apparent that transport of 03 and NOX and VOC from distant sources can provide
 4   significant contributions to local [Os]  even in areas where there is substantial photochemical
 5   production.  There are a number of transport phenomena occurring either in the upper boundary
 6   layer or in the free troposphere which can contribute to high Os values at the surface. These
 7   phenomena include stratospheric-tropospheric exchange (STE), deep and shallow convection,
 8   low-level jets, and the so-called "conveyor belts" that serve to characterize flows around frontal
 9   systems.
10
11   Convective Transport
12          Crutzen and Gidel (1983), Gidel (1983), and Chatfield and Crutzen (1984) hypothesized
13   that convective clouds played an important role in rapid atmospheric vertical transport of trace
14   species and first tested simple parameterizations of convective transport in atmospheric chemical
15   models.  At nearly the same time, evidence was shown of venting the boundary layer by shallow,
16   fair weather cumulus clouds  (e.g., Greenhut et al., 1984; Greenhut, 1986).  Field experiments
17   were conducted in 1985 which resulted in verification of the hypothesis that deep convective
18   clouds are instrumental in atmospheric transport of trace constituents (Dickerson et al., 1987).
19   Once pollutants are lofted to  the middle and upper troposphere, they typically have a much
20   longer chemical lifetime and with the  generally stronger winds at these altitudes, they can be
21   transported large distances from their  source regions. Transport of NOX from the boundary layer
22   to the upper troposphere by convection tends to dilute the higher in the boundary layer
23   concentrations and extend the NOX lifetime from less than 24 hours to several days.
24   Photochemical reactions occur during this long-range transport. Pickering et al. (1990)
25   demonstrated that venting of boundary layer NOX by convective clouds (both shallow and deep)
26   causes enhanced Os production in the free troposphere. The dilution of NOX at the surface can
27   often increase Os production efficiency. Therefore, convection aids in the transformation of
28   local pollution into a contribution to global atmospheric pollution.  Downdrafts within
29   thunderstorms tend to bring air with less NOX from the middle troposphere into the boundary
30   layer. Lightning produces NO which  is directly injected chiefly into the middle  and upper
31   troposphere.  The total global production of NO by lightning remains uncertain,  but is on the
32   order of 10% of the total.

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 1   Observations of the Effects ofConvective Transport
 2          The first unequivocal observations of deep convective transport of boundary layer
 3   pollutants to the upper troposphere were documented by Dickerson et al. (1987).
 4   Instrumentation aboard three research aircraft measured CO, Os, NO, NOX, N0y, and
 5   hydrocarbons in the vicinity of an active mesoscale convective system near the
 6   Oklahoma/Arkansas border during the 1985 PRE-STORM experiment. Anvil penetrations about
 7   two hours after maturity found greatly enhanced mixing ratios inside the cloud of all of the
 8   aforementioned species compared with outside it.  Nitric oxide mixing ratios in the anvil
 9   averaged 3 to 4 ppbv, with individual 3-min observations reaching 6 ppbv; boundary layer NOX
10   was typically 1.5 ppbv or less outside the cloud. Therefore, the anvil observations represent a
11   mixture of boundary layer NOX and NOX contributed by lightning. Luke et al. (1992)
12   summarized the air chemistry data from all 18 flights during PRE-STORM by categorizing each
13   case according to synoptic flow patterns. Storms in the maritime tropical flow regime
14   transported large amounts of CO, Os, and N0y into the upper troposphere with the
15   midtroposphere remaining relatively clean. During frontal passages a combination of stratiform
16   and convective clouds mixed pollutants more uniformly into the middle and upper levels.
17          Prather and Jacob (1997) and Jaegle et al. (1997) noted that precursors of HOX are also
18   transported to the upper troposphere by deep convection, in addition to primary pollutants (e.g.,
19   NOX, CO, VOCs). The HOX precursors of most importance are water vapor, HCHO, H202,
20   CHsOOH, and acetone. The hydroperoxyl radical is critical for oxidizing NO to N02 in the Os
21   production process as described above.
22          Over remote marine areas, the effects of deep convection on trace gas distributions differ
23   from those over moderately polluted continental regions.  Chemical measurements taken by the
24   NASA ER-2 aircraft during the Stratosphere-Troposphere Exchange Project (STEP) off the
25   northern coast of Australia show the influence of very deep convective events.  Between 14.5
26   and 16.5 km on the February 2-3,  1987 flight, chemical profiles that included pronounced
27   maxima in CO, water vapor, and CCN, and minima of N0y, and Os (Pickering et al., 1993).
28   Trajectory analysis showed that these air parcels likely were transported from convective cells
29   800-900 km upstream. Very low marine boundary layer mixing ratios of N0y and Os in this
30   remote region were apparently transported  upward in the convection. A similar result was noted
31   in CEPEX (Central Equatorial Pacific Experiment; Kley et al., 1996) and in INDOEX (Indian

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 1    Ocean Experiment) (deLaat et al, 1999) where a series of ozonesonde ascents showed very low
 2    upper tropospheric 03 following deep convection. It is likely that similar transport of low-ozone
 3    tropical marine boundary layer air to the upper troposphere occurs in thunderstorms along the
 4    east coast of Florida. Deep convection occurs frequently over the tropical Pacific. Low-ozone
 5    and low-NOx convective outflow likely will descend in the subsidence region of the subtropical
 6    eastern Pacific, leading to some of the cleanest air that arrives at the west coast of the United
 7    States.
 8          The discussion above relates to the effects of specific convective events. Observations
 9    have also been conducted by NASA aircraft in survey mode, in which the regional effects of
10    many convective events can be measured. The SONEX (Subsonic Assessment Ozone and
11    Nitrogen Oxides Experiment) field program in 1997 conducted primarily upper tropospheric
12    measurements over the North Atlantic. The regional effects of convection over North America
13    and the Western Atlantic on upper tropospheric NOX were pronounced (Crawford et al., 2000;
14    Allen et al., 2000).  A discussion of the results of model calculations of convection and its effects
15    can be found in Section AX2.7.
16
17    Effects on Photolysis Rates and Wet Scavenging
18          Thunderstorm clouds are optically very thick, and, therefore, have major effects on
19    radiative fluxes and photolysis  rates. Madronich (1987) provided modeling estimates of the
20    effects of clouds of various optical depths on photolysis rates.  In the upper portion of a
21    thunderstorm anvil, photolysis is likely to be enhanced by a factor of 2 or more due to multiple
22    reflections off the ice crystals.  In the lower portion and beneath the cloud, photolysis is
23    substantially decreased. With enhanced photolysis rates, the NO/NOz ratio in the upper
24    troposphere is driven to larger values than under  clear-sky conditions. Existing experimental
25    evidence seems to confirm, at least qualitatively these model results (Kelley et al., 1994).
26          Thunderstorm updraft regions, which contain copious amounts of water, are regions
27    where efficient scavenging of soluble species can occur (Balkanski et al., 1993). Nitrogen
28    dioxide itself is not very soluble and therefore wet scavenging is not a major removal process for
29    it.  However, a major NOX reservoir species, HN03 is extremely soluble.  Very few direct field
30    measurements of the amounts of specific trace gases that are scavenged in storms are available.
31    Pickering et al. (2001) used a combination of model estimates of soluble species that did not
32    include wet scavenging and observations of these species from the upper tropospheric outflow

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 1   region of a major line of convection observed near Fiji. Over 90% of the and in the outflow air
 2   appeared to have been removed by the storm. About 50% of CH3OOH and about 80% of HCHO
 3   had been lost.
 4          Convective processes and small-scale turbulence transport pollutants both upward and
 5   downward throughout the planetary boundary layer and the free troposphere. Ozone and its
 6   precursors (NOX, CO, and VOCs) can be transported vertically by convection into upper part of
 7   the mixed layer on one day, then transported overnight as a layer of elevated mixing ratios,
 8   perhaps by a nocturnal low-level jet, and then entrained into a growing convective boundary
 9   layer downwind and brought back to the surface.
10          Because NO and N02 are only slightly soluble, they can be transported over longer
11   distances in the gas phase than can more soluble species which can be depleted by deposition to
12   moist surfaces, or taken up more readily on aqueous surfaces of particles.  During transport, they
13   can be transformed into reservoir species such as HNOs, PANs, and NzOs.  These species can
14   then contribute to local NOX concentrations in remote areas. For example, it is now well
15   established that PAN decomposition provides a major source of NOX in the remote troposphere
16   (Staudt et al., 2003). PAN decomposition in subsiding air masses from Asia over the eastern
17   Pacific could make an important contribution to 03 and NOX enhancement in the United States
18   (Kotchenruther et al., 2001; Hudman et al., 2004).  Further details about mechanisms for
19   transporting ozone and its precursors were described at length in CD06.
20
21
22   AX2.6    SOURCES AND EMISSIONS  OF NITROGEN OXIDES,
23              AMMONIA, AND SULFUR DIOXIDE
24          All three of the species listed in the title to this section have both natural and
25   anthropogenic sources. In Section AX2.6.1, interactions of NOX with the terrestrial biosphere are
26   discussed. Because of the tight coupling between processes linking emissions and deposition,
27   they are discussed together. In Section AX2.6.2, emissions of NOX, NH3, and S02 are discussed.
28   Field studies evaluating emissions inventories are discussed in Section AX2.6.3.
29
30   AX2.6.1   Interactions of Nitrogen Oxides with the Biosphere
31          Nitrogen oxides affect vegetated ecosystems, and in turn the atmospheric chemistry of
32   NOX is influenced by vegetation.  Extensive research on nitrogen inputs from the atmosphere to

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 1   forests was conducted in the 1980s as part of the Integrated Forest Study, and is summarized by
 2   Johnson and Lindberg (1992). The following sections discuss sources of NOX from soil,
 3   deposition of NOX to foliage, reactions with biogenic hydrocarbons, and ecological effects of
 4   nitrogen deposition.
 5
 6   NOX Sources
 1
 8   Soil NO
 9          Nitric oxide NO from soil metabolism is the dominant, but not exclusive, source of
10   nitrogen oxides from the biosphere to the atmosphere. As noted below, our understanding of
11   N02 exchange with vegetation suggests that there should be emission of N02 from foliage when
12   ambient concentrations are less than about 1 ppb. However, Lerdau et al. (2000) have pointed
13   out that present understanding of the global distribution of NOX is not consistent with a large
14   source that would be expected in remote forests if N02 emission was important when
15   atmospheric concentrations were below the compensation point.
16          The pathways for nitrification and denitrification include two gas-phase intermediates,
17   NO and NzO, some of which can escape. While N20 is of interest for its greenhouse gas
18   potential and role in stratospheric chemistry it is not considered among the reactive nitrogen
19   oxides important for urban and regional air quality and will not  be discussed further.
20   Temperature and soil moisture are critical factors that control the rates of reaction and
21   importantly the partitioning between NO and N20 which depend on oxygen levels: in flooded
22   soils where oxygen levels are low, N20 is the dominant soil nitrogen gas; as soil dries, allowing
23   more 02 to diffuse, NO emissions increase. In very dry soils microbial activity is inhibited and
24   emissions of both N20 and NO decrease. Nitrogen metabolism in soil is strongly dependent on
25   the substrate concentrations. Where nitrogen is limiting, nitrogen is efficiently retained and little
26   gaseous nitrogen is released. Where nitrogen is in excess of demand, gaseous nitrogen emissions
27   increase; consequently, soil NO  emissions are highest in fertilized agriculture and tropical soils
28   (Davidson and Kingerlee, 1997; Williams et al., 1992).
29
30   Sinks
31          Several reactive nitrogen are species are deposited to vegetation, among them,  HN03,
32   N02, PAN, and organic nitrates.


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 1   HNO3
 2          Deposition of HN03 appears to be relatively simple. Field observations based on
 3   concentration gradients and recently using eddy covariance demonstrate rapid deposition that
 4   approaches the aerodynamic limit (as constrained by atmospheric turbulence) in the Wesely
 5   (1989) formulation based on analogy to resistance.  Surface resistance for HNOs uptake by
 6   vegetation is negligible. Deposition rates are independent of leaf area or stomatal conductance,
 7   implying that deposition occurs to branches, soil, and leaf cuticle as well as internal leaf surfaces.
 8          Deposition velocities (Vd) typically exceed  1 cm s^and exhibit a daily pattern controlled
 9   by turbulence characteristics:  midday maximum and lower values at night when there is stable
10   boundary layer.
11
12   Deposition of NO 2
13          Nitrogen dioxide interaction with vegetation is more complex. Application of 15N-
14   labeled Nitrogen Dioxide demonstrates that Nitrogen Dioxide is  absorbed and metabolized by
15   foliage (Siegwolf et al., 2001; Mocker et al., 1998;  Segschneider et al., 1995; Weber et al.,
16   1995). Exposure to N02 induces nitrate reductase (Weber et al.,  1995, 1998), a necessary
17   enzyme for assimilating oxidized nitrogen.  Understanding of NOz interactions with foliage is
18   largely based on leaf cuvette and growth  chamber studies, which expose foliage or whole plants
19   to controlled levels of NOz and measure the fraction of NOz removed from the chamber air.  A
20   key finding is that the  fit of NOz flux to NOz concentration, has a non-zero intercept, implying a
21   compensation point or internal concentration. In studies at very low N02 concentrations
22   emission from foliage is observed (Teklemariam and Sparks, 2006).  Evidence for a
23   compensation point is not solely based on the fitted intercept. Nitrogen dioxide uptake rate to
24   foliage is  clearly related to stomatal conductance. Internal resistance is variable, and may be
25   associated with concentrations of reactive species such as ascorbate in the plant tissue that react
26   with NOz (Teklemariam and Sparks, 2006). Foliar NOz emissions show some dependence on
27   nitrogen content (Teklemariam and Sparks, 2006).  Internal NOz appears to derive from plant
28   nitrogen metabolism.
29          Two approaches to modeling N02 uptake by vegetation are the resistance-in-series
30   analogy which considers flux  (F) as the product of concentration (C) and Vd, where is related to
31   the sum of aerodynamic, boundary layer, and internal resistances (Ra, Rt>, and Rc; positive fluxes
32   are from atmosphere to foliage)

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 1                                          F=C¥d                               (AX2-42)
 2                                    yd = (Ra + Rb + Rcr!                         (AX2-43)
 3          Ra and Rb and controlled by turbulence in the mixed layer; Rc is dependent on
 4   characteristics of the foliage and other elements of the soil, and may be viewed as 2 combination
 5   of resistance internal to the foliage and external on the cuticle, soils, and bark. This approach is
 6   amenable to predicting deposition in regional air quality models (Wesely,  1989). Typically, the
 7   NOz, Vd is less than that for Os, due to the surface's generally higher resistance to NOz uptake,
 8   consistent with NCVs lower reactivity.
 9          Alternatively, NOz exchange with foliage can be modeled from a physiological viewpoint
10   where the flux from the leaf is related to the stomatal conductance and a concentration gradient
1 1   between the ambient air and interstitial air in the leaf.  This approach best  describes results for
12   exchange with individual foliage elements, and is expressed per unit leaf (needle) area. While
13   this approach provides linkage to leaf physiology, it is not straightforward to scale up from the
14   leaf to ecosystem scale :
15                                             sa-i                             (AX2-44)
16          This model implicitly associates the compensation point with a finite internal
17   concentration. Typically observed compensation points are around 1 ppb. Finite values of
18   internal NOz concentration are consistent with metabolic pathways that include oxides of
19   nitrogen.  In this formulation, the uptake will be linear with N02 concentration, which is
20   typically observed with foliar chamber studies.
21          Several studies have shown the UV dependence of NOz emission, which implies some
22   photo-induced surface reactions that release N02.  Rather than model this as a UV-dependent
23   internal concentration, it would be more realistic to add an additional term to account for
24   emission that is dependent on light levels and other surface characteristics:
25                                       sa-         S                            (AX2-45)
26          The mechanisms for surface emission are discussed below.  Measurement of NOz flux is
27   confounded by the rapid interconversion of NO, NOz, and Os (Gao et al., 1991).
28

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 1   PAN Deposition
 2          Peroxyacetyl nitrate is phytotoxic, so clearly it is absorbed at the leaf. Observations
 3   based on inference from concentration gradients and rates of decline at night (Shepson et al.,
 4   1992; Schrmipf et al., 1996) and leaf chamber studies (Teklemariam and Sparks, 2004) have
 5   indicated that PAN uptake is slower than that of Os; however, recent work in coniferous canopy
 6   with direct eddy covariance PAN flux measurements indicated a Vd more similar to that of Os.
 7   Uptake of PAN is under stomatal control, has a non-zero  deposition at night, and is influenced by
 8   leaf wetness (Turnipseed et al., 2006). On the other hand, flux measurements determined by
 9   gradient methods over a grass surface showed a Vd closer to 0.1 cm s'1, with large uncertainty
10   (Doskey et al., 2004).  A factor of 10 uncertainty remains in Vd 0.1-1 cm s"1 giving a range.
11   Whether the discrepancies are methodological or indicate intrinsic differences between different
12   vegetation is unknown. Uptake of PAN is smaller than its thermal decomposition in all cases.
13
14   Organic Nitrates
15          The biosphere also interacts with NOX through hydrocarbon emissions and their
16   subsequent reactions to form multi-functional organic nitrates. Isoprene nitrates are  an important
17   class of these.  Isoprene reacts with OH to form a radical  that adds N02 to form a hydroxyalkyl
18   nitrate. The combination of hydroxyl and nitrate functional group makes these compounds
19   especially soluble with low vapor pressures; they likely deposit rapidly (Shepson et al., 1996;
20   Treves et al., 2000). Many other unsaturated hydrocarbons  react by analogous routes.
21   Observations at Harvard Forest show a substantial fraction of total N0y not accounted for by
22   NO, NOz and PAN, which is attributed to the organic nitrates (Horii et al., 2006, Munger et al.,
23   1998). Furthermore, the total N0y flux exceeds the sum of  HNOs, NOX, and PAN, which implies
24   that the organic nitrates are a substantial fraction of nitrogen deposition. Other observations that
25   show evidence of hydoxyalkyl nitrates include those of Grossenbacher et al. (2001) and Day
26   etal. (2003).
27          Formation of the hydroxyalkyl nitrates occurs after VOC + OH reaction.  In some sense,
28   this mechanism is just an alternate pathway for OH to react with NOX to form a rapidly
29   depositing species.  If VOC were not present, OH would be available to react with NOz when it
30   is present instead to form HNOs.
31
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 1   HONO
 2          Nitrous acid formation on vegetative surfaces at night has long been observed based on
 3   measurements of positive gradients (Harrison and Kitto, 1994). Surface reactions of N02
 4   enhanced by moisture were proposed to explain these results. Production was evident at sites
 5   with high ambient N02; at low concentration, uptake of HONO exceeded the source.
 6   Daytime observations of HONO when rapid photolysis is expected to deplete ambient
 7   concentrations to very low levels implies a substantial source of photo-induced HONO formation
 8   at a variety of forested sites where measurements have been made. Estimated source strengths
 9   are 200-1800 pptv hr1 in the surface layer (Zhou et al., 2002a, 2003), which is about 20 times
10   faster than all nighttime sources.  Nitrous acid sources could be important to OH/H02 budgets as
11   HONO is rapidly photolyzed by sunlight to OH and NO.  Additional evidence of light-dependent
12   reactions to produce HONO comes from discovery of a HONO artifact in pyrex sample inlet
13   lines exposed to ambient light. Either covering the inlet or washing it eliminated the HONO
14   formation  (Zhou et al., 2002b). Similar reactions might serve to explain observations of UV-
15   dependent production of NOX in empty foliar cuvettes that had been exposed to ambient air (Hari
16   et al., 2003; Raivonen et al., 2003).
17          Production of HONO in the dark is currently believed to occur via a heterogeneous
18   reaction involving N02 on wet surfaces (Jenkin et al., 1988; Pitts et al., 1984; He et al., 2006;
19   Sakamaki et al., 1983), and it is proposed that the mechanism has first-order dependence in both
20   N02 and H20 (Kleffmann et al., 1998; Svensson et al.,  1987) despite the stoichiometry.
21   However, the molecular pathway of the mechanism is still under debate. Jenkin et al. (1988)
22   postulated a H20-N02 water complex reacting with gas phase N02 to produce HONO, which is
23   inconsistent with the formation of an N204 intermediate leading to HONO as proposed by
24   Finlayson-Pitts et al. (2003). Another uncertainty is whether the reaction forming HONO is
25   dependent on water vapor (Svensson et al.,  1987; Stutz et al., 2004) or water adsorbed on
26   surfaces (Kleffmann et al., 1998).  Furthermore, the composition of the surface and the available
27   amount of surface or surface-to-volume ratio can significantly influence the HONO production
28   rates (Kaiser and Wu, 1977; Kleffmann et al., 1998; Svensson et al., 1987),  which may explain
29   the difference in the rates observed between laboratory and atmospheric measurements.
30          There is no consensus on a chemical mechanism for photo-induced HONO production.
31   Photolysis of HNOs or N0s~ absorbed on ice or in surface water films has been proposed

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 1    (Honrath et al., 2002; Ramazan et al., 2004; Zhou et al., 2001, 2003).  Alternative pathways
 2    include N02 interaction with organic surfaces such as humic substances (George et al., 2005;
 3    Stemmler et al., 2006).  Note that either N03~ photolysis or heterogeneous reaction of N02 are
 4    routes for recycling deposited nitrogen oxides back to the atmosphere in an active form. Nitrate
 5    photolysis would return nitrogen that heretofore was considered irreversibly deposited, surface
 6    reactions between N02 and water films or organic molecules would decrease the effectiveness of
 7    observed N02 deposition if the HONO were re-emitted.
 8
 9    Fast Homogeneous Reactions
10          Inferences from  observations at Blodgett Forest (Cohen et al. in prep) suggest that
11    radicals from 03 + VOC react with NOX in the canopy to produce HN03 and organic nitrates
12    among other species. This mechanism would contribute to canopy retention of soil NO emission
13    in forests with high VOC possibly more effectively than the NO to N02 conversion and foliar
14    uptake of N02 that has been proposed to reduce the amount of soil NO that escapes to the supra-
15    canopy atmosphere (Jacob and Bakwin, 1991).
16
17    Some NO 2 and HNOs Flux Data from Harvard Forest
18
19    Observations from TDL Measurements of NO 2
20          Harvard Forest is a rural site in central Massachusetts, where ambient NOX, N0y, and
21    other  pollutant concentrations and fluxes of total N0y have been measured since 1990 (Munger
22    et al., 1996).  An intensive study in 2000 utilized a Tunable Diode Laser Absorption
23    Spectrometer (TDLAS)  to measure N02 and HNOs. TDLAS has an inherently fast response, and
24    for species such as N02 and HN03 with well-characterized spectra it provides an absolute and
25    specific measurement. Absolute concentrations of HNOs were measured, and the flux inferred
26    based on the dry deposition inferential method that uses momentum flux measurements to
27    compute a deposition velocity and derives an inferred flux (Wesely and Hicks, 1977; Hicks et al.,
28    1987). Direct eddy covariance calculations for HNOs were not possible because the atmospheric
29    variations were attenuated by interaction with the inlet walls despite very short residence time
30    and use of fluorinated silane coatings to make the inlet walls more hydrophobic. Nitrogen Oxide
31    response was adequate to allow both concentration and eddy covariance flux determination.
32    Simultaneously, NO and N0y eddy covariance fluxes  were determined with two separate 03


      September 2007                         AX2-41      DRAFT-DO NOT QUOTE OR CITE

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 1   chemiluminescence detectors, one equipped with a H2-gold catalyst at the inlet to convert all
 2   reactive nitrogen compounds to NO. Additionally, the measurements include concentration
 3   gradients for NO, N02, and Os over several annual cycles to examine their vertical profiles in the
 4   forest canopy.
 5          Overall, the results show typical N02 concentrations of 1 ppb under clean-air conditions
 6   and mean concentrations up to 3 ppb at night and 1 ppb during daytime for polluted conditions.
 7   Net positive fluxes (emission) of N02 were evident in the daytime and negative fluxes
 8   (deposition) were observed at night (Figure AX2.6-1). Nitric oxide fluxes were negative during
 9   the daytime and near zero at night.
10          In part the opposite NO and N02 fluxes are simply consequences of variable N0/N02
11   distributions responding to vertical gradients in light intensity and Os concentration, which
12   resulted in no net flux of NOX (Gao et al., 1993).  In the Harvard Forest situation, the NO and
13   N02 measurements were not at the same height above the canopy, and the resulting differences
14   derive at least in part from the gradient in flux magnitude between the two inlets
15   (Figure AX2.6-2).
16          At night, when NO concentrations are near 0  due to titration by ambient 03 there is not a
17   flux of NO to offset N02 fluxes. Nighttime data consistently show N02 deposition (Figure
18   AX2.6-3), which increases with increasing N02 concentrations. Concentrations above 10 ppb
19   were rare at this site, but the few high N02 observations suggest a nonlinear dependence on
20   concentration. The data fit a model with Vd of -0.08 plus an enhancement term that was second
21   order in N02 concentration. The second order term implies that N02 deposition rates to
22   vegetation in polluted urban sites would be considerably larger than what was observed at this
23   rural site.
24          After accounting for the N0-N02 null cycle the net NOX flux could be derived. Overall,
25   there was a net deposition of NOX during the  night and essentially zero flux in the day, with large
26   variability in the magnitude and sign of individual flux observations (Figure AX2.6-3). For the
27   periods with [N02] > 2 ppb, deposition was always observed.  These canopy-scale field
28   observations are consistent with  a finite compensation point for N02 in the canopy that offsets
29   foliar uptake or even reverses it when concentrations are especially low.  At concentrations
30   above the compensation point, NOX is absorbed by the canopy. Examination of concentration
31   profiles corroborates the flux measurements (Figure AX2.6-4). During daytime for low-NOx

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                      NW
                                                          SW
 o
 E
 u
 i
 o
      o--,-•,-,-
JC
ty    ?
E


I   "
—'   -2
X
_3
||    _,4
        [NO]
        [NOJ
        [OJ/10
        t^~t.*:i~T
         F NO
         FO/10

                      luT
                                                            -+-
                       12

                    Hours
                                18
   6      12      18

       Hours
Figure AX2.6-1.
                  Diel cycles of median concentrations (upper panels) and fluxes (lower
                  panels) for the Northwest clean sector, left panels) and Southwest
                  (polluted sector, right panels) wind sectors at Harvard Forest, April-
                  November, 2000, for NO, NO2, and O3/10. NO and O3 were sampled
                  at a height of 29 m, and NO2 at 22 m. Vertical bars indicate 25th and
                  27th quartiles for NO and NO2 measurements.  NO2 concentration
                  and nighttime deposition are enhanced under southwesterly
                  conditions, as are O3 and the morning NO maximum.
Source: Horiietal. (2004).
September 2007
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                                    Simple Model
             100
              80
            ,  60
           D5
           "5
              40
              20
               0
                            Ii
   NO
                                        NO,
                                  NO   '   \  NO.
Figure AX2.6-2.
0.0   0.2   0.4   0.6   0.8   1.0-2    -1    0     1     2
   Concentration (nmol mol"1)        Flux (nmol mol"1 cm s"1)

  Simple NOX photochemical canopy model outputs.  Left panel,
  concentrations of NO (dashed) and NO2 (solid); right, fluxes of NO
  (dashed) and NO2 (solid).  Symbols indicate measurement heights for
  NO (29m) and NO2 (22m) at Harvard Forest. The model solves the
  continuity equation for NO concentration at 200 levels, d/dz(-
  Kc(dNO/dz)) = PNO - LNO, where PNO = [NO]/tl, LNO = [NO]/t2,
  and zero net deposition or emission of NOX is allowed. NOX (NO +
  NO2) is normalized to Ippb. tl = 70s in this example. Due to the
  measurement height difference, observed upward NO2 flux due to
  photochemical cycling alone should be substantially larger than
  observed downward NO flux attributable to the same process.
Source: Horii (2002).
September 2007
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                                   FNO2 (night) = F0+ V0 [NO2] + a [NO2]2
                       5-
                   o
                   _
                   E
                   "o
                   E
                   LL.
                   cT
                      -10-
                      -15-
                      -20-
    Figure AX2.6-3.
                                   Hourly Data (fitted) •
                                   Nightly Medians   +
                            Vf= -0.08 ±0.03 (cms"')
                            a = -0,013 ±0.001 (nmor1 mol cm s~1)
                            R2=0.63
                                   I
                           0
                  10      15      20
                     [NOJ (nmol mol'1)
        25
30
Hourly (dots) and median nightly (pluses) NOi flux vs. concentration,
with results of least-squares fit on the hourly data (curve). The flux is
expressed in units of concentration times velocity (nmol mol'1 cm s'1)
in order to simplify the interpretation of the coefficients in the least-
squares fit.  Pressure and temperature corrections have been taken
into account in the conversion from density to mixing ratio.
    Source: Horiietal. (2004).

1   conditions, there is a local maximum in the concentration profile near the top of the canopy
2   where Os has a local minimum, which is consistent with foliar emission or light-dependent
3   production of NOX in the upper canopy.  Depletion is evident for both NOX and 03 near the forest
4   floor. Air reaching the ground has passed through the canopy where uptake is efficient and the
5   vertical exchange rates near the ground are slow. At night, the profiles generally decrease with
6   decreasing height above the ground, showing only uptake. At higher concentrations, the daytime
7   NOX concentrations are nearly constant through the canopy; no emission is evident from  the
8   sunlit leaves.
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                                       NOv PROFILES
    Canopy
     Top
              30--
25--
           0J
              5 -"
      NO2 //NOX
         xo

        xo
                                Night Low NOx
                                       o
                              -O^
                                 25"
                                               5 --
                                                    Night High NOx
               0.70  0.75  0.80  0.85  15   20   25    30
                                                  3,4   3.8   4.2   4.6 14 16  18 20 22  24
     Canopy
      Top —
25--
             20
           .5?
           "5
                          NOV
                                Day Low NOx
                                 25 t x
                                               o -•'
                                                   Day High NOx   o
               060  0.65 0.70 075 0.80 28  30  32  34  36    4.2 4.4  4.6  4.8  5.0  22 23 24 25 26 27 28
                 Concentration (nmol mol"1)
                                     Concentration (nmol mol"1)
    Figure AX2.6-4.     Averaged profiles at Harvard Forest give some evidence of some
                        input near the canopy top from light-mediated ambient reactions, or
                        emission from open stomates.
    Source: Horiietal. (2004).


1          Figure AX2.6-5 compares observed fluxes of all the observed species. The measured

2   NOX and estimated PAN fluxes are small relative to the observed total N0y flux.  In clean air,

3   HN03 accounts for nearly all the N0y flux and the sum of all measured species is about equal to
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                                 Summer 2000
                       NW
                                                      SW
    12--
 u
 o
 o
 o  10
 I   8
 O
 E   6
      --NO
    NOx+HNO3+PAN	
    NO*
 4

 2
 0

1.2 -
                            \
 c
 g
 "•§  0.4
 ££
 LL
    0.0 --
    -5
 "o
 E  -15
    -25
                               ^
                                                                15
                                                                   20
Figure AX2.6-5.
               Summer (June-August) 2000 median concentrations (upper panels),
               fractions of NOy (middle panels), and fluxes (lower panels) of NOy and
               component species separated by wind direction (Northwest on the left
               and Southwest on the right). Vertical lines in the flux panels show
               25th and 75th quartiles of F(NOy) and F(HNO3); negative fluxes
               represent deposition; F(NOX) is derived from eddy covariance F(NO)
               and F(NO2) measurements (corrected for photochemical cycling),
               F(HNC>3) is inferred, and F(NOy) was measured by eddy covariance.
               The sum of NOX, HNOs, and PAN accounts for all of the NOy
               concentration and flux for Northwesterly (unpolluted background)
               flows, whereas up to 50% of NOy and F(NOy) under Southwesterly
               flows are in the form of reactive nitrogen species whose fluxes are not
               measured or estimated here.
Source: Horiietal. (2006).
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 1   the N0y concentration. However, in polluted conditions, unmeasured species are up to 25% of
 2   the N0y, and HN03 fluxes cannot account for all the total N0y flux observed.  Likely these
 3   unmeasured N0y species are hydroxyalkyl nitrates and similar compounds and are rapidly
 4   deposited.  Although NOz uptake may be important to the plant, because it is an input directly to
 5   the interior of foliage that can be used immediately in plant metabolism, it is evidently not a
 6   significant part of overall nitrogen deposition to rural sites.  The deposition of HNOs and
 7   multifunctional organic nitrates are the largest elements of the nitrogen dry deposition budget.
 8   Two key areas of remaining uncertainty are the production of HONO over vegetation and the
 9   role of very reactive biogenic VOCs. HONO is important because its photolysis is a source of
10   OH radicals,  and its formation may represent an unrecognized mechanism to regenerate
11   photochemically active NOX from nitrate that had been considered terminally removed from the
12   atmosphere.
13
14   Ecosystem Effects
15   In addition to the contribution to precipitation acidity, atmospheric nitrogen oxides have
16   ecological effects.  Total loading by both and wet and dry deposition is the relevant metric for
17   considering ecosystem impacts.  At low inputs, nitrogen deposition adds essential nutrients to
18   terrestrial ecosystems. Most temperate forests are nitrogen limited; thus the inputs stimulate
19   growth. Anthropogenic nitrogen may influence some plant species different and alter the
20   distribution of plant species (cf. Wedin and Tilman, 1996).  At high nitrogen loading, where
21   nitrogen inputs exceed nutrient requirements, deleterious effects including forest decline
22   associated with 'nitrogen saturation' are seen (Aber at al., 1998; Driscoll et al., 2003).  In aquatic
23   ecosystems, however, nitrogen is may or may not be limiting, but in brackish waters atmospheric
24   deposition of anthropogenic nitrogen is suspected of contributing to eutrophication of some
25   coastal waters and lakes (see Bergstrom and Jansson, 2006; Castro and Driscoll, 2002).
26
27   AX2.6.2     Emissions of NOX, NH3, and SO2
28
29   Emissions ofNOx
30          Estimated annual emissions of NOX, NHs, and SOz for 2002 (U.S. Environmental
31   Protection Agency, 2006) are shown in Table AX2.6-1. Methods for estimating emissions of
32   criteria pollutants, quality assurance procedures, and examples of emissions calculated by using

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 1   data are given in U.S. Environmental Protection Agency (1999). Discussions of uncertainties in
 2   current emissions inventories and strategies for improving them can be found in NARSTO
 3   (2005).
 4          As can be seen from the table, combustion by stationary sources, such as electrical
 5   utilities and various industries, accounts for roughly half of total anthropogenic emissions of
 6   NOX.  Mobile sources account for the other half, with highway vehicles representing the major
 7   mobile source component. Approximately half the mobile source emissions are contributed by
 8   diesel engines, the remainder are emitted by gasoline-fueled vehicles and other sources.
 9          Emissions of NOX associated with combustion arise from contributions from both fuel
10   nitrogen and atmospheric nitrogen.  Combustion zone temperatures greater than about 1300 K
11   are required to fix atmospheric N2:
12                                     »2^2^<-™                          (AX2-46)
13   Otherwise, NO can be formed from fuel N according to this reaction:

H                       CaHbOcNd + 02 -> xC02 + yH20 + zNO            (AX2-47)

     In addition to NO formation by the schematic reactions given above, some N02 and CO
15   are also formed depending on temperatures, concentrations of OH and H02 radicals and 02
16   levels. Fuel nitrogen is highly variable in fossil fuels, ranging from 0.5 to 2.0 percent by weight
17   (wt %) in coal to 0.05% in light distillates  (e.g., diesel fuel), to 1.5 wt % in heavy fuel oils (UK
18   AQEG, 2004). The ratio of N02 to NOX in primary emissions ranges from 3 to 5 % from
19   gasoline engines, 5 to 12% from heavy-duty diesel trucks, 5 to 10% from vehicles fueled by
20   compressed natural gas and from 5 to  10% from stationary sources. In addition to NOX, motor
21   vehicles also emit HONO, with ratios  of HONO to NOX ranging from 0.3% in the Caldecott
22   Tunnel, San Francisco Bay (Kirchstetter and Harley, 1996) to 0.5 to 1.0% in studies in the
23   United Kingdom (UK AQEG, 2004).  The N02 to NOX ratios in emissions from turbine jet
24   engines are as high as 32 to 35 % during taxi and  takeoff (CD93). Sawyer et al. (2000) have
25   reviewed the factors associated with NOX emissions by mobile sources. Marine transport
26   represents a minor source of NOX,  but it constitutes a larger source in the EU where it is expected
27   to represent about two-thirds of land-based sources (UK AQEG, 2004).


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 1   NOX Emissions from Natural Sources (Soil, Wild Fires, and Lightning)
 2
 3   Soil
 4          Emission rates of NO from cultivated soil depend mainly on fertilization levels and soil
 5   temperature.  About 60% of the total NOX emitted by soils occurs in the central corn belt of the
 6   United States. The oxidation of NHs, emitted mainly by livestock and soils, leads to the
 7   formation of NO, also NH4+ and N0s~ fertilizers lead to NO emissions from soils.  Estimates of
 8   emissions from natural sources are less certain than those from anthropogenic sources.  On a
 9   global scale, the contribution of soil emissions to the oxidized nitrogen budget is on the order of
10   10% (van Aardenne et al., 2001; Finlayson-Pitts and Pitts, 2000; Seinfeld and Pandis, 1998), but
11   NOX emissions from fertilized fields are highly variable. Soil NO emissions can be estimated
12   from the fraction of the applied fertilizer nitrogen emitted as NOX, but the flux varies strongly
13   with land use and temperature. Estimated globally averaged fractional applied nitrogen loss as
14   NO varies from 0.3% (Skiba et al., 1997) to 2.5% (Yienger and Levy, 1995). Variability within
15   biomes to which fertilizer is applied, such as shortgrass versus tallgrass prairie, accounts for a
16   factor of three in uncertainty (Williams et al.,  1992; Yienger and Levy,  1995; Davidson and
17   Kingerlee, 1997).
18          The local contribution  can be much greater than the global average, particularly in
19   summer and especially where  corn is grown extensively. Williams et al. (1992) estimated that
20   contributions to NO budgets from soils in Illinois are about 26% of the emissions from industrial
21   and  commercial processes in that State.  In Iowa, Kansas, Minnesota, Nebraska, and South
22   Dakota, all states with smaller human populations, soil emissions may dominate the NO budget.
23   Conversion of NHs to NOs (nitrification) in aerobic soils appears to be the dominant pathway to
24   NO. The mass and chemical form of nitrogen (reduced or oxidized) applied to soils, the
25   vegetative cover, temperature, soil moisture, and agricultural practices such as tillage all
26   influence the amount of fertilizer nitrogen released as NO.
27          Emissions of NO from soils peak in summer when Os formation is also at a maximum.
28   An NRC panel report (NRC, 2002) outlined the role of agriculture in emissions of air pollutants
29   including NO and NH3.  That report recommends immediate implementation of best
30   management practices to control these emissions, and further research to quantify the magnitude
31   of emissions and the impact of agriculture on air quality. Civerolo and Dickerson (1998) report
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 1   that use of the no-till cultivation technique on a fertilized cornfield in Maryland reduced NO
 2   emissions by a factor of seven.
 3
 4   NOxfrom Biomass Burning
 5          During biomass burning, nitrogen is derived mainly from fuel nitrogen and not from
 6   atmospheric Nz, since temperatures required to fix atmospheric Nz are likely to be found only in
 7   the flaming crowns of the most intense boreal forest fires. Nitrogen is present mainly in plants as
 8   amino (NHz) groups in amino acids. During combustion, nitrogen is released mainly in
 9   unidentified forms, presumably as N2, with very little remaining in fuel ash. Apart from N2, the
10   most abundant species in biomass burning plumes is NO.  Emissions of NO account for only
11   about 10 to 20% relative to fuel N (Lobert et al., 1991). Other species such as N02, nitriles,
12   ammonia, and other nitrogen compounds account for a similar amount. Emissions of NOX are
13   about 0.2 to 0.3% relative to total biomass burned (e.g., Andreae,  1991; Radke et al.,  1991).
14   Westerling et al. (2006) have noted that the frequency and intensity of wildfires in the western
15   United States have increased substantially since 1970.
16
17   Lightning Production of NO
18          Annual global production of NO by lightning is the most uncertain source of reactive
19   nitrogen. In the last decade, literature values of the global average production rate range from
20   2 to 20 Tg N per year. However, the most likely range is from 3 to 8 Tg N per year, because the
21   majority of the recent estimates fall in this range. The large uncertainty stems from several
22   factors: (1) a large range of NO production rates per meter of flash length (as much as two orders
23   of magnitude); (2) the open question of whether cloud-to-ground (CG) flashes and intracloud
24   flashes (1C) produce substantially different amounts of NO; (3) the global flash rate; and (4) the
25   ratio of the number of 1C flashes to the number of CG flashes. Estimates of the amount of NO
26   produced per flash have been made based on theoretical considerations (e.g., Price et al., 1997),
27   laboratory experiments (e.g., Wang et al., 1998); field experiments (e.g., Stith et al.,  1999;
28   Huntrieser et al., 2002,  2007) and through a combination of cloud-resolving model simulations,
29   observed lightning flash rates, and anvil measurements of NO (e.g., DeCaria et al., 2000, 2005;
30   Ott et al., 2007). The latter method was also used by Pickering et al. (1998), who showed that
31   only ~5 to 20% of the total NO produced by lightning in a given storms exists in the boundary
32   layer at the end of a thunderstorm. Therefore, the direct contribution to boundary layer 03

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 1   production by lightning NO is thought to be small. However, lightning NO production can
 2   contribute substantially to 03 production in the middle and upper troposphere.  DeCaria et al.
 3   (2005) estimated that up to 10 ppbv of ozone was produced in the upper troposphere in the first
 4   24 hours following a Colorado thunderstorm due to the injection of lightning NO.  A series of
 5   midlatitude and subtropical thunderstorm events have been simulated with the model of DeCaria
 6   et al. (2005), and the derived NO production per CG flash averaged 500 moles/flash while
 7   average production per 1C flash was 425 moles/flash (Ott et al., 2006).
 8          A major uncertainty in mesoscale and global chemical transport models is the
 9   parameterization of lightning flash rates. Model variables such as cloud top height, convective
10   precipitation rate, and upward cloud mass flux have been used to estimate flash rates. Allen  and
11   Pickering (2002) have evaluated these methods against observed flash rates from satellite, and
12   examined the effects on ozone production using each method.
13
14   Uses of Satellite Data to Derive Emissions
15          Satellite data have been shown to be useful for optimizing estimates of emissions of NOz.
16   (Leue et  al., 2001; Martin et al., 2003; Jaegle et al., 2005).  Satellite-borne instruments such as
17   GOME (Global Ozone Monitoring Experiment; Martin et al., 2003; and references therein) and
18   SCIAMACHY  (Scanning Imaging Absorption Spectrometer for Atmospheric Chartography;
19   Bovensmann et al., 1999) retrieve tropospheric columns of NOz, which can then be combined
20   with model-derived chemical lifetimes of NOX to yield emissions of NOX.
21          Top-down inference of NOX emission inventory from the satellite observations of NOz
22   columns by mass balance requires at minimum three pieces of information: the retrieved
23   tropospheric NOz column, the ratio of tropospheric NOX to NOz columns, and the NOX lifetime
24   against loss to stable reservoirs. A photochemical model has been used to provide information
25   on the latter two pieces of information.  The method is generally applied exclusively to land
26   surface emissions, excluding lightning. Tropospheric N02 columns are insensitive to lightning
27   NOX emissions since most of the lightning  NOX in the upper troposphere is present as NO at the
28   local time of the satellite measurements (Ridley et al., 1996), owing to the slower reactions of
29   NO with 03 there.
30          Jaegle et al. (2005) applied additional information on the spatial distribution of emissions
31   and on fire activity to partition NOX emissions into sources from fossil fuel combustion, soils,
32   and biomass burning.  Global a posteriori estimates of soil NOX emissions are 68% larger than

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 1   the a priori estimates. Large increases are found for the agricultural region of the western United
 2   States during summer, increasing total U.S. soil NOX emissions by a factor of 2 to 0.9 Tg N yr"1.
 3   Bertram et al. (2005) found clear signals in the SCIAMACHY observations of short intense NOX
 4   pulses following springtime fertilizer application and subsequent precipitation over agricultural
 5   regions of the western United States.  For the agricultural region in North-Central Montana, they
 6   calculate a yearly SCIAMACHY top-down estimate that is 60% higher than a commonly used
 7   model of soil NOX emissions by Yienger and Levy (1995).
 8          Martin et al. (2006) retrieved tropospheric nitrogen dioxide (N02) columns for
 9   May 2004 to April 2005 from the SCIAMACHY satellite instrument to derive top-down NOX
10   emissions estimates via inverse modeling with a global chemical transport model (GEOS-Chem).
11   The top-down emissions were combined with a priori information from a bottom-up emission
12   inventory with error weighting to achieve an improved a posteriori estimate of the global
13   distribution of surface NOX emissions. Their a posteriori inventory improves the GEOS-Chem
14   simulation of NOX, PAN, and HNOs with respect to airborne in situ measurements over and
15   downwind of New York City.  Their a posteriori inventory shows lower NOX emissions from the
16   Ohio River valley during summer than during winter, reflecting recent controls on NOX
17   emissions from electric utilities. Their a posteriori inventory is highly consistent (R2 = 0.82,
18   bias = 3%) with the NEI99 inventory for the United States. In contrast, their a posteriori
19   inventory is 68% larger than a recent inventory by Streets et al. (2003) for East Asia for the year
20   2000.
21
22   Emissions ofNH3
23          Emissions of NHs show a strikingly different pattern from those of NOX. Three-way
24   catalysts used in motor vehicles emit small amounts of NHs as a byproduct during the reduction
25   of NOX. Stationary combustion sources make only a small contribution to emissions of NHs
26   because efficient combustion favors formation of NOX and, NH3 from combustion is produced
27   mainly by inefficient, low temperature fuel combustion. For these reasons, most emissions of
28   NHs arise from fertilized soils and from livestock.
29          The initial step in the oxidation of atmospheric NHs to NO is by reaction with OH
30   radicals.  However, the lifetime of NH3 from this pathway is sufficiently long (-1-2 months
31   using typical OH values 1-2 x 106/cm3) that it is a small sink compared to uptake of NHs by
32   cloud drops, dry deposition, and aerosol particles.  Thus, the gas-phase oxidation of NHs makes a

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 1   very small contribution as a source of NO. Holland et al. (2005) estimated wet and dry
 2   deposition of NHX, based on measurements over the continental United States, and found that
 3   emissions of NH3 in the National Emissions Inventory are perhaps underestimated by about a
 4   factor of two to three. Reasons for this imbalance include under-representation of deposition
 5   monitoring sites in populated areas and the neglect of off-shore transport in their estimate.  The
 6   use of fixed deposition velocities that do not reflect local conditions at the time of measurement
 7   introduces additional uncertainty into their estimates of dry deposition.
 8
 9   Emissions ofSO2
10          As can be seen from Table AX2.6-1, emissions of S02 are due mainly to the combustion
11   of fossil fuels by electrical utilities and industry.  Transportation related sources make only a
12   minor contribution. As a result, most S02 emissions originate from point sources. Since sulfur
13   is a volatile  component of fuels, it is almost quantitatively released during combustion and
14   emissions can be calculated on the basis of the sulfur content of fuels to greater accuracy than for
15   other pollutants such as NOX or primary PM.
16          The major natural sources of S02 are volcanoes and biomass burning and DMS oxidation
17   over the oceans. S02 constitutes a relatively minor fraction (0.005% by volume) of volcanic
18   emissions (Holland, 1978).  The ratio of H2S to S02 is highly variable in volcanic gases. It is
19   typically much less than one, as in the Mt. Saint Helen's eruption (Turco et al., 1983). However,
20   in addition to being degassed from magma, H2S can be produced if ground waters, especially
21   those containing organic matter, come into contact with volcanic gases. In this case, the ratio of
22   H2S to S02 can be greater than one.  H2S produced this way would more likely be emitted
23   through side vents than through  eruption columns (Pinto et al., 1989).  Primary particulate sulfate
24   is a component of marine aerosol and is also produced by wind erosion of surface soils.
25          Volcanic sources of S02 are limited to the Pacific Northwest, Alaska, and Hawaii. Since
26   1980, the Mount St. Helens volcano in the Washington Cascade Range (46.20 N,  122.18 W,
27   summit 2549 m asl) has been a variable source of S02. Its major effects came in the explosive
28   eruptions of 1980, which primarily affected the northern part of the mountainous western half of
29   the United States.  The Augustine volcano near the mouth of the Cook Inlet in southwestern
30   Alaska (59.363 N, 153.43 W, summit 1252 m asl) has had variable S02 emission since its last
31   major eruptions in 1986.  Volcanoes in the Kamchatka peninsula of eastern region of Siberian
32   Russia do not significantly effect surface S02 concentrations in northwestern North America.

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 1   The most serious effects in the United States from volcanic S02 occurs on the island of Hawaii.
 2   Nearly continuous venting of S02 from Mauna Loa and Kilauea produces S02 in such large
 3   amounts that > 100 km downwind of the island S02 concentrations can exceed 30 ppbv
 4   (Thornton and Bandy, 1993). Depending on wind direction, the west coast of Hawaii (Kona
 5   region) has had significant deleterious effects from S02 and acidic sulfate aerosols for the past
 6   decade.
 7          Emissions of S02 from burning vegetation are generally in the range of 1 to 2% of the
 8   biomass burned (see e.g., Levine et al., 1999).  Sulfur is bound in amino acids in vegetation.
 9   This organically bound sulfur is released during combustion.  However, unlike nitrogen, about
10   half of the sulfur initially present in vegetation is found in the ash (Delmas, 1982).  Gaseous
11   emissions are mainly in the form of S02 with much smaller amounts of H2S and OCS. The ratio
12   of gaseous nitrogen  to sulfur emissions is about 14, very close to their ratio in plant tissue
13   (Andreae, 1991).  The ratio of reduced nitrogen and sulfur species such as NHs and H2S to their
14   more oxidized forms, such as NO and S02, increases from flaming to smoldering phases of
15   combustion, as emissions of reduced species are favored by lower temperatures and 02 reduced
16   availability.
17          Emissions of reduced sulfur species are associated typically with marine organisms living
18   either in pelagic or coastal zones and with anaerobic bacteria in marshes and estuaries.
19   Mechanisms for their oxidation were discussed in Section AX2.2.  Emissions of dimethyl sulfide
20   (DMS) from marine plankton represent the largest single  source of reduced sulfur species to the
21   atmosphere  (e.g., Berresheim et al., 1995). Other sources such as wetlands and terrestrial plants
22   and soils probably account for less than 5% of the DMS global flux, with most of this coming
23   from  wetlands.
24          The coastal and wetland sources of DMS have a dormant period in the fall/winter from
25   senescence of plant  growth. Marshes die back  in fall and winter, so dimethyl sulfide emissions
26   from  them are lower, reduced light levels in winter at mid to high latitudes reduce cut
27   phytoplankton growth which also tends to reduce DMS emissions. Western coasts at mid to high
28   latitudes have reduced levels of the light that drive photochemical production and  oxidation of
29   DMS. Freezing at mid and high latitudes affects the release of biogenic sulfur gases, particularly
30   in the nutrient-rich regions around Alaska. Transport of S02 from regions of biomass burning
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 1   seems to be limited by heterogeneous losses that accompany convective processes that ventilate
 2   the surface layer and the lower boundary layer (Thornton et al., 1996, TRACE-P data archive).
 3          However, it should be noted that reduced sulfur species are also produced by industry.
 4   For example, DMS is used in petroleum refining and in petrochemical production processes to
 5   control the formation of coke and carbon monoxide. In addition, it is used to control dusting in
 6   steel mills. It is also used in a range of organic syntheses. It also has a use as a food flavoring
 7   component.  It can also be oxidized by natural or artificial means to dimethyl sulfoxide (DMSO),
 8   which has several important solvent properties.
 9
10   AX2.6.3   Field Studies Evaluating Emissions Inventories
11          Comparisons of emissions model predictions with observations have been performed in a
12   number of environments. A number of studies of ratios of concentrations of CO to NOX and
13   NMOC to NOX during the early 1990s in tunnels and ambient air (summarized in Air Quality
14   Criteria for Carbon Monoxide (U.S. Environmental Protection Agency, 2000)) indicated that
15   emissions of CO and NMOC were systematically underestimated in emissions inventories.
16   However, the results of more recent studies have been mixed in this regard, with many studies
17   showing agreement to within ±50% (U.S. Environmental Protection Agency, 2000).
18   Improvements in many areas have resulted from the process of emissions model development,
19   evaluation, and further refinement.  It should be remembered that the conclusions from these
20   reconciliation studies depend on the assumption that NOX emissions are predicted correctly by
21   emissions factor models. Roadside remote sensing data indicate that over 50% of NMHC and
22   CO emissions are  produced by less than about 10% of the vehicles (Stedman et al., 1991). These
23   "super-emitters" are typically poorly maintained vehicles. Vehicles of any age engaged in off-
24   cycle operations (e.g., rapid accelerations) emit much more than if operated in normal driving
25   modes.  Bishop and Stedman (1996) found that the most important variables governing CO
26   emissions are fleet age and owner maintenance.
27          Emissions inventories for North America can be evaluated by comparison to measured
28   long-term trends and or ratios of pollutants in ambient air. A decadal field study of ambient CO
29   at a rural site in the Eastern United States (Hallock-Waters et al., 1999) indicates a downward
30   trend consistent with the downward trend in estimated emissions over the period 1988 to 1999
31   (U.S. Environmental Protection Agency, 1997), even when a global downward trend is
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 1   accounted for. Measurements at two urban areas in the United States confirmed the decrease in
 2   CO emissions (Parrish et al., 2002). That study also indicated that the ratio of CO to NOX
 3   emissions decreased by almost a factor of three over 12 years (such a downward trend was noted
 4   in AQCD 96). Emissions estimates (U.S. Environmental Protection Agency, 1997) indicate a
 5   much smaller decrease in this ratio, suggesting that NOX emissions from mobile sources may be
 6   underestimated and/or increasing. Parrish et al. (2002) conclude that Os photochemistry in U.S.
 7   urban areas may have become more N0x-limited over the past decade.
 8          Pokharel et al. (2002)  employed remotely sensed emissions from on-road vehicles and
 9   fuel use data to estimate emissions in Denver.  Their calculations indicate a continual decrease in
10   CO, HC, and NO emissions from mobile sources over the 6-year study period.  Inventories based
11   on the ambient data were 30 to 70% lower for CO, 40% higher for HC, and 40 to 80% lower for
12   NO than those predicted by the MOBILE6 model.
13          Stehr et al. (2000) reported simultaneous measurements of CO,  SOz, and N0y at an East
14   Coast site. By taking advantage of the nature of mobile sources (they emit NOX and CO but little
15   S02) and power plants (they emit NOX and S02 but little CO), the authors evaluated emissions
16   estimates for the eastern United States. Results indicated that coal combustion contributes 25 to
17   35% of the total NOX emissions in rough agreement with  emissions inventories (U.S.
18   Environmental Protection Agency, 1997).
19          Parrish et al.  (1998) and Parrish and Fehsenfeld (2000) proposed methods to derive
20   emission rates by examining measured ambient ratios among individual VOC, NOX and N0y.
21   There is typically a strong correlation among measured values for these species because emission
22   sources are geographically collocated, even when individual sources are different. Correlations
23   can be used to derive emissions ratios between species, including adjustments for the impact of
24   photochemical aging. Investigations of this type  include  correlations between CO and N0y (e.g.,
25   Parrish et al., 1991), between  individual VOC species and N0y (Goldan et al., 1995, 1997, 2000)
26   and between various individual VOC (Goldan et al., 1995, 1997; McKeen and Liu, 1993;
27   McKeen et al., 1996).  Buhr et al. (1992) derived emission estimates from principal component
28   analysis  (PCA) and other statistical methods. Many of these studies are summarized in Trainer
29   et al. (2000), Parrish et al. (1998), and Parrish and Fehsenfeld (2000). Goldstein and Schade
30   (2000) also used species correlations to identify the relative impacts of anthropogenic and
31   biogenic emissions.  Chang et al. (1996, 1997)  and Mendoza-Dominguez and Russell (2000,

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 1    2001) used the more quantative technique of inverse modeling to derive emission rates, in
 2    conjunction with results from chemistry-transport models.
 3
 4
 5    AX2.7     METHODS USED TO CALCULATE CONCENTRATIONS OF
 6               NITROGEN OXIDES AND THEIR CHEMICAL
 7               INTERACTIONS IN THE ATMOSPHERE
 8          Atmospheric chemistry and transport models are the major tools used to calculate the
 9    relations among Os, other oxidants, and their precursors, the transport and transformation of air
10    toxics, the production of secondary organic aerosol, the evolution of the particle size distribution,
11    and the production and deposition of pollutants affecting ecosystems. Chemical transport
12    models are driven by emissions inventories for primary species such as the precursors for Os and
13    PM and by meterological fields produced by other numerical models. Emissions of precursor
14    compounds can be divided into anthropogenic and natural source categories. Natural sources can
15    be further divided into biotic (vegetation, microbes, animals) and abiotic (biomass burning,
16    lightning) categories. However, the distinction between natural sources and anthropogenic
17    sources is often difficult to make as human activities affect directly, or indirectly, emissions from
18    what would have been considered natural sources during the preindustrial era. Emissions from
19    plants and animals used in agriculture have been referred to as anthropogenic or natural in
20    different applications. Wildfire emissions may be considered to be natural, except that forest
21    management practices may have led to the buildup of fuels on the forest floor, thereby altering
22    the frequency and severity of forest fires. Needed meteorological quantities such as winds and
23    temperatures are taken from operational analyses, reanalyses, or circulation models.  In most
24    cases, these are off-line analyses, i.e., they are not modified by radiatively active species such as
25    03  and particles generated by the model.
26          A brief overview of atmospheric chemistry-transport models is given in Section AX2.7.1.
27    A discussion of emissions inventories of precursors used by these models is given in Section
28    AX2.7.2. Uncertainties in emissions estimates have also been discussed in Air Quality Criteria
29    for Particulate Matter (U.S. Environmental Protection Agency, 2004). Chemistry-transport
30    model evaluation and an evaluation of the reliability of emissions inventories are presented in
31    Section AX2.7.4.
32
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 1   AX2.7.1    Chemistry-Transport Models
 2          Atmospheric CTMs have been developed for application over a wide range of spatial
 3   scales ranging from neighborhood to global. Regional scale CTMs are used:  1)  to obtain better
 4   understanding of the processes controlling the formation, transport, and destruction of gas-and
 5   particle-phase criteria and hazardous air pollutants; 2)  to understand the relations between Os
 6   concentrations and concentrations of its precursors such as NOX and VOCs, the factors leading to
 7   acid deposition, and hence to possible damage to ecosystems; and 3)  to understand relations
 8   among the concentration patterns of various pollutants that may exert adverse health effects.
 9   Chemistry Transport Models are also  used for determining control strategies for 03 precursors.
10   However, this application has met with varying degrees of success because of the highly
11   nonlinear relations between Os and emissions of its precursors, and uncertainties in emissions,
12   parameterizations of transport, and chemical production and loss terms. Uncertainties in
13   meteorological variables and emissions can be large enough to lead to significant errors in
14   developing control strategies (e.g., Russell and Dennis, 2000; Sillman et al., 1995).
15          Global scale CTMs are used to address issues associated with climate change,
16   stratospheric ozone depletion, and to provide boundary conditions for regional scale models.
17   CTMs include mathematical (and often simplified) descriptions of atmospheric transport, the
18   transfer of solar radiation through the atmosphere, chemical reactions, and removal to the surface
19   by turbulent motions and precipitation for pollutants emitted into the model domain. Their upper
20   boundaries extend anywhere from the top of the mixing layer to the mesopause (about 80 km in
21   height), to  obtain more realistic boundary conditions for problems involving stratospheric
22   dynamics.  There is a trade-off between the size of the modeling domain and the  grid resolution
23   used in the CTM that is imposed by computational resources.
24          There are two major formulations of CTMs in current use.  In the first approach, grid-
25   based, or Eulerian, air quality models, the region to be modeled (the modeling domain) is
26   subdivided into a three-dimensional array of grid cells.  Spatial derivatives in the species
27   continuity  equations are cast in finite-difference there are also some finite-element models, but
28   not many applications form over this grid, and a system of equations for the concentrations of all
29   the chemical species in the model are solved numerically at each grid point.  Time dependent
30   continuity  (mass conservation) equations are solved for each species including terms for
31   transport, chemical production and destruction, and emissions and deposition (if relevant), in

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 1   each cell. Chemical processes are simulated with ordinary differential equations, and transport
 2   processes are simulated with partial differential equations. Because of a number of factors such
 3   as the different time scales inherent in different processes, the coupled, nonlinear nature of the
 4   chemical process terms, and computer storage limitations, all of the terms in the equations are
 5   not solved simultaneously in three dimensions. Instead, operator splitting, in which terms in the
 6   continuity equation involving individual processes are solved sequentially, is used. In the second
 7   CTM formulation, trajectory or Lagrangian models, a large number of hypothetical air parcels
 8   are specified as following wind trajectories. In these models, the original system of partial
 9   differential equations is transformed into a system of ordinary differential equations.
10          A less common approach is to use a hybrid Lagrangian/Eulerian model, in which certain
11   aspects of atmospheric chemistry and transport are treated with a Lagrangian approach and
12   others are treaded in an Eulerian manner (e.g., Stein et al., 2000).  Each approach has its their
13   advantages and disadvantages.  The Eulerian approach is more general in that it includes
14   processes that mix air parcels and allows integrations  to be carried out for long periods during
15   which individual air parcels lose their identity.  There are, however, techniques for including the
16   effects of mixing in Lagrangian models such as FLEXPART (e.g., Zanis et al., 2003), ATTILA
17   (Reithmeier and  Sausen, 2002),  and CLaMS (McKenna et al., 2002).
18
19   Regional Scale Chemistry Transport Models
20          Major modeling efforts within the U.S. Environmental Protection Agency center on the
21   Community Multiscale Air Quality modeling system (CMAQ, Byun and Ching, 1999; Byun and
22   Schere, 2006). A number of other modeling platforms using Lagrangian and Eulerian
23   frameworks have been reviewed in the 96 AQCD for Os (U.S. Environmental Protection
24   Agency,  1997), and in Russell and Dennis (2000). The capabilities of a number of CTMs
25   designed to study local- and regional-scale air pollution problems are summarized by Russell and
26   Dennis (2000). Evaluations of the performance of CMAQ are given in Arnold et al. (2003), Eder
27   and Y (2005), Appel et al. (2005), and Fuentes and Raftery (2005). The domain of CMAQ can
28   extend from several hundred km to the hemispherical  scale.  In addition, both of these classes of
29   models allow the resolution of the calculations over specified areas to vary.  CMAQ is most
30   often driven by the MM5 mesoscale meteorological model (Seaman, 2000), though it may be
31   driven by other meteorological  models (e.g., RAMS). Simulations of Os episodes over regional
32   domains  have been performed with a horizontal resolution as low as 1 km, and smaller

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 1    calculations over limited domains have been accomplished at even finer scales. However,
 2    simulations at such high resolutions require better parameterizations of meteorological processes
 3    such as boundary layer fluxes, deep convection and clouds (Seaman, 2000), and finer-scale
 4    emissions. Finer spatial resolution is necessary to resolve features such as urban heat island
 5    circulations; sea, bay, and land breezes; mountain and valley breezes, and the nocturnal low-level
 6    jet.
 7          The most common approach to setting up the horizontal domain is to nest a finer grid
 8    within a larger domain of coarser resolution. However, there are other strategies such as the
 9    stretched grid (e.g., Fox-Rabinovitz et al., 2002) and the adaptive grid.  In a stretched grid, the
10    grid's resolution continuously varies throughout the domain, thereby eliminating any potential
11    problems with the sudden change from one resolution to another at the boundary. Caution
12    should be exercised in using such a formulation, because certain parameterizations that are valid
13    on a relatively coarse grid scale (such as convection) may not be valid on finer scales. Adaptive
14    grids are not fixed at the start of the simulation, but instead adapt to the needs  of the simulation
15    as it evolves (e.g., Hansen et al., 1994). They have the advantage that they can resolve processes
16    at relevant spatial scales. However, they can be very slow if the situation to be modeled is
17    complex.  Additionally, if adaptive grids are used for separate meteorological, emissions, and
18    photochemical models, there is no reason a priori why the resolution of each grid should match,
19    and the gains realized from increased resolution in one model will be wasted in the transition to
20    another model.  The use of finer horizontal resolution in CTMs will necessitate finer-scale
21    inventories of land use and better knowledge of the exact paths of roads, locations of factories,
22    and, in general, better methods for locating sources and estimating their emissions.
23          The vertical resolution of these CTMs is variable, and usually configured to have higher
24    resolution near the surface and decreasing aloft. Because the height of the boundary layer is of
25    critical importance in simulations of air quality, improved resolution of the boundary layer height
26    would likely improve air quality simulations.  Additionally, current CTMs do not adequately
27    resolve fine scale features such as the nocturnal low-level jet in part because little is known about
28    the nighttime boundary layer.
29          CTMs require time-dependent, three-dimensional wind fields for the period of
30    simulation. The winds may be either generated by a model using initial fields alone or with four-
31    dimensional data assimilation to improve the model's performance, fields (i.e., model equations

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 1   can be updated periodically or "nudged", to bring results into agreement with observations.
 2   Modeling efforts typically focus on simulations of several days' duration, the typical time scale
 3   for individual 03 episodes, but there have been several attempts at modeling longer periods.  For
 4   example, Kasibhatla and Chameides (2000) simulated a four-month period from May to
 5   September of 1995 using MAQSIP.  The current trend in modeling applications is towards
 6   annual simulations. This trend is driven in part by the need to better understand observations of
 7   periods of high wintertime PM (e.g., Blanchard et al., 2002)  and the need to simulate Os episodes
 8   occurring outside of summer.
 9          Chemical kinetics mechanisms (a set of chemical reactions) representing the important
10   reactions occurring in the atmosphere are used in CTMs to estimate the rates of chemical
11   formation and destruction of each pollutant simulated as a function of time. Unfortunately,
12   chemical mechanisms that explicitly treat the reactions of each individual reactive species are too
13   computationally demanding to be incorporated into CTMs. For example, a master chemical
14   mechanism includes approximately 10,500 reactions involving 3603 chemical species (Derwent
15   et al., 2001).  Instead, "lumped" mechanisms, that group compounds of similar chemistry
16   together, are used.  The chemical mechanisms used in existing photochemical Os models contain
17   significant uncertainties that may limit the accuracy of their predictions; the accuracy of each of
18   these mechanisms is also limited by missing chemistry.  Because of different approaches to the
19   lumping of organic compounds into surrogate groups, chemical mechanisms can produce
20   somewhat different results under similar conditions. The CB-IV chemical mechanism (Gery
21   et al., 1989), the RADM II mechanism (Stockwell et al., 1990),  the SAPRC (e.g., Wang et al.,
22   2000a,b; Carter, 1990) and the RACM mechanisms can be used in CMAQ. Jimenez et al. (2003)
23   provide brief descriptions of the features of the main mechanisms in use and they compared
24   concentrations of several key species predicted by seven chemical mechanisms in a box model
25   simulation over 24 h. The average deviation from the average of all mechanism predictions for
26   03 and NO  over the daylight period was less than 20%, and was 10% for N02 for all
27   mechanisms. However, much larger deviations were found for HNOs, PAN, HOz, H-zOz, CzFu,
28   and C5H8 (isoprene). An analysis for OH radicals was not presented.  The large deviations
29   shown for most species imply differences between the calculated lifetimes of atmospheric
30   species and the assignment of model simulations to either N0x-limited or radical quantity limited
31   regimes between mechanisms. Gross and Stockwell (2003) found small differences between

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 1   mechanisms for clean conditions, with differences becoming more significant for polluted
 2   conditions, especially for NOz and organic peroxy radicals. They caution modelers to consider
 3   carefully the mechanisms they are using.  Faraji et al. (2006) found differences of 40% in peak
 4    Ih Os in the Houston-Galveston-Brazoria area between simulations using SAPRAC and CB4.
 5   They attributed differences in predicted Os concentrations to differences in the mechanisms of
 6   oxidation of aromatic hydrocarbons.
 7          CMAQ and other CTMs (e.g., PM-CAMx) incorporate processes and interactions of
 8   aerosol-phase chemistry (Mebust et al., 2003).  There have also been several attempts to study
 9   the feedbacks of chemistry on atmospheric dynamics using meteorological models, like MM5
10   (e.g., Grell et al., 2000; Liu et al., 2001a; Lu et al., 1997; Park et al., 2001). This coupling is
11   necessary to simulate accurately feedbacks such as may be caused by the heavy aerosol loading
12   found in forest fire plumes (Lu et al., 1997;  Park et al., 2001), or in heavily polluted areas.
13   Photolysis rates in CMAQ can now be calculated interactively with model produced Os, NOz,
14   and aerosol fields (Binkowski et al., 2007).
15          Spatial and temporal characterizations of anthropogenic and biogenic precursor emissions
16   must be specified as inputs to a CTM. Emissions inventories have been compiled on grids of
17   varying resolution for many hydrocarbons, aldehydes, ketones, CO, NHs, and NOX. Emissions
18   inventories for many species require the application of some algorithm for calculating the
19   dependence of emissions on physical variables such as temperature and to convert the
20   inventories into formatted emission files required by a CTM.  For example, preprocessing of
21   emissions data for CMAQ is done by the SMOKE (Spare-Matrix Operator Kernel Emissions)
22   system. For many species, information concerning the temporal variability of emissions  is
23   lacking, so long-term (e.g., annual or Os-season) averages are used in short-term, episodic
24   simulations. Annual emissions estimates are often modified by the emissions model to produce
25   emissions more characteristic of the time of day and  season.  Significant errors in emissions can
26   occur if an  inappropriate time dependence or a default profile is used. Additional complexity
27   arises in model calculations because different chemical mechanisms are based on different
28   species, and inventories constructed for use with another mechanism must be adjusted to reflect
29   these differences. This problem also complicates comparisons of the outputs of these models
30   because one chemical mechanism may produce some species not present in another mechanism
31   yet neither  may agree with the measurements.

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 1          In addition to wet deposition, dry deposition (the removal of chemical species from the
 2    atmosphere by interaction with ground-level surfaces) is an important removal process for
 3    pollutants on both urban and regional scales and must be included in CTMs. The general
 4    approach used in most models is the resistance in series method, in which where dry deposition
 5    is parameterized with a Vd, which is represented as Vd = (ra + rb + r^1 where ra, it,, and rc
 6    represent the resistance due to atmospheric turbulence, transport in the fluid sublayer very near
 7    the elements of surface such as leaves or soil, and the resistance to uptake of the surface itself.
 8    This approach works for a range of substances, although it is inappropriate  for species with
 9    substantial emissions from the surface or for species whose deposition to the surface depends on
10    its concentration at the surface itself. The approach is also modified somewhat for aerosols: the
11    terms rb and rc are replaced with a surface Vd to account for gravitational settling. In their
12    review, Wesley and Hicks (2000) point out several shortcomings of current knowledge  of dry
13    deposition. Among those shortcomings are difficulties in representing dry  deposition over
14    varying terrain where horizontal advection plays a significant role in determining the magnitude
15    of ra and difficulties in adequately determining a Vd for extremely stable conditions such as those
16    occurring at night (e.g., Mahrt, 1998).  Under the best of conditions, when a model is exercised
17    over a relatively small area where dry deposition measurements have been  made, models still
18    commonly show uncertainties at least as large as ±30% (e.g., Massman et al., 1994; Brook et al.,
19    1996; Padro, 1996). Wesely and Hicks (2000) state that an important result of these comparisons
20    is that the current level of sophistication of most dry deposition models is relatively low, and that
21    deposition estimates therefore must rely heavily  on empirical data. Still larger uncertainties exist
22    when the surface features in the built environment are not well known or when the surface
23    comprises a patchwork of different surface types, as is common in the eastern United States.
24          The initial conditions, i.e., the concentration fields of all species computed by a  model,
25    and the boundary conditions,  i.e., the concentrations of species along the horizontal and upper
26    boundaries of the model domain throughout the simulation must be specified at the beginning  of
27    the simulation. It would be best to specify initial and boundary conditions  according to
28    observations.  However, data for vertical profiles of most species of interest are sparse.  The
29    results of model simulations over larger, preferably global, domains can also be used. As may be
30    expected, the influence of boundary conditions depends on the lifetime of the species under
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 1    consideration and the time scales for transport from the boundaries to the interior of the model
 2    domain (Liu etal.,2001b).
 3          Each of the model components described above has an associated uncertainty, and the
 4    relative importance of these uncertainties varies with the modeling application. The largest
 5    errors in photochemical modeling are still thought to arise from the meteorological and
 6    emissions inputs to the model (Russell and Dennis,  2000). Within the model itself, horizontal
 7    advection algorithms are  still thought to be significant source of uncertainty (e.g., Chock and
 8    Winkler, 1994), though more recently, those errors are thought to have been reduced (e.g.,
 9    Odman et al., 1996). There are also indications that problems with mass conservation continue
10    to be present in photochemical and meteorological models (e.g., Odman and Russell, 1999);
11    these can result in significant simulation errors. The effects of errors in initial conditions can be
12    minimized by including several days "spin-up" time in a simulation to allow the model to be
13    driven by emitted species before the simulation of the period of interest begins.
14          While the effects  of poorly specified boundary conditions propagate through the model's
15    domain, the effects of these errors remain undetermined.  Because many meteorological
16    processes occur on spatial scales which are smaller than the model grid spacing (either
17    horizontally or vertically) and thus are not calculated explicitly, parameterizations of these
18    processes must be used and these introduce additional uncertainty.
19          Uncertainty also arises  in modeling the chemistry of Os formation because it is highly
20    nonlinear with respect to  NOX concentrations.  Thus, the volume of the grid cell into which
21    emissions are injected is important because the nature of Os chemistry (i.e., Os production or
22    titration) depends in a complicated way on the concentrations of the precursors and the OH
23    radical as noted earlier. The use of ever-finer grid spacing allows  regions of Os titration to be
24    more clearly separated  from regions of Os production. The use of grid spacing fine enough to
25    resolve the chemistry in individual power-plant plumes is too demanding of computer resources
26    for this to be attempted in most simulations. Instead, parameterizations of the effects of sub-
27    grid-scale processes such as these must be developed; otherwise serious errors can result if
28    emissions are allowed to  mix through an excessively large grid volume before the chemistry step
29    in a model calculation is performed. In light of the significant differences between atmospheric
30    chemistry taking place  inside and outside of a  power plant plume (e.g., Ryerson et al., 1998 and
31    Sillman, 2000), inclusion of a separate, meteorological module for treating  large, tight plumes is

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 1    necessary. Because the photochemistry of 03 and many other atmospheric species is nonlinear,
 2    emissions correctly modeled in a tight plume may be incorrectly modeled in a more dilute plume.
 3    Fortunately, it appears that the chemical mechanism used to follow a plume's development need
 4    not be as detailed as that used to simulate the rest of the domain, as the inorganic reactions are
 5    the most important in the plume see (e.g., Kumar and Russell, 1996). The need to include
 6    explicitly plume-in-grid chemistry only down to the level of the smallest grid disappears if one
 7    uses the adaptive grid approach mentioned previously, though such grids are more
 8    computationally intensive. The differences in simulations are significant because they can lead
 9    to significant differences  in the calculated sensitivity of 03 to its precursors (e.g., Sillman et al.,
10    1995).
11           Because the chemical production and loss terms in the continuity equations for individual
12    species are coupled, the chemical calculations must be performed iteratively until calculated
13    concentrations converge to within some preset criterion. The number of iterations and the
14    convergence criteria chosen also  can introduce error.
15
16    Global Scale CJMs
17           The importance of global transport of Os and Os precursors and their contribution to
18    regional 03 levels in the United States is slowly becoming apparent. There are presently on the
19    order of 20 three-dimensional global models that have been developed by various groups to
20    address problems in tropospheric chemistry.  These models resolve synoptic meteorology,
21    Os-NOx-CO-hydrocarbon photochemistry, have parameterizations for wet and dry deposition,
22    and parameterize sub-grid scale vertical mixing processes  such as convection. Global models
23    have proven useful for testing and advancing scientific understanding beyond what is possible
24    with observations alone.  For example, they can calculate quantities of interest that cannot be
25    measured directly, such as the export of pollution from one continent to the global atmosphere  or
26    the response of the atmosphere to future perturbations to anthropogenic emissions.
27           Global simulations are typically conducted at a horizontal resolution of about 200 km2.
28    Simulations of the effects of transport from long-range transport link multiple horizontal
29    resolutions from the global to the local scale. Finer resolution will only improve scientific
30    understanding to the extent that the governing processes are more accurately described at that
31    scale.  Consequently,  there is a critical need for observations at the appropriate scales to evaluate
32    the scientific understanding represented by the models.

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 1          During the recent IPCC-AR4 tropospheric chemistry study coordinated by the European
 2   Union project Atmospheric Composition Change:  the European Network of excellence
 3   (ACCENT), 26 atmospheric CTMs were used to estimate the impacts of three emissions
 4   scenarios on global atmospheric composition, climate, and air quality in 2030 (Dentener et al.,
 5   2006a). All models were required to use anthropogenic emissions developed at IIASA (Dentener
 6   et al., 2005) and GFED version 1  biomass burning emissions (van der Werf et al., 2003) as
 7   described in Stevenson et al. (2006). The base simulations from these models were evaluated
 8   against a suite of present-day observations.  Most relevant to this assessment report are the
 9   evaluations with ozone and N02,  and for nitrogen and sulfur deposition (Stevenson et al., 2006;
10   van Noije et al., 2006; Dentener et al., 2006a), which are summarized briefly below.
11          An analysis of the standard deviation of zonal mean and tropospheric column Os reveals
12   large inter-model variability in the tropopause region and throughout the polar troposphere,
13   likely reflecting differences in model tropopause levels and the associated stratospheric injection
14   of Os to the troposphere (Stevenson et al., 2006).  Ozone distributions in the tropics also exhibit
15   large standard deviations (-30%), particularly as compared to the mid-latitudes (-20%),
16   indicating larger uncertainties in the processes that influence ozone in the tropics: deep tropical
17   convection, lightning NOX, isoprene emissions and chemistry, and biomass burning emissions
18   (Stevenson etal., 2006).
19          Stevenson et al., (2006) found that the model ensemble mean (MEM) typically captures
20   the observed seasonal cycles to within one standard deviation.  The largest discrepancies
21   between the MEM and observations include: (1) an underestimate of the amplitude of the
22   seasonal cycle at 30°-90°N with a 10 ppbv overestimate of winter ozone, possibly due to the lack
23   of a seasonal  cycle in anthropogenic emissions or to shortcomings in the stratospheric influx of
24   Os, and (2) an overestimate of Os throughout the northern tropics. However, the  MEM was
25   found to capture the observed seasonal cycles in the Southern Hemisphere, suggesting that the
26   models adequately represent biomass burning and natural emissions.
27          The mean present-day global ozone budget across the current generation of CTMs differs
28   substantially from that reported in the IPCC TAR, with a  50% increase in the mean chemical
29   production (to 5100 Tg Os  yr"1), a 30% increase in the chemical and deposition loss terms (to
30   4650 and 1000 Tg Os yr"1, respectively) and a 30% decrease in the mean stratospheric input flux
31   (to 550 Tg Os yr"1) (Stevenson et al., 2006).  The larger chemical terms as compared to the IPCC

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 1   TAR are attributed mainly to higher NOX (as well as an equatorward shift in distribution) and
 2   isoprene emissions, although more detailed NMHC schemes and/or improved representations of
 3   photolysis, convection, and stratospheric-tropospheric exchange may also contribute (Stevenson
 4   etal.,2006).
 5          A subset of 17 of the 26 models used in the Stevenson et al. (2006) study was used to
 6   compare with three retrievals of NOz columns from the GOME instrument (van Noije et al.,
 7   2006) for the year 2000. The higher resolution models reproduce the observed patterns better,
 8   and the correlation among simulated and retrieved columns improved for all models when
 9   simulated values are smoothed to a 5° x 5° grid, implying that the models do not accurately
10   reproduce the small-scale features of N02 (van Noije et al., 2006). Van Noije et al. (2006)
11   suggest that variability in simulated N02 columns may reflect a model differences in OH
12   distributions and the resulting NOX lifetimes, as well as differences in vertical mixing which
13   strongly affect partitioning between NO and NOz. Overall, the models tend  to underestimate
14   concentrations in the retrievals in industrial regions (including the eastern United States) and
15   overestimate  them in biomass burning regions (van Noije et al., 2006).
16          Over the eastern United States, and industrial regions more generally, the spread in
17   absolute column abundances is generally larger among the retrievals than among the models,
18   with the discrepancy among the retrievals particularly pronounced in winter (van Noije et al.,
19   2006), suggesting that the models are biased low, or that the European retrievals may be biased
20   high as the Dalhousie/SAO retrieval is closer to the model estimates.  The lack of seasonal
21   variability in  fossil fuel combustion emissions may contribute to a wintertime model
22   underestimate (van Noije et al., 2006) that is manifested most strongly over Asia. In biomass
23   burning regions, the models generally reproduce the timing of the seasonal cycle of the
24   retrievals, but tend to overestimate the seasonal cycle amplitude, partly due to lower values in the
25   wet season, which may reflect an underestimate in wet season soil NO emissions (van Noije
26   et al., 2006; Jaegle et al., 2004, 2005).
27
28   Deposition in Global CTMs
29          Both wet and dry deposition are highly parameterized in global CTMs. While all current
30   models implement resistance schemes for dry deposition, the generated Vd generated from
31   different models can vary highly across terrains (Stevenson et al., 2006). The accuracy of wet
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 1   deposition in global CTMs is tied to spatial and temporal distribution of model precipitation and
 2   the treatment of chemical scavenging. Dentener et al. (2006b) compared wet deposition across
 3   23 models with available measurements around the globe. Figures AX2.7-1 and AX2.7-2 below
 4   extract the results of a comparison of the 23-model mean versus observations from Dentener
 5   et al. (2006b) over the eastern United States for nitrate and sulfate deposition, respectively.  The
 6   mean model results  are strongly correlated with the observations (r > 0.8), and usually capture
 7   the magnitude of wet deposition to within a factor of 2 over the eastern United States (Dentener
 8   et al., 2006b). Dentener et al. (2006b) conclude that 60-70% of the participating models capture
 9   the measurements to within 50% in regions with quality controlled observations. This study then
10   identified world regions receiving >1000 mg (N) rrf2 yr"1 (the "critical load") and found that
11   20% of the natural vegetation (non-agricultural) in the United States is exposed  to nitrogen
12   deposition in excess of the critical load threshold (Dentener et al., 2006b).
13
14   Modeling the Effects of Convection
15          The effects of deep convection can be simulated using cloud-resolving models, or in
16   regional or global models in which the convection is parameterized.  The Goddard Cumulus
17   Ensemble (GCE) model (Tao and Simpson, 1993) has been used by Pickering et al. (1991;
18   1992a,b; 1993; 1996), Scala et al. (1990) and Stenchikov et al. (1996) in the analysis of
19   convective transport of trace gases. The cloud model  is nonhydrostatic and contains a detailed
20   representation of cloud microphysical processes.  Two- and three-dimensional versions of the
21   model have been applied in transport analyses. The initial conditions for the model are usually
22   from a sounding of temperature, water vapor and winds representative of the region of storm
23   development. Model-generated wind fields can be used to perform air parcel trajectory analyses
24   and tracer advection calculations.
25          Such methods were used by Pickering et al. (1992b) to examine transport of urban
26   plumes by deep convection. Transport of an Oklahoma City plume by the 10-11 June 1985
27   PRE-STORM squall line was simulated with the 2-D GCE model. This major squall line passed
28   over the Oklahoma  City metropolitan area, as well as more rural  areas to the north. Chemical
29   observations  ahead of the squall line were conducted by the PRE-STORM aircraft. In this event,
30   forward trajectories from the boundary layer at the leading edge of the storm showed that almost
31   75% of the low-level inflow was transported to altitudes exceeding 8 km.  Over 35% of
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                        600
    Figure AX2.7-1.
                        400
                     T3
                     O
                        200
                                               Ave, model: 227 Ave, Mea, 195 r; 0,82 n = 226
                                               2 param. fit: y = 51.1 + 0.90x
                                               1 param. fit: y = 1,Q8x
                                               Percentage within ± 50%: 74.8
                                         200           400
                                          Measurement
                                              600
Scatter plot of total nitrate (HNOs plus aerosol nitrate) wet deposition
(mg(N)m 2yr-1) of the mean model versus measurements for the
North American Deposition Program (NADP) network. Dashed lines
indicate factor of 2. The gray line is the result of a linear regression
fitting through 0.
    Source: Dentener et al. (2006b).

1   the air parcels reached altitudes over 12 km.  Tracer transport calculations were performed for
2   CO, NOX, 03, and hydrocarbons.  Rural boundary layer NOX was only 0.9 ppbv, whereas the
3   urban plume contained about 3 ppbv.  In the rural case, mixing ratios of 0.6 ppbv were
4   transported up to 11 km.  Cleaner air descended at the rear of the storm lowering NOX at the
5   surface from 0.9 to 0.5 ppbv.  In the urban plume, mixing ratios in the updraft core reached
6   1 ppbv between 14 and 15 km. At the surface, the main downdraft lowered the NOX mixing
7   ratios from 3 to 0.7 ppbv.
8
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                     1000
                       800 -
                   o>
                   T3
                   O
                       600 -
                       400 -
                       200
                Ave. model: 383 Ave. Meas: 322 r: 0.87 n = 226
                2 param fit: y = 114.0 + 0.77x
                1 param fit: y = 1.00x
                percentage within ± 50%: 66.0
                          0
200      400      600
          Measurement
      800
1000
                                                                                     2
     Figure AX2.7-2.     Same as Figure AX2.7-1 but for sulfate wet deposition (mg(S)m  yr ).

     Source: Dentener et al. (2006b).

 1          Regional chemical transport models have been used for applications such as simulations
 2   of photochemical Os production, acid deposition, and fine PM. Walcek et al. (1990) included a
 3   parameterization of cloud-scale aqueous chemistry, scavenging, and vertical mixing in the
 4   chemistry model of Chang et al. (1987). The vertical distribution of cloud microphysical
 5   properties and the amount of sub-cloud-layer air lifted to each cloud layer are determined using a
 6   simple entrainment hypothesis (Walcek and Taylor, 1986). Vertically integrated 03 formation
 7   rates over the northeast U. S. were enhanced by -50% when the in-cloud vertical motions were
 8   included in the model.
 9          Wang et al. (1996) simulated the 10-11 June 1985 PRE-STORM squall line with the
10   NCAR/Penn State Mesoscale Model (MM5; Grell et al., 1994; Dudhia,  1993). Convection was
11   parameterized as a sub-grid-scale process in MM5 using the Kain Fritsch (1993) scheme. Mass
     September 2007
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 1   fluxes and detrainment profiles from the convective parameterization were used along with the
 2   3-D wind fields in CO tracer transport calculations for this convective event.
 3          Convective transport in global chemistry and transport models is treated as a sub-grid-
 4   scale process that is parameterized typically using cloud mass flux information from a general
 5   circulation model or global data assimilation system. While GCMs can provide data only for a
 6   "typical" year, data assimilation systems can provide "real" day-by-day meteorological
 7   conditions, such that CTM output can be compared directly with observations of trace gases.
 8   The NASA Goddard Earth Observing System Data Assimilation System (GEOS-1 DAS and
 9   successor systems; Schubert et al., 1993; Bloom et al., 1996;  Bloom et al., 2005) provides
10   archived global data sets for the period 1980 to present, at 2°  x 2.5° or better resolution with
11   20 layers or more in the vertical. Deep convection is parameterized with the Relaxed
12   Arakawa-Schubert scheme (Moorthi and Suarez,  1992) in GEOS-1 and GEOS-3 and with the
13   Zhang and McFarlane (1995) scheme in GEOS-4. Pickering  et al. (1995) showed that the cloud
14   mass fluxes from GEOS-1 DAS are reasonable for the 10-11  June 1985 PRE-STORM squall line
15   based on comparisons with the GCE model (cloud-resolving model) simulations of the same
16   storm. In addition, the GEOS-1 DAS cloud mass fluxes compared favorably with the regional
17   estimates of convective transport for the central U. S. presented by Thompson et al. (1994).
18   However, Allen et al. (1997) have shown that the GEOS-1 DAS  overestimates the amount and
19   frequency of convection in the tropics and  underestimates the convective activity over
20   midlatitude marine storm tracks.
21          Global models with parameterized  convection and lightning have been run to examine
22   the roles of these processes over North America.  Lightning contributed 23% of upper
23   tropospheric N0y over the SONEX region  according to the UMD-CTM modeling analysis of
24   Allen et al.  (2000). During the summer of 2004 the NASA Intercontinental Chemical Transport
25   Experiment - North America (INTEX-NA) was conducted primarily over the eastern two-thirds
26   of the United States, as a part of the International Consortium for Atmospheric Research on
27   Transport and Transformation (ICARTT).  Deep convection was prevalent over this region
28   during the experimental period.  Cooper et al. (2006) used a particle dispersion model simulation
29   for NOX to show that 69-84% of the upper  tropospheric Os enhancement over the region in
30   Summer 2004 was due to lightning NOX. The remainder of the enhancement was due to
31   convective transport of Os from the boundary layer or other sources of NOX. Hudman et al.

     September 2007                         AX2-72      DRAFT-DO NOT QUOTE  OR CITE

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 1    (2007) used a GEOS-Chem model simulation to show that lightning was the dominant source of
 2    upper tropospheric NOX over this region during this period. Approximately 15% of North
 3    American boundary layer NOX emissions were shown to have been vented to the free troposphere
 4    over this region based on both the observations and the model.
 5
 6    AX2.7.2   CTM Evaluation
 7          The comparison of model predictions with ambient measurements represents a critical
 8    task for establishing the accuracy of photochemical models and evaluating their ability to serve
 9    as the basis for making effective control strategy decisions. The evaluation of a model's
10    performance, or its adequacy to perform the tasks for which it was designed can only be
11    conducted within the context of measurement errors and artifacts.  Not only are there analytical
12    problems, but there are also problems in assessing the representativeness of monitors at ground
13    level for comparison with model values which represent typically an average over the volume of
14    a grid box.
15          Evaluations of CMAQ are given in Arnold et al. (2003) and Fuentes and Raftery (2005).
16    Discrepancies between model predictions and observations can be used to point out gaps in
17    current understanding of atmospheric chemistry and to  spur improvements in parameterizations
18    of atmospheric chemical and physical processes. Model evaluation does not merely involve a
19    straightforward comparison between model predictions and the concentration field of the
20    pollutant of interest.  Such comparisons may not be meaningful because it is difficult to
21    determine if agreement between model predictions and observations truly represents an accurate
22    treatment of physical and chemical processes in the CTM or the effects of compensating errors in
23    complex model routines.  Ideally, each of the model components (emissions inventories,
24    chemical mechanism, meteorological driver) should be evaluated individually. However, this is
25    rarely done in practice.
26          Chemical transport models for Os formation at the urban/regional scale have traditionally
27    been evaluated based on their ability to simulate correctly Os. A series of performance statistics
28    that measure the  success of individual model simulations to represent the observed distribution
29    of ambient 03, as represented by a network of surface measurements at the urban scale were
30    recommended by the EPA (U.S. Environmental Protection Agency, 1991; see also Russell and
31    Dennis, 2000). These statistics consist of the following:
     September 2007                         AX2-73      DRAFT-DO NOT QUOTE OR CITE

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 1          •     Unpaired peak 03 concentration within a metropolitan region (typically for a
 2                single day) .
 3          •     Normalized bias equal to the summed difference between model and measured
 4                hourly concentrations divided by the sum of measured hourly concentrations.
 5          •     Normalized gross error, equal to the summed unsigned (absolute value) difference
 6                between model and measured hourly concentrations divided by the sum of
 7                measured hourly concentrations.
 8
 9   Unpaired peak prediction accuracy, Au;
                                   {-p\X> t Jmax ~ *- o\x < * )max  ^Jnnn/
                             A,.- — - - *100%,
                                             '  '
10                                       Co(x''/max                             (AX2-48)
11   Normalized bias, D;

                                1  N  {Cn(jr;,/)-C,,(*;,0}
                          D = — X     ;    ,  	         ,/ = 1,24,
12                             ^'=/        Co(-M)                               (AX2-49)
13   Gross error, Ed (for hourly observed values of 03 >60ppb)
14                               N i=!        co(xi-fi                             (AX2-50)
15          The following performance criteria for regulatory models were recommended in U.S.
16   Environmental Protection Agency (1991): unpaired peak Os to within ±15% or ±20%;
17   normalized bias within ± 5% to ± 15%; and normalized gross error less than 30% to 35%, but
18   only when Os the concentration >60 ppb.  This can lead to difficulties in evaluating model
19   performance since nighttime and diurnal cycles are ignored. A major problem with this method
20   of model evaluation is that it does not provide any information about the accuracy of Os-
21   precursor relations predicted by the model. The process of Os formation is sufficiently complex
22   that models can predict Os correctly without necessarily representing the Os formation process
23   properly. If the Os formation process is incorrect, then the modeled source-receptor relations
24   will also be incorrect.
     September 2007                         AX2-74       DRAFT-DO NOT QUOTE OR CITE

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 1          Studies by Sillman et al. (1995, 2003), Reynolds et al. (1996), and Pierce et al. (1998)
 2   have identified instances in which different model scenarios can be created with very different
 3   Os-precursor sensitivity, but without significant differences in the predicted 03 fields.
 4   Figures AX2.7-3a,b provides an example.  Referring to the  Os-NOx-VOC isopleth plot
 5   (Figure AX2.7-4), it can be seen that similar Os concentrations can be found for photochemical
 6   conditions that have very different sensitivity to NOX and VOCs.
 7          Global-scale CTMs have generally been evaluated by comparison with measurements for
 8   a wide array of species, rather than just for 03 (e.g., Wang et al.,  1998; Emmons et al., 2000; Bey
 9   et al., 2001; Hess, 2001; Fiore et al., 2002). These have included evaluation of major primary
10   species (NOX,  CO, and selected VOCs) and an array of secondary species (HN03, PAN, H202)
11   that are often formed concurrently with Os. Models for urban and regional Os have also been
12   evaluated against a broader ensemble of measurements in a few cases, often associated with
13   measurement intensives (e.g., Jacobson et al., 1996; Lu et al.,  1997; Sillman et al., 1998).  The
14   results of a comparison between observed and computed concentrations from Jacobson et al.
15   (1996) for the  Los Angeles Basin are shown in Figures AX2.7-5a,b.
16          The highest concentrations of primary species usually occur in close proximity to
17   emission sources (typically in urban centers) and  at times when dispersion rates are low.  The
18   diurnal cycle includes high concentrations  at night, with maxima during the morning rush hour,
19   and low concentrations during the afternoon (Figure AX2.7-5a).  The afternoon minima are
20   driven by the much greater rate of vertical mixing at that time. Primary species  also show a
21   seasonal maximum during winter, and are often high during fog episodes in winter when vertical
22   mixing, is suppressed. By contrast, secondary species such as Os are typically highest during the
23   afternoon (the  time of greatest photochemical activity), on sunny days and during summer.
24          During these conditions, concentrations of primary species may be relatively low.  Strong
25   correlations between primary and secondary species are generally observed only in downwind
26   rural areas where all anthropogenic species are simultaneously elevated.  The difference in the
27   diurnal cycles  of primary species  (CO, NOX, and ethane) and secondary species  (03, PAN, and
28   HCHO) is evident in Figure AX2.7-5b.
29          Models for urban and regional chemistry have been  evaluated less extensively than
30   global-scale models in part because the urban/regional context presents a number of difficult
     September 2007                         AX2-75      DRAFT-DO NOT QUOTE OR CITE

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            .Q
            Q.

            U
            3
            K.
             CO
                20
            •3  10
                 o
                -5
                      >*
                  100       120      140      160
                                     Ozone(ppb)
                                           -x
                                                         *
                                            180
                200
    35

^  30
13
0.
-S
c
               25

               20
                15
                10
                 0
                                             x
                                         XX
                                       X
                                                    X
                                      X
                                                  X
                  100       120      140      160
                                     Ozone (ppb)
                                            180
                200
Figure AX2.7-3a,b. Impact of model uncertainty on control strategy predictions for Os for
                  two days (August lOa and lib, 1992) in Atlanta, GA. The figures
                  show the predicted reduction in peak Os resulting from 35%
                  reductions in anthropogenic VOC emissions (crosses) and from 35%
                  reductions in NOX (solid circles) in a series of model scenarios with
                  varying base case emissions, wind fields, and mixed layer heights.
Source: Results are plotted from tabulated values published in Sillman et al. (1995, 1997).
September 2007
                         AX2-76
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                   ~  10,00
3.16
                   IN
                    E
                    u
                    6
                   £
                    o
                    E
                   C>4
                   O
                   ^    1.0
                    c
                   •|  0.316
                    E
                   LJJ

                   9    0.1
                                        Q.
                                        a.
                                        n
                                       O
                            1.0     3.16      10.0     31.6     100.0

                          VOC Emission Rate (1012 molec. cm-2 s-1)

Figure AX2.7-4.     Ozone isopleths (ppb) as a function of the average emission rate for
                   NOX and VOC (1012 molec. cm"2 s *) in zero dimensional box model
                   calculations. The isopleths (solid lines) represent conditions during
                   the afternoon following 3-day calculations with a constant emission
                   rate, at the hour corresponding to maximum Os. The ridge line
                   (shown by solid circles) lies in the transition from NOx-saturated to
                   NOx-limited conditions.
September 2007
             AX2-77
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E
Q.

S

O
*•*
CO
               Ui
               E
               Q.
               Q.
               O)
              _c
              'x
               a
               S
               g
               ~
               re
               O)
0,30


0.25


0.20


0.15


0.10


0.05


0.00




0.30


0.25


0.20


0.15


0.10


0.05


0.00





  6


  5


  4


  3


  2


  1


  0
Figure AX2.7-5a.
                          Reseda

                          o3(g)
                         	  Predicted
                         	Observed
                      o
     16   24    32    40    48    56   64   72

       Hour After First Midnight
Reseda

NOX (g)
                                     	  Predicted
                                     	Observed
                               16   24   32   40    48    56    64   72

                                 Hour After First Midnight
                          Riverside

                          C0(g)
                         	  Predicted
                         	Observed
                           l.l.l
                               16   24   32   40    48    56    64   72

                                 Hour After First Midnight
 Time series for measured gas-phase species in comparison with results

 from a photochemical model. The dashed lines represent

 measurements, and solid lines represent model predictions (in parts

 per million, ppmv) for August 26-28,1988 at sites in southern

 California. The horizontal axis represents hours past midnight,

 August 25. Results represent Os and NOX at Reseda and CO at

 Riverside.
Source: Jacobson et al. (1996).
September 2007
                    AX2-78
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                  0,060

              |   0.050
              Q.
              3  0.040
              o
              '•    0.030
              0)  0.020

              s  °-010
                  0.000
    0.030

|   0.025
a
3  0.020
O
*j   0.015
a:
en  0.010

~   0.005

    0.000
                  0.020
              S*
              E  0.016
              a.
              3
              'Q'  0.012
              *•*
              ro
              OC  QQQQ
              0>

              !E  0.004
              2
                  0.000
           Claremont
           Ethane (g)
                                       —— Predicted
                                        O   Observed
                                16   24   32   40   48   56    64    72
                                 Hour After First Midnight
                          Claremont
                          Formaldehyde (g)
                                  	 Predicted
                                  O   Observed
                                                               I
                      0    8    16   24   32   40   48   56    64    72
                                 Hour After First Midnight
       Los Angeles
       PAN (g)
                                      	 Predicted
                                      	Observed
                                16   24   32   40   48   56
                                 Hour After First Midnight
                                           64
                                                      72
Figure AX2.7-5b.
Time series for measured gas-phase species in comparison with results
from a photochemical model.  The circles represent measurements,
and solid lines represent model predictions (in parts per million,
ppmv) for August 26-28,1988 at sites in southern California.  The
horizontal axis represents hours past midnight, August 25. Results
represent ethane and formaldehyde at Claremont and PAN at Los
Angeles.
Source: Jacobson et al. (1996).
September 2007
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 1    challenges.  Global-scale models typically represent continental-scale events and can be
 2    evaluated effectively against a sparse network of measurements. By contrast, urban/regional
 3    models are critically dependent on the accuracy of local emission inventories and event-specific
 4    meteorology, and must be evaluated separately for each urban area that is represented.
 5          The evaluation of urban/regional models is also limited by the availability of data.
 6    Measured NOX and speciated VOC concentrations are widely available through the EPA PAMs
 7    network, but questions have been raised about the accuracy of those measurements and the data
 8    have not yet been analyzed thoroughly.  Evaluation of urban/regional models versus
 9    measurements has generally relied on results from a limited number of field studies in the United
10    States.  Short-term, research-grade measurements for species relevant to 03 formation, including
11    VOCs, NOX, PAN, HN03, and H202 are also available at selected rural and remote sites (e.g.,
12    Daum et al., 1990, 1996; Martin et al., 1997; Young et al., 1997; Thompson et al., 2000; Hoell
13    et al., 1997, 1999; Fehsenfeld et al.,  1996a; Emmons et al., 2000; Hess, 2001; Carroll et al.,
14    2001). The equivalent measurements are available for some polluted rural sites in the eastern
15    United States, but only at a few urban locations (Meagher et al.,  1998; Hiibler et al., 1998;
16    Kleinman et al., 2000, 2001;  Fast et al., 2002; new SCAQS-need reference). Extensive
17    measurements have also been made in Vancouver (Steyn et al.,  1997) and in several European
18    cities (Staffelbach et al., 1997; Prevot et al., 1997, Dommen et al., 1999; Geyer et al., 2001;
19    Thielman et al., 2001; Martilli et al., 2002; Vautard et al., 2002).
20          The results of straightforward comparisons between observed and predicted
21    concentrations of Os can be misleading because of compensating errors, although this possibility
22    is diminished when a number of species are compared. Ideally, each of the main modules of a
23    CTM system (for example, the meteorological model and the chemistry and radiative transfer
24    routines) should be evaluated separately. However,  this is rarely done in practice.  To better
25    indicate how well physical and chemical processes are being represented in the model,
26    comparisons of relations between concentrations measured in the field and concentrations
27    predicted by the model can be made. These comparisons could involve ratios and correlations
28    between species.  For example, correlation coefficients could be calculated between primary
29    species as a means of evaluating the accuracy of emission inventories or between secondary
30    species as a means of evaluating the treatment of photochemistry in the model.  In addition,
31    spatial relations involving individual species (correlations, gradients)  can also be used as a means

      September 2007                         AX2-80      DRAFT-DO NOT QUOTE OR CITE

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1   of evaluating the accuracy of transport parameterizations. Sillman and He (2002) examined
2   differences in correlation patterns between Os and NOZ in Los Angeles, CA, Nashville, TN, and
3   various sites in the rural United States. Model calculations (Figure AX2.7-6) show differences in
4   correlation patterns associated with differences in the sensitivity of Os to NOX and VOCs.
5   Primarily N0x-sensitive (N0x-limited) areas in models show a strong correlation between Os and
6   NOZ with a relatively steep slope, while primarily VOC-sensitive (N0x-saturated) areas in
7   models show lower Os for a given NOZ and a lower Os-N0z slope. They found that differences
8   found in measured data ensembles were matched by predictions from chemical transport models.
            250
               0
    Figure AX2.7-6.
                                                   20
                                              NOZ (ppb)
Correlations for Os versus NOZ (NOy-NOx) in ppb from chemical
transport models for the northeast corridor,  Lake Michigan,
Nashville, the San Joaquin Valley, and Los Angeles. Each location is
classified as NOx-limited or NOx-sensitive (circles), NOx-saturated or
VOC-sensitive (crosses), mixed or with near-zero sensitivity (squares),
and dominated by NOX titration (asterisks) based on the model
response to reduced NOX and VOC.
    Source: Sillman and He (2002).
    September 2007
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 1          Measurements in rural areas in the eastern United States show differences in the pattern
 2   of correlations for 03 versus NOZ between summer and autumn (Jacob et al., 1995; Hirsch et al.,
 3   1996), corresponding to the transition from N0x-limited to N0x-saturated patterns, a feature
 4   which is also matched by CTMs.
 5          The difference in correlations between secondary species in N0x-limited to NOX-
 6   saturated environments can also be used to evaluate the accuracy of model predictions in
 7   individual applications.  Figures AX2.7-7a and AX2.7-7b  show results for two different model
 8   scenarios for Atlanta. As shown in the figures, the first model scenario predicts an urban plume
 9   with high N0y and 03 formation apparently suppressed by high N0y. Measurements show much
10   lower N0y in the Atlanta plume.  This error was especially significant because the model
11   locations sensitive to NOX.  The second model scenario (with primarily N0x-sensitive
12   conditions) shows much better agreement with measured values. Figure AX2.7-8a,b shows
13   model-measurement comparisons for secondary species in Nashville, showing better agreement
14   with measured with conditions. Greater confidence in the predictions made by CTMs will be
15   gained by the application of techniques such as these on a more routine basis.
16          The ability of chemical mechanisms to calculate the concentrations of free radicals under
17   atmospheric conditions was tested in the Berlin Ozone Experiment, BERLIOZ (Volz-Thomas
18   et al., 2003)  during July and early August at a site located  about 50 km NW of Berlin.  (This
19   location was chosen because 03 episodes in central Europe are often associated with SE winds.)
20          Concentrations of major compounds such as 03, hydrocarbons, etc., were fixed at
21   observed values. In this regard, the protocol used in this evaluation is an example of an
22   observationally high N0y were not sensitive to NOX, while locations with lower N0y were
23   primarily based method. Figure AX2.7-9 compares the concentrations of ROz, HOz, and  OH
24   radicals predicted by RACM and MCM with observations made by the laser-induced
25   fluorescence (LIF) technique and by matrix isolation ESR spectroscopy  (MIESR).  Also shown
26   are the production rates of 03 calculated using radical concentrations predicted by the
27   mechanisms and those obtained by measurements, and measurements of NOX concentrations. As
28   can be seen, there is good agreement between measurements of R02, H02, OH, radicals with
29   values predicted by both mechanisms at high concentrations of NOX (>10 ppb). However, at
30   lower NOX concentrations, both mechanisms substantially overestimate OH concentrations and
     September 2007                         AX2-82       DRAFT-DO NOT QUOTE OR CITE

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            200
                              10
      20
NOy (PP^
      30
40
                              10
      20
NOy (ppb)
      30
40
Figure AX2.7-7a,b.  Evaluation of model versus measured Os versus NOy for two model
                   scenarios for Atlanta.  The model values are classified as NOX- limited
                   (circles), NOx-saturated (crosses), or mixed or with low sensitivity to
                   NOX (squares).  Diamonds represent aircraft measurements.
Source: Sillman et al. (1997).
September 2007
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        .Q
        Q.
         n
        O
                             10
     20
 NOZ (ppb)
      30
40
                             10          20           30
                                2H2O2 + NOZ (ppb)
                               40
Figure AX2.7-8a,b.  Evaluation of model versus: (a) measured Os versus NOZ and (b) Os
                  versus the sum 2H2O2 + NOZ for Nashville, TN. The model values are
                  classified as NOx-limited (gray circles), NOx-saturated (X's), mixed or
                  near-zero sensitivity (squares), or dominated by NOX titration (filled
                  circles). Diamonds represent aircraft measurements.
Source: Sillman et al. (1998).
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 1   moderately overestimate H02 concentrations. Agreement between models and measurements is
 2   generally better for organic peroxy radicals, although the MCM appears to overestimate their
 3   concentrations somewhat. In general, the mechanisms reproduced the H02 to OH and R02 to
 4   OH ratios better than the individual measurements. The production of Os was found to increase
 5   linearly with NO (for NO < 0.3 ppb) and to decrease with NO (for NO > 0.5 ppb).
 6          OH and H02 concentrations measured during the PM2.5 Technology Assessment and
 7   Characterization Study conducted at Queens  College in New York City in the summer of 2001
 8   were also compared with those predicted by RACM (Ren et al., 2003). The ratio of observed to
 9   predicted H02 concentrations over a diurnal cycle was 1.24 and the ratio of observed to predicted
10   OH concentrations was about 1.10 during the day, but the mechanism significantly
11   underestimated OH concentrations during the night.
12
13
14   AX2.8    SAMPLING AND ANALYSIS OF NITROGEN AND
15              SULFUR  OXIDES
16
17   AX2.8.1   Availability and Accuracy of Ambient Measurements for NOy
18          Section AX2.8.1-AX2.8.4 focus on current methods and on promising new technologies,
19   but no attempt is made here to cover the extensive development of these methods or of methods
20   such as wet chemical techniques, no longer in widespread use. More detailed discussions of
21   these methods may be found elsewhere (U.S. Environmental Protection Agency, 1993, 1996).
22   McClenny (2000), Parrish and Fehsenfeld (2000), and Clemitshaw (2004) reviewed methods for
23   measuring NOX and N0y compounds. Discussions in Sections 2.8.1-2.8.4 center on
24   chemiluminescence and optical Federal Reference and Equivalent Methods (FRM and FEM,
25   respectively).
26          The use of methods such as observationally based methods or source apportionment
27   models, either as stand-alone methods or as a basis for evaluating chemical transport models, is
28   often limited by the availability and accuracy of measurements. Measured NOX and speciated
29   VOC concentrations are widely available in the United States through the PAMS network.
30   However, challenges have been raised about both the accuracy of the measurements and their
31   applicability.
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 1          The PAMs network currently includes measured NO and NOX. However, Cardelino and
 2   Chameides (2000) reported that measured NO during the afternoon was frequently at or below
 3   the detection limit of the instruments (1 ppb), even in large metropolitan regions (Washington,
 4   DC; Houston, TX; New York, NY). Nitric dioxide measurements are made with commercial
 5   chemilluminescent detectors with hot molybdenum converters.  However, these measurements
 6   typically include a wide variety of other reactive N species, such as organic nitrates in addition to
 7   NOX, and cannot be interpreted as a "pure" NOX measurement (see summary in Parrish and
 8   Fehsenfeld, 2000).  Detection of these species can be considered an interference or a cross
 9   sensitivity useful for understanding the  chemistry of the air.
10          Total reactive nitrogen (N0y) is included in the PAMS network only at a few sites. The
11   possible expansion of PAMS to include more widespread N0y measurements has been suggested
12   (McClenny, 2000). N0y measurements are also planned for inclusion in the NCore network
13   (U.S. Environmental Protection Agency, 2005).  A major issue to be considered when measuring
14   NOX and N0y is the possibility that HNOs, a major component of N0y, is sometimes lost in inlet
15   tubes and not measured (Luke et al., 1998; Parrish and Fehsenfeld, 2000). This problem is
16   especially critical if measured N0y is used to identify N0x-limited versus N0x-saturated
17   conditions. The problem is substantially alleviated although not necessarily completely solved
18   by using much shorter inlets on N0y monitors than on NOX monitors and by the use of surfaces
19   less likely to take up HN03. The correlation between 03 and N0y differs for N0x-limited versus
20   N0x-saturated locations, but this difference is driven primarily by differences in the ratio of Os to
21   HNOs. If HNOs were omitted from the N0y measurements, then the measurements would
22   represent a biased estimate and their use would be problematic.
23
24   AX2.8.1.1  Calibration Standards
25          Calibration gas standards of NO, in Nz (certified at  concentrations of approximately 5 to
26   40 ppm)  are obtainable from the Standard Reference Material (SRM) Program of the  National
27   Institute of Standards and Technology (NIST), formerly the National Bureau of Standards
28   (NBS), in Gaithersburg, MD. These SRMs are supplied as compressed gas mixtures at about
29   135 bar (1900 psi) in high-pressure aluminum cylinders containing 800 L of gas at standard
30   temperature and pressure, dry (STPD) National Bureau of Standards, 1975; Guenther et al.,
31   1996). Each cylinder is supplied with a certificate stating concentration and uncertainty. The
32   concentrations are certified to be accurate to ±1 percent relative to the stated values. Because of

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 1   the resources required for their certification, SRMs are not intended for use as daily working
 2   standards, but rather as primary standards against which transfer standards can be calibrated.
 3          Transfer stand-alone calibration gas standards of NO in N2 (at the concentrations
 4   indicated above) are obtainable from specialty gas companies. Information as to whether a
 5   company supplies such mixtures is obtainable from the company, or from the SRM Program of
 6   NIST. These NIST Traceable Reference Materials (NTRMs) are purchased directly from
 7   industry and are supplied as compressed gas mixtures at approximately 135 bar (1900 psi) in
 8   high-pressure aluminum cylinders containing 4,000 L of gas at STPD. Each cylinder is supplied
 9   with a certificate stating concentration and uncertainty. The concentrations are certified to be
10   accurate to within ±1 percent of the stated values (Guenther et al., 1996). Additional details can
11   be found in the previous AQCD for Os (U.S. Environmental Protection Agency,  1996).
12
13   AX2.8.1.2 Measurement of Nitric Oxide
14
15   Gas-phase Chemiluminescence (CL) Methods
16          Nitric oxide can be measured reliably using the principle of gas-phase
17   chemiluminescence induced by the reaction of NO with Os at low pressure. Modern commercial
18   NOX analyzers have sufficient sensitivity and specificity for adequate  measurement in urban and
19   many rural locations (U.S. Environmental Protection Agency, 1993, 1996, 2006). Research
20   grade CL instruments have been compared under realistic field conditions to spectroscopic
21   instruments, and the results indicate that both methods are reliable (at concentrations relevant to
22   smog studies) to better than 15 percent with 95 percent confidence. Response times are on the
23   order of 1 minute.  For measurements meaningful for understanding Os formation, emissions
24   modeling, and N deposition, special care must be taken to zero and calibrate the instrument
25   frequently. A chemical zero, obtained by reacting the NO up-stream and out of view of the
26   photomultiplier tube, is preferred because it accounts for interferences such as light emitting
27   reactions with unsaturated hydrocarbons. Calibration should be performed with NTRM-of
28   compressed NO in N2.  Standard additions of NO at the inlet will account for  NO loss or
29   conversion to N02 in the lines. In summary, CL methods, when operated carefully in an
30   appropriate manner, can be suitable for measuring or monitoring NO  (e.g., Crosley, 1996).
31
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 1   Spectroscopic Methods for Nitric Oxide
 2          Nitric oxide has also been successfully measured in ambient air with direct Spectroscopic
 3   methods; these include two-photon laser-induced fluorescence (TPLIF), tunable diode laser
 4   absorption spectroscopy (TDLAS), and two-tone frequency-modulated spectroscopy (TTFMS).
 5   These were reviewed thoroughly in the previous AQCD and will be only briefly summarized
 6   here.  The Spectroscopic methods demonstrate excellent sensitivity and selectivity for NO with
 7   detection limits on the order of 10 ppt for integration times of 1 min. Spectroscopic methods
 8   compare well with the CL method for NO in controlled laboratory air, ambient air, and heavily
 9   polluted air (e.g., Walega et al.,  1984; Gregory et al., 1990; Kireev et al., 1999). These
10   Spectroscopic methods remain in the research arena due to their complexity, size, and cost, but
11   are essential for demonstrating that CL methods are reliable for monitoring NO concentrations
12   involved in Os formation—from around 20 ppt to several hundred of ppb.
13          Atmospheric pressure laser ionization followed by mass spectroscopy has also been
14   deployed for detection of NO and N02.  Garnica et al. (2000) describe a technique involving
15   selective excitation at one wavelength followed by ionization at a second wavelength. They
16   report good selectivity and detection limits well below 1 ppb.  The practicality  of the instrument
17   for ambient monitoring, however, has yet to be demonstrated.
18
19   AX2.8.1.3  Measurements of Nitrogen Dioxide
20
21   Gas-Phase Chemiluminescence Methods
22          Reduction of N02 to NO, on the surface of a heated (to 300 to 400  °C) molybdenum
23   oxide substrate followed by detection of the chemiluminescence produced during the reaction of
24   NO with Os at low pressure as described earlier for measurement of NO serves as the basis of the
25   FRM for measurement of ambient N02. However, the substrate used in the reduction of N02 to
26   NO is not specific to N02; hence the chemiluminescence analyzers are subject  to interference
27   nitrogen oxides other than N02 produced by oxidized N0y compounds, or NOZ. Thus, this
28   technique will overestimate N02 concentrations particularly in areas downwind of sources of NO
29   and N02 as NOX is oxidized to NOZ in the  form of PANs and other organic nitrates, and HNOs
30   and HN04. Many of these compounds are reduced at the catalyst with nearly the same efficiency
31   as N02. Interferences have also been found from a wide range of other compounds as described
32   in the latest AQCD for N02.

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 1    Other Methods
 2          Nitrogen dioxide can be selectively converted to NO by photolysis.  For example,
 3    (Ryerson et al., 2000) developed a gas-phase chemiluminescence method using a photolytic
 4    converter based on a Hg lamp with increased radiant intensity in the region of peak N02
 5    photolysis (350 to 400 nm) and producing conversion efficiencies of 70% or more in less than
 6    Is.  Metal halide lamps with conversion efficiency of about 50% and accuracy on the order of
 7    20% (Nakamura, et al., 2003) have been used. Because the converter produces little radiation at
 8    wavelengths less than 350 nm, interferences from HNOs and PAN are minimal. Alternative
 9    methods to photolytic reduction followed by CL are desirable to test the reliability of this widely
10    used technique.  Any method based on a conversion to measured species presents potential for
11    interference a problem. Several atmospheric species, PAN and HOzNOz for example, dissociate
12    to N02 at higher temperatures.
13          Laser induced fluorescence for N02 detection involves excitation of atmospheric N02
14    with laser light emitted at wavelengths too long to induce photolysis. The resulting excited
15    molecules relax in a photoemissive mode and the fluorescing photons are counted.  Because
16    collisions would rapidly quench the electronically excited N02, the reactions are conducted at
17    low pressure. Matsumi et al. (2001) describe a comparison of LIF with a photofragmentation
18    chemiluminescence instrument. The LIF system involves excitation at 440 nm with a multiple
19    laser system.  They report sensitivity of 30 ppt in 10 s and good agreement between the two
20    methods under laboratory conditions at mixing ratios up to 1.0 ppb. This high-sensitivity LIF
21    system has yet to undergo long-term field tests. Cleary et al. (2002) describe field tests of a
22    system that uses continuous, supersonic expansion followed by excitation at 640 nm with a
23    commercial cw external-cavity tunable diode laser. More recently, LIF has been successfully
24    used to detect N02 with accuracy of about 15% and detections limits well below 1 ppb.  When
25    coupled with thermal dissociation, the technique also measures peroxy nitrates such as PAN,
26    alkyl nitrates, HN04 and HN03 (Cohen,  1999; Day et al., 2002; Farmer et al., 2006; Perez et al.,
27    2007; Thornton et al., 2003). This instrument can have very fast sampling rates be fast (>1 Hz)
28    and shows good correlation with chemiluminescent techniques, but remains a research-grade
29    device.
30          Nitrogen Dioxide can be detected by differential optical absorption spectroscopy (DOAS)
31    in an open, long-path system by measuring narrow band absorption features over a background

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 1   of broad band extinction (e.g., Stutz et al, 2000; Kim and Kim, 2001). A DOAS system
 2   manufactured by OPSIS is designated as a Federal Equivalent Method for measuring N02.
 3   DOAS systems can also be configured to measure NO, HONO, and N03 radicals.  Typical
 4   detection limits are 0.2 to 0.3 ppbv for NO, 0.05 to 0.1 ppbv for N02, 0.05 to 0.1 ppbv for
 5   HONO, and 0.001 to 0.002 ppbv for N03, at path lengths of 0.2, 5, 5, and 10 km, respectively.
 6   The obvious advantage  compared to fixed point measurements is that concentrations relevant to
 7   a much larger area are obtained, especially if multiple targets are used. At the same time, any
 8   microenvironmental artifacts are minimized over the long path integration.  A major limitation in
 9   this technique had involved inadequate knowledge of absorption cross sections.  Harder et al.
10   (1997) conducted an experiment in rural Colorado involving simultaneous measurements of N02
11   by DOAS and by photolysis followed by chemiluminescence. They found differences of as
12   much as 110% in clean  air from the west, but for N02 mixing ratios in excess of 300 ppt, the two
13   methods agreed to better than 10%. Stutz (2000) cites two intercomparisons of note. Nitric
14   oxide was measured by  DOAS, by photolysis of N02 followed by chemiluminescence, and by
15   LIF during July 1999 as part of the SOS in Nashville, TN. On average, the three methods agreed
16   to within 2%, with some larger differences likely caused by spatial variability over the DOAS
17   path.  In another study in Europe, and a multi-reflection set-up over a 15 km path, negated the
18   problem of spatial averaging here agreement with the chemiluminescence detector following
19   photolytic conversion was excellent (slope = 1.006 ± 0.005; intercept = 0.036 ±  0.019; r = 0.99)
20   over a concentration range from about 0.2 to 20 ppbv.
21          Nitric oxide can also be detected from space with DOAS-like UV spectroscopy
22   techniques (Kim  et al., 2006; Ma et al., 2006).  These measurements appear to track well with
23   emissions estimates and can be a useful  indicator of column content as well as for identifying hot
24   spots in sources.  See also Richter et al., 2005.  Leigh (2006) report on a DOAS  method that uses
25   the sun as a light source and compares well with an in situ chemiluminescence detector in an
26   urban environment.
27          Chemiluminescence on the surface of liquid Luminol has also been used for measurement
28   of N02 (Gaffney et al.,  1998; Kelly et al., 1990; Marley et al., 2004; Nikitas et al.,  1997; Wendel
29   etal., 1983). This technique is sensitive and linear, and more specific than hot MoOx.  Luminol
30   does not emit light when exposed to NHOs or alkyl nitrates, but does react with  PAN. This
31   interference can be removed by chromatographic separation prior to detection and the resulting

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 1   measurement compares well with more specific techniques for moderate to high (> 1 ppb) mixing
 2   ratios of N02.
 3          Several tunable diode laser spectroscopy techniques have been used successfully for N02
 4   detection (Eisele et al., 2003; Osthoff et al., 2006). These devices remain research grade
 5   instruments, not yet practical for urban monitoring.
 6
 7   Measurements of Total Oxidized Nitrogen Species, NOy
 8          Gold catalyzed CO, or H2 reduction or as conversion on hot molybdenum oxide catalyst
 9   have been used to reduce N0y to NO before then detection by chemiluminescence  (Fehsenfeld
10   et al., 1987; Crosley, 1996). Both techniques offer generally reliable measurements, with
11   response times on the order of 60 s and a linear dynamic range demonstrated in field
12   intercomparisons from about 10 ppt to 10's of ppb.  Under certain conditions, HCN, NH3, RN02,
13   and CH3CN can be converted to NO, but at normal concentrations and humidity these are minor
14   interferences. Thermal decomposition followed by LIF has also been used for N0y detection, as
15   described above. In field comparisons, instruments based on these two principles generally
16   showed good agreement (Day et al., 2002).  The experimental uncertainty is estimated to be of
17   15-30%.
18
19   AX2.8.1.4  Monitoring for NOi Compliance Versus Monitoring for Ozone Formation
20          Regulatory measurements of N02 have been focused on demonstrating compliance with
21   the NAAQS for N02. Today, few locations violate that standard, but N02 and related N0y
22   compounds remain among the most important atmospheric trace gases to measure and
23   understand.  Commercial instruments for NO/NOX detection are  generally constructed with an
24   internal converter for reduction of N02 to NO, and generate a signal referred to as NOX.  These
25   converters, generally constructed of molybdenum oxides  (MoOx), reduce not only N02 but also
26   most other N0y species. Unfortunately, with an internal converter, the instruments may not give
27   a faithful indication of N0y either—reactive species such as HNOs will adhere to the walls of the
28   inlet system.  Most recently, commercial vendors such as Thermo Environmental (Franklin, MA)
29   have offered N0/N0y detectors with external Mo converters.  If such instruments are calibrated
30   through the inlet with a reactive nitrogen species such as propyl nitrate,  they give accurate
31   measurements of total N0y, suitable for evaluation of photochemical models. (Crosley, 1996;
32   Fehsenfeld et al., 1987; Nunnermacker et al., 1998; Rodgers and Davis, 1989).  Under conditions

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 1   of fresh emissions, such as in urban areas during the rush hour, N0y ~ NOX and these monitors
 2   can be used for testing emissions inventories (Dickerson, et al., 1995; Parrish, 2006). The State
 3   of Maryland for example is making these true N0y measurements at the Piney Run site in the
 4   western part of the state.  These data produced at this site can be more reliably compared to the
 5   output of CMAQ and other chemical transport models.
 6
 7   Summary of Methods for Measuring NO 2
 8          A variety of techniques exist for reliable monitoring of atmospheric NOz and related
 9   reactive nitrogen species.  For demonstration of compliance with the NAAQS for N02,
10   commercial chemiluminescence instruments are adequate. For certain conditions, luminol
11   chemiluminescence is adequate.  Precise measurements of NOz can be made with research grade
12   instruments such as LIF and TDLS. For path-integrated concentration determinations UV
13   spectroscopic methods provide useful information. Commercial NOX instruments are sensitive to
14   other N0y species, but do not measure N0y quantitatatively. N0y instruments with external
15   converters offer measurements more useful for comparison to chemical transport model
16   calculations.
17
18   AX2.8.2   Measurements of HNO3
19          Accurate measurement of HNOs, has presented a long-standing analytical challenge to
20   the atmospheric chemistry community. In this context, it is useful to consider the major factors
21   that control HNOs partitioning between the gas and deliquesced-particulate phases in ambient
22   air. In equation form,

                                   K                K
23                       HN03g <-£*> [HN03ai/] <^>[H+] + [NO3~]           (AX2_51)

24   where  KH is the Henry's Law constant in M atrrf * and Ka is the acid dissociation constant in M.
25          Thus, the primary controls on HN03 phase partitioning are its thermodynamic properties
26   (KH, Ka, and associated temperature corrections), aerosol liquid water content (LWC), solution
27   pH, and kinetics.  Aerosol LWC and pH are controlled by the relative mix of different acids and
28   bases in the system, hygroscopic properties of condensed compounds, and meteorological
29   conditions (RH, temperature, and pressure). It is evident from relationship AX2-51 that, in the
30   presence of chemically distinct aerosols of varying acidities (e.g., super-pm predominantly sea

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 1   salt and sub-pm predominantly S aerosol), HN03 will partition preferentially with the less-acidic
 2   particles; and this is consistent with observations (e.g., Huebert et al., 1996; Keene and Savoie,
 3   1998; Keene et al., 2002).  Kinetics are controlled by atmospheric concentrations of HN03 vapor
 4   and particulate N03~ and the size distribution and  corresponding atmospheric lifetimes of
 5   particles against deposition.  Sub-pm diameter aerosols typically equilibrate with the gas phase
 6   in seconds to minutes while super-um aerosols require hours to a day or more (e.g., Meng and
 7   Seinfeld, 1996; Erickson et al., 1999). Consequently, smaller aerosol size fractions are typically
 8   close to thermodynamic equilibrium with respect to HN03 whereas larger size fractions (for
 9   which atmospheric lifetimes against deposition range from hours to a few days) are often
10   undersaturated (e.g., Erickson et al., 1999; Keene and Savioe, 1998).
11          Many sampling techniques for HN03 (e.g., annular denuder, standard filterpack and mist-
12   chamber samplers) employ upstream prefilters to remove particulate species from sample air.
13   However, when chemically distinct aerosols with different pHs (e.g., sea salt and S aerosols) mix
14   together on a bulk filter, the acidity of the bulk mixture will be greater than that of the less acidic
15   aerosols with which most N03~ is associated. This change in pH may cause the bulk mix to be
16   supersaturated with respect to HN03 leading to volatilization and, thus, positive measurement
17   bias in HN03 sampled downstream.  Alternatively, when undersaturated super-pm size fractions
18   (e.g., sea salt)  accumulate on a bulk filter and chemically interact over time with HN03 in the
19   sample air stream, scavenging may lead to negative bias in HN03 sampled downstream.
20   Because the magnitude of both effects will vary as functions of the overall composition and
21   thermodynamic state of the multiphase system, the combined influence can cause net positive or
22   net negative measurement bias in resulting data. Pressure drops across particle filters can also
23   lead to artifact volatilization and associated positive bias in HN03 measured downstream.
24          Widely used methods for measuring HN03 include standard filterpacks configured with
25   nylon or alkaline-impregnated filters (e.g., Goldan et al., 1983; Bardwell et al., 1990), annular
26   denuders (EPA Method IP-9), and standard mist chambers (Talbot et al., 1990).  Samples from
27   these instruments are typically analyzed by ion chromatography. Intercomparisons of these
28   measurement techniques (e.g., Hering et al., 1988; Tanner et al.,  1989; Talbot et al., 1990)  report
29   differences on the order of a factor of two or more.
30          More recently, sensitive HN03 measurements based on the principle of Chemical
31   lonization Mass Spectroscopy (CIMS) have been reported (e.g., Huey et al., 1998; Mauldin

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 1   et al., 1998; Furutani and Akimoto, 2002; Neuman et al, 2002).  CMS relies on selective
 2   formation of ions such as SiFs^-HNOs or HSO^-HNOs followed by detection via mass
 3   spectroscopy.  Two CMS techniques and a filter pack technique were intercompared in Boulder,
 4   CO (Fehsenfeld et al.,  1998). Results indicated agreement to within 15% between the two CMS
 5   instruments and between the CMS and filterpack methods under relatively clean conditions with
 6   HNOs mixing ratios between 50 and 400 pptv.  In more polluted air, the filterpack technique
 7   generally yielded higher values than the CMS suggesting that interactions between chemically
 8   distinct particles on bulk filters is a more important source of bias in polluted continental air.
 9   Differences were also greater at lower temperature when particulate N03~ corresponded to
10   relatively greater fractions of total N03~.
11
12   AX2.8.3   Techniques for Measuring Other NOy Species
13          Methods for sampling and analysis of alkyl nitrates in the atmosphere have been
14   reviewed by Parrish and Fehsenfeld (2000). Peroxyacetylnitrate, PPN, and MPAN are typically
15   measured using a chromatograph followed by electron capture detectors or GC/ECD (e.g.,
16   Gaffney et al.,  1998), although other techniques such as FTIR could also be used. Field
17   measurements  are made using GC/ECD with a total uncertainty of ± 5 pptv +15% (Roberts
18   etal.,1998).
19          In the IMPROVE network and in the EPA's speciation network, particulate nitrate in the
20   PM2.5 size range is typically collected on nylon filters downstream of annular denuders coated
21   with a basic solution capable of removing acidic gases such as HN03, HN02, and S02. Filter
22   extracts are then analyzed by ion chromatography (1C) for nitrate, sulfate, and chloride. Nitrite
23   ions are also measured by this technique but their concentrations are almost always beneath
24   detection limits.  However, both of these networks measure nitrate only in the PM2.5 fraction.
25   Because of interactions with more highly acidic components on filter surfaces, there could be
26   volatilization of nitrate in PMio samples. These effects are minimized if separate aerosol size
27   fractions are collected, i.e., the more acidic PM2.s  and the more alkaline PMio-2.5 as in a
28   dichotomous sampler or multistage impactor.
29
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 1   AX2.8.4   Remote Sensing of Tropospheric NO2 Columns for Surface NOX
 2               Emissions and Surface NO2 Concentrations
 3          Table AX2.8-1 contains an overview of the three satellite instruments that are used
 4   retrieve tropospheric N02 columns from measurements of solar backscatter. All three
 5   instruments are in polar sun-synchronous orbits with global measurements in the late morning
 6   and early afternoon.  The spatial resolution of the measurement from SCIAMACHY is 7 times
 7   better than that from GOME (Ozone Monitoring Instrument), and that from OMI (Ozone
 8   Monitoring Instrument) is 40 times better than that from GOME.
 9          Figure AX2.8-1 shows tropospheric N02 columns retrieved from SCIAMACHY.
10   Pronounced enhancements are evident over major urban and industrial emissions.  The high
11   degree of spatial heterogeneity over the southwestern United States provides empirical evidence
12   that most of the tropospheric NO2 column is concentrated in the lower troposphere.
13   Tropospheric N02 columns are more sensitive to NOX in the lower troposphere than in the upper
14   troposphere (Martin et al., 2002). This sensitivity to NOX in the lower troposphere is due to the
15   factor of 25 decrease in the N02/N0 ratio from the surface to the upper troposphere (Bradshaw
16   et al., 1999) that is driven by the temperature dependence of the NO + 03 reaction.  Martin et al.
17   (2004a) integrated in situ airborne measurements of N02 and found that during summer the
18   lower mixed layer contains 75% of the tropospheric N02 column over Houston and Nashville.
19   However, it should be noted that these measurements are also sensitive to surface albedo and
20   aerosol loading.
21          The retrieval involves three steps: (1) determining total N02 line-of-sight (slant) columns
22   by spectral fitting of solar backscatter measurements, (2) removing the stratospheric columns by
23   using data from remote regions where the tropospheric contribution to the column is small, and
24   (3) applying an air mass factor (AMF) for the scattering atmosphere to convert tropospheric slant
25   columns into vertical columns. The retrieval uncertainty is determined by (1) and (2) over
26   remote regions where there is little tropospheric N02, and by (3) over regions in regions of
27   elevated tropospheric N02 (Martin et al., 2002; Boersma et al., 2004).
28          The paucity of in situ N02 measurements motivates the inference of surface N02
29   concentrations from satellite measurements of tropospheric N02 columns. This prospect would
30   take  advantage of the greater sensitivity  of tropospheric N02 columns to NOX in the lower
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               0
1
           8
10
     Figure AX2.8-1.     Tropospheric NOi columns (molecules NOi/ cm ) retrieved from the
                         SCIAMACHY satellite instrument for 2004-2005.
     Source: Martin et al. (2006).

 1   troposphere than in the upper troposphere as discussed earlier.  Tropospheric N02 columns show
 2   a strong correlation with in situ N02 measurements in northern Italy (Ordonez et al., 2006).
 3          Quantitative calculation of surface N02 concentrations from a tropospheric N02 column
 4   would require information on the relative vertical profile. Comparison of vertical profiles of
 5   N02 in a chemical transport model (GEOS-Chem) versus in situ measurements over and
 6   downwind of North America shows a high degree of consistency (Martin et al., 2004b; Martin
 7   et al., 2006), suggesting that chemical transport models could be used to infer the relationship
 8   between surface N02 concentrations and satellite observations of the tropospheric N02 column.
 9          However, the satellites carrying the spectrometer (GOME/SCIAMACHY/OMI) are in
10   near polar, sun-synchronous orbits. As a result, these measurements are made only once per day,
11   typically between about 10:00 to 11:00 a.m. or 1 p.m. local time, during a brief overflight. Thus
12   the utility of these measurements is limited as they would likely miss short-term features.
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 1   AX2.8.5   SAMPLING AND ANALYSIS FOR SO2
 2          Currently, ambient S02 is measured using instruments based on pulsed fluorescence.  The
 3   UV fluorescence monitoring method for atmospheric S02 was developed to improve upon the
 4   flame photometric detection (FPD) method for S02, which in turn had displaced the
 5   pararosaniline wet chemical method for SOz measurement. The pararosaniline method is still the
 6   FRM for atmospheric SOz, but is rarely used because of its complexity and slow response, even
 7   in its automated forms. Both the UV fluorescence and FPD methods are designated as FEMs by
 8   the EPA, but UV fluorescence has largely supplanted the FPD approach because of the UV
 9   method's inherent linearity, sensitivity, and the absence of consumables, such as the hydrogen
10   gas needed for the FPD method.
11          Basically, S02 molecules absorb ultraviolet (UV) light at one wavelength and emit UV
12   light at longer wavelengths.  This process is known as fluorescence, and involves the excitation
13   of the SOz molecule to a higher energy (singlet) electronic state. Once excited, the molecule
14   decays non-radiatively to a lower energy electronic state from which it then decays to the
15   original, or ground, electronic state by emitting a photon of light at a longer wavelength (i.e.,
16   lower energy) than the original, incident photon. The process can be summarized by the
17   following equations:
18                                   ow^nvj ^ow2                          (AX2-52)

19                                   S02*-»S02 +hv2                         (AX2-53)
20   where SO2* represents the excited state of SOz, h vi, and h v2 represent the energy of the
21   excitation and fluorescence photons, respectively, and hv2
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 1   optical bandwidth filter is placed in front of the PMT to filter out any stray light from the UV
 2   lamp. A lens is located between the filter and the PMT to focus the fluorescence onto the active
 3   area of the detector and optimize the fluorescence signal. The Detection Limit (DL) for a non-
 4   trace level S02 analyzer is 10 parts per billion (ppb) (Code of Federal Regulations, Volume 40,
 5   Part 53.23c). The S02 measurement method is subject to both positive and negative interference.
 6
 7   Sources of Positive Interference
 8          The most common source of interference is from other gases that fluoresce in a similar
 9   fashion to S02 when exposed to far UV radiation. The most significant of these are polycyclic
10   aromatic hydrocarbons (PAHs); of which naphthalene is a prominent example. Xylene is
11   another hydrocarbon that can cause interference.
12          Such compounds absorb UV photons and fluoresce in the region of the S02 fluorescence.
13   Consequently, any such aromatic hydrocarbons that are in the optical chamber can act as a
14   positive interference. To remove this source of interference, the high sensitivity S02 analyzers,
15   such as those to be used in the NCore network (U.S. Environmental Protection Agency, 2005),
16   have hydrocarbon scrubbers to remove these compounds from the sample  stream before the
17   sample air enters the optical chamber.
18          Another potential source of positive interference is nitric oxide (NO).  NO fluoresces in  a
19   spectral region that is close to the S02 fluorescence. However, in high sensitivity S02 analyzers,
20   the bandpass filter in front of the PMT is designed to prevent NO fluorescence from reaching the
21   PMT and being detected. Care must be exercised when using multicomponent calibration gases
22   containing both NO and S02 that the NO rejection ratio of the S02 analyzer is sufficient to
23   prevent NO  interference.  The most common source of positive bias  (as constrasted with positive
24   spectral interference) in high-sensitivity S02 monitoring is stray light reaching the optical
25   chamber. Since S02 can be electronically excited by a broad range of UV wavelengths, any
26   stray light with an appropriate wavelength that enters the optical chamber  can excite S02 in the
27   sample and increase the fluorescence signal.
28          Furthermore, stray light at the wavelength of the S02 fluorescence  that enters the optical
29   chamber may impinge on the PMT and increase the fluorescence signal. Several design features
30   are incorporated to minimize the stray light that enters the chamber.  These features include the
31   use of light filters, dark surfaces, and opaque tubing to prevent light from entering the chamber.
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 1          Luke (1997) reported the positive artifacts of a modified pulsed fluorescence detector
 2   generated by the co-existence of NO, CS2, and a number of highly fluorescent aromatic
 3   hydrocarbons such as benzene, toluene, o-xylene, m-xylene, p-xylene, m-ethyltoluene,
 4   ethylbenzene, and 1,2,4-trimethylbenzene. The positive artifacts could be reduced by using a
 5   hydrocarbon "kicker" membrane. At a flow rate of 300 standard cc min"1 and a pressure drop of
 6   645 torr across the kicker, the interference from ppm levels of many aromatic hydrocarbons was
 7   eliminated entirely.
 8          Nicks and Benner (2001) described a sensitive S02 chemiluminescence detector, which
 9   was based on a differential measurement where response from ambient S02 is determined by the
10   difference between air containing S02 and air scrubbed of S02 where both air samples contain
11   other detectable sulfur species, and the positive artifact could also be reduced through this way.
12
13   Sources of Negative Interference
14          Nonradiative deactivation (quenching) of excited S02 molecules can occur from
15   collisions with common molecules in air, including nitrogen, oxygen, and water. During
16   collisional quenching, the excited S02 molecule transfers energy, kinetically allowing the S02
17   molecule to return to the original lower energy state without emitting a photon.  Collisional
18   quenching results in a decrease in the S02 fluorescence and results in the underestimation of S02
19   concentration in the air sample. The concentrations of nitrogen and oxygen are constant in the
20   ambient air, so quenching from those species at a surface site is also constant, but the water
21   vapor content of air can vary. Luke (1997) reported that the response of the detector could be
22   reduced by about 7% and 15% at water vapor mixing ratios of 1 and 1.5 mole percent
23   (RH = 35 to 50% at 20-25 °C and 1 atm  for a modified pulsed fluorescence detector (Thermo
24   Environmental Instruments, Model 43s).  Condensation of water vapor in sampling lines must be
25   avoided, as it can absorb S02 from the sample air. The simplest approach to avoid condensation
26   is to heat sampling lines to a temperature above the expected dew point, and within a few
27   degrees of the controlled optical bench temperature. At very high S02 concentrations, reactions
28   between electronically excited S02 and ground state S02 to form S03 and SO might occur
29   (Calvert et al., 1978).  However, this possibility has not been examined.
30
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 1   Other Techniques for Measuring SO 2
 2          A more sensitive S02 measurement method than the UV-fluorescence method was
 3   reported by Thornton et al. (2002). Thornton et al (2002) reported an atmospheric pressure
 4   ionization mass spectrometer. The high measurement precision and instrument sensitivity were
 5   achieved by adding isotopically labeled SOz (34S1602) continuously to the manifold as an internal
 6   standard.  Field studies showed that the method precision was better than 10% and the limit of
 7   detection was less than 1 pptv for a sampling interval of Is.
 8          Sulfur Dioxide can be measured by LIF at around 220 nm (Matsumi et al., (2005).
 9   Because the laser wavelength is alternately tuned to an S02 absorption peak at 220.6 and bottom
10   at 220.2 nm, and the difference signal at the two wavelengths is used to extract the S02
11   concentration, the technique eliminates interference from either absorption or fluorescence by
12   other species and has high sensitivity (5 pptv in 60 sec). Sulfur Dioxide can also be measured by
13   the same DOAS instrument that can measure NOz.
14          Photoacoutsic techniques have been employed for S02 detection, but they generally have
15   detection limits suitable only for source monitoring (Gondal,  1997; Gondal and Mastromarino,
16   2001).
17          Chemical Ionization Mass Spectroscopy (CIMS) utilizes ionization via chemical
18   reactions in the gas phase to determine an unknown sample's mass spectrum and identity. High
19   sensitivity (10 ppt or better) has been achieved with uncertainty of ~ 15% when a charcoal
20   scrubber is used for zeroing and the sensitivity is measured with isotopically labeled 34S02
21   (Hanke et al., 2003; Huey et al., 2004; Hennigan et al., 2006).
22
23   AX2.8.6    Sampling and Analysis for Sulfate, Nitrate, and Ammonium
24
25   Sampling Artifacts
26          Sulfate,  nitrate, and ammonium are commonly present in PM2.5. Most PM2.5 samplers
27   have a size-separation device to separate particles so  that only those particles approximately
28   2.5 pm or less are collected on the sample filter.  Air  is drawn through the sample filter at a
29   controlled flow rate by a pump located downstream of the sample filter. The systems have two
30   critical flow rate components for the capture of fine particulate: (1) the flow of air through the
31   sampler must be at a flow rate that ensures that the size  cut at 2.5 pm occurs; and (2) the flow
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 1   rate must be optimized to capture the desired amount of particulate loading with respect to the
 2   analytical method detection limits.
 3          When using the system described above to collect sulfate, nitrate and particulate
 4   ammonium, sampling artifacts can occur because of:  (1) positive sampling artifact for sulfate,
 5   nitrate, and particulate ammonium due to chemical reaction; and (2) negative sampling artifact
 6   for nitrate and ammonium due to the decomposition and evaporation.
 7
 8   Sampling and Analysis Techniques
 9
10   Denuder-Filter Based Sampling and Analysis Techniques for Sulfate, Nitrate, and Ammonium
11          There are two major PM speciation ambient air-monitoring networks in the United States:
12   the Speciation Trend Network (STN), and the Interagency Monitoring of Protected Visual
13   Environments (IMPROVE) network. The current STN samplers include three filters: (1) Teflon
14   for equilibrated mass and elemental analysis including elemental sulfur; (2) a HNOs denuded
15   nylon filter for ion analysis including NOs and S04, (3) a quartz-fiber filter for elemental and
16   organic carbon. The IMPROVE sampler, which collects two 24-h samples per week,
17   simultaneously collects one sample of PMio  on a Teflon filter, and three samples of PM2.5 on
18   Teflon, nylon, and quartz filters.  PM2.5 mass concentrations are determined gravimetrically from
19   the PM2.s Teflon filter sample. The PM2.s Teflon filter sample is also used to determine
20   concentrations of selected elements. The PM2.s nylon filter sample, which is preceded by a
21   denuder to remove acidic gases, is analyzed to determine nitrate and sulfate aerosol
22   concentrations.  Finally, the PM2.5 quartz filter sample is analyzed for OC and EC using the
23   thermal-optical reflectance (TOR) method. The STN and the IMPROVE networks represent a
24   major advance in the measurement of nitrate, because the combination of a denuder  (coated with
25   either Na2COs or MgO) to remove HNOs vapor and a Nylon filter to adsorb HNOs vapor
26   volatilizing from the collected ammonium nitrate particles overcomes the loss of nitrate from
27   Teflon filters.
28          The extent to which sampling artifacts for particulate NH3+ have been adequately
29   addressed in the current networks is not clear.  Recently, new denuder-filter sampling systems
30   have been developed to measure sulfate, nitrate, and ammonium with an adequate correction of
31   ammonium sampling artifacts. The denuder-filter system, Chembcomb  Model 3500 speciation
32   sampling cartridge developed by Rupprecht & Patashnick Co, Inc. could be used to collect

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 1   nitrate, sulfate, and ammonium simultaneously. The sampling system contains a single-nozzle
 2   size-selective inlet, two honeycomb denuders, the aerosol filter and two backup filters (Keck and
 3   Wittmaack, 2005). The first denuder in the system is coated with 0.5% sodium carbonate and
 4   1% glycerol and collects acid gases such as HCL, SOz, HONO, and HNOs. The second denuder
 5   is coated with 0.5% phosphoric acid in methanol for collecting NHs.  Backup filters collect the
 6   gases behind denuded filters. The backup filters are coated with the same solutions as the
 7   denuders. A similar system based on the same principle was applied by Possanzini et al. (1999).
 8   The system contains two NaCl-coated annular denuders followed by other two denuders coated
 9   with NaCOs/glycerol and citric acid, respectively. This configuration was adopted to remove
10   HN03 quantitatively on the first NaCl denuder.  The third and forth denuder remove S02 and
11   NH3, respectively. A polyethylene cyclone and a two-stage filter holder containing three filters
12   is placed downstream  of the denuders.  Aerosol fine particles are collected on a Teflon
13   membrane. A backup nylon filter and a subsequent citric acid impregnated filter paper collect
14   dissociation products (HNOs and NHs) of ammonium nitrate evaporated from the filtered
15   particulate matter.
16          Several traditional and new methods could be used to quantify elemental S  collected on
17   filters: energy dispersive X-ray fluorescence, synchrotron induced X-ray fluorescence, proton
18   induced X-ray emission (PIXE), total reflection X-ray fluorescence, and scanning electron
19   microscopy. Energy dispersive X-ray fluorescence (EDXRF) (Method 10-3.3, U.S.
20   Environmental Protection Agency, 1997;  see 2004 PM CD for details) and PIXE are the most
21   commonly used methods. Since sample filters often contain very small amounts of particle
22   deposits, preference is given to methods that can accommodate small sample sizes  and require
23   little or no sample preparation or operator time after the samples  are placed into the analyzer.  X-
24   ray fluorescence (XRF) meets these needs and leaves the sample  intact after analysis so it can be
25   submitted for additional examinations by other methods as needed. To obtain the greatest
26   efficiency and sensitivity, XRF typically places the filters in a vacuum which may cause volatile
27   compounds (nitrates and organics) to evaporate. As a result, species that can volatilize such as
28   ammonium nitrate and certain organic compounds can be lost during the analysis.  The effects of
29   this volatilization are important if the PTFE filter is to be subjected to subsequent analyses of
30   volatile species.
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 1          Polyatomic ions such as sulfate, nitrate, and ammonium are quantified by methods such
 2    as ion chromatography (1C) (an alternative method commonly used for ammonium analysis is
 3    automated colorimetry). All ion analysis methods require a fraction of the filter to be extracted
 4    in deionized distilled water for sulfate and NaCOs/NaHCOs solution for nitrate and then filtered
 5    to remove insoluble residues prior to analysis. The extraction volume should be as small as
 6    possible to avoid over-diluting the solution and inhibiting the detection of the desired
 7    constituents at levels typical of those found in ambient PM2.s samples.  During analysis, the
 8    sample extract passes through an ion-exchange column which separates the ions in time for
 9    individual quantification, usually by an electroconductivity detector. The ions are identified by
10    their elution/retention times and are quantified by the conductivity peak area or peak height.
11          In a side-by-side comparison of two of the major aerosol monitoring techniques (Hains
12    et al., 2007), PM2.5 mass and major contributing species were well correlated among the  different
13    methods with r-values in excess of 0.8.  Agreement for mass, sulfate, OC, TC, and ammonium
14    was good while that for nitrate and BC was weaker. Based on reported uncertainties, however,
15    even daily concentrations of PM2.s mass and major contributing species were often significantly
16    different at the 95% confidence level. Greater values of PM2.5 mass and individual species were
17    generally reported from Speciation Trends Network methods than from the Desert Research
18    Institute Sequential Filter Samplers. These differences can only be partially accounted for by
19    known random errors.  The authors concluded that the current uncertainty estimates used in the
20    STN network may underestimate the actual uncertainty.
21
22    Positive Sampling Artifacts
23          The reaction of S02 (and other acid gases) with basic sites on glass fiber filters or with
24    basic coarse particles on the filter leads to the formation of sulfate (or other nonvolatile salts,
25    e.g., nitrate, chloride).  These positive artifacts lead to the overestimation of total mass, and
26    sulfate, and probably also nitrate concentrations. These problems were largely overcome by
27    changing  to quartz fiber or Teflon filters and by the separate collection of PM2.5.  However, the
28    possible reaction of acidic gases with basic coarse particles remains a possibility, especially with
29    PMio and PMio-2.s measurements. These positive artifacts could be effectively eliminated by
30    removing acidic gases in the sampling line with denuders coated with NaCl or Na2COs.
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 1          Positive sampling artifacts also occur during measurement of particulate NH4. The
 2    reaction of NHs with acidic particles (e.g. 2NHs + IH^SC^ - (NH^ZSC^), either during sampling
 3    or during transportation, storage, and equilibration could lead to an overestimation of particulate
 4    NH4 concentrations.  Techniques have been developed to overcome this problem: using a
 5    denuder to remove NHs during sampling and to protect the collected PM from NHs (Suh et al.,
 6    1992, 1994; Brauer et al., 1991; Koutrakis et al., 1988a,b; Keck and Wittmaack, 2006;
 7    Possanzini et al., 1999; Winberry et al., 1999). Hydrogen fluoride, citric acid, and phosphorous
 8    acids have been used as coating materials for the NH3 denuder. Positive artifacts for particulate
 9    NH4 can also be observed during sample handling due to contamination. No chemical analysis
10    method, no matter how accurate or precise, can adequately represent atmospheric concentrations
11    if the filters to which these methods are applied are improperly handled. Ammonia is emitted
12    directly from human sweat, breath and smoking. It can then react with acidic aerosols on the
13    filter to form ammonium  sulfate, ammonium bisulfate and ammonium nitrate if the filter was not
14    properly handled (Sutton et al., 2000).  Therefore, it is important to keep filters away from
15    ammonia sources, such as human breath, to minimize neutralization of the acidic compounds.
16    Also, when filters are handled, preferably in a glove box, the analyst should wear gloves that are
17    antistatic and powder-free to act as an effective contamination barrier.
18
19    Negative Sampling Artifact
20          Although sulfate is relatively stable on a Teflon filter, it is now well known that
21    volatilization losses of particulate nitrates occur during sampling.
22          For nitrate, the effect on the accuracy of atmospheric particulate measurements from
23    these volatilization losses is more significant for PM2.5 than for PMio. The FRM for PM2.5 will
24    likely suffer a loss of nitrates similar to that experienced with other simple filter collection
25    systems. Sampling artifacts resulting from the loss of particulate nitrates represents a significant
26    problem in areas such as southern California that experience high loadings of nitrates. Hering
27    and Cass (1999) discussed errors in PM2.s mass measurements due to the volatilization of
28    particulate nitrate.  They examined data from two field measurement campaigns that were
29    conducted in southern California:  (1) the Southern California Air Quality Study (SCAQS)
30    (Lawson, 1990) and (2) the 1986 CalTech study (Solomon et al.,  1992). In both these studies,
31    side-by-side sampling of PM2.5 was conducted.  One sampler collected particles directly onto a
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 1   Teflon filter.  The second sampler consisted of a denuder to remove gaseous HN03 followed by
 2   a nylon filter that absorbed the HN03 as it evaporated from NITXN03. In both studies, the
 3   denuder consisted of MgO-coated glass tubes (Appel et al., 1981). Fine particulate nitrate
 4   collected on the Teflon filter was compared to fine particulate nitrate collected on the denuded
 5   nylon filter. In both studies, the PM2.5 mass lost because of ammonium nitrate volatilization
 6   represented a significant fraction of the total PM2.5 mass. The fraction of mass lost was higher
 7   during summer than during fall (17% versus 9% during the SCAQS study, and 21% versus 13%
 8   during the CalTech study). In regard to percentage loss of nitrate, as opposed to percentage loss
 9   of mass discussed above, Hering and Cass (1999) found that the amount of nitrate remaining on
10   the Teflon filter samples was on average 28% lower than that on the denuded nylon filters.
11          Hering and Cass  (1999) also analyzed these data by extending the evaporative model
12   developed by Zhang and McMurry (1987).  The extended model used by Hering and Cass (1999)
13   takes into account the dissociation of collected particulate ammonium nitrate on Teflon filters
14   into HNOs and NHs via three mechanisms:  (1) the scrubbing of HNOs and NHs in the sampler
15   inlet (John et al.  (1988) showed that clean PMio inlet surfaces serve as an effective denuder for
16   HN03); (2) the heating of the filter substrate above ambient temperature by sampling; and (3) the
17   pressure drop across the Teflon filter.  For the sampling systems modeled, the flow-induced
18   pressure drop was measured to be less than 0.02 atm, and the corresponding change in vapor
19   pressure was 2%, so losses driven by pressure  drop were not considered to be significant in this
20   work.  Losses from Teflon filters were found to be higher during the summer than during the
21   winter, higher during the day compared to night, and reasonably consistent with modeled
22   predictions.
23          Finally, during the SCAQS (Lawson, 1990) study, particulate samples also were collected
24   using a Berner impactor and greased Tedlar substrates in size ranges from 0.05 to 10 pm in
25   aerodynamic diameter. The Berner impactor PM2.5 nitrate  values were much closer to those
26   from the denuded nylon filter than those from the Teflon filter, the impactor nitrate values being
27   -2% lower than the nylon filter nitrate for the fall measurements and -7% lower for the summer
28   measurements. When the impactor collection was compared to the Teflon filter collection for a
29   nonvolatile species (sulfate), the results were in agreement. Chang et al. (2000) discuss reasons
30   for reduced loss of nitrate from impactors.
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 1          Brook and Dann (1999) observed much higher nitrate losses during a study in which they
 2   measured particulate nitrate in Windsor and Hamilton, Ontario, Canada, by three techniques:
 3   (1) a single Teflon filter in a dichotomous sampler, (2) the Teflon filter in an annular denuder
 4   system (ADS), and (3) total nitrate including both the Teflon filter and the nylon back-up filter
 5   from the ADS.  The Teflon filter from the dichotomous sampler averaged only 13% of the total
 6   nitrate, whereas the Teflon filter from the ADS averaged 46% of the total nitrate.  The authors
 7   concluded that considerable nitrate was lost from the dichotomous sampler filters during
 8   handling, which included weighing and X-ray fluorescence (XRF) measurement in a vacuum.
 9          Kim et al. (1999) also examined nitrate-sampling artifacts by comparing denuded and
10   non-denuded quartz and nylon filters during the PMio Technical Enhancement Program (PTEP)
11   in the South Coast Air Basin of California. They observed negative nitrate artifacts (losses) for
12   most measurements; however, for a significant number of measurements, they observed positive
13   nitrate artifacts.  Kim et al. (1999) pointed out that random measurement errors make it difficult
14   to measure true amounts of nitrate loss.
15          Diffusion denuder samplers, developed primarily to measure particle strong acidity
16   (Koutrakis et al., 1988b, 1992), also can be used to study nitrate volatilization. Such techniques
17   were used to measure loss of particulate  nitrate from Teflon filters in seven U.S. cities (Babich
18   et al., 2000). Measurements were made  with two versions of the Harvard-EPA Annular Denuder
19   System  (HEADS). HN03 vapor was removed by a Na2C03-coated denuder.  Particulate nitrate
20   was the sum of nonvolatile nitrate collected on a Teflon filter and volatized nitrate collected on a
21   NazCOs-coated filter downstream of the Teflon filter (full HEADS) or on a Nylon filter
22   downstream of the Teflon filter (Nylon HEADS). It was found that the full HEADS (using a
23   Na2C03 filter) consistently underestimated the total particulate nitrate by approximately 20%
24   compared to the nylon HEADS.  Babich et al. (2000) found significant nitrate losses in
25   Riverside, CA; Philadelphia, PA; and Boston, MA, but not in Bakersfield, CA; Chicago, IL;
26   Dallas, TX; or Phoenix, AZ, where measurements were made only during the winter. Tsai and
27   Huang (1995) used a diffusion denuder to study the positive and negative artifacts on glass and
28   quartz filters. They found positive artifacts attributed to S02 and HN03 reaction with basic sites
29   on glass fibers and basic particles and negative artifacts attributed to loss of HNOs and HC1 due
30   to volatilization of N^NOs and NH4C1 and reaction of these species with acid sulfates.
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 1          Volatile compounds can also leave the filter after sampling and prior to filter weighing or
 2    chemical analysis. Losses of NOs, NH4, and Cl from glass and quartz-fiber filters that were
 3    stored in unsealed containers at ambient air temperatures for 2 to 4 weeks prior to analysis
 4    exceeded 50 percent (Witz et al., 1990).  Storing filters in sealed containers and under
 5    refrigeration will minimize these losses.
 6          Negative sampling artifacts due to decomposition and volatilization are also significant
 7    for particulate ammonium. Ammonium particulates, especially NH4 NS nitrate NH4 Cl are very
 8    sensitive to some environmental factors, such as temperature, relative humidity, acidity of
 9    aerosols, as well as to filter type (Spurny, 1999; Keck and Wittmaack, 2005). Any change in
10    these parameters during the sampling period influences the position of the equilibrium between
11    the particle phase and the gas phase. Keck and Wittmaack (2005) observed that at temperatures
12    below OC,  acetate-nitrate, quartz fiber, and Teflon filters could properly collect particulate NH4
13    NHs and Cl.  At temperature above OC, the salts were lost from quartz fiber and Teflon filters,
14    more so the higher the temperature and with no significant difference between quartz fiber and
15    Teflon filters. The salts were lost completely from denuded quartz fiber filters above about 20C,
16    and from  non-undenuded quartz fiber and Teflon filters above about 25C. It is anticipated that
17    current sampling techniques  underestimate NH4  concentrations due to the volatilization of NH4,
18    but fine particle mass contains  many acidic compounds and consequently, a fraction of
19    volatilized NH4 (in the form  of NHs) can be  retained on a PTFE filter by reaction with the acid
20    compounds.  Therefore, it is  reasonable to assume that NH4 loss will be less than the nitrate loss.
21    Techniques have been applied  to particulate ammonium sampling to correct particulate
22    ammonium concentrations due to evaporation: a backup filter coated with hydrofluoric acids,
23    citric acid, or phosphorous acids, is usually introduced to absorb the  evaporated ammonium (as
24    ammonia); the total ammonium concentration is the sum of the particle phase ammonium
25    collected on the Teflon filter and the ammonia concentration collected on the backup filter.
26
27    Other Measurement Techniques
28
29    Nitrate
30          An integrated collection and vaporization cell was developed by Stolzenburg and Hering
31    (2000) that provides automated, 10-min resolution monitoring of fine-particulate nitrate.  In this
32    system, particles are collected by a humidified impaction process and analyzed in place by flash

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 1   vaporization and chemiluminescent detection of the evolved NOX. In field tests in which the
 2   system was collocated with two FRM samplers, the automated nitrate sampler results followed
 3   the results from the FRM, but were offset lower.  The system also was collocated with a HEADS
 4   and a SASS speciation sampler (MetOne Instruments). In all these tests, the automated sampler
 5   was well correlated to other samplers with slopes near 1 (ranging from 0.95 for the FRM to 1.06
 6   for the HEADS) and correlation coefficients ranging from 0.94 to 0.996. During the Northern
 7   Front Range Air Quality Study in Colorado (Watson et al., 1998), the automated nitrate monitor
 8   captured the 12-min variability in fine-particle nitrate concentrations with a precision of
 9   approximately ±0.5 pg/m3 (Chow et al., 1998).  A comparison with denuded filter
10   measurements followed by ion chromatographic (1C)  analysis  (Chow and Watson,  1999) showed
11   agreement within ± 0.6 pg/m3 for most of the measurements, but exhibited a discrepancy of a
12   factor of two  for the elevated nitrate periods. More recent intercomparisons took place during
13   the 1997 Southern California Ozone Study (SCOS97) in Riverside, CA. Comparisons with
14   14 days of  24-h denuder-filter sampling gave a correlation coefficient of R2 = 0.87 and showed
15   no significant bias (i.e., the regression slope is not significantly different from 1). As currently
16   configured, the system has a detection limit of 0.7 pg/m3 and a precision of 0.2 pg/m3.
17
18   Sulfate
19          Continuous methods for the quantification of aerosol sulfur compounds first remove
20   gaseous sulfur (e.g., S02, H2S) from the sample stream by a  diffusion tube denuder followed by
21   the analysis of particulate sulfur (Cobourn et al., 1978; Durham et al., 1978; Huntzicker et al.,
22   1978; Mueller and Collins, 1980;  Tanner et al., 1980). Another approach is to measure total
23   sulfur and gaseous sulfur separately by alternately removing particles from the sample stream.
24   Particulate  sulfur  is obtained as the difference between the total and gaseous sulfur (Kittelson
25   et al., 1978).  The total sulfur content is measured by a flame photometric detector  (FPD) by
26   introducing the sampling stream into a fuel-rich, hydrogen-air  flame (e.g., Stevens  et al., 1969;
27   Farwell and Rasmussen, 1976) that reduces sulfur compounds  and measures the intensity of the
28   chemiluminescence from electronically excited sulfur molecules  (S2*). Because the formation
29   of S2* requires two sulfur atoms,  the intensity of the chemiluminescence is theoretically
30   proportional to the square of the concentration of molecules  that contain a single sulfur atom.
31   In practice, the exponent is between 1 and  2 and depends on the sulfur compound being analyzed
32   (Dagnall et al., 1967; Stevens et al., 1971).  Calibrations are  performed using both particles and

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 1   gases as standards. The FPD can also be replaced by a chemiluminescent reaction with ozone
 2   that minimizes the potential for interference and provides a faster response time (Benner and
 3   Stedman, 1989, 1990). Capabilities added to the basic system include in situ thermal analysis
 4   and sulfuric acid speciation (Cobourn et al., 1978; Huntzicker et al., 1978; Tanner et al., 1980;
 5   Cobourn and Husar, 1982). Sensitivities for particulate sulfur as low as 0.1 pg/m3, with time
 6   resolution ranging from 1 to 30 min, have been reported. Continuous measurements of
 7   particulate sulfur content have also been obtained by on-line XRF analysis with resolution of
 8   30 min or less (Jaklevic et al., 1981).  During a field-intercomparison study of five different
 9   sulfur instruments, Camp et al. (1982) reported four out of five FPD systems agreed to within
10   ±5% during a 1-week sampling period.
11
12
13   AX2.9    POLICY RELEVANT BACKGROUND CONCENTRATIONS OF
14              NITROGEN AND SULFUR OXIDES
15          Background concentrations of nitrogen and sulfur oxides used for purposes of informing
16   decisions about NAAQS are referred to as Policy Relevant  Background (PRB) concentrations.
17   Policy Relevant Background concentrations are those concentrations that would occur in the
18   United States in the absence of anthropogenic emissions in  continental North America (defined
19   here as the United States, Canada, and Mexico). Policy Relevant Background concentrations
20   include contributions from natural sources everywhere in the world and from anthropogenic
21   sources outside these three countries.  Background levels so defined facilitate separation of
22   pollution levels that can be controlled by U.S. regulations (or through international agreements
23   with neighboring countries) from levels that are generally uncontrollable by the United States.
24   EPA assesses risks to human health and environmental effects from NOz and SOz levels in
25   excess of PRB concentrations.
26          Contributions to PRB concentrations include natural emissions  of NOz, SOz, and
27   photochemical reactions involving natural emissions of reduced nitrogen and sulfur compounds,
28   as well as their long-range transport from outside North America.  Natural sources of N02 and  its
29   precursors include biogenic emissions, wildfires, lightning, and the stratosphere. Natural sources
30   of reduced nitrogen compounds, mainly NHs, include biogenic emissions and wildfires. Natural
31   sources of reduced sulfur species include anaerobic microbial activity in wetlands and volcanic
32   activity. Volcanos and biomass burning are the major natural source of SOz.  Biogenic

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 1   emissions from agricultural activities are not considered in the formation of PRB concentrations.
 2   Discussions of the sources and estimates of emissions are given in Section AX2.6.2.
 3
 4   Analysis of PRB Contribution to Nitrogen and Sulfur oxide Concentrations and Deposition
 5                 over the United States
 6          The MOZART-2 global model of tropospheric chemistry (Horowitz et al., 2003) is used
 7   to diagnose the PRB contribution to nitrogen and sulfur oxide concentrations, as well as to total
 8   (wet plus dry)  deposition. The model setup for the present-day simulation has been published in
 9   a series of papers from a recent model intercomparison (Dentener et al., 2006a,b; Shindell et al.,
10   2006; Stevenson et al., 2006; van Noije et al., 2006). MOZART-2 is driven by National Center
11   for Environmental Prediction meteorological fields and IIASA 2000 emissions at a resolution of
12   1.9° x  1.9° with 28 sigma levels in the vertical, and it includes gas- and aerosol phase chemistry.
13   Results shown in Figures AX2.9-1 to AX2.9-5 are for the meteorological year 2001.  Note that
14   color images are available on the web. An additional "policy relevant background" simulation
15   was conducted in which continental North American anthropogenic emissions were set to zero.
16          We first examine the role of PRB in contributing to N02 and S02 concentrations in
17   surface air.  Figure AX2.9-1 shows the annual mean N02  concentrations in surface air in the base
18   case simulation (top panel) and the PRB simulation (middle panel), along with the percentage
19   contribution of the background to the total base case N02 (bottom panel). Maximum
20   concentrations in the base case simulation occur along the Ohio River Valley and in the
21   Los Angeles basin. While present-day concentrations are often above 5 ppbv, PRB is less than
22   300 pptv over most of the continental United States, and less than 100 pptv in the eastern United
23   States.  The distribution of PRB (middle panel of Figure AX2.9-1) largely reflects the
24   distribution of soil NO emissions, with some local enhancements due to biomass burning such as
25   is seen in western Montana. In the northeastern United States, where present-day N02
26   concentrations are highest, PRB contributes <1% to the total.
27          The spatial pattern of present-day S02 concentrations over the United States is similar to
28   that of N02, with highest concentrations (>5 ppbv) along the Ohio River valley (upper panel
29   Figure AX2.9-2).  Background S02 concentrations are orders of magnitude smaller, below
30   10 pptv over much of the United States (middle panel of Figure AX2.9-2). Maximum PRB
31   concentrations of S02 are 30 ppt.  In the Northwest where there are geothermal sources of S02,
32   the contribution of PRB to total S02 is 70 to 80%.  However, with the exception of the West

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                                        Total
                                      100°W
                                 ao°w
                                     Background
                 25°N
                         120°W
                   100°W
ao°w
                             Percent Background Contribution
Figure AX2.9-1.
Annual mean concentrations of NOi (ppbv) in surface air over the
United States in the present-day (upper panel) and policy relevant
background (middle panel) MOZART-2 simulations.  The bottom
panel shows the percentage contribution of the background to the
present-day concentrations. Please see text for details.
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                                       Total
                       iao°W
               so°w
                                    Background
                       iao°w
                            Percent Background Contribution
                       120°W
 ioo°w
so°w
Figure AX2.9-2.    Same as Figure AX2.9-1 but for SO2 concentrations.
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                                      Total
                                    Background
                       120°W
 100°W
                           Percent Bacl^round Contribution
Figure AX2.9-3.    Same as for Figure AX2.9-1 but for wet and dry deposition of HNO:
                                                                  -2 -K
                                         '3?
                  NH4NO3, NOX, HO2NO2, and organic nitrates (mg N m  y  ).
September 2007
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                                      Total
                       lao'W
 IQCfW
                                    Background
                            Percent Background Contribution
                       13D°W
 100°W
Figure AX2.9-4.    Same as Figure AX2.9-1 but for SOX deposition (SO2 + SO4)
                  (mg S m V1).
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                    MOZART-2 SOIL NO.
                                                            GEOS-Chem SOIL NO.
        50°N
        45°N
        40°N
        35°N
        30°N
        25°N
                        S3°N
                        45°N
                        40°N
                        35°N
                        30°N
              1ZO°W
                         1QO°W
                                    SO°W
                                                      130°W
                                         100CW
        50°N
        40°N
        35°N
        30°N
        25°N
                  MOZART-2 Surface NOx JUL
              12D°W
 100°W
so°w
                        50°N
                        45°N
                        40°N
                        35°N
                        30°N
                        Z5°N
                                   GEOS-Chem Surface NO..
                                                      120°W
                                                                 100°W
                                                                            ao°w
    Figure AX2.9-5.
July mean soil NO emissions (upper panels; 1 x 10 9 molecules cm 2 s1)
and surface PRB NOX concentrations (lower panels; pptv) over the
United States from MOZART-2 (left) and GEOS-Chem (right) model
simulations in which anthropogenic Os precursor emissions were set
to zero in North America.
1   Coast where volcanic SOz emissions enhance PRB concentrations, the PRB contributes <1% to
2   present-day S02 concentrations in surface air (bottom panel Figure AX2.9-2).
3          The spatial pattern of N0y (defined here as HN03, NH4N03, NOX, H02N02, and organic
4   nitrates) wet and dry deposition is shown in Figure AX2.9-3.  Figure AX2.9-3 (upper panel)
5   shows that highest values are found in the eastern United States in and downwind of the Ohio
6   River Valley. The pattern of nitrogen deposition in the PRB simulation (Figure AX2.9-3, middle
7   panel), however, shows maximum deposition centered over Texas and in the Gulf Coast region,
8   reflecting a combination of nitrogen emissions from lightning in the Gulf region, biomass
9   burning in the Southeast, and from microbial activity in soils (maximum in central Texas and
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 1   Oklahoma). The bottom panel of Figure AX2.9-3 shows that the PRB contribution to nitrogen
 2   deposition is less than 20% over the eastern United States, and typically less than 50% in the
 3   western United States where N0y deposition is low (25-50 mg N rrf2 yr"1).
 4          Present-day SOX (SOz + SC^ =) deposition is largest in the Ohio River Valley, likely due
 5   to coal-burning power plants in that region, while background deposition is typically at least an
 6   order of magnitude smaller (Figure AX2.9-4).  Over the eastern United States, the background
 7   contribution to SOX deposition is <10%, and it is even smaller (<1%) where present-day SOX
 8   deposition is highest. The contribution of PRB to sulfate deposition is highest in the western
 9   United States (>20%) because of geothermal sources of S02 and oxidation of dimethyl sulfide in
10   the surface of the eastern Pacific.
11          Thus far, the discussion has focused on results from the MOZART-2 tropospheric
12   chemistry model.  In Figure AX2.9-5, results from MOZART-2 are compared with those from
13   another tropospheric chemistry model, GEOS-Chem (Bey et al., 2001), which was previously
14   used to diagnose PRB Os (Fiore et al.,  2003; U.S. Environmental Protection Agency, 2006). In
15   both models, the surface PRB NOX concentrations tend to mirror the distribution of soil NO
16   emissions, which are highest in the Midwest.  The higher soil NO emissions in GEOS-Chem (by
17   nearly a factor of 2)  as compared to MOZART-2 reflect different assumptions regarding the
18   contribution to soil NO emissions largely through fertilizer, since GEOS-Chem total soil NO
19   emissions are actually higher than MOZART-2 (0.07 versus 0.11 Tg N) over the United States in
20   July.  Even with the larger PRB soil NO emissions, surface NOX concentrations in GEOS-Chem
21   are typically below 500 pptv.
22          It is instructive to also consider measurements of SOz at relatively remote monitoring
23   sites, i.e., site located in sparsely populate areas not subject to obvious local sources of pollution.
24   Berresheim et al. (1993) used a type of atmospheric pressure ionization mass spectrometer
25   (APIMS) at Cheeka Peak, WA (48.30N 124.62W, 480 m asl), in April 1991 during a field study
26   for DMS oxidation products.  Sulfur Dioxide concentrations ranged between 20 and 40 pptv.
27   Thornton et al. (2002) have also used an APIMS with an isotopically labeled internal standard to
28   determine background S02 levels.  S02 concentrations of 25 to 40 pptv were observed in
29   northwestern Nebraska in October 1999 at 150m above ground using the NCAR C-130
30   (Thornton, unpublished data).  These data are comparable to remote central south Pacific
31   convective boundary layer SOz (Thornton et al., 1999).

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 1          Volcanic sources of S02 in the UNITED STATES are limited to the Pacific Northwest,
 2   Alaska, and Hawaii.  Since 1980 the Mt. St. Helens volcano in Washington Cascade Range
 3   (46.20 N, 122.18 W,  summit 2549 m asl) has been a variable source of S02. Its major impact
 4   came in the explosive eruptions of 1980, which primarily affected the northern part of the
 5   mountain west of the UNITED STATES. The Augustine volcano near the mouth of the Cook
 6   Inlet in southwestern Alaska (59.363 N, 153.43 W, summit 1252 m asl) has had S02 emissions
 7   of varying extents since its last major eruptions in 1986. Volcanoes in  the Kamchatka peninsula
 8   of eastern region of Siberian Russia do not particularly impact the surface concentrations in the
 9   northwestern NA.  The most serious impact in the United States from volcanic S02 occurs on the
10   island of Hawaii. Nearly continuous venting of S02 from Mauna Loa and Kilauea produce S02
11   in such large amounts so that > 100 km downwind of the island S02 concentrations can exceed
12   30 ppbv (Thornton and Bandy, 1993).  Depending on the wind direction the west coast of Hawaii
13   (Kona region) has had significant impacts from S02 and acidic sulfate aerosols for the past
14   decade. Indeed, S02 levels in Volcanoes National Park, HI exceeded the  3-h and the 24-h
15   NAAQS in 2004 -2005.  The area's design value is 0.6 ppm for the 3-h, and 0.19 ppm for the
16   24-h NAAQS (U.S. Environmental Protection Agency, 2006).
17          Overall, the background contribution to nitrogen and sulfur oxides over the United States
18   is relatively small,  except for S02 in areas where there is volcanic activity.
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     TABLE AX2.3-1.  ATMOSPHERIC LIFETIMES OF SULFUR DIOXIDE AND
   REDUCED SULFUR SPECIES WITH RESPECT TO REACTION WITH OH, NO3,
  	AND CL RADICALS	
                          OH                      NO3                      Cl
Compound
SO2
CH3-S-CH3
H2S
CS2
DCS
CH3-S-H
CH3-S-S-CH3
k x 1012
1.6
5.0
4.7
1.2
0.0019
33
230
T
7.2d
2.3d
2.2 d
9.6 d
17y
8.4 h
1.2 h
k x 1012
NA
1.0
NA
<0.0004
<0.0001
0.89
0.53
T

1.1 h

>116d
> 1-3 y
1.2 h
2.1 h
k x 1012
NA
400
74
<0.004
<0.0001
200
NA
T

29 d
157 d
NR
NR
58 d

 Notes:
 NA = Reaction rate coefficient not available. NR = Rate coefficient too low to be relevant as an atmospheric loss mechanism.
 Rate coefficients were calculated at 298 K and 1 atmosphere.
 y = year, d = day. h = hour.  OH = 1 x 106/cm3; N03 = 2.5 x 108/cm3; Cl = 1 x 103/cm3.
 1 Rate coefficients were taken from JPL Chemical Kinetics Evaluation No. 14 (JPL, 2003).
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  TABLE AX2.4-la. RELATIVE CONTRIBUTIONS OF VARIOUS REACTIONS TO
  THE TOTAL S(IV) OXIDATION RATE WITHIN A SUNLIT CLOUD, 10 MINUTES
	AFTER CLOUD FORMATION	
	Reaction	% of Totala	% of Totalb	
 Gas Phase
 OH + S02                              3.5                      3.1
 Aqueous Phase
 03 + HS03"                             0.6                      0.7
 03 + S032~                              7.0                      8.2
 H202 + S03"                            78.4                     82.1
 CH3OOH + HS03"                       0.1                      0.1
 HN04 + HS03~                          9.0                      4.4
 HOONO + HS03"                        <0.1                     <0.1
 HS05~ + HS03~                          1.2                      <0.1

 HS05~ + Fe2+	0.6	
 a In the absence of transition metals.
 b In the presence of iron and copper ions.

Source: Adapted from Warneck (1999).
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     TABLE AX2.4-lb. RELATIVE CONTRIBUTIONS OF VARIOUS GAS AND
  AQUEOUS PHASE REACTIONS TO AQUEOUS NITRATE FORMATION WITHIN
	A SUNLIT CLOUD, 10 MINUTES AFTER CLOUD FORMATION	
	Reaction	% of Totala	% of Total b	
 Gas Phase
 OH + N02 + M                       57.7                       67.4
 Aqueous Phase
 N205g + H20                          8.1                       11.2
 N03 + Cr                           <0.1                       0.1
 N03 + HSO;f                         0.7                        1.0
 N03 + HCOO~                        0.6                       0.8
 HN04 + HS03~                       31.9                       20.5
 HOONO + NOs"                       0.8                       <0.1
 03 + N02"	
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 TABLE AX2.6-1. EMISSIONS OF NITROGEN OXIDES, AMMONIA, AND SULFUR
                DIOXIDE IN THE UNITED STATES IN 2002
2002 Emissions (Tg/year)
Source Category
TOTAL ALL SOURCES
FUEL COMBUSTION TOTAL
FUEL COMB. ELEC. UTIL.
Coal
Bituminous
Subbituminous
anthracite & lignite
Other
Oil
Residual
Distillate
Gas
Natural
Process
Other
Internal Combustion
FUEL COMBUSTION INDUSTRIAL
Coal
Bituminous
Subbituminous
anthracite & lignite
Other
Oil
Residual
Distillate
Other
Gas
Natural
Process
Other
Other
wood/bark waste
liquid waste
Other
Internal Combustion
NO,1

23.19
9.11
5.16
4.50
2.90
1.42
0.18
<0.01
0.14
0.13
0.01
0.30
0.29
0.01
0.05
0.17
3.15
0.49
0.25
0.07
0.04
0.13
0.19
0.09
0.09
0.01
1.16
0.92
0.24
<0.01
0.16
0.11
0.01
0.04
1.15
NH3

4.08
0.02
<0.01
<0.01




<0.01


<0.01


<0.01
<0.01
<0.01
<0.01




<0.01



<0.01



<0.01



<0.01
S02

16.87
14.47
11.31
10.70
8.04
2.14
0.51

0.38
0.36
0.01
0.01


0.21
0.01
2.53
1.26
0.70
0.10
0.13
0.33
0.59
0.40
0.16
0.02
0.52



0.15



0.01
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  TABLE AX2.6-1 (cont'd). EMISSIONS OF NITROGEN OXIDES, AMMONIA, AND
             SULFUR DIOXIDE IN THE UNITED STATES IN 2002
2002 Emissions (Tg/year)
FUEL COMB. OTHER
Commercial/Institutional Coal
Commercial/Institutional Oil
Commercial/Institutional Gas
Misc. Fuel Comb. (Except Residential)
Residential Wood
Residential Other
distillate oil
bituminous/subbituminous coal
Other
INDUSTRIAL PROCESSES TOTAL
CHEMICAL & ALLIED PRODUCT MFC
Organic Chemical Mfg
Inorganic Chemical Mfg
sulfur compounds
Other
Polymer & Resin Mfg
Agricultural Chemical Mfg
ammonium nitrate/urea mfg.
Other
Paint, Varnish, Lacquer, Enamel Mfg
Pharmaceutical Mfg
Other Chemical Mfg
METALS PROCESSING
Non-Ferrous Metals Processing
Copper
Lead
Zinc
Other
Ferrous Metals Processing
Metals Processing NEC
NO,1
0.80
0.04
0.08
0.25
0.03
0.03
0.36
0.06
0.26
0.04
1.10
0.12
0.02
0.01


<0.01
0.05


0.00
0.00
0.03
0.09
0.01




0.07
0.01
NH3
<0.01
<0.01
<0.01
<0.01
<0.01





0.21
0.02
<0.01
<0.01


<0.01
0.02
<0.01
0.02


<0.01
<0.01
<0.01




<0.01
<0.01
S02
0.63
0.16
0.28
0.02
0.01
<0.01
0.16
0.15
<0.01
<0.01
1.54
0.36
0.01
0.18
0.17
0.02
<0.01
0.05


0.00
0.00
0.12
0.30
0.17
0.04
0.07
0.01
<0.01
0.11
0.02
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  TABLE AX2.6-1 (cont'd). EMISSIONS OF NITROGEN OXIDES, AMMONIA, AND
             SULFUR DIOXIDE IN THE UNITED STATES IN 2002
2002 Emissions (Tg/year)
PETROLEUM & RELATED INDUSTRIES
Oil & Gas Production
natural gas
Other
Petroleum Refineries & Related Industries
fluid catalytic cracking units
Other
Asphalt Manufacturing
OTHER INDUSTRIAL PROCESSES
Agriculture, Food, & Kindred Products
Textiles, Leather, & Apparel Products
Wood, Pulp & Paper, & Publishing Products
Rubber & Miscellaneous Plastic Products
Mineral Products
cement mfg
glass mfg
Other
Machinery Products
Electronic Equipment
Transportation Equipment
Miscellaneous Industrial Processes
SOLVENT UTILIZATION
Degreasing
Graphic Arts
Dry Cleaning
Surface Coating
Other Industrial
Nonindustrial
Solvent Utilization NEC
NO,1
0.16
0.07


0.05


0.04
0.54
0.01
<0.01
0.09
<0.01
0.42
0.24
0.01
0.10
<0.01
<0.01
<0.01
0.01
0.01
<0.01
<0.01
<0.01
<0.01
<0.01
<0.01
<0.01
NH3
<0.01
<0.01


<0.01
<0.01
<0.01

0.05
<0.01
<0.01
<0.01
<0.01
<0.01



<0.01
<0.01

0.05
<0.01
<0.01
<0.01
<0.01
<0.01
<0.01


S02
0.38
0.11
0.11
0.01
0.26
0.16
0.07
0.01
0.46
0.01
<0.01
0.10
<0.01
0.33
0.19

0.09
<0.01
<0.01
<0.01
0.02
<0.01
<0.01
<0.01
<0.01
<0.01
<0.01


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  TABLE AX2.6-1 (cont'd). EMISSIONS OF NITROGEN OXIDES, AMMONIA, AND
             SULFUR DIOXIDE IN THE UNITED STATES IN 2002
2002 Emissions (Tg/year)
STORAGE & TRANSPORT
Bulk Terminals & Plants
Petroleum & Petroleum Product Storage
Petroleum & Petroleum Product Transport
Service Stations: Stage II
Organic Chemical Storage
Organic Chemical Transport
Inorganic Chemical Storage
Inorganic Chemical Transport
Bulk Materials Storage
WASTE DISPOSAL & RECYCLING
Incineration
Industrial
Other
Open Burning
Industrial
land clearing debris
Other
POTW
Industrial Waste Water
TSDF
Landfills
Industrial
Other
Other
NO,1
<0.01
<0.01
<0.01
<0.01
<0.01
<0.01
0.01
<0.01
<0.01
0.01
0.17
0.06


0.10



<0.01
<0.01
<0.01
<0.01


<0.01
NH3
<0.01
<0.01
<0.01
<0.01

<0.01

<0.01

<0.01
0.14
<0.01


<0.01



0.14
<0.01
<0.01
<0.01


<0.01
S02
0.01
<0.01
<0.01
<0.01
<0.01
<0.01
<0.01
<0.01
<0.01
<0.01
0.03
0.02

<0.01
<0.01
<0.01

<0.01
<0.01
<0.01
<0.01
<0.01
<0.01
<0.01
<0.01
September 2007
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  TABLE AX2.6-1 (cont'd). EMISSIONS OF NITROGEN OXIDES, AMMONIA, AND
             SULFUR DIOXIDE IN THE UNITED STATES IN 2002
2002 Emissions (Tg/year)
TRANSPORTATION TOTAL
HIGHWAY VEHICLES
Light-Duty Gas Vehicles & Motorcycles
light-duty gas vehicles
Motorcycles
Light-Duty Gas Trucks
light-duty gas trucks 1
light-duty gas trucks 2
Heavy-Duty Gas Vehicles
Diesels
heavy-duty diesel vehicles
light-duty diesel trucks
light-duty diesel vehicles
OFF-HIGHWAY
Non-Road Gasoline
Recreational
Construction
Industrial
lawn & garden
Farm
light commercial
Logging
airport service
railway maintenance
recreational marine vessels
Non-Road Diesel
Recreational
Construction
Industrial
lawn & garden
Farm
light commercial
Logging
airport service
railway maintenance
recreational marine vessels
NOX 1 NH3
12.58 0.32
8.09 0.32
2.38 0.20
2.36
0.02
1.54 0.10
1.07
0.47
0.44 <0.01
3.73 <0.01
3.71
0.01
0.01
4.49 <0.01
0.23 <0.01
0.01
0.01
0.01
0.10
0.01
0.04
<0.01
<0.01
<0.01
0.05
1.76 <0.01
0.00
0.84
0.15
0.05
0.57
0.08
0.02
0.01
<0.01
0.03
S02
0.76
0.30
0.10
0.10
0.00
0.07
0.05
0.02
0.01
0.12



0.46
0.01










0.22










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  TABLE AX2.6-1 (cont'd). EMISSIONS OF NITROGEN OXIDES, AMMONIA, AND
                  SULFUR DIOXIDE IN THE UNITED STATES IN 2002
             2002 Emissions (Tg/year)
       NOX
NH,
 SO,
 Aircraft
 Marine Vessels
   Diesel
   residual oil
   Other
 Railroads
 Other
   liquefied petroleum gas
   compressed natural gas
 MISCELLANEOUS
 Agriculture & Forestry
   agricultural crops
   agricultural livestock
 Other Combustion
 Health Services
 Cooling Towers
 Fugitive Dust
 Other
 Natural Sources
        0.09
        1.11
        1.11
        0.98
        0.32
        0.29
        0.04
        0.39
       <0.01
<0.01
 3.53
 3.45
<0.01
 2.66
 0.08
                  0.01
                  0.18
 0.05
 0.00
 0.10
<0.01
                                          0.10
        3.10
 0.03
 1 Emissions are expressed in terms of N02.
 2 Estimate based on Guenther et al. (2000).
Source: U.S. Environmental Protection Agency (2006).
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         TABLE AX2.8-1.  SATELLITE INSTRUMENTS USED TO RETRIEVE
                            TROPOSPHERIC NO2 COLUMNS.


Instrument
GOME

SCIAMACHY

OMI



Coverage
1995-2002

2002-

2004-


Typical U.S.
Measurement Time
10:30-11:30 AM

10:00-11:00 AM

12:45-1:45 PM

Typical
Resolution
(km)
320x40

30x60

13x24


Return Time
(days)1
3

6

1


Instrument
Overview
Burrows et al.
(1999)
Bovensmann
etal. (1999)
Levelt et al.
(2006)
  Return time is reported here for cloud free conditions. Note that due to precession of the satellite's orbit, return measurements are close to
 but not made over the same location. In practice, clouds decrease observation frequency by a factor of 2.
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 i        AX3. CHAPTER 3 ANNEX - A FRAMEWORK FOR
 2          MODELING HUMAN EXPOSURES TO  SO2 AND
 3                       RELATED AIR POLLUTANTS
 4
 5
 6   AX3.1   INTRODUCTION:  CONCEPTS, TERMINOLOGY, AND
 7             OVERALL SUMMARY
 8          Predictive (or prognostic) exposure modeling studies1, specifically focusing on 862,
 9   could not be identified in the literature, though, often, statistical (diagnostic) analyses have been
10   reported using data obtained in various field exposure studies. However, existing prognostic
11   modeling systems for the assessment of inhalation exposures can in principle be directly applied
12   to, or adapted for, SO2 studies; specifically, such systems include APEX, SHEDS, and
13   MENTOR-1 A, to be discussed in the following sections. Nevertheless, it should be mentioned
14   that such applications will be constrained by data limitations, such as the degree of ambient
15   concentration characterization (e.g., concentrations at the local level) and quantitative
16   information on indoor sources and sinks.
17          Predictive models of human exposure to ambient air pollutants such as 862 can be
18   classified and differentiated based upon a variety of attributes.  For example, exposure models
19   can be classified as:
20   •      models of potential (typically maximum) outdoor exposure versus models of actual
21          exposures (the latter including locally modified microenvironmental exposures, both
22          outdoor and indoor),
23   •      Population Based Exposure Models (PBEM) versus Individual Based Exposure Models
24          (ffiEM),
25   •      deterministic versus probabilistic (or statistical) exposure models,
26   •      observation-driven versus mechanistic air quality models (see Section AX3.4 for
27          discussions about the construction, uses and limitations of this class of mathematical
28          models.
     1 i.e. assessments that start from emissions and demographic information and explicitly consider the physical and
      chemical processes of environmental and microenvironmental transport and fate, in conjunction with human
      activities, to estimate inhalation intake and uptake.

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 1           Some points should be made regarding terminology and essential concepts in exposure
 2    modeling, before proceeding to the overview of specific developments reported in the current
 3    research literature:
 4           First, it must be understood that there is significant variation in the definitions of many of
 5    the terms used in the exposure modeling literature; indeed, the science of exposure modeling is a
 6    rapidly evolving field and the development of a standard and commonly accepted terminology is
 7    an ongoing process (see, e.g., WHO, 2004).
 8           Second, it should also be mentioned that, very often, procedures that are called exposure
 9    modeling, exposure estimation, etc. in the scientific literature, may in fact refer to only a sub-set
10    of the complete set of steps or components required for a comprehensive exposure assessment.
11    For example, certain self-identified exposure modeling studies focus solely on refining the sub-
12    regional or local spatio-temporal dynamics of pollutant concentrations (starting from raw data
13    representing monitor observations or regional grid-based model estimates). Though not
14    exposure studies per se, such efforts have value and are included in the discussion of the next
15    sub-section, as they provide potentially useful tools that can be used in a complete exposure
16    assessment. On the other hand, formulations that are self-identified as exposure models but
17    actually focus only on  ambient air quality predictions,  such as chemistry-transport models, are
18    not included in the discussion that follows.
19           Third, the process of modeling human exposures to ambient pollutants (traditionally
20    focused on ozone) is very often identified explicitly with population-based modeling, while
21    models describing the  specific mechanisms affecting the exposure of an actual individual (at
22    specific locations) to an air contaminant (or to a group of co-occurring gas and/or aerosol phase
23    pollutants) are usually  associated with studies focusing specifically on indoor air chemistry
24    modeling.
25           Finally, fourth, the concept of microenvironments, introduced in earlier sections of this
26    document, should be clarified further,  as it is critical in developing procedures for exposure
27    modeling. In the past,  microenvironments have typically been defined as individual or aggregate
28    locations (and  sometimes even as activities taking place within a location) where a homogeneous
29    concentration of the pollutant is encountered.  Thus a microenvironment has often been
30    identified with an ideal (i.e.  perfectly mixed) compartment of classical compartmental modeling.
31    More recent and general definitions view the microenvironment as a control volume, either

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 1    indoors or outdoors, that can be fully characterized by a set of either mechanistic or
 2    phenomenological governing equations, when appropriate parameters are available, given
 3    necessary initial and boundary conditions. The boundary conditions typically would reflect
 4    interactions with ambient air and with other microenvironments. The parameterizations of the
 5    governing equations generally include the information on attributes of sources and sinks within
 6    each microenvironment. This type of general definition allows for the concentration within a
 7    microenvironment to be non-homogeneous (non-uniform), provided its spatial profile and
 8    mixing properties can be fully predicted or characterized. By adopting this definition, the
 9    number of microenvironments used in a study is kept manageable, but variability in
10    concentrations in each of the microenvironments can still be taken into account.
11    Microenvironments typically used to determine exposure include indoor residential
12    microenvironments, other indoor locations (typically occupational microenvironments), outdoors
13    near roadways, other outdoor locations, and in-vehicles. Outdoor locations near roadways are
14    segregated from other outdoor locations (and can be further classified into street canyons,
15    vicinities of intersections, etc.) because emissions from automobiles alter local concentrations
16    significantly compared to background outdoor levels. Indoor residential microenvironments
17    (kitchen, bedroom, living room, etc. or aggregate home microenvironment) are typically
18    separated from other indoor locations because of the time spent there and potential differences
19    between the residential environment and the work/public environment.
20          Once the actual individual and relevant activities and locations (for Individual Based
21    Modeling), or the sample population and associated spatial (geographical) domain (for
22    Population Based Modeling) have been defined along with the temporal framework of the
23    analysis (time period and resolution), the comprehensive modeling of individual/population
24    exposure to SO2 (and related pollutants) will in general require seven steps (or components, as
25    some of them do not have to be performed in sequence) that are listed below. This list represents
26    a composite based on approaches and frameworks described in the literature over the last twenty -
27    five years (Ott, 1982; Ott, 1985; Lioy, 1990; U.S. Environmental Protection Agency, 1992;
28    Georgopoulos and Lioy, 1994; U.S. Environmental Protection Agency, 1997; Price et  al., 2003;
29    Georgopoulos et al., 2005; WHO, 2005; U.S. Environmental Protection Agency, 2006a;
30    Georgopoulos and Lioy, 2006)  as well  on the structure of various inhalation exposure models
31    (NEM/pNEM, HAPEM, SHEDS, REHEX, EDMAS, MENTOR, ORAMUS, APEX, AIRPEX,

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 1   AIRQUIS, etc., to be discussed in the following section) that have been used in the past or in

 2   current studies to specifically assess inhalation exposures. Figure AX3.1-1, adapted from

 3   Georgopoulos et al. (2005), schematically depicts the sequence of steps involved that are

 4   summarized here (and further discussed in the following sub-sections).
i.a. Emissions: NEI (NET, NTI), state; Processing with SMOKE,
EMS-HAP, MOBILE/MOVES, NONROAD, FAAED, BEIS, etc.
i.b. Meteorology: NWS, NCDC; Modeling MMS, RAMS, CALMET
i.e. Land Use/ Land Cover, Topography: NLDC (USGS), etc.
*
Estimate background ;
levels of air pollutants j
through I
a. multivariate spatio- |
temporai analysis of |
monitor data j
b. emissions-based air ^^
quality modeling \
(with regional, j
grid-based models: 1
ModelS-3/ CMAQ, CAM* j
and REMSAD) I
* A
J . Estimate local outdoor
> - pollutant levels that
characterize Hie ambient air of
an administrative unit (such as
census tract) or a conveniently
defined grid through
a. spatiotemporal statistical
analysis of monitor data
b. application of urban scale
model at high resolution
c. subgrld (e.g. plume-in-grfd)
modeling
d. data/ model assimilation

-u; Develop database of ]
- :' individual subjects \
attributes (residence ft I
work location, housing >
characteristics, age, \
gender, race, income, etc.) j-
a. collect study-specific ]"*
information j
b. supplement with \
available relevant local, j
regional, and national ]
demographic j
information j
1 Develop activity event
"*> {or exposure event)
sequences for each individual
of the study for the exposure
period
a. collect study-specific
information
b. supplement with other
available data
c. organize time-activity
database in format
compatible with CHAD
t t
/ Study-speciflc survey / Study-specific survey
(also US Census, (or default from
US Housing Survey) CHAD, NHAPS)

^
s
— *
ii.a. Emissions: EMS-HAP
ii.b. Local Meteorology — Local
Effects; RAMS, FLUENT
*
Estimate levels and
... temporal profiles of
pollutants in various
microenvironments (streets,
residences, offices, restaurants,
vehicles, etc.) through
a. regression of observational
data
b. simple linear mass balance
c. lumped (nonlinear) uE
gas/aerosol chemistry models
d« combined chemistry 8t CFD
(DNS, LES, RANS) models
*
Calculate appropriate
Inhalation rates for the
members of the sample
population, combining the
physiological attributes of the
study subjects and the
activities pursued during the
individual exposure events
t
/ ICRP and Other
Physiological & METS
Databases

— — \
1
^
• i

Calculate ™|P Biologically
exposures/ i based
intakes target tissue
dose modeling
A
> *
j


     Figure AX3.1-1.
             Schematic description of a general framework identifying the
             processes (steps or components) involved in assessing inhalation
             exposures and doses for individuals and populations. In general
             terms, existing comprehensive exposure modeling systems such as
             SHEDS, APEX, and MENTOR-1A follow this framework.
     Source: Figure adapted with modifications from Georgopoulos et al. (2005).
 5
 6
 9
10
1.     Estimation of the background or ambient levels of both 862 and related
      pollutants.  This is done through either (or a combination of):
      a.     multivariate spatio-temporal analysis of fixed monitor data, or
      b.     emissions-based, photochemical, air quality modeling (typically with a
             regional, grid-based model such as Models-3/CMAQ or CAMx) applied in
             a coarse resolution mode.
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 1          2.     Estimation of local outdoor pollutant levels of both 862 and related pollutants.
 2                 These levels could typically characterize the ambient air of either an
 3                 administrative unit (such as a census tract, a municipality, a county, etc.) or a
 4                 conveniently defined grid cell of an urban scale air quality model.  Again, this
 5                 may involve either (or a combination of):
 6                 a.      spatio-temporal statistical analysis of monitor data, or
 7                 b.      application of an urban multi-scale, grid based model (such as CMAQ or
 8                        CAMx) at its highest resolution (typically around 2-4 km), or
 9                 c.      correction of the estimates of the regional model using some scheme that
10                        adjusts for observations and/or for subgrid chemistry and mixing
11                        processes.
12
13          3.     Characterization of relevant attributes of the individuals or populations under
14                 study (residence and work locations, occupation, housing data, income, education,
15                 age, gender, race, weight, and other physiological characteristics). For Population
16                 Based Exposure Modeling (PBEM) one can either:
17                 a.      select a fixed-size sample population of virtual individuals in a way that
18                        statistically reproduces essential demographics (age, gender, race,
19                        occupation, income, education) of the administrative population unit used
20                        in the assessment (e.g., a sample of 500 people is typically used to
21                        represent the demographics of a given census tract, whereas a sample of
22                        about 10,000 may be  needed to represent the demographics of a county),
23                        or
24                 b.      divide the population-of interest into a set of cohorts representing selected
25                        subpopulations where the cohort is defined by characteristics known to
26                        influence exposure.
27
28          4.     Development of activity event (or exposure event) sequences for each member of
29                 the sample population (actual or virtual) or for each cohort for the exposure
30                 period.  This could utilize:
31                 a.      study-specific information, if available
32                 b.      existing databases based on composites of questionnaire information from
33                        past studies
34                 c.      time-activity databases, typically in a format compatible with U.S.
35                        Environmental Protection Agency's Consolidated Human Activity
36                        Database (CHAD  - McCurdy et al., 2000)
37
38          5.     Estimation of levels and temporal profiles of both SC>2 and related pollutants in
39                 various outdoor and indoor microenvironments such as street canyons, roadway
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 1                 intersections, parks, residences, offices, restaurants, vehicles, etc.  This is done
 2                 through either:
 3                 a.      linear regression of available observational data sets,
 4                 b.      simple mass balance models (with linear transformation and sinks) over
 5                        the volume (or a portion of the volume) of the microenvironment,
 6                 c.      lumped (nonlinear) gas or gas/aerosol chemistry models, or
 7                 d.      detailed combined chemistry and Computational Fluid Dynamics
 8                        modeling.
 9
10          6.     Calculation of appropriate inhalation rates for the members of the sample
11                 population, combining the physiological attributes of the (actual or virtual) study
12                 subjects and the activities pursued during the individual exposure events.
13
14          7.     Calculation of target tissue dose through biologically based modeling estimation
15                 (specifically, respiratory dosimetry modeling in the case of SC>2 and related
16                 reactive pollutants) if sufficient information is available.
17
18          Implementation of the above framework for comprehensive exposure modeling has
19    benefited significantly from recent advances and expanded availability of computational
20    technologies such as Relational  Database Management Systems (RDBMS) and Geographic
21    Information Systems (GIS) (Purushothaman and Georgopoulos, 1997, 1999a,b; Georgopoulos
22    et al., 2005).
23          In fact, only relatively recently comprehensive, predictive, inhalation exposure modeling
24    studies for ozone, PM, and various air toxics, have attempted to address/incorporate all the
25    components of the general framework described here. In practice, the majority of past exposure
26    modeling studies have either incorporated only subsets of these components or treated some of
27    them in a simplified manner, often focusing on the importance of specific factors affecting
28    exposure.  Of course, depending on the objective of a particular modeling study,  implementation
29    of only a limited number of steps may be necessary. For example, in a regulatory setting, when
30    comparing the relative effectiveness of emission control strategies, the focus can be on expected
31    changes  in ambient levels (corresponding to those observed at NAAQS monitors) in relation to
32    the density of nearby populations. The outdoor levels of pollutants, in conjunction with basic
33    demographic information, can thus be used to calculate upper bounds of population exposures
34    associated with ambient air (as opposed to total exposures that would include contributions from
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 1   indoor sources) useful in comparing alternative control strategies. Though the metrics derived
 2   would not be quantitative indicators of actual human exposures, they can serve as surrogates of
 3   population exposures associated with outdoor air, and thus aid in regulatory decision making
 4   concerning pollutant standards and in studying the efficacy of emission control strategies. This
 5   approach has been used in studies performing comparative evaluations of regional and local
 6   emissions reduction strategies in the eastern United States (e.g., Purushothaman and
 7   Georgopoulos, 1997; Georgopoulos et al., 1997a; Foley et  al., 2003).
 8
 9
10   AX3.2   POPULATION EXPOSURE MODELS: THEIR EVOLUTION
11             AND CURRENT  STATUS
12          Existing comprehensive inhalation exposure models consider the trajectories of
13   individual human subjects (actual or virtual), or of appropriately defined cohorts, in space and
14   time as sequences of exposure events. In these sequences,  each event is defined by time, a
15   geographic location, a microenvironment, and the activity of the subject. U.S. Environmental
16   Protection Agency offices (OAQPS and NERL) have supported the most comprehensive efforts
17   in developing models implementing this general concept (see, e.g., Johnson, 2002), and these
18   efforts have resulted in the NEM/pNEM (National Exposure Model and Probabilistic National
19   Exposure Model - Whitfield et al., 1997), HAPEM (Hazardous Air Pollutant Exposure Model -
20   Rosenbaum, 2005), SHEDS (Simulation of Human Exposure and Dose System - Burke et al.,
21   2001), APEX (Air Pollutants Exposure model - U.S. Environmental Protection Agency,
22   2006b,c), and MENTOR (Modeling Environment for Total Risk studies - Georgopoulos et al.,
23   2005; Georgopoulos and Lioy, 2006) families of models. European efforts have produced some
24   formulations with similar general attributes as the above U.S. models but, generally, involving
25   simplifications in some of their components. Examples of European models addressing
26   exposures to photochemical oxidants (specifically ozone) include the AirPEx (Air Pollution
27   Exposure) model (Freijer et al., 1998), which basically replicates the pNEM approach and has
28   been applied to the Netherlands, and the AirQUIS (Air Quality Information System) model
29   (Clench-Aas et al., 1999).
30          The NEM/pNEM,  SHEDS, APEX, and MENTOR-1A (MENTOR for One-Atmosphere
31   studies) families of models provide exposure estimates defined by concentration and breathing
32   rate for each individual exposure event, and then average these estimates over periods typically

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 1   ranging from one h to one year. These models allow simulation of certain aspects of the

 2   variability and uncertainty in the principal factors affecting exposure.  An alternative approach is

 3   taken by the HAPEM family of models that typically provide annual average exposure estimates

 4   based on the quantity of time spent per year in each combination of geographic locations and

 5   microenvironments. The NEM, SHEDS, APEX, and MENTOR-type models are therefore

 6   expected to be more appropriate for pollutants with complex chemistry such as SC>2, and could

 7   provide useful information for enhancing related health assessments.

 8

 9          More specifically, regarding the consideration of population demographics and activity

10   patterns:

11          1.     pNEM divides the population of interest into representative cohorts based on the
12                 combinations of demographic characteristics (age, gender, and employment),
13                 home/work district, residential cooking fuel and replicate number, and then
14                 assigns an activity diary record from CHAD (Consolidated Human Activities
15                 Database) to  each cohort according to demographic characteristic, season, day-
16                 type (weekday/weekend)  and temperature.
17          2.     HAPEM6 divides the population of interest into demographic groups based on
18                 age, gender and race, and then for each demographic group/day-type
19                 (weekday/weekend) combination, selects multiple activity patterns randomly
20                 (with replacement) from CHAD and combines them to find the averaged annual
21                 time allocations for group members in each census tract for different day types.
22          3.     SHEDS, APEX, and MENTOR-1A generate population demographic files, which
23                 contain a user-defined number of person records for each census tract of the
24                 population based on proportions of characteristic variables (age, gender,
25                 employment, and housing) obtained from the population of interest, and then
26                 assign a matching activity diary record from CHAD to each individual record of
27                 the population based on the characteristic variables.  It should be mentioned that,
28                 in the formulations of these models, workers may commute from one census tract
29                 to another census tract for work. So, with the specification of commuting
30                 patterns, the variation of exposure concentrations due to commuting between
31                 different census tracts can be captured.
32
33          The essential attributes of the pNEM, HAPEM, APEX,  SHEDS, and MENTOR-1A

34   models are summarized in Table AX3.2-1.

35          The conceptual approach originated by the SHEDS models was modified and expanded

36   for use in the development of MENTOR-1 A (Modeling Environment for Total Risk - One

37   Atmosphere).  Flexibility was incorporated into this modeling system, such  as the option of

38   including detailed indoor chemistry and other relevant microenvironmental  processes, and


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 1    providing interactive linking with CHAD for consistent definition of population characteristics
 2    and activity events (Georgopoulos et al., 2005).
 3          NEM/pNEM implementations have been extensively applied to ozone studies in the
 4    1980s and 1990s. The historical evolution of the pNEM family of models of OAQPS started
 5    with the introduction of the first NEM model in the 1980s (Biller et al., 1981).  The first such
 6    implementations of pNEM/Os in the 1980s used a regression-based relationship to estimate
 7    indoor ozone concentrations from outdoor concentrations. The second generation of pNEM/Os
 8    was developed in 1992 and included a simple mass balance model to estimate indoor ozone
 9    concentrations. A report by Johnson et al. (2000) describes this version of pNEM/Os and
10    summarizes the results of an initial application of the model to 10 cities.  Subsequent
11    enhancements to pNEM/O3 and its input databases included revisions to the methods used to
12    estimate equivalent ventilation rates, to determine commuting patterns, and to adjust ambient
13    ozone levels to simulate attainment of proposed NAAQS. During the mid-1990s, the
14    Environmental Protection Agency applied updated versions of pNEM/Os to three different
15    population groups in selected cities:  (1) the general population of urban residents, (2) outdoor
16    workers, and (3) children who tend to spend more time outdoors than the average child. This
17    version of pNEM/Os used a revised probabilistic mass balance model to determine ozone
18    concentrations over one-h periods in indoor and in-vehicle microenvironments (Johnson, 2001).
19          In recent years, pNEM has been replaced by (or "evolved to") the Air Pollution Exposure
20    Model (APEX).  APEX differs from earlier pNEM models in that the probabilistic features of the
21    model are incorporated into a Monte Carlo framework (Langstaff, 2007; U.S. Environmental
22    Protection Agency, 2006b,c).  Like SHEDS and MENTOR-1 A, instead of dividing the
23    population-of-interest into a set of cohorts, APEX generates individuals as if they were being
24    randomly sampled from the population. APEX provides each generated individual with a
25    demographic profile that specifies values  for all parameters required by the model.  The values
26    are selected from distributions and databases that are specific to the age, gender,  and other
27    specifications stated in the demographic profile. The Environmental Protection Agency has
28    applied APEX to the study of exposures to ozone and other criteria pollutants; APEX can be
29    modified and used for the estimation of SC>2 exposures, if required.
30          Reconfiguration of APEX for use  with SC>2 or other pollutants would require significant
31    literature review, data analysis, and modeling efforts.  Necessary  steps include determining

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 1    spatial scope and resolution of the model; generating input files for activity data, air quality and
 2    temperature data; and developing definitions for microenvironments and pollutant-
 3    microenvironment modeling parameters (penetration and proximity factors, indoor source
 4    emissions rates, decay rates, etc.) (ICF Consulting, 2005).  To take full advantage of the
 5    probabilistic capabilities of APEX, distributions of model input parameters should be used
 6    wherever possible.
 7
 8
 9    AX3.3    CHARACTERIZATION OF AMBIENT CONCENTRATIONS OF
10              SO2 AND RELATED AIR POLLUTANTS
11          As mentioned earlier, background and regional outdoor concentrations of pollutants over
12    a study domain may be estimated through emissions-based mechanistic modeling, through
13    ambient data based modeling, or through a combination of both. Emissions-based models
14    calculate the spatio-temporal fields of the pollutant concentrations using precursor emissions and
15    meteorological conditions as inputs and using numerical representations of transformation
16    reactions to drive outputs.  The ambient data based models typically calculate spatial or spatio-
17    temporal distributions of the pollutant through the use of interpolation schemes, based on either
18    deterministic or stochastic models for allocating monitor station observations to the nodes of a
19    virtual regular grid covering the region of interest.  The geostatistical technique of kriging
20    provides various standard procedures for generating an  interpolated spatial distribution for a
21    given time, from data at a set of discrete points.  Kriging approaches were evaluated by
22    Georgopoulos et al. (Georgopoulos et al., 1997b) in relation to the calculation of local ambient
23    ozone concentrations for exposure assessment purposes, using either monitor observations or
24    regional/urban photochemical model outputs.  It was found that kriging is severely limited by the
25    nonstationary character of the concentration patterns of reactive pollutants; so the advantages this
26    method has in  other fields of geophysics do not apply here.  The above study showed that the
27    appropriate semivariograms had to be hour-specific, complicating the automated reapplication of
28    any purely spatial interpolation over an extended time period.
29          Spatio-temporal distributions of pollutant concentrations such as ozone, PM, and various
30    air toxics have alternatively been obtained using methods of the Spatio-Temporal Random Field
31    (STRF) theory (Christakos and Vyas, 1998a,b).  The STRF approach interpolates monitor data in
32    both space and time simultaneously.  This method can thus analyze information on temporal

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 1   trends which cannot be incorporated directly in purely spatial interpolation methods such as
 2   standard kriging. Furthermore, the STRF method can optimize the use of data which are not
 3   uniformly sampled in either space or time.  STRF was further extended within the Bayesian
 4   Maximum Entropy (BME) framework and applied to ozone interpolation studies (Christakos and
 5   Hristopulos, 1998;  Christakos and Kolovos, 1999; Christakos, 2000). It should be noted that
 6   these studies formulate an over-arching scheme for linking air quality with population dose and
 7   health effects; however, they  are limited by the fact that they do not include any
 8   microenvironmental effects. MENTOR has incorporated STRF/BME methods as one of the
 9   steps for performing a comprehensive analysis of exposure to ozone and PM (Georgopoulos
10   etal.,2005).
11          The issue of subgrid variability (SGV) from the perspective of interpreting and evaluating
12   the outcomes of grid-based, multiscale, photochemical air quality simulation models is discussed
13   in Ching et al. (2006), who suggest a framework that can provide for qualitative judgments on
14   model performance based on  comparing observations to the grid predictions and its SGV
15   distribution. From the perspective of Population Exposure Modeling, the most feasible/practical
16   approach for treating subgrid  variability of local  concentrations is probably through 1) the
17   identification and proper characterization of an adequate number of outdoor microenvironments
18   (potentially related to different types of land use  within the urban area as well as to proximity to
19   different types of roadways) and 2) then, concentrations in these microenvironments will have to
20   be adjusted from the corresponding local background ambient concentrations through either
21   regression of empirical data or various types of local atmospheric dispersion/transformation
22   models. This is discussed further in the next subsection.
23
24
25   AX3.4   CHARACTERIZATION OF MICROENVIRONMENTAL
26             CONCENTRATIONS
27          Once the background  and local ambient spatio-temporal concentration patterns have been
28   derived, microenvironments that can represent either outdoor or indoor settings when individuals
29   come in contact with the contaminant of concern (e.g., 802) must be characterized. This process
30   can involve modeling of various local sources and sinks, and interrelationships between ambient
31   and microenvironmental concentration levels.  Three general approaches have been used in the
32   past to model microenvironmental concentrations:

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 1    •      Empirical (typically linear regression) fitting of data from studies relating ambient/local
 2          and microenvironmental concentration levels to develop analytical relationships.
 3    •      Parameterized mass balance modeling over, or within, the volume of the
 4          microenvironment.  This type of modeling has ranged from very simple formulations, i.e.
 5          from models assuming ideal (homogeneous) mixing within the microenvironment (or
 6          specified portions of it) and only linear physicochemical transformations (including
 7          sources and sinks), to models incorporating analytical solutions of idealized dispersion
 8          formulations (such as Gaussian plumes), to models that take into account aspects of
 9          complex multiphase chemical and physical interactions and nonidealities in mixing.
10    •      Detailed Computational Fluid Dynamics (CFD) modeling of the outdoor or indoor
11          microenvironment, employing either a Direct Numerical Simulation (DNS) approach, a
12          Reynolds Averaged Numerical Simulation (RANS) approach, or a Large Eddy
13          Simulation (LES) approach, the latter typically for outdoor situations (see, e.g., Milner
14          et al., 2005; Chang and Meroney, 2003; Chang, 2006).
15
16          Parameterized mass balance modeling is the approach currently preferred for exposure
17    modeling for populations. As discussed earlier, the simplest microenvironmental setting
18    corresponds to a homogeneously mixed compartment, in contact with possibly both
19    outdoor/local environments as well as other microenvironments. The air quality of this idealized
20    microenvironment is affected mainly by the following processes:
21          a.     Transport processes: These can include advection/convection and dispersion that
22                 are affected by local processes and obstacles such as vehicle induced turbulence,
23                 street canyons, building structures, etc.
24          b.     Sources and sinks: These can include local outdoor emissions, indoor emissions,
25                 surface deposition, etc.
26          c.     Transformation processes:  These can include local outdoor as well as indoor gas
27                 and aerosol phase chemistry, such as formation of secondary organic and
28                 inorganic aerosols.
29
30          Exposure modeling also requires information on activity patterns to determine time spent
31    in various microenvironments and estimates of inhalation rates to characterize dose. The next
32    two subsections describe recent work done in these areas.
33

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 1    AX3.4.1   Characterization of Activity Events
 2          An important development in inhalation exposure modeling has been the consolidation of
 3    existing information on activity event sequences in the Consolidated Human Activity Database
 4    (CHAD) (McCurdy, 2000; McCurdy et al., 2000).  Indeed, most recent exposure models are
 5    designed (or have been re-designed) to obtain such information from CHAD which incorporates
 6    24-h time/activity data developed from numerous surveys.  The surveys include probability-
 7    based recall studies conducted by Environmental Protection Agency and the California Air
 8    Resources Board, as well as real-time diary studies conducted in individual U.S. metropolitan
 9    areas using both probability-based and volunteer subject panels. All ages of both genders are
10    represented in CHAD.  The data for each subject consist of one or more days of sequential
11    activities, in which each activity is defined by start time, duration, activity type (140 categories),
12    and microenvironment classification (110 categories). Activities vary from one min to one h in
13    duration, with longer activities being subdivided into clock-hour durations to facilitate exposure
14    modeling.  A distribution of values for the ratio of oxygen uptake rate  to body mass (referred to
15    as metabolic equivalents or METs) is provided for each activity type listed in CHAD. The forms
16    and parameters of these distributions were determined through an extensive review of the
17    exercise and nutrition literature.  The primary source of distributional  data was Ainsworth et al.
18    (1993), a compendium developed specifically to facilitate the coding of physical activities and to
19    promote comparability across studies.
20
21    AX3.4.2   Characterization of Inhalation  Intake and Uptake
22          Use of the information in CHAD provides a rational way for incorporating realistic
23    intakes into exposure models by linking inhalation  rates to  activity information. As mentioned
24    earlier, each cohort of the pNEM-type models, or each (virtual or actual) individual of the
25    SHEDS, MENTOR, APEX, and HAPEM4 models, is assigned an exposure event sequence
26    derived from activity diary data.  Each exposure event is typically defined by a start time, a
27    duration, assignments to a geographic location and microenvironment, and an indication of
28    activity level.  The most recent versions of the above models have defined activity levels using
29    the activity classification coding  scheme incorporated into  CHAD. A  probabilistic module
30    within these models converts the activity classification code of each exposure event to an energy
31    expenditure rate, which in turn is converted into an estimate of oxygen uptake rate. The oxygen


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 1    uptake rate is then converted into an estimate of total ventilation rate (yE)5 expressed in liters
 2    min"1. Johnson (2001) reviewed briefly the physiological principles incorporated into the
 3    algorithms used in pNEM to convert each activity classification code to an oxygen uptake rate
 4    and describes the additional steps required to convert oxygen uptake to VE.
 5          McCurdy (1997a,b, 2000) has recommended that the ventilation rate should be estimated
 6    as a function of energy expenditure rate.  The energy expended by an individual during a
 7    particular activity can be expressed as EE = (MET)(RMR) in which EE is the average energy
 8    expenditure rate (kcal min"1) during the activity and RMR is the resting metabolic rate of the
 9    individual expressed in terms of number of energy units expended per unit of time (kcal min"1).
10    MET (the metabolic equivalent of tasks) is a ratio specific to the activity and is dimensionless. If
11    RMR is specified for an individual, then the above equation requires only an activity-specific
12    estimate of MET to produce an estimate of the energy expenditure rate for a given activity.
13    McCurdy et al. (2000) developed distributions of MET for the activity classifications appearing
14    in the CHAD database.
15
16
17    AX3.5   CONCLUDING COMMENTS
18          An issue that should be mentioned in closing is that of evaluating comprehensive
19    prognostic exposure modeling  studies, for either individuals or populations, with field data.
20    Although databases that would be adequate for performing a comprehensive evaluation are not
21    expected to be available any time soon, there have been a number of studies,  reviewed in earlier
22    sections of this Chapter, that can be used to start building the necessary information base.  Some
23    of these studies report field observations of personal, indoor, and outdoor levels and have also
24    developed simple semi-empirical personal exposure models that were parameterized using the
25    observational data and regression techniques.
26          In conclusion, though existing inhalation exposure modeling systems have evolved
27    considerably in recent years, limitations of available modeling methods and data in relation to
28    potential 862 studies should be taken into account. Existing prognostic modeling systems for
29    inhalation exposure can in principle be directly applied to, or adapted for, 862 studies; APEX,
30    SHEDS, and MENTOR-1A are candidates. However, such applications would be constrained by
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1   data limitations such as ambient characterization at the local scale and by lack of quantitative
2   information for indoor sources and sinks.
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  TABLE AX3.2-1. THE ESSENTIAL ATTRIBUTES OF THE PNEM, HAPEM, APEX,
                        SHEDS, AND MENTOR-1A

Exposure Estimate

Characterization of
the High-End
Exposures
Typical Spatial
Scale/Resolution


Temporal
Scale/Resolution
Population Activity
Patterns Assembly


Microenvironment
Concentration
Estimation







Microenvironmental
(ME) Factors


Specification of
Indoor Source
Emissions
Commuting Patterns
Exposure Routes

Potential Dose
Calculation
Physiologically
Based Dose
Variability/
Uncertainty
pNEM
Hourly
averaged
Yes


Urban
areas/Census
tract level

A yr/one h

Top-down
approach


Non-steady-
state and
steady-state
mass balance
equations (hard-
coded)




Random
samples from
probability
distributions
Yes (gas-stove,
tobacco
smoking)
Yes
Inhalation

Yes

No

Yes

HAPEM
Annual averaged

No


Ranging from
urban to national/
Census tract
level
A yr/one h

Top-down
approach


Linear
relationship
method (hard-
coded)






Random samples
from probability
distributions

Available; set to
zero in HAPEM6

Yes
Inhalation

No

No

No

APEX
Hourly averaged

Yes


Urban
area/Census tract
level

A yr/one h

Bottom-up
"person-
oriented"
approach
Non-steady-state
mass balance and
linear regression
(flexibility of
selecting
algorithms)




Random samples
from probability
distributions

Yes (multiple
sources defined
by the user)
Yes
Inhalation

Yes

No

Yes

SHEDS
Activity event
based
Yes


Urban
areas/Census
tract level

A yr/event based

Bottom-up
"person-
oriented"
approach
Steady -state
mass balance
equation
(residential) and
linear regression
(non-residential)
(hard-coded)



Random samples
from probability
distributions

Yes (gas-stove,
tobacco smoking,
other sources)
Yes
Inhalation

Yes

Yes

Yes

MENTOR-1A
Activity event
based
Yes


Multiscale/
Census tract level


A yr/activity event
based time step
Bottom-up
"person-oriented"
approach

Non-steady-state
mass balance
equation with
indoor air
chemistry module
or regression
methods
(flexibility of
selecting
algorithms)
Random samples
from probability
distributions

Yes (multiple
sources defined by
the user)
Yes
Multiple
(optional)
Yes

Yes

Yes (Various
"Tools")
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12          G. (2003) Construction of a comprehensive chemical exposure framework using person
13          oriented modeling. Prepared for:  The Exposure Technical Implementation Panel,
14          American Chemistry Council; contract #1338. Annandale, VA: The LifeLine Group.
15          Available: http://www.thelifelinegroup.org/lifeline/docs.htm [6 March, 2007].
16   Purushothaman, V.; Georgopoulos, P. G. (1997) Computational tools to aid the estimation and
17          visualization of potential human exposure to ozone. In: Proceedings of the Air & Waste
18          Management Association Specialty Conference on Computing in Environmental
19          Resource Management; December, 1996; Research Triangle Park, NC. Pittsburgh, PA:
20          A&WMA; VIP-68; pp. 17-28.
21   Purushothaman, V.; Georgopoulos, P. G. (1999a) Evaluation of regional emissions control
22          strategies for ozone utilizing population exposure metrics: a new GIS-based approach
23          applied to the July 1995 episode over the OTAG domain. Piscataway, NJ: Environmental
24          and Occupational Health Sciences Institute, Ozone Research Center; ORC technical
25          report, ORC-TR99-02.
26   Purushothaman, V.; Georgopoulos, P. G. (1999b) Integrating photochemical modeling,
27          geostatistical techniques and geographical information systems for ozone exposure
28          assessment. Piscataway, NJ: Environmental and Occupational Health Sciences Institute,
29          Ozone Research Center; ORC technical  report, ORC-TR99-01.
30   Rosenbaum, A. (2005) The HAPEMS user's guide - hazardous air pollutant exposure model,
31          version 5. Prepared for: U.S. Environmental Protection Agency. Research Triangle Park,
32          NC: ICF Consulting.
33   U.S. Environmental Protection Agency. (1992)  Final guidelines for exposure assessment.
34          Research Triangle Park, NC: National Center for Environmental Assessment; EPA/600Z-
35          92/001.
36   U.S. Environmental Protection Agency. (1997)  Exposure factors handbook.  Washington, DC:
37          Office of Research and Development, National Center for Environmental Assessment;
38          report nos. EPA/600/P-95/002Fa-c.
39   U.S. Environmental Protection Agency. (2006a) Air quality criteria for ozone and related
40          photochemical oxidants. Research Triangle Park, NC: National Center for Environmental
41          Assessment; report no. EPA/600/R-05/004aF-cF. 3v. Available:
42          http://cfpub.epa.gov/ncea/ [24 March, 2006].


     September  2007                        AX3-19      DRAFT-DO NOT QUOTE OR CITE

-------
 1   U.S. Environmental Protection Agency. (2006b) Total risk integrated methodology (TRIM) air
 2          pollutants exposure model documentation (TREVI.Expo/APEX, version 4). Volume I:
 3          User's guide. Research Triangle Park, NC: U.S. Environmental Protection Agency.
 4          Available: http://www.epa.gov/ttn/fera/data/apex/APEX4UsersGuideJuly2006.pdf [7
 5          March, 2007].
 6   U.S. Environmental Protection Agency. (2006c) Total risk integrated methodology (TRIM) air
 7          pollutants exposure model documentation (TREVI.Expo/APEX, version 4). Volume II:
 8          technical support document. Research Triangle Park, NC: U.S. Environmental Protection
 9          Agency. Available: http://www.epa.gov/ttn/fera/data/apex/APEX4TSDJuly2006.pdff7
10          March, 2007].
11   Whitfield, R. G.; Richmond, H. M.; Johnson, T. R. (1997) Overview of ozone human exposure
12          and health risk analyses used in the U.S. EPA's review of the ozone air quality standard.
13          In: Proceedings of the U.S.-Dutch International Symposium on Air Pollution in the 21st
14          Century; April; Noordwijk, The Netherlands. Argonne, IL:  Argonne National Laboratory;
15          ANL/DIS/CP-92660. Available: http://www.osti.gov/dublincore/gpo/servlets/purl/9748-
16          Nh3avx/webviewable/9748.pdf (22 July 2003).
17   World Health Organization (WHO). (2004) IPCS risk assessment terminology. Part 2: IPCS
18          glossary of key exposure assessment terminology. Geneva,  Switzerland: IPCS
19          Harmonization Project document no. 1. Available:
20          http://www.who.int/ipcs/methods/harmonization/areas/ipcsterminologypartsland2.pdf
21          [19 April, 2007].
22   World Health Organization (WHO). (2005) Principles of characterizing and applying human
23          exposure models. Geneva, Switzerland: World Health Organization. (IPCS
24          harmonization project document; no. 3). Available:
25          http://whqlibdoc.who.int/publications/2005/9241563117_eng.pdf [7 March, 2007].
26
27
      September 2007                         AX3-20      DRAFT-DO NOT QUOTE OR CITE

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  AX4. CHAPTER 4 ANNEX - TOXICOLOGICAL
      STUDIES OF THE HEALTH EFFECTS
              OF SULFUR OXIDES
September 2007            AX4-1  DRAFT-DO NOT QUOTE OR CITE

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                           TABLE AX4-1. PHYSIOLOGICAL EFFECTS OF SO2 EXPOSURE
to
o
o
X
i±

to
o
o

2
o
H

O
c
o
H
W

O
^
O
HH
H
W
Concentration Duration
Acute and Subacute Exposures
~1 ppm 1 h
(2.62 mg/m3);
head only

1 ppm 3 h/day for 6 days;
(2.62 mg/m3); animals evaluated for up
nose only to 48 h following
exposure; exposures
occurred in a furnace
5 ppm 45 min
(13.1 mg/m3);
apperantly
intratracheal







5 ppm 2 h/day for 13 wks
(13.1 mg/m3);
whole body




Species

Hartley guinea pig,
male, age not
reported, 200-300 g,
n = 8-23/group
Hartley guinea pig,
male, age not
reported, 250-320 g,
n= <18 group/time
point
Rabbit, sex not
reported, adult, mean
2.0 kg,
n = 5-9/group;
rabbits were
mechanically
ventilated




New Zealand White
rabbit, male and
female, 1 -day -old,
weight not reported,
n = 3-4/group,
immunized against
Alternaria tennis
Effects

An 1 1% increase in pulmonary resistance and 12% decrease in
dynamic compliance were observed. Neither effect persisted into
the 1-h period following exposure. No effects were observed for
breathing frequency, tidal volume, or min volume.
No effect was observed on residual volume, functional reserve
capacity, vital capacity, total lung capacity, respiratory
frequency, tidal volume, pulmonary resistance, or pulmonary
compliance at 1 or 48 h after the last exposure.

Bivagotomy had no effect on SO2-induced increases in lung
resistance (54% increase before vagotomy and 56% increase after
vagotomy). Reflex bronchoconstrictive response to
phenyldiguanide (intravenously administered) was eliminated by
exposure to SO2 but SO2 had no effect on lung resistance induced
by intravenously -administered histamine. The study authors
concluded that (1) vagal reflex is not responsible for
SO2-induced increase in lung resistance and (2) transient
alteration in tracheobronchial wall following SO2 exposure
may have reduced accessibility of airway nervous receptors
to phenyldiguanide.
No effects on lung resistance, dynamic compliance,
transpulmonary pressure, tidal volume, respiration rate, or min
volume.




Reference

Amdur et al.
(1983)


Conner et al.
(1985)



Barthelemy
etal. (1988)









Douglas et al.
(1994)






-------
                                    TABLE AX4-1 (cont'd).  PHYSIOLOGICAL EFFECTS OF SO2 EXPOSURE
           Concentration
                       Duration
                             Species
                                                 Effects
                                                                  Reference
to
o
o
          Subchronic and Chronic Exposure
15 or 50 ppm
(39.3 or
131mg/m3);
intratracheal
exposure
2 h/day, 4 or 5 days/wk,
for 5 mos (low dose
group) or 10-11 mos
(high dose group);
study authors stated
that physiological
changes were observed
within 5 mos; there was
a 7-9 mo recovery
period
Mongrel dogs, adult,
sex not reported,
10-20 kg;
n= 3-4/group
(3 hyperresponsive,
3 hyporesponsive,
and 1 avg
responsive)
At 15 ppm, there was no clinical evidence of bronchitis; pulmonary
resistance increased by 35-38% in 2 of 3 dogs, and dynamic lung
compliance decreased in 1 of 3 dogs, but the physiological changes were
not significant for the group as a whole. At 50 ppm, cough and mucous
hypersecretion were observed; the symptoms ceased during the recovery
period. Pulmonary resistance increased by 56% during the treatment
period and an additional 28% during the recovery period for a total
increase of 99%; dynamic lung compliance decreased in 2 of 4 dogs and
increased in 1 of 4 dogs during treatment but there were no significant
changes in the group as a whole. Study authors considered 15 ppm to
be the lower limit of exposure that failed to produce physiological
changes.
Scanlon
etal.
(1987)
X
O
o
2
o
H
O
c
o
H
W
O
V
O
HH
H
W
1 ppm
(2.62 mg/m3);
whole body
5 h/day, 5 days/wk for
4 mos
Sprague-Dawley rat,
male, young adult,
initial weight not
reported,
n= 12-15/data point
Physiological tests were conducted in anesthetized animals; many of the
tests were conducted while the rat was allowed to breathe spontaneously
and during paralysis. SO2 exposure resulted in an 11% decrease in
residual volume (only during paralysis) and reduced quasistatic
compliance (only examined in paralyzed animals).  Study authors noted
that because residual volume was only decreased in paralyzed rats
and the magnitude of effect was very small, it may have been due to
chance. Quasistatic compliance values were observed to be very
high in controls and may have accounted for the effect in the
treatment group.
Smith et al.
(1989)

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                                TABLE AX4-2. INFLAMMATORY RESPONSES FOLLOWING SO2 EXPOSURE
to
o
o
X
O
o
2
o
H
o
c
o
H
W
O
^
O
HH
H
W
Concentration Duration
Acute/Subacute/Subchronic
10 ppm (26.2 mg/m3); 4 h
nose only



14, 28, or 56 mg/m3; 4 h/day for 7 days
(5.35, 10.7, or
21.4 ppm); whole body




Species

Outbred Swiss
mouse, female, age
and weight not
reported, n = 107
experimental value
Kunming albino
mouse, male, age
not reported,
18-22 g,
n = 10/group


Effects

No evidence was seen of inflammatory response in terms
of total cell number, lymphocyte/polymorphonuclear
leukocytes differentials, or total protein level taken from
BAL fluid.

In lung tissue, in vivo SO2 exposure (low, mid
concentrations) significantly elevated levels of the
pro-inflammatory cytokines interleukin-6 and tumor
necrosis factor-a, but did not affect levels of the
anti-inflammatory cytokine transforming growth
factor-pi. In serum, the only effect observed was a
low-dose elevation of tumor necrosis factor- a.
Reference

Clarke et al.
(2000)



Meng et al.
(2005a)





          5, 50, or 100 ppm (13.1,
          131, or 262 mg/m3);
          whole body
                        5 h/day for 7-28 days
Wistar rat, male,
7 wks old, weight
not reported,
n = 4-5/treatment
group, 8 controls
No lung injury was observed and evidence of
inflammatory response was only observed in the 100 ppm
group.  A 4-fold increase in BAL fluid leukocyte numbers
was observed in the 100 ppm group at day 14; the increase
lessened at days 21 and 28 but remained higher than
controls.  The number of macrophages in BAL fluid was
increased at day 28 in the 100 ppm group. Neutrophil
numbers were 120 times higher than controls at day 14 in
the 100 ppm group but returned to normal by day 21.
Blood neutrophils were depleted in rats exposed to
50 ppm on days 7-21 but were increased in rats exposed to
5 ppm (significant) and 100 ppm (non-significant) at day
14.  Lung epithelial permeability was not affected.
Langley-Evans
etal. (1996)
BAL = bronchoalveolar lavage

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                     TABLE AX4-3.  EFFECTS OF SO2 EXPOSURE ON HYPERSENSITIVITY/ALLERGIC REACTIONS
             Concentration
                          Duration
                          Species
                                                 Effects
                                                             Reference
to
o
o
X
O
o
2
o
H
O
c
o
H
W
O
^
O
HH
H
W
          Antigen Sensitization/Allergic Reactions - Acute/Subacute
5ppm(13.1 mg/m);
head only
0.1 ppm
(0.26 mg/m3); whole
body; with and
without exposure to
ovalbumin
0.1, 4.3, or 16.6 ppm
(0,0.26, 11.3, or
43.5 mg/m3); whole
body; animals were
sensitized to
ovalbumin on the last
3 days of exposure.
4h
                                5 h/day for 5 days.
                                8 h/day for 5 days
Sheep, sex and age not
reported, mean weight
38 ± 7 kg, n = 7/group
                   Dunkin-Hartley guinea
                   pig, male, age not
                   reported, 250-350 g,
                   n = 7-12/group
                   Perlbright-White
                   Guinea pig, female,
                   age not reported,
                   300-350 g, n= 5 or
                   6/group (14 controls)
Acute exposure to 5 ppm SO2 did not produce significant airway   Abraham et al.
changes (pulmonary resistance, static compliance, dynamic        (1981)
compliance, tidal volume, breathing frequency) in either normal
or allergic (sensitized to Ascaris suum antigen) sheep, nor
increase airway reactivity (measured as pulmonary resistance
increase after aerosolized carbachol provocation) in normal
sheep.  However, 5 ppm SO2 did significantly increase airway
reactivity in allergic sheep, which have antigen-induced
airway responses similar to humans with allergic airway
disease, and thus may model airway responses to SO2 in a
sensitive human subpopulation.

After bronchial challenge, the ovalbumin/SO2-exposed group had   Park et al.
significantly increased enhanced pause (indicator of airway        (2001)
obstruction) and eosinophil counts in B AL fluids than all other
groups, including the SO2 group.  The bronchial and lung tissue
of this group showed infiltration of inflammatory cells,
bronchiolar epithelial damage, and mucus and cell plug in the
lumen. Study authors concluded that low level SO2 may
enhance the development of ovalbumin-induced asthmatic
reactions in guinea pigs.

Bronchial provocation with ovalbumin was conducted every       Riedel et al.
other day for 2 wks, starting at 1 wk after the last exposure.        (1988)
Numbers of animals displaying symptoms of bronchial
obstruction after ovalbumin provocation was increased in all SO2
groups compared to air-exposed groups. Anti-ovalbumin
antibodies (IgG total and IgGl) were increased in BAL fluid and
serum of SO2-exposed compared to air-exposed controls, with
statistical significance obtained for IgG total in BAL fluid at
>4.3 ppm SO2 and in serum at all SO2 concentrations. Results
indicate that in this model, subacute exposure to even low
concentrations of SO2 can potentiate allergic sensitization of
the airway.

-------
                 TABLE AX4-3 (cont'd).  EFFECTS OF SO2 EXPOSURE ON HYPERSENSITIVITY/ALLERGIC REACTIONS
            Concentration
                           Duration
                                                    Species
                                                                         Effects
                                                                                   Reference
to
o
o
          Antigen Sensitization/Allergic Reactions - Subchronic
                    4 h/day, 5 days/wk, 6
                    wks
5 ppm
(13.1mg/m3);
whole body;
sensitized with
Candida albicans
on day 1 and wk 4

General Bronchial Reactivity Studies - Acute
          5 ppm
          (13.1mg/m3);
          whole body
                    2h
Hartley guinea pig, male,   Respiratory challenge with Candida albicans was conducted
	.	__ _,   ™« _    2 wks ^gj. ^ last exposure At 15 h after challenge
                         increased number of SO2-exposed animals displayed
                         prolonged expiration, inspiration, or both.  Study authors
                         concluded that exposure to SO2 increased dyspneic
                         symptoms.
                                                       Hartley guinea pig, male,
                                                       age not reported, -200 g,
                                                       n = 12/group
                                             New Zealand White
                                             rabbit, sex not reported,
                                             apparently 3 mos old,
                                             2.2-3. 1 kg, n=6/group
                         No effect on airway responsiveness to inhaled histamine, as
                         measured by provocation concentrations of histamine
                         required to increase pulmonary resistance by 50% and
                         decrease dynamic compliance by 35%.
                                                                                                          Kitabatake
                                                                                                          etal. (1992,
                                                                                                          1995)
                                                                                                          Douglas et al.
                                                                                                          (1994)
X
O
O
2
O
H
O
c
o
H
W
O
V
O
HH
H
W
10 or 30 ppm (26.2
or 78.6 mg/m3);
intratracheal
                    5 min; a second exposure
                    was conducted 20 days
                    later, after exposure to
                    the antiallergic drug
General Bronchial Reactivity Studies - Chronic
15 or 50 ppm
(39.3 or
131 mg/m3);
intratracheal
2 h/day, 4 or 5 days/wk
for 5 mos (low dose
group) or 10-11 mos
(high dose group); study
authors stated that
physiological changes
were observed within 5
mos; there was a 7-9 mo
recovery period.
                         Mongrel dogs, male and
                         female, age and weight
                         not reported;
                         n = 5-15/group
Mongrel dogs, adult, sex
not reported, 10-20 kg;
n= 3-4/group
(3 hyperresponsive,
3 hyporesponsive, and
1 avg responsive)
                         No effect was observed at 10 ppm. At 30 ppm               Lewis and
                         hyperresponsiveness and hypersensitivity to aerosolized       Kirchner
                         methacholine and 5-hydroxytryptamine was observed for up   (1984)
                         to 24 h following exposure. Twenty days later, pretreatment
                         with aerosolized 4% Wy-41,195 or disodium cromoglycate
                         (antiallergic drugs) at high doses lessened the
                         methacholine-induced hypersensitivity observed after
                         exposure to 30 ppm SO2. The calculations used to determine
                         hyperresponsive and hyperreactivity were not clear.
                                                                     Bronchial reactivity in response to inhaled histamine or        Scanlon et al.
                                                                     methacholine was not affected in either treatment group, as     (1987)
                                                                     determined by the concentration of histamine or
                                                                     methacholine required to double pulmonary resistance or the
                                                                     concentrations required to decrease dynamic compliance by
                                                                     65% (ED65).
         BAL = bronchoalveolar lavage
         IgG = immunoglobulin

-------
September 2007

Concentration
Clearance - Subchronic
5 ppm (13.1 mg/m3);
TABLE AX4-4.
Duration
2 h/day, 5 days/wk
EFFECTS OF SO2 EXPOSURE ON HOST LUNG DEFENSES
Species
F344/Crl rat, male and
Effects
There was no effect on pulmonary clearance of
Reference
Wolff etal. (1989)
                                                        weight not reported,
                                                        n = 6/sex/group
                                                                          1.0 uM).
           Immune Responses - Acute/Subacute
           10 ppm (26.2 mg/m);
           nose only
                        4h
Specific pathogen-free
white Swiss mice, female,
5 wks old, 20-23 g,
n = 5/group
                                                  No effect was observed on in situ
                                                  Fc-receptor-mediated phagocytosis of sheep red blood
                                                  cells by AM, which was assessed 3 days after
                                                  exposure to SO2.
Jakab etal. (1996)
X
O
O
2
o
H
O
c
o
H
W
O
V
O
HH
H
W
10 ppm (26.2 mg/m3)
SO2; nose only
           10 ppm (26.2 mg/m );
           whole body
4 h                   Outbred Swiss mouse,
                      female, age and weight
                      not specified,
                      n = 10/experimental value

24 h, 1 wk, 2 wks, or   OF^ mice, female, age
3 wks                 not reported, mean 20.6 g,
                      n = 768 (32/group)
                            No effect on in situ AM phagocytosis (data not
                            shown) or on intrapulmonary bactericidal activity
                            toward Staphylococcus aureus.
                                                                          Respiratory challenge withKlebsiellapneumoniae
                                                                          resulted in increased mortality and decreased survival
                                                                          time in the 1, 2, and 3 wk SO2 exposure groups
                                                                          compared to controls. Differences did not correlate
                                                                          with exposure length.
                                                                                                                                       Clarke et al. (2000)
                                                                               Azoulay-Dupuis
                                                                               etal. (1982)
AM = alveolar or pulmonary macrophages
MAD = median aerodynamic diameter
MMAD = mass median aerodynamic diameter

-------
                             TABLE AX4-5.  EFFECTS OF SO2 EXPOSURE ON CARDIOVASCULAR ENDPOINTS
to
o
o
X
i±
oo
o
o
2
o
H
O
c
o
H
W
O
V
O
HH
H
W
Concentration Duration
In Vitro Exposure
Bisulfite/sulfite, Not reported
1:3 molar/molar,
10 uM


Bisulfite/sulfite, Not reported
1:3 molar/molar,
10 uM
Species
Ventricular myocytes
isolated from Wistar
rats, adult, 200-300 g,
n=8


Ventricular myocytes
isolated from Wistar
rats, adult, 200-300 g,
Effects
Effects of the 10 uM bisulfite/sulfite mixture on sodium
current included a shift of steady state inactivation curve to a
more positive potential, a shift of the time-dependent recovery
from inactivation curve to the left, accelerated recovery, and
shortened inactivation and activation time constants. It was
concluded that the bisulfite/sulfite mixture stimulated cardiac
sodium channels.
Effects of the 10 uM bisulfite/sulfite mixture on
voltage-dependent L-type calcium currents included a shift of
steady-state activation and inactivation to more positive
Reference
Nie and Meng
(2005)


Nie and Meng
(2006)
                                                    n=;
Acute/Subacute Exposure
           1.0, 2.5, or 5 ppm
           (2.62, 6.55, or
           13.1 mg/m3) in
           cold dry air;
           apparently
           intratracheal
                  In pre-exposure period:
                  15-min exposure to warm
                  humid air, 10-min
                  exposure to cold dry air,
                  and 15-min exposure to
                  warm humid air.  In
                  exposure period: 10-min
                  exposures to each SO2
                  concentration or cold dry
                  air were preceded and
                  folio wed by 15-min
                  exposures to warm humid
                  air.
Duncan-Hartley
guinea pigs, male,
age and weight not
reported,
n= 7-12/group,
mechanically
ventilated; animals
were hyperventilated
during cold air and
SO2 exposure to
simulate exercise
                                                                 potentials, accelerated recovery from inactivation, and
                                                                 shortened fast and slow time inactivation constants. Study
                                                                 authors stated that their results suggested the possibility
                                                                 cardiac injury following SO2 inhalation.
Arterial blood pressure increased transiently during exposure
to 5 ppm SO2 in cold dry air. No analyses were done to
determine the effects on blood pressure were caused by
exposure to cold air or SO2.
Halinen et al.
(2000a)

-------
                         TABLE AX4-5 (cont'd).  EFFECTS OF SO2 EXPOSURE ON CARDIOVASCULAR ENDPOINTS
               Concentration
                         Duration
                     Species
                         Effects
Reference
to
o
o
X
O
o
2
o
H
O
c
o
H
W
O
V
O
HH
H
W
Acute/Subacute Exposure

1 ppm (2.62 mg/m3) in
cold dry air; apparently
intratracheal
           1 ppm (2.62 mg/m3);
           nose only
10, 20, or 40 ppm (26.2,
52.4, or 105 mg/m3);
whole body

10, 20, or 40 ppm (26.2,
52.4, or 104.8 mg/m3);
whole body
5, 50, or 100 ppm (13.1,
131, or 262 mg/m3);
whole body
22, 56, or 112 mg/m3
(8.4, 21, or 43 ppm);
whole body
60 min      Duncan-Hartley guinea pigs,
            male, age and weight not
            reported, n = 8-9/group,
            mechanically ventilated;
            animals were hyperventilated
            during cold air and SO2
            exposure to simulate exercise

4 h         F344 rat, male, 18 mos old,
            weight not reported, n = 20
            (crossover design)


6 h         Wistar rat, male, 7-8 wks old,
            180-200 g;n= 10/group


6 h/day      Wistar rat, male, 7-8 wks old,
for 7 days   180-200 g; n = 10/group
5 h/day      Wistar rat, male, 7 wks old,
for         weight not reported,
7-28 days    n = 4-5/treatment group,
            8 controls
6 h/day      Kunming albino mice, male
for 7 days   and female, 5 wks old,
            19±2g, n = 10/sex/group
Blood pressure and heart rate increased similarly with exposure     Halinen et al.
to cold dry air or SO2 in cold dry air. Blood pressure generally      (2000b)
increased during the first 10-20 min of exposure and remained
steady from that point forward. The increase in heart rate was
gradual. No analyses were done to determine if the effects on
blood pressure were caused by exposure to cold air or SO2.


SO2 exposure had no effect on spontaneous arrythmia frequency     Nadziejko et al.
in aged rats.  Study authors urged caution in the                (2004)
interpretation of effects because occurrence of arrhythmias in
aged rats was sporadic and variable from day to day.

A dose-related decrease in blood pressure was observed at          Meng et al.
> 20 ppm.                                                    (2003b)


Dose-related decreases in blood pressure were observed on         Meng et al.
exposure day 3 in the 10 ppm group, exposure days 2-6 in the       (2003b)
20 ppm group, and all exposure days in the 40 ppm group. The
study authors noted possible adaptive mechanism in the low
but not the high dose group.

GSH was depleted in the heart at 5 and 100 ppm.  At 50 ppm,       Langley-Evans
GSH level decreased in heart at 7 days and returned to normal by    et al. (1996)
14 days. No effects were observed for other GSH-related
enzymes. Injury and inflammation were not assessed in heart, but
assessment in lung revealed no effect.

Changes observed in heart (concentrations of effect) included:      Meng et al.
lower SOD activity in males and females (> 8.4 ppm), higher        (2003a)
TEARS level in males and females (>8.4 ppm), lower GPx
activity in males (8.4 and 21 ppm; also 43 ppm according to text)
and lower GSH level in males (43 ppm). Study authors
concluded that SO2  induced oxidative damage in hearts of
mice.

-------
 %                       TABLE AX4-5 (cont'd). EFFECTS OF SO2 EXPOSURE ON CARDIOVASCULAR ENDPOINTS
"C       ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^=^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^=
 r+
 g            Concentration           Duration              Species                                 Effects                              Reference
 cr       	
 ^         Acute/Subacute Exposure
 to
 o         22, 64, or 148 mg/m3    6 h/day for 7 days      Kunming-strain       GSH, GST, and glucose-6-phosphate dehydrogenase activities   Wu and Meng
           (8.4, 24.4, or                                 mice, male, age not    were decreased in the heart at 148 mg/m3.                     (2003)
           56.5 ppm); whole                             reported, 18-20 g,
           body                                        n = 10/group

           GPx = glutathione peroxidase
           GSD = geometric standard deviation
           GSH = glutathione
           GST = glutathione-S-transferase
           MMAD = mass median aerodynamic diameter
           SOD = superoxide dismutase
           TEARS = thiobarbituric acid-reactive substances
 O
 o
 2
 o
 H
O
 c
 o
 H
 W
 O
 V
 O
 HH
 H
 W

-------
                       TABLE AX4-6.  NERVOUS SYSTEM—NEUROPHYSIOLOGY AND BIOCHEMISTRY EFFECTS
                                                              OF SO2 AND DERIVATIVES
             Concentration
                          Duration
           Species
                       Effects
Reference
to
o
o
>
O
O
2
O
H
O
c
o
H
W
O
V
O
HH
H
W
In Vitro/Ex Vivo

1, 10, 50, or 100 uM
SO2 derivatives (1:3,
NaHSO3 to Na2SO3)
                                Not specified
          1 or 10 uM SO2
          derivatives
          (l:3,NaHSO3to
          Na2S03)
                      2-4 min
Wistar rat, sex not reported,
6-12 days old, weight and
number not reported; typical
observations made on
60 isolated hippocampal neurons
per concentration
Wistar rat, both sexes,
10-15 days old, weight and
number not reported; n = 6-13
isolated dorsal root ganglion
neurons avgd per endpoint
Exposure to SO2 derivatives (sulfite, bisulfite) reversibly     Du and Meng
increased the amplitude of potassium channel TOCs in a     (2004a)
dose-dependent and voltage-dependent manner. Compared
to controls, 10 uM SO2 shifted inactivation of
depolarization toward more positive potentials without
significantly affecting the activation process. By
increasing maximal TOC conductance and delaying
TOC inactivation, micromolar concentrations of SO2
derivatives may increase the excitability of
hippocampal neurons and thus contribute to the
enhanced neuronal activity associated with SO2
intoxication.

Maximum sodium current amplitudes for both TTX-S and    Du and Meng
TTX-R channels were increased by exposure to SO2         (2004b)
derivatives (10 or 1 uM, respectively), with amplitudes
diminished at more negative evoking potentials and
enhanced at less negative or positive potentials.  SO2
derivatives (a) slowed both current activation and
inactivation for both types of sodium channels; (b) shifted
activation currents to more positive potentials, increasing
threshold voltages for action potential generation and
contributing to reduced neuron excitability; and (c) caused
even larger counteracting positive shifts in inactivation
voltages tending to increase dorsal root ganglion neuron
excitability. On balance, the data suggest micromolar
concentrations of sulfite/bisulfite can increase the
excitability of dorsal root ganglion neurons, providing a
basis for SO2-associated neurotoxicity.

-------
                  TABLE AX4-6 (cont'd).  NERVOUS SYSTEM—NEUROPHYSIOLOGY AND BIOCHEMISTRY EFFECTS
                                                              OF SO2 AND DERIVATIVES
              Concentration
                            Duration
                             Species
                                                  Effects
                                                        Reference
to
o
o
to
O
o
2
o
H
O
c
o
H
W
O
V
O
HH
H
W
In Vitro/Ex Vivo

0.01, 0.1,0.5, or luM
SO2 derivatives (1:3,
NaHSO3 to Na2SO3)
                                 Not specified, but
                                 brief ("added to the
                                 external solution just
                                 before each
                                 experiment")
                     Wistar rat, both sexes,
                     10-15 days old, weight and
                     number not reported;
                     n = 6-15 isolated dorsal root
                     ganglion neurons avgd per
                     endpoint
          Acute/Subacute/Subchronic Exposure
22, 64, or 148 mg/m3
(8.4, 24.4, or
56.5 ppm); whole body
6 h/day for 7 days
Kunming-strain mice, male,
age not reported, 18-20 g,
n = 10/group
                           In isolated dorsal root ganglion neurons, SO2 derivatives       Du and
                           increased HVA-/Ca amplitudes in a concentration- and         Meng
                           depolarizing voltage-dependent manner (EC50 was ~0.4 uM)   (2006)
                           by altering Ca channel properties. This effect was partially
                           reversible by SO2 derivative washout, and was
                           PKI-inhibitable, indicating involvement of PKA and
                           secondary messengers.  Additionally, exposure caused a
                           positive shift in reversal potential. SO2 derivatives also
                           delayed activation and inactivation of Ca channels, but the
                           latter was more pronounced, thus overall prolonging action
                           potential duration and increasing HVA-/Ca.  Exposure also
                           slowed the fast component and accelerated the slow
                           component of recovery from Ca channel inactivation.  Thus,
                           <1 uM sulfite/bisulfite caused prolonged opening and
                           altered properties of Ca channels, elevated HVA-/Ca, and
                           abnormal Ca signaling with neuronal cell injury.
                           Authors speculate these effects may correlate to SO2
                           inhalation toxicity, perhaps leading to abnormal
                           regulation via peripheral neuron Ca channels of
                           nociceptive impulse transmission.
Decreased glutathione, glucose-6-phosphate dehydrogenase,   Wu and
and GST activities were observed in the brain at 64 and       Meng
148 mg/m3.                                             (2003)

-------
                  TABLE AX4-6 (cont'd). NERVOUS SYSTEM—NEUROPHYSIOLOGY AND BIOCHEMISTRY EFFECTS
                                                              OF SO2 AND DERIVATIVES
             Concentration
                          Duration
                           Species
                                                     Effects
                                                            Reference
to
o
o
O
o
2
o
H
O
c
o
H
W
O
V
O
HH
H
W
10 ppm (26.2 mg/m );
whole body
Ih/dayfor21or
24 days
Guinea pig, sex not
reported, adult, 250-500 g,
n = 12/group (6/subgroup)
           10 ppm (26.2 mg/m3);
           whole body
                      1 h/day for
                      30 days
                  Charles Foster rat, male,
                  adult, 150-200 g,
                  n = 12/group (6/subgroup)
The effects of SO2 exposure on lipid profiles, lipid peroxidation     Haider
and lipase activity in three regions of the brain (cerebral            et al.
hemisphere, CH; cerebellum, CB; brain stem, BS) were            (1981)
examined. Significant (p < 0.001-0.05) findings include
reductions in total lipids (CH, BS; also CB, but nonsignificant)
and free fatty acids (CH, CB, BS). PL were elevated in CH, but
reduced in CB; Choi was elevated in CH, but reduced in CB and
BS; and esterified fatty acids were elevated in CB, but reduced in
CH and BS. Levels of malonaldehyde and lipase activity were
elevated in all regions. Results indicate that subacute brief
exposures to SO2 can lead to degradation  of brain lipids, with
the exact nature of the lipid alterations dependent upon brain
region.

The effects of SO2 exposure on lipid profiles, lipid peroxidation     Haider
and lipase activity in three regions of the brain (cerebral            et al.
hemisphere, CH; cerebellum, CB; brain stem, BS) were            (1982)
examined. Significant (p < 0.001-0.05) findings include
reductions in total lipids (CH, BS, CB), while PL were elevated
only in CB. Choi was elevated in CH and CB, but not BS; and
gangliosides were elevated in CB and BS, but reduced in CH.
Lipid peroxidation (malonaldehyde formation) was elevated in
whole brain and all regions (although nonsignificantly in BS), as
was lipase activity in CH, the only tissue examined. Despite
regional differences in PL and Choi changes, Choi/PL ratios were
elevated in all three brain regions (again nonsignificantly in BS).
Results are somewhat different than those seen in guinea pig
(Haider et al., 1981), but again suggest that subacute brief
exposures to SO2 can lead to degradation  of brain lipids, with
the exact nature of the lipid alterations dependent upon brain
region.

-------
                   TABLE AX4-6 (cont'd). NERVOUS SYSTEM—NEUROPHYSIOLOGY AND BIOCHEMISTRY EFFECTS
                                                                OF SO2 AND DERIVATIVES
              Concentration
                           Duration
                           Species
                                                    Effects
                                                               Reference
to
o
o
>
O
O
2
O
H
O
c
o
H
W
O
V
O
HH
H
W
10 ppm (26.2 mg/m )
SO2 alternated with
20 ppm (14.7 mg/m3)
H2S; whole body
1 h/day for 30 days
(alternating SO2 or
H2S)
Guinea pig, sex and age
not reported, 250-400 g,
n = 18/group in 2 groups
(6/group in some
subgroups)
           10 ppm (26.2 mg/m3)
           (± iv alloxan to induce
           experimental type 1
           diabetes); whole body
                       1 h/day, 7 days/wk
                      for 6 wks
                    Swiss albino rat, male,
                    3 mos old, weight not
                    reported, n = 10/group in
                    4 groups
The effects of alternating SO2 + H2S exposure on lipid profiles, lipid   Haider and
peroxidation and lipase activity in four regions of the brain (cerebral   Hasan
hemisphere, CH; basal ganglia, BG; cerebellum, CB; brain stem,       (1984)
BS) and in the spinal cord (SC) were examined.  Significant
(p < 0.001-0.05) findings include reductions in total lipids and Choi,
and elevated lipid peroxidation (malonaldehyde formation) and
lipase activity, in all brain regions and SC. Choi/PL ratios were also
reduced in all tissues (but nonsignificantly in BG and CB). For
other parameters (PL, free fatty acids, esterified fatty acids, and
gangliosides), changes were observed in most tissues but were
region-specific.  Results indicate that subacute brief, alternating
exposures to SO2 or H2S lead to degradation of brain lipids,
again with the exact nature of the lipid alterations dependent
upon brain/spinal cord region.  Additionally, some of the effects
observed for this mixture vary from those seen with SO2 alone
(Haider et al., 1981,1982).

In retina tissue, exposure elevated SOD activity and reduced GPx      Agar et al.
and catalase activities.  TEARS were elevated only in non-diabetic     (2000)
rats exposed to SO2. In brain tissue, exposure elevated SOD and
reduced GPx activities in both non-diabetics and diabetics, while
catalase activities were not affected; TEARS were elevated in both
non-diabetics and diabetics. With respect to VEPs, exposure
prolonged latencies in 4 of 5 VEP components in non-diabetics and
5 of 5 in diabetics, while reducing virtually all peak-to-peak
amplitudes in non-diabetics and diabetics. For many endpoints, SO2
effects were additive to those resulting from the induced diabetic
condition. In summary, brain and retinal anti-oxidant and lipid
peroxidation status, as well as neuro-visual performance were
affected by subchronic exposure to brief periods of 10 ppm SO2,
and these effects were exacerbated by a diabetic condition.

-------
                  TABLE AX4-6 (cont'd). NERVOUS SYSTEM—NEUROPHYSIOLOGY AND BIOCHEMISTRY EFFECTS
                                                              OF SO2 AND DERIVATIVES
             Concentration
                         Duration
         Species
                         Effects
Reference
to
o
o
>
O
O
2
O
H
O
c
o
H
W
O
V
O
HH
H
W
Subchronic/Chronic Exposure
           10 ppm (26.2 mg/m )
           (± iv alloxan to induce
           experimental type 1
           diabetes); whole body
                      1 h/day,
                      7 days/wk for
                      6 wks
Rat, male, 3 mos old,
weight not reported,
n = 10/group in 4 groups
          10 ppm (26.2 mg/m3);
          whole body
                      1 h/day,
                      7 days/wk for
                      6 wks
Swiss albino rat, male, 3,
12, or 24 mos old, weight
not reported, n = 10/group
in 6 groups
In brain tissue, SO2 exposure elevated SOD and reduced GPx      Kiiciikatay
activities in both non-diabetics and diabetics, while catalase        et al.
activities were not affected; TEARS were elevated in both         (2003)
non-diabetics and diabetics. With respect to afferent peripheral
nerve pathways (SEPs), exposure prolonged latencies in 4 of 4
SEP components in both non-diabetics and diabetics; also altered
were some inter-peak latencies (non-diabetics and diabetics) and
some peak-to-peak amplitudes (non-diabetics only).  In some
cases, SO2 effects were additive to those resulting from the
induced diabetic condition. In summary, brain anti-oxidant
and lipid peroxidation status, as well as afferent peripheral
nerve pathways, were affected by subchronic exposure to
10 ppm SO2, and these effects were exacerbated by a diabetic
condition. Authors suggest that SO2 exposure could
potentiate the incidence and/or severity of diabetes.

Effects of aging ± SO2 exposure on levels of lipid peroxidation     Yargicoglu
(TEARS), antioxidant enzyme status (catalase, GPx, SOD), and    et al.
afferent peripheral nerve pathways (SEPs) were monitored in the   (1999)
brain of young (Y, 3  mo), middle-aged (M, 12 mo) and old (O,
24 mo) rats.  In addition to age-related changes, SO2 exposure
significantly  (p < 0.0001-0.02) elevated TEARS and SOD, while
reducing GPx (Y, M, O); catalase levels were not affected.  Of
4 monitored SEP component peaks, SO2 significantly
(p < 0.01-0.05) prolonged latencies in groups Y (4/4) and M
(1/4), but not in O (0/4).  Peak-to-peak amplitudes were
decreased in Y, (2/3) and increased in M (1/3), but not affected in
O (0/3). Taken together, these data indicate that subchronic
exposure to brief periods of 10 ppm SO2 can impact afferent
peripheral nerve pathways and the lipid peroxidation and
antioxidant enzyme status of the brain.

-------
                  TABLE AX4-6 (cont'd). NERVOUS SYSTEM—NEUROPHYSIOLOGY AND BIOCHEMISTRY EFFECTS
                                                              OF SO2 AND DERIVATIVES
           Concentration
                   Duration
                         Species
                                                          Effects
                                                                   Reference
to
o
o
O
O
2
O
H
O
c
o
H
W
O
V
O
HH
H
W
Subchronic/Chronic Exposure
           10 ppm
           (26.2 mg/m3);
           whole body
                 1 h/day,
                 7 days/wk
                 for 6 wks
              Swiss albino rat, male, 3, 12,
              or 24 mos old, weight not
              reported, n = 10/group in
              6 groups
          Neurodevelopment/Neurobehavior
32 or 65 ppm
(83.8 or
170 mg/m3);
whole body

5, 12, or 30 ppm
(13.1, 31.4, or
78.6  mg/m3);
whole body
                           Gestation
                           day 7-18
Near
continuous
(80% of
time)
exposure
from 9 days
before
mating
through the
12-14thday
of pregnancy
CD-I mouse dams were
exposed; numbers of dams
exposed and offspring
evaluated not indicated

CD-I mouse, adult male and
female parental animals were
exposed (n = 10/group/sex)
and male and female offspring
(n = 8 litters/group, fostered by
unexposed dams at birth) were
evaluated at 2-18 days of age;
adult male offspring also
evaluated (n = 8/group)
                              Effects of aging ± SO2 exposure on levels of lipid peroxidation            Kilic
                              (TEARS), antioxidant enzyme status (catalase, GPx, SOD), and visual     (2003)
                              system function (VEPs) were monitored in the brain and eye (retina and
                              lens) of young (Y, 3 mo), middle-aged (M, 12 mo) and old (O, 24 mo)
                              rats.  In addition to age-related changes, SO2 exposure significantly
                              (p < 0.0001-0.04) elevated TEARS in brain and lens (Y, M, O),  and in
                              retina (Y); reduced GPx in brain (Y) and lens (Y, M, O); reduced
                              catalase in retina (Y, M, O); and elevated SOD in brain (Y, M), retina
                              (Y, M, O) and lens (M, O). Of 5 monitored VEP component peaks, SO2
                              prolonged latencies in groups Y (4/5), M (3/5) and O (1/5). Taken
                              together, these data indicate that subchronic exposure to brief
                              periods of 10 ppm SO2 can impact the visual system and the  lipid
                              peroxidation and antioxidant enzyme status of the brain and eye.
                                            Righting and negative geotaxis reflexes were delayed at both             Singh
                                            concentrations.                                                     (1989)
Offspring: No effects observed for birth weight, postnatal body weight     Petruzzi
gain, somatic and neurobehavioral development (e.g., eyelid and ear       et al.
opening, incisor eruption, and reflex development); no postnatal           (1996)
developmental data were shown by study authors. No effects observed
in passive avoidance testing of adult males.  Adults: Observation of
behavior outside the exposure chamber on exposure days 3, 6, and
9 revealed dose-related increases in digging and decreases in grooming
by females in the 30 ppm group on exposure day 9; non-dose related
increases were observed for crossing and wall rearing by females in the
30 ppm group on exposure day 9. Observance of behaviors in 2 breeding
pairs/group in the 12 and 30 ppm groups revealed increased rearing and
social interaction in the 30 ppm group shortly after the start of exposure,
followed by return to baseline levels; effects were generally of greater
magnitude in males.

-------
                    TABLE AX4-6 (cont'd). NERVOUS SYSTEM—NEUROPHYSIOLOGY AND BIOCHEMISTRY EFFECTS
                                                                  OF SO2 AND DERIVATIVES
            Concentration
                         Duration
           Species
                          Effects
 Reference
to
o
o
Neurodevelopment/Neurobehavior

5, 12, or 30 ppm   Near continuous (90%  CD-I mouse, adult male and
           (13.1, 31.4, or
           78.6 mg/m3);
           whole body
                  of time) exposure
                  from 9 days before
                  mating through the
                  14th day of pregnancy
female parental animals were
exposed and adult male
offspring (fostered by
unexposed dams at birth) were
evaluated at -120 days of age,
n= 11-12 offspring/group
In 20-min encounters with unexposed males, prenatally-exposed
males compared to controls displayed (dose(s) of effect, time of
testing effect observed) increased duration of serf grooming
(5 ppm, 15-20 min), decreased frequency and duration of tail
rattling (>5 ppm at 5-10 min and 12 ppm at 10-15 min), and
decreased duration of defensive postures (> 12 ppm, 0-5 min).
Study authors also noted a non-significant decrease in freezing
(apparently at all dose levels) and non-significant increases in
social exploration (apparently at all doses) and rearing
(apparently at > 12 ppm).
Fiore et al.
(1998)
           CAT = catalase
           Choi = cholesterol
           GPx = Se-dependent glutathione peroxidase
           GST = glutathione-S-transferase
           HVA-/ca = high-voltage activated calcium currents
           PKA = cyclic AMP-dependent protein kinase A
           PKI = synthetic peptide inhibitor of PKA
           PL = phospholipids
                                                                         SEPs = somatosensory-evoked potentials
                                                                         SOD = Cu,Zn-superoxide dismutase
                                                                         TEARS = thiobarbituric acid-reactive substances
                                                                         TOC = potassium channel transient outward currents
                                                                         TTX = tetrodotoxin
                                                                         TTX-R = tetrodotoxin-resistant
                                                                         TTX-S = tetrodotoxin-sensitive
                                                                         VEPs = visual-evoked potentials
O
o
2
o
H
O
c
o
H
W
O
V
O
HH
H
W

-------
                                  TABLE AX4-7.  REPRODUCTIVE AND DEVELOPMENTAL EFFECTS OF SO2
           Concentration ppm
                          Duration
                          Species
                                                Effects
                                                          Reference
to
o
o
oo
O
o
2
o
H
O
c
o
H
W
O
^
O
HH
H
W
          Reproductive Organ Effects - Subacute/Subchronic
22, 56, orll2mg/m3
(8.4, 21, or 43 ppm);
whole body
6 h/day for 7 days
           10 or 30 ppm
           (26.2 or 78.6 mg/m3);
           whole body
                      6 h/day,
                      ~5 days/wk for
                      21 wks (total of
                      99 days)
          Developmental/Reproductive
32 or 65 ppm
(83.8 or 170 mg/m3);
whole body
           5, 12, or 30 ppm
           (13.1, 31.4, or
           78.6 mg/m3); whole
           body
                                 Gestation day
                                 7-18
                      Near continuous
                      (80% of time)
                      exposure from
                      9 days before
                      mating through
                      the 12-14thday
                      of pregnancy
Kunming albino mice, male,
5 wks old, 19 ± 2 g,
n = 10/group
                  Sprague-Dawley CD rat,
                  male, 8 wks old, weight not
                  reported, n = 70/group in
                  3 groups (inhalation series)
                  CD-I mouse dams were
                  exposed; numbers of dams
                  exposed and offspring
                  evaluated not indicated

                  CD-I mouse, adult male
                  and female parental animals
                  were exposed
                  (n = 10/group/sex) and male
                  and female offspring
                  (n = 8 litters/group, fostered
                  by unexposed dams at birth)
                  were evaluated at 2-18 days
                  of age; adult male offspring
                  also evaluated (n = 8/group)
Changes observed in mouse testes (concentrations of
effects) included decreased activities of SOD (43 ppm,
possibly at 21 ppm according to text) and GPx
(>21 ppm), increased catalase activity (8.4 and 21 ppm),
decreased GSH level (>21 ppm), and increased TEARS
levels (>8.4 ppm). The study authors concluded that
SO2 can induce oxidative damage in testes of mice.

No significant (p < 0.05) effect on testes histopathology
was found, although there was a very slight and probably
biologically insignificant increase in relative testes
weight.  (0.61 ± 0.02 vs. 0.56 ± 0.02, %body weight).
                           No significant effects were observed for number of live
                           pups born/litter. Pup birth weight was lower at 65 ppm.
                           Righting and negative geotaxis reflexes were delayed at
                           both concentrations.

                           Decreased food and water intake were observed in
                           parental males and females of the 12 and 30 ppm groups
                           at the start of mating (exposure days 9-13). No effects
                           observed for mating or successful pregnancies. There
                           were no effects on litter sizes, sex ratio, or neonatal
                           mortality (data not shown by study authors). No effects
                           observed for birth weight, postnatal body weight gain,
                           somatic and neurobehavioral development (e.g., eyelid
                           and ear opening, incisor eruption, and reflex
                           development); no postnatal developmental data were
                           shown by study authors.  No effects observed in passive
                           avoidance testing of adult males.
Meng and Bai (2004)
                                                                                Gunnison et al.
                                                                                (1987)
                                                     Singh (1989)
                                                     Petruzzi et al. (1996)

-------
                              TABLE AX4-7 (cont'd). REPRODUCTIVE AND DEVELOPMENTAL EFFECTS OF SO2
           Concentration ppm
                         Duration
                             Species
                                                    Effects
                                                          Reference
to
o
o
           Developmental/Reproductive
5, 12, or 30 ppm
(13.1, 31.4, or
78.6 mg/m3); whole
body
           5 ppm
           (13.1 mg/m3);
           whole body
Near continuous
(90% of time)
exposure from
9 days before
mating through
the 14th day of
pregnancy
                     2 h/day for
                     13wks
CD-I mouse, adult male and
female parental animals were
exposed and adult male
offspring (fostered by
unexposed dams at birth) were
evaluated at -120  days of age,
n= 11-12 offspring/group
                   New Zealand White rabbit,
                   male and female,
                   n = 3-4/group, 1-day-old,
                   immunized against Alternaria
                   tenuis
In 20-min encounters with unexposed males,
prenatally-exposed males compared to controls
displayed (dose(s) of effect, time of testing effect
observed) increased duration of self grooming (5 ppm,
15-20 min), decreased frequency and duration of tail
rattling (>5 ppm at 5-10 min and 12 ppm at 10-15 min),
and decreased duration of defensive postures
(> 12 ppm,0-5 min). Study authors also noted a
non-significant decrease in freezing (apparently at all
dose levels) and non-significant increases in social
exploration (apparently at all doses) and rearing
(apparently at > 12 ppm).

Following subchronic exposure beginning in the
neonatal period, there were no effects on lung resistance,
dynamic compliance, transpulmonary pressure, tidal
volume, respiration rate, or min volume.
Fioreetal. (1998)
                                                                                    Douglas etal. (1994)
           GPx = glutathione peroxidase
           GSH = glutathione
           SOD = superoxide dismutase
           TEARS = thiobarbituric acid-reactive substances
O
o
2
o
H
O
c
o
H
W
O
V
O
HH
H
W

-------
                                               TABLE AX4-8.  HEMATOLOGICAL EFFECTS OF SO2
            Concentration
                    Duration
      Species
                               Effects
Reference
to
o
o
to
o
O
O
2
O
H
O
c
o
H
W
O
^
O
HH
H
W
Acute/Subacute Exposure

0.87 ppm            24 h
(2.36 mg/m3);
whole body
          Subchronic Exposure

          286 mg/m3          5 h/day
          (100 ppm); whole    for
          body. The units      28 days
          were initially
          reported as ug/m3
          but were corrected
          per correspondence
          with the study
          author.
Swiss Albino rat,
male, age not
reported, 250-300;
n=51, 50
                               Wistar rat, male,
                               7 wks old, weight
                               not reported,
                               n=4-16
Effects of SO2 exposure included increased hematocrit, sulfhemoglobin and      Baskurt (1988)
osmotic fragility and decreased whole blood and packed cell viscosities.  RBC
number, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin
concentration, and plasma viscosity were not significantly altered.
                     Dams were fed diets containing casein at 180 [control], 120, 90, or 60 g/kg       Langley-Evans
                     during pregnancy and their offspring were exposed to air or SO2 as adults. In     et al. (1997);
                     blood of offspring, SO2 exposure significantly reduced the numbers of           Langley Evans
                     circulating total leukocytes and lymphocytes in the 180 and 120 g/kg dietary      (2007)
                     groups; neutrophils numbers were not affected in any group.  GSH levels in the
                     180 and 60 g/kg (but not the two intermediate) dietary groups were reduced by
                     SO2 exposure.  This study provides information for an extremely high
                     concentration level but is being acknowledged here with the unit corrected
                     to verify that a low-concentration level study was not missed.
10 ppm
(26.2 mg/m3);
whole body


10 ppm
(26.2 mg/m3);
whole body


10 ppm
(26.2 mg/m3);
whole body




1 h/day
for
30 days


1 h/day,
7 days/
wkfor
6 wks

1 h/day
for
45 days




Guinea pig, sex and
age not reported,
250-450 g,
n = 12/group

Swiss Albino rat,
male, 3 mos old,
weight not reported,
n = 10 per group in
4 groups
Rat, sex and age not
reported, 214-222 g,
n = 6-8 per group




SO2 exposure resulted in RBC membrane lipoperoxidation (elevated levels of
malonyldialdehyde) and other oxidative damage (elevated osmotic fragility
ratios and levels of methemoglobin and sulfhemoglobin). All these effects
were significantly (p < 0.05) mitigated by injections of Vitamin E+C three
times per wk.
RBC parameters were monitored in non-diabetic rats, non-diabetic rats
exposed to SO2, alloxan-induced diabetic rats, and diabetic rats exposed to
SO2. In both non-diabetic and diabetic rats exposed to SO2, levels of GPx,
catalase, GSH, GST, and TEARS were elevated in RBC while those of SOD
were reduced.
SO2 exposure significantly elevated levels of methemoglobin, sulfhemoglobin
and malonyldialdehyde, the latter of which was substantially reversed by
Vitamin E+C treatment. RBC osmotic fragility was increased by SO2, and
again partially mitigated by Vitamin E+C. SO2 elevated RBC, white blood
cell, hemoglobin and hematocrit values, but not mean corpuscular volume,
mean corpuscular hemoglobin or mean corpuscular hemoglobin concentration.
Vitamin E+C exposure did not affect these parameters.
Etlik et al.
(1995)



Agar et al.
(2000)



Etlik et al.
(1997)






-------
                                           TABLE AX4-8 (cont'd). HEMATOLOGICAL EFFECTS OF SO2
              Concentration
                            Duration
       Species
                        Effects
Reference
to
o
o
Acute/Subacute Exposure

10 ppm (26.2 mg/m3);   1 h/day, 7 days/wk
whole body             for 8 wks
           10 ppm (26.2 mg/m3);    1 h/day, 7 days/wk
           whole body            for 6 wks
Swiss-Albino rat, male,
2.5-3.0 mos old, weight
not reported, n = 30
(14 controls, 16 treated)
                                             Albino rat, male, 3, 12,
                                             and 24 mos old, mean
                                             weight 213-448 g,
                                             n = 10/group
Decreased Cu,Zn- SOD activity, increased GPx and GST      Gumus.lu et al.
activity, and increased TEARS formation were observed in    (1998)
RBC of treated rats. No significant effect on
glucose-6-phosphate dehydrogenase or catalase levels was
observed.

Enzyme and GSH activity (GPx, catalase, GSH, and GST)     Yargicoglu et al.
were increased and copper-zinc SOD activity was decreased   (2001)
inRBCs of all experimental groups compared to controls.
RBCs in older rats had lower levels of all antioxidants
enzymes and increased TEARS activity compared to
younger rats.
to
GSH = glutathione
GPx = glutathione peroxidase
GST = glutathione-S-transferase
HP = hydrolyzed protein
RBC = red blood cell or erythrocyte
SOD = superoxide dismutase
TEARS = thiobarbituric acid-reactive substance
O
o
2
o
H
O
c
o
H
W
O
V
O
HH
H
W

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to
o
o
                                             TABLE AX4-9. ENDOCRINE SYSTEM EFFECTS OF SO2
Concentration
5 or 10ppm(13.1 or
26.2 mg/m3); whole
body






Duration
24 h/day for
15 days







Species
Sprague-Dawley CD rat, male, age
not reported, 250-275 g,
n = 9/subgroup in 9 subgroups






Effects
Subjects were rats fed standard diet (normal) or high
cholesterol diet, and rats with streptozotocin-induced
diabetes fed standard diet. In diabetic rats, there was no
effect on glucose levels. Exposure to > 5 ppm lowered
plasma insulin level in normal and hypercholesterolemic
diet groups, but elevated it (non-significantly) in diabetic
rats. In each rat model, inhalation of SO2 at levels
without overt effects affected insulin levels. Specific
effects varied according to diet or diabetes.
Reference
Lovati et al.
(1996)







          10 ppm (26.2 mg/m3);
          whole body
1 h/day,
7 days/wk for
6 wks
Swiss Albino rat, male, 3 mos old,
weight not reported, n = 10/group
Effects were compared in non-diabetic rats and rats with   Agar et al.
alloxan induced diabetes.  SO2 increased blood glucose    (2000)
in diabetic and non-diabetic rats.
to
to
          10 ppm (26.2 mg/m3);
          whole body
1 h/day,
7 days/wk for
6 wks
Rat, male, 3 mos old, weight not
reported, n = 10/group in 4 groups
Effects were compared in normal rats and rats with       Kiicukatay et al.
alloxan induced diabetes.  SO2 elevated blood glucose     (2003)
levels in both non-diabetics and diabetics.
O
O
2
O
H
O
c
o
H
W
O
V
O
HH
H
W

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                       TABLE AX4-10. EFFECTS OF SO2 EXPOSURE ON RESPIRATORY SYSTEM MORPHOLOGY
            Concentration
                         Duration
                             Species
                                              Effects
                                                        Reference
to
o
o
          Acute/Subacute Exposure
1 ppm (2.6 mg/m );
nose only
3 h/day for 6 days;
animals evaluated for
up to 72 h following
exposure
Hartley guinea pig, male,
age not reported,
250-320 g,
n = 14/group/time point
In combined group of SO2 exposed animals and furnace gas       Conner et al.
controls, no alveolar lesions were observed.                    (1985)
          Subchronic/Chronic Exposure
to
5 ppm (13 mg/m );
nose only


1 ppm
(2.62 mg/m3);
whole body


2 h/day, 5 days/wk for
4 wks


5 h/day, 5 days/wk for
4 or 8 mos; half the
animals in the 8-mo
group were allowed to
recover for 3 mos.
F344/Crl rat, male and
female, 10-11 wks old,
weight not reported,
n = 3/sex/group
Sprague-Dawley rat,
male, young adult, initial
weight not reported,
n= 12-15/data point

No nasal or pulmonary lesions.



At 4 mos of SO2 exposure, increases were observed for
incidence of bronchial epithelial hyperplasia (80 vs. 40% in
controls) and numbers of nonciliated epithelial cells (31.1 vs.
27.7% in controls); neither effect persisted past 4 mos of
exposure.
Wolff etal.
(1989)


Smith et al.
(1989)



O
o
2
o
H
O
c
o
H
W
O
V
O
HH
H
W

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                                               TABLE AX4-11.  CARCINOGENIC EFFECTS OF SO2
               Concentration
                              Duration
                          Species
                                            Effects
                                                              Reference
to
o
o
to
O
o
2
o
H
O
c
o
H
W
O
V
O
HH
H
W
Pulmonary Effects - SO?

0, 10, or 30 ppm (0, 26.2,
or 78.6 mg/m3) SO2
(whole body) ± 1 mg
B[a]P

0, 100 or 400 ppm W, or
[400 ppm W + 40 ppm
Mo] in a low-Mo diet,
±B[a]P (See Effects
column) ±B[a]P
SO2: 21 wk, 5 day/wk
(minus holidays),
6 h/day

High W, low Mo diet:
21 wk, 7 day/wk

B[a]P: 15 wk, once
per wk starting wk 4
Rat,
Sprague-Dawley,
male, 9 wk old,
~315-340 g,
n = 20-74/group
Purpose was to investigate carcinogenic/cocarcinogenic effects of
SO2 inhalation or dietary-induced high levels of systemic
sulfite/bisulfite in conjunction with trachea! installation of B[a]P.
High drinking water levels of W in conjunction with low-Mo feed
induce sulfite oxidase deficiency in rats, and thus high systemic
levels of sulfite and bisulfite (at 0, 100 or 400 ppm W, mean plasma
sulfite was 0, 0 or 44 uM, while mean tracheal sulfite + bisulfite
was 33, 69 or 550 nmol/g wet wt). Mortality in B[a]P groups
(-50% after -380-430 d) was due almost exclusively to SQCA of
the respiratory tract; survival rate was excellent for other groups
(-50% mortality after -620-700 d). Results indicate no SQCA
was induced in any of the SO2 inhalation or systemic
sulfite + bisulfite groups, nor were incidences in the B[a]P
groups enhanced by such coexposures. This lack of
cocarcinogenicity  does not support the hypothesis that SO2
exposure could elevate systemic sulfite/bisulfite, generating
GSSO3H, which would inhibit GST and reduce intracellular
GSH, thus interfering with a major detoxication pathway for
B[a]P and enhancing its carcinogenicity. Authors note that due
to the high incidence of animals with tumors in the B[a]P only
groups (65/72 and 63/72), cocarcinogenicity of  SO2 or
sulfite + bisulfite could only have been demonstrated by
shortening of tumor induction time and/or increased rate of
SQCA appearance—neither were observed.
Gunnison
etal.
(1988)

-------
                                          TABLE AX4-11 (cont'd). CARCINOGENIC EFFECTS OF SO2
             Concentration
                           Duration
                           Species
                                              Effects
                                                            Reference
to
o
o
to
O
o
2
o
H
O
c
o
H
W
O
^
O
HH
H
W
Pulmonary Effects - SO2

0, 0.2 mL C, or
{0.2 mL
DEP+C ± [4 ppm
(10.48 mg/m3)SO2 or
6ppm(11.28mg/m3)
NO2 or 4 ppm
SO2 + 6ppmNO2]};
whole body
          [Note: 0.2 mL
          CBP = Img; 0.2 mL
          DEcCBP = 1 mg
          CBP + 2.5mgDEP)]
0, C, or {25 mg
SPM+C ± [4 ppm
(10.48 mg/m3)SO2 or
6ppm(11.28mg/m3)
NO2 or 4 ppm
SO2 + 6ppmNO2]};
whole body
SO2 and/or NO2:
10 mo, 16 h/day

CBP or DEcCBP:
4 wk, once/wk by
intratracheal infusion
Rat, SPF F344/M,
male, 6 wk old, wt
not reported,
n = 23-30 per group
in 6 groups
SO2 and/or NO2:
11 mo, 16 h/day

C ± SPM: 4 wk,
once/wk by
intratracheal injection
Rat, SPF Fisher 344,
male, 5 wk old, wt
not reported, n = 5
per group in 6 groups
Purpose was to study effects of DEP on rat lung tumorigenesis     Ohyama et al.
and possible tumor promoting effects of SO2 or NO2 singly or      (1999)
together.  Alveolar hyperplasia and adenoma were significantly
(p < 0.01-0.05) increased over controls in the CBP group, but not
the DEcCBP group.  This was ascribed to induction of alveolitis
and AM infiltration (a tumor response specific to rat and of
questionable relevance to humans) in the former group, but
apparently prevented by DEP in the latter.  Alveolar
bronchiolization near small hyaline masses of deposited DEcCBP
was observed in all DEcCBP groups, the masses presumably
allowing long-term exposure to DEP extracts by contacted
alveolar epithelium.  DNA adducts were found only in the three
gas-exposed groups. Discounting the CBA group, elevated
alveolar hyperplasia was seen only in the DEcCBP + NO2 group,
and elevated incidences of alveolar adenoma in the
DEcCBP  + SO2 and particularly the DEcCBP + NO2 groups;
neither effect was observed with coexposure to both gases—
speculated by the authors to perhaps result from inhibition of the
stronger NO2 promotion by HSO3~. Thus, SO2 appears to have
weaker capacity than NO2 for promoting tumor induction
(and perhaps  genotoxicity) by DEP extract, and may
antagonize  such effects by NO2 during coexposure of the
gases.

Purpose was to study effects of Tokyo air SPM, with or without    Ito et al.
coexposure to  SO2 or NO2 or their combination, on the            (1997)
development of proliferative lesions of PEC. PEC hyperplasia
was significantly (p < 05) increased by exposure to SPM, but
coexposure to either gas or their mixture was without
additional effect. No PEC papillomas were observed in
control groups, while a few were seen in the SPM groups,
irrespective of gas coexposures.  Thus, SO2 demonstrated no
tumor promotion or cocarcinogenic properties.  [Study did
not describe the nature of the carbon (C) used.]

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                                                    TABLE AX4-11 (cont'd).  CARCINOGENIC EFFECTS OF SO2
 to
 o
 o
 to
 O
 O
 2
 O
 H
O
 c
 o
 H
 W
 O
 ^
 O
 HH
 H
 W
Concentration
Pulmonary Effects
0 or [10 ppm
(26.2 mg/m3)
SO2 + 5 ppm
(9.4 mg/m3)
NO2] ± [3 or
6 mg/kg bw of
DEN]; exposure
to gases whole
body





Duration
-SO2
SO2 + NO2: 6,
10.5, 15, or 18 mo,
5 day/wk, 19 h/day

DEN: once by
s.c. injection,
~2 wk after the
start of inhalation
exposure





Species

Hamster, Syrian
golden, both
sexes, 10 wk old,
bw not reported,
n = 40/sex per
each of
12 exposure
groups






Effects

The principle focus of this large study was to examine whether two inhaled
diesel-exhaust emission preparations (± particulates) could enhance the
tumorigenesis of injected DEN. An ancillary aim was to see whether inhalation
of the irritant SO2 + NO2 mixture could cause similar enhancement of DEN
tumorigenicity. Gas mixture exposure did not affect bw gain, but slightly
shortened survival times (although significantly only for females). Apart from
effects attributed to DEN, serial sacrifices showed progressive increases in
ciliated trachea! cell aberrations and in number of trachea! mucosal cells. In the
lung, gas mixture-related effects were limited to a progressing alveolar lesion
involving lining with bronchiolar epithelium and the presence of some
pigment-containing AM, and to a mild, diffuse thickening of the alveolar septa.
SO2 + NO2 exposure did not by itself elevate tumor rate in the upper
respiratory tract, nor did it enhance increases induced by DEN. Thus the
mixture appeared to have no tumor inducing or promoting effects.
Reference

Heinrich
etal. (1989)












Nonpulmonary Effects - SO?
0 or 6 ppm (0 or
15.72 mg/m3)
SO2, ± 0.2 ppm
(600 ug/m3);
whole body;
NDMA


20 mo, 5 day/wk,
4 h/day






Rat,
Sprague-Dawley,
female, age and
wt not reported,
n = 36 per group
in 4 relevant
groups

This is a preliminary report for observations after 20 mo (800 h inhalation in
200 exposures, with calculated inhaled cumulative doses of 77 mg SO2 and
2-3 mg NDMA per rat). The effects of NDMA ± SO2 inhalation were studied.
Group mortality was as follows: control (3/36), SO2 (5/36), NDMA (4/36),
NDMA + SO2 (7/36). The only tumors observed were nasal: control (0), SO2
(0), NDMA (1), NDMA + SO2 (3). No observable parameters, including
body wt gain, were affected by the additional SO2 exposure; assessment of
tumor incidence effects could not yet be performed.
Klein et al.
(1989)






Dae = aerodynamic diameter
AM = alveolar macrophage
B[a]P = benzo[a]pyrene
BHPN = N-bis(2-hydroxypropyl) nitrosamine
C = carbon or carbon black particles
DEN = diethylnitrosamine
DEP+C = DEP extract-coated C
DEcCBP = DEP extract coated carbon black particles
DEP = diesel exhaust particles
GSH = glutathione
GSSO3H = glutathione S-sulfonate
GST = glutathione-S-transferase
NDMA = N-nitroso-dimethylamine
Mo = molybdenum
PEC = pulmonary endocrine cells
SPM = suspended particulate matter extract
SPF = specific pathogen free
SQCA = squamous cell carcinoma
W = tungsten

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                                TABLE AX4-12.  RESPIRATORY SYSTEM BIOCHEMISTRY EFFECTS OF SO2
               Concentration
                              Duration
           Species
                Effects
    Reference
to
o
o
Oxidation and Antioxidant Defenses -
Subacute/Subchronic Exposure
          22, 56, orll2mg/m3
          (8.4, 21, or 43 ppm);
          whole body
                         6 h per day for 7 days
Kunming albino mice, male and
female, 5 wks old, 19 ± 2 g,
n = 10/sex/group
to
Changes observed in lung tissue
(concentrations of effect) included higher
SOD activity in males (8.4 ppm) and
females (8.4 and 21 ppm), lower SOD
activity in males (21 and 43 ppm) and
females (43 ppm), increased GPx activity in
males and females (8.4 ppm), decreased
GPx activity in males and females
(>21 ppm), decreased catalase activity in
males (43 ppm), decreased reduced GSH
level in males and females (>8.4 ppm),
increased TEARS level in males (>8.4 ppm)
and females >21 ppm).  Study authors
concluded that sulfur dioxide induced
oxidative damage in lungs of mice.
Meng et al. (2003a)
O
O
2
o
H
O
c
o
H
W
O
V
O
HH
H
W
          22, 64, or 148 mg/m3
          (8.4, 24.4, or 56.5 ppm);
          whole body
                         6 h/day for 7 days
Kunming-strain mice, male, age
not reported, 18-20 g,
n = 10/group
Glucose-6-phosphate dehydrogenase and
GST activity were decreased in lung at
64 and 148 mg/m3. Lung GSH levels were
reduced in the 22 and 148 mg/m3 exposure
groups. Administration of buckthorn seed
oil increased GST and decreased TEARS
activity compared to mice exposed to
42 mg/m3 SO2 alone.
Wu and Meng
(2003)

-------
                            TABLE AX4-12 (cont'd). RESPIRATORY SYSTEM BIOCHEMISTRY EFFECTS OF SO2
             Concentration
                        Duration
          Species
                      Effects
     Reference
to
o
o
to
oo
Oxidation and Antioxidant Defenses -
Subacute/Subchronic Exposure
          5, 50, or 100 ppm
          (13.1, 131, or
          262 mg/m3);
          whole body
                    5 h/day for
                    7-28 days
Wistar rat, male, 7 wks old,
weight not reported,
n = 4-5/treatment group,
8 controls
In the 5 and 100 ppm groups, GSH in BAL fluid
decreased at 7 days and increased at 21 days; at 28 days
GSH returned to normal in the 5 ppm group and further
increased in the 100 ppm group.  GSH was depleted in the
lung, at 5 and 100 ppm but not at 50 ppm. With respect
to GSH-related enzymes, exposure to 5 ppm lowered
GCS, GPx, GST, and GRed activity in the lung. Effects
in the 100 ppm group were similar to the 5 ppm group,
except that lung GPx was not reduced. Exposure to
50 ppm did not affect lung GST, but reduced the number
of inflammatory cells in circulation and decreased GCS,
GPx, GRed, and GT in the lung.  Study authors
concluded that sulfitolysis of glutathione disulphide
occurs in vivo during SO2 exposure and that SO2 is a
potent glutathione depleting agent, even in the absence
of pulmonary injury.
Langley-Evans et al.
(1996)
O
O
2
o
H
O
c
o
H
W
O
V
O
HH
H
W
          10 ppm
          (26.2 mg/m3);
          whole body
                     1 h/day,
                     7 days/wk for
                     6 wks
Swiss albino rat, male, 3, 12,
or 24 mos old, 210-450 g,
n = 9-1 I/group in 6 groups
Effects of age on SO2-induced oxidative effects in lung
tissue were observed in young (3-mo-old), middle aged
(12-mo-old), and old (24-mo old) rats. SO2 exposure
significantly elevated TEARS, SOD, GPx, and GST in all
age groups; reduced catalase in young and middle-aged
rats, but did not affect catalase in old rats.  In rats not
exposed to SO2,  SOD, GPx and GST increased with age
and catalase decreased with age. General observations in
SO2-exposed animals were increases in SOD, GPx,  and
TEARS with age. The authors of the AQCD toxicology
chapter noted that while lipid peroxidation increased with
age, relative TEARS increases in response to SO2 were
inversely correlated with age (i.e., largest percent increase
seen in young rats).
Gumus.lu et al.
(2001)

-------
                            TABLE AX4-12 (cont'd).  RESPIRATORY SYSTEM BIOCHEMISTRY EFFECTS OF SO2
               Concentration
                              Duration
       Species
                     Effects
    Reference
to
o
o
to
VO
Oxidation and Antioxidant Defenses -
Subacute/Subchronic Exposure
          286 mg/m3 (-101 ppmby
          study author calculations);
          whole body
          Note: The study
          mistakenly listed units of
          jig/m3 and it was verified
          with the study authors
          that the units should
          have been listed as
          mg/m3.
                         5 h/day for 28 days
Wistar rat, male, 7 wks
old, weight not
reported, n = 4-16
This study explored the effects of maternal diet protein
restriction during gestation on offspring lung enzyme
responses after SO2 exposure in adulthood. Adult
offspring representing different maternal dietary
concentrations of casein (180 [control],  120, 90 or
60 g/kg) were exposed either to air or SO2. GSH levels
in B AL fluid and the lung were not affected either by
maternal diet or SO2 exposure. In the lung GRed and
GT were not affected by SO2 in any maternal diet group;
GPx was reduced only in the 120 g/kg maternal diet
group; GCS was elevated in the 180 and 60 g/kg groups;
and GST was reduced in the 180, 120 and 90 g/kg
groups (to the level seen in both the air- and
SO2-exposed 60 g/kg maternal diet groups). This study
does not provide information relevant to ambient
exposures, but is being mentioned in this table to
record that a low-concentration level study was not
overlooked.
Langley-Evans
etal. (1997);
Langley Evans
et al. (2007)
O
O
2
o
H
O
c
o
H
W
O
V
O
HH
H
W

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                             TABLE AX4-12 (cont'd).  RESPIRATORY SYSTEM BIOCHEMISTRY EFFECTS OF SO2
             Concentration
                         Duration
         Species
                        Effects
    Reference
to
o
o
Differential Gene Expression
Subacute Exposure
           14, 28, or 56 mg/m3
           (5.35, 10.70, or
           21.40ppm);
           whole body
                      6 h/day for 7 days
Wistar Rat, male, age not
reported, 180-200 g,
n = 6/group in 4 groups
Repeated acute exposure caused significant (p < 0.001-0.05)
concentration-dependent reductions in enzyme activities and
gene expression in the lung for both CYP1A1 and CP1A2.
Effects were seen at the mid and high concentrations, but not
the low. Authors speculate that underlying mechanisms may
involve oxidative stress and/or cytokine release, and may
represent an adaptive response to minimize cell damage.
Qin and Meng
(2005)
           14, 28, or 56 mg/m3
           (5.35, 10.70, or
           21.40ppm);
           whole body
                      6 h/day for 7 days
Wistar rat, male, age not
reported, 180-200 g,
n = 6/group in 4 groups
SO2 exposure caused significant concentration-dependent
changes in the mRNA (mid and high concentrations) and
protein expression (all concentrations in lung, but statistical
significance not indicated) of apoptosis-related genes:
increases for box andp53 apoptosis-promoting genes, and
decreases for the apoptosis-repressing gene bcl-2.
Caspase-3 activity (occurring early in apoptosis process) was
also increased at the mid and high concentration.
Bai and Meng
(2005a)
O
O
2
o
H
O
c
o
H
W
O
V
O
HH
H
W
BAL = bronchoalveolar lavage
CYP = Cytochrome P450
GCS = y-glutamylcysteine synthetase
GSH = glutathione
GT = y-glutamyl transpeptidase
GST = glutathione S-transferase
GPx = glutathione peroxidase
GRed = glutathione reductase
SOD = superoxide dismutase
TEARS = thiobarbituric acid-reactive substances

-------
                              TABLE AX4-13.  RESPIRATORY SYSTEM EFFECTS OF SO2 IN DISEASE MODELS
             Concentration
                           Duration
                             Species
                                              Effects
                                                            Reference
to
o
o
>
I ppm
(2.62 mg/m3);
whole body
5 h/day, 5 days/wk for
4 or 8 mos; half the
animals in the 8-mo
group were allowed to
recover for 3 mos.
Sprague-Dawley rat,
male, young adult,
initial weight not
reported,
n= 12-15/data point
Respiratory system exposure effects on "normal" and
emphysema-like lungs (elastase induced) were assessed by
morphological (e.g., histopathology and morphometry) and
physiological (e.g., lung function and volume measured during
spontaneous breathing and paralysis) endpoints. At 4 mos of
SO2 exposure, bronchial alveolar hyperplasia was increased in
normal animals, but reduced in elastase-treated animals, and
numbers of nonciliated epithelial cells were increased (by
12%) in normal but not elastase-treated animals; neither
morphological observation persisted past 4 mos of exposure.
Physiological tests conducted at 4 mos of exposure revealed
decreased residual volume and quasistatic compliance  in
normal SO2-exposed animals during paralyses, and decreased
residual volume/total lung capacity ratio during spontaneous
breathing and decreased nitrogen washout slope during
paralysis in elastase-treated, SO2-exposed animals.  After
8 mos of exposure, lung volume  and incidence of alveolar
emphysema were elevated by SO2 only in the elastase-treated
animals; those effects were not observed in the recovery
period. Authors concluded that elastase-induced
emphysema persisted but obscured rather than enhanced
SO2 effects.  It was indicated that the model lacked tar
residues typically found in the lungs of smokers.
                                                                                                                                     Smith et al.
                                                                                                                                     (1989)
O
O
2
o
H
O
c
o
H
W
O
V
O
HH
H
W

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                                  TABLE AX4-14. EFFECTS OF MIXTURES CONTAINING SO2 AND OZONE
to
o
o
                   Concentration
SO2 (ppm) Ozone (ppm)
Acute/Subacute Exposure
3 ppm 0.3
(7.9 mg/m3);
head only


Duration Species
5 h/day for 3 days Sheep, sex not
reported, adult,
23 -50 kg, n = 6


Endpoints
Tracheal mucus
velocity
Ciliary beat
frequency
Interaction
Decreased by 40% immediately
after exposure and 25% at 24 h
postexposure to the mixture of the
2 compounds. The effects of
either compound alone were not
reported.
No effect

Reference
Abraham
etal.
(1986)


          Chronic/Subchronic Exposure
to
O
O
2
o
H
O
c
o
H
W
O
V
O
HH
H
W
13.2 mg/m3
(5.0 ppm) in
addition to
1.04 mg/m3
ammonium
sulfate; whole
body
                           0.2 mg/m3
                           (0.10 ppm)
5 h/day,
5 days/wk for
up to 103 days
GDI mice, female,
3-4 wks old, weight not
reported,
n = 360/group total
(14-154/group in each
assay)
Mortality rate after
Streptococcus
aerosol challenge
                                                                        Alveolar
                                                                        macrophage
                                                                        bactericidal activity
                                                                        towards inhaled
                                                                        K. pneumoniae

                                                                        Counts, viability,
                                                                        and ATP levels in
                                                                        cells obtained by
                                                                        pulmonary lavage
Increased in groups exposed to      Aranyi
ozone alone and mixture of ozone,   et al.
SO2, and ammonium sulfate.        (1983)
                                                            Increased trend (non-significant)
                                                            in ozone group but significantly
                                                            increased in mixture group.
                                                            No effect of either treatment

-------
                             TABLE AX4-14 (cont'd).  EFFECTS OF MIXTURES CONTAINING SO2 AND OZONE
                   Concentration
to
o
o
o
o
2
o
H
O
c
o
H
W
O
V
O
HH
H
W
S02 (ppm)
1 ppm
(2.62 mg/m3);
whole body




Ozone (ppm)
1 ppm in
addition to
3 ppm
trans-2-butene



Duration
23 h/day,
7 days/wk, for
4 wks




Species Endpoints
Golden hamster, male, age Lung volumes
not reported, -105 g,
n = 14 or 15/group; mild
emphysema was induced
in some animals by
intratracheal
administration of elastase
Interaction
End expiratory volume, residual
volume, total lung capacity and
vital capacity were unaffected in
the mixture versus air exposure
group in normal or emphysematous
hamsters.

Reference
Raub et al.
(1983)





                                                                                   Respiratory system
                                                                                   compliance
                                                                                   Distribution of
                                                                                   ventilation (N2
                                                                                   washout slope)


                                                                                   Diffusion capacity
                                                                                   for carbon
                                                                                   monoxide
Unaffected in the mixture versus air
exposure group in normal or
emphysematous hamsters.

The N2 slope decreased in the
mixture versus air exposure group
in both normal and emphysematous
hamsters.

Significantly increased in the
mixture versus air-exposed normal
animals. Although the text reported
an increase in the mixture versus
air-exposed emphysematous
animals, Figure 3 of the study
indicated that the effect was very
small and did not obtain statistical
significance.  Significantly lower in
emphysematous versus normal
hamsters exposed to the mixture.
The authors noted a significant
interaction between exposure to
the mixture and emphysema.

-------
to
o
o
                             TABLE AX4-14 (cont'd). EFFECTS OF MIXTURES CONTAINING SO2 AND OZONE
                  Concentration
            SO2 (ppm)     Ozone (ppm)
Duration
Species
Endpoints
Interaction
Reference
                                                                               Histopathology      Inflammatory lesions were found
                                                                                                  in the lungs of emphysematous
                                                                                                  hamsters exposed to air or the
                                                                                                  mixture. Hyperplasia incidence
                                                                                                  was higher in emphysema
                                                                                                  hamsters exposed to the mixture
                                                                                                  versus air.  Inflammatory lesions
                                                                                                  were similar in emphysematous
                                                                                                  hamsters exposed to air or the
                                                                                                  mixture. Data were not shown for
                                                                                                  histopathology data.

                                                                               Overall author       Animals with impaired lung
                                                                               conclusion          function may have decreased
                                                                                                  capacity to compensate for the
                                                                                                  pulmonary insult caused by
                                                                                                  exposure to a complex pollutant
                                                                                                  mixture.
O
O
2
O
H
O
c
o
H
W
O
V
O
HH
H
W

-------
                     TABLE AX4-15.  EFFECTS OF SO2 LAYERED ON METALLIC OR CARBONACEOUS PARTICLES
to
o
o
O
O
2
o
H
O
c
o
H
W
O
V
O
HH
H
W
                  Concentration
             SO,
Metal (mg/m3)
                                           Duration
Species
Endpoints
                                                                                  Interaction
Reference
~ 1 ppm
(2.6 mg/m3);
whole body




Zinc oxide: 0.8, 3 h
2.7, or 6.0 mg/m3
(0.05 uM projected
area diameter,
GSD 2.0) (sulfate,
sulfite, and sulfur
trioxide detected)
Hartley guinea Vital capacity
pig, male, age not
reported,
240-300 g,
n = 7-16/group


No effect with exposure to 7.8 mg/m3 zinc
oxide alone and 2.7 mg/m3 zinc oxide in
combination with SO2, but decreased with
exposure to 0.8 and 6.0 mg/m3 zinc oxide in
combination with SC>2.


Lam et al.
(1982)





                       7.8
                                                 Total lung capacity
                                                                         Diffusion capacity
                                                                         for carbon monoxide
                                                                         and ratio of
                                                                         diffusion capacity
                                                                         for carbon monoxide
                                                                         to total lung capacity
                                                                         or alveolar volume.

                                                                         Alveolar volume
                                 No effect with exposure to 7.8 mg/m3 zinc
                                 oxide alone, but decreased with exposure to
                                 6.0 mg/m3 zinc oxide in combination with
                                 S02.

                                 No effect with exposure to 7.8 mg/m3 zinc
                                 oxide alone, but decreased with exposure to
                                 2.7 and 6.0 mg/m3 zinc oxide in
                                 combination with SO?.
                                                                     No effect with exposure to 7.8 mg/m3 zinc
                                                                     oxide alone, but decreased with exposure to
                                                                     6.0 mg/m3 zinc oxide in combination with
                                                                     S02.
~1 ppm 0
(2.6 mg/m3);
head only

1 h Hartley guinea
pig, male, age not
reported,
200-300 g,
n = 8-23/group
Pulmonary function SO2 exposure alone resulted in an 1 1%
increase in resistance and 12% decrease in
compliance.

Amdur
etal.
(1983)


-------
                TABLE AX4-15 (cont'd).  EFFECTS OF SO2 LAYERED ON METALLIC OR CARBONACEOUS PARTICLES
                       Concentration
to
o
o
               SO,
                     Metal (mg/m3)
                           Species     Endpoints
    Interaction
            Reference
Concentration
O
O
2
O
H
O
c
o
H
W
O
^
O
HH
H
W
          ~1 ppm
          (2.6 mg/m3)
          ~1 ppm
          (2.6 mg/m3)
          ~1 ppm
          (2.6 mg/m3)
~1 ppm
(2.6 mg/m3)
                Zinc oxide: -1-2 (0.05 uM
                projected area diameter,
                GSD 2.0); mixed at 24 °C
                and 30% RH

                -1-2; mixed at 24 °C and
                30% RH
                                                                            Pulmonary function
                                                  Pulmonary function
                -1-2; mixed at 480 °C and
                30% RH
                                                  Pulmonary function
-1-2; mixed at 480 °C and
80% RH with addition of
water vapor downstream


-1-2; mixed at 480 °C and
30% RH with addition of
water vapor during
mixing.
                                                                  Pulmonary function
Pulmonary function
Zinc oxide exposure alone resulted in
a 9% decrease in compliance that
persisted 1 h after exposure.


A 12% decrease in compliance and
decreased tidal volume that persisted
1 h after exposure, and decreased min
volume.  There was no evidence of
new compound formation.  Study
authors concluded that effects on
tidal volume and min volume
mostly likely represented an
additive effect.

A 12% decrease in compliance and
decreased tidal volume that persisted
1 h after exposure and a 12% increase
in resistance and decreased min
volume.  There was no evidence of
new compound formation.

A 13% decrease in compliance that
persisted 1 h after exposure and a
29% increase in resistance. Sulfite
formation was observed.

A 19% increase in resistance that
persisted 1 h after exposure,
decreased tidal volume immediately
after exposure, and a 26% decrease in
compliance 1 h after exposure.
Sulfate, sulfite, and sulfur trioxide
formation was observed.

-------
                TABLE AX4-15 (cont'd). EFFECTS OF SO2 LAYERED ON METALLIC OR CARBONACEOUS PARTICLES
                    Concentration
to
o
o
O
o
2
o
H
O
c
o
H
W
O
V
O
HH
H
W
                SO,
 Metal (mg/m3)    Duration
                                                     Species
                         Endpoints
                              Interaction
                                   Reference
1.10-1.25 ppm Copperoxide: Ih
(2.9-3.3 mg/m3); 1.16-2.70
head only (O.I uM)
Hartley guinea pig, Pulmonary
male, age not resistance
reported, 275-375 g;
n = 8/group
Increased 32-47% during exposure
and at 1 and 2 h postexposure when
SO2 and copper oxide were mixed at
37 °C, a condition that resulted in
formation of 0.36 umol/m3 sulfite
on the copper oxide particles. No
effect was observed with the
compounds were mixed at 141 1 °C,
a condition that led to the formation
of sulfate on the copper oxide
particles.
Chen et al.
(1991)
          1.02 ppm
          (2.7 mg/m3);
          head only
1.10 ppm
(2.9 mg/m3)

1.08 ppm
(2.8 mg/m3)
Zinc oxide: 0
(0.05 uM median
diameter, GSD
2.0)

2.76
                                   Ih
Hartley guinea pig,
male, age not
reported, 290-410 g,
n = 6-9/group
                                                                             Dynamic lung
                                                                             compliance
Baseline pulmonary
resistance at 2 h
following exposure
                                                                   Airway
                                                                   hyperresponsiveness
                                                                   to acetylcholine
No effect when mixed under
conditions that led to the formation
of either sulfate or sulfite on
particles.

No effect in any group.
                                        No effect with exposure to SO2 or
                                        zinc oxide alone; compared to
                                        furnace controls (3% argon).
                                        Hyperresponsiveness increased in
                                        both groups exposed to
                                        SO2-layered zinc oxide particles.
Chen et al.
(1992)
0.87
2.34

-------
                TABLE AX4-15 (cont'd). EFFECTS OF SO2 LAYERED ON METALLIC OR CARBONACEOUS PARTICLES
to
o
o
oo
o
o
2
o
H
O
c
o
H
W
O
V
O
HH
H
W
Concentration
SO2 Metal (mg/m3)
10 ppm 0
(26.2 mg/m3);
nose only

Duration Species
4 h Swiss mice,
female, 5 wks
old, 20-23 g,
n = 5/group
Endpoints
AM Fc-receptor
mediated phagocytosis
of sheep red blood cells
at 3 days after exposure
Interaction
Dose-dependent reductions in AM
phagocytosis were observed at each
concentration of SO2 mixed with carbon
black aerosol at 85% relative humidity,
Reference
Jakab et al.
(1996)
5 ppm
(13.1 mg/m3)
10 ppm
(26.2 mg/m3)
Carbon black:
10 mg/m3 (0.3 uM,
GSD 2.7)

10 mg/m3 (formed
6 ug sulfate at 85%
humidity)

10 mg/m3 (formed
13.7 ug sulfate at
85% humidity)
                                                                                    the only conditions under which SO2
                                                                                    significantly chemisorbed to carbon black
                                                                                    aerosol and oxidized to sulfate. AM
                                                                                    phagocytic activity was reduced
                                                                                    somewhat immediately after exposure
                                                                                    (Day 0), was minimal on Days 1 and 3,
                                                                                    began increasing on Day 7, and was fully
                                                                                    recovered by Day 14. No effects were
                                                                                    observed with exposure to SO2 or carbon
                                                                                    black alone.  The data indicate that
                                                                                    environmentally relevant  respirable
                                                                                    carbon particles can act as effective
                                                                                    vectors for delivering toxic amounts of
                                                                                    acid SO42 to distal parts of the lung.

-------
                TABLE AX4-15 (cont'd).  EFFECTS OF SO2 LAYERED ON METALLIC OR CARBONACEOUS PARTICLES
to
o
o
VO
O
O
2
O
H
O
c
o
H
W
O
^
O
HH
H
W
Concentration
S02
20ppm
(52.4 mg/m3)
10 ppm
(26.2 mg/m3);
nose only
Metal (mg/m3)
10 mg/m3 (formed
48.7 ug sulfate at
85% humidity)
0
Duration

4 h once or
for 4, 5, or
6 days
Species

Outbred Swiss
mouse, female, age
and weight not
Endpoints

Inflammatory
response after a
single 4-h exposure
Interaction

There was no effect on total cell
number, lymphocyte/PMN differentials,
or total protein levels in B AL fluid in
Reference

Clarke
etal.
(2000)
10 ppm
(26.2 mg/m3)
                           Carbon black:
                           10 mg/m3 (10%
                           humidity)
                           Carbon black:
                           10 mg/m3 in 85%
                           humidity to
                           generate 8 ug/m3
                           acid sulfate
Carbon black:
10 mg/m3 in 10%
humidity to
generate 41 ug/m3
acid sulfate
                                                          specified, n = 10 or
                                                          12 per
                                                          experimental
                                                          value.
                                                                   AM Fc-mediated
                                                                   phagocytosis after a
                                                                   single 4-h exposure


                                                                   Intrapulmonary
                                                                   bactericidal activity
                                                                   toward
                                                                   Staphylococcus
                                                                   aureus
                                                                                        any group.
                                                                       Suppressed by acid sulfate coated
                                                                       particles (at -140 ug/m3) at 1, 3, and
                                                                       7 days postexposure; values returned to
                                                                       normal by Day 14.

                                                                       Decreased by a single 4-h exposure to
                                                                       sulfate coated particles (at -140 ug/m3)
                                                                       at 1 and 3 days postexposure, with
                                                                       recovery by Day 7.  Suppression was
                                                                       also observed after 5 and 6 days of
                                                                       repeated exposure to -20 ug/m3 sulfate
                                                                       coated particles a condition more
                                                                       relevant to potential ambient human
                                                                       exposures.

-------
           TABLE AX4-15 (cont'd). EFFECTS OF SO2 LAYERED ON METALLIC OR CARBONACEOUS PARTICLES
to
o
o
Concentration
S02
10 ppm
(26.2 mg/m3)
1 ppm
(2.62 mg/m3)

1 ppm
(2.6 mg/m3);
nose only

Metal (mg/m3) Duration
Carbon black:
10 mg/m3 in 85%
humidity to
generate 137 ug/m3
acid sulfate
Carbon black:
1 mg/m3 in 85%
humidity to
generate
20 ug/m3acid
sulfate:
Zinc oxide: 3 h/day for 6 days;
6 (0.05 uM animals evaluated
projected area for up to 72 h
diameter, GSD 2.0) following exposure

Species Endpoints Interaction



Hartley guinea Right lung to No effect by SO2. Increased for 48 h in
pig, male, age body weight group exposed to SO2-layered zinc oxide.
not reported, ratio
250-320 g,
n = 5-18/group/
time point
Reference



Conner
etal.
(1985)

O
o

2
o
H

O
c
o
H
W

O
V
O
HH
H
W

-------
                 TABLE AX4-15 (cont'd).  EFFECTS OF SO2 LAYERED ON METALLIC OR CARBONACEOUS PARTICLES
                 Concentration
to
o
o
             SO,
Metal (mg/m3)    Duration    Species
                                                                 Endpoints
Interaction
Reference
>

-k
          1 ppm        0
          (2.6 mg/m3)
                                      Right lung wet to
                                      dry weight ratio

                                      Lung morphology
                                                              Trachea! secretory
                                                              cell concentration.

                                                              Epithelial
                                                              permeability

                                                              DNA synthesis
                                                              (3H-tymidien
                                                              uptake) terminal
                                                              bronchial cells

                                                              Lung volumes
                                                                                 No effect by SO2. Increased at 1 h after exposure in
                                                                                 SO2-layered zinc oxide group.

                                                                                 No lesions were observed in the SO2 group.  In the group
                                                                                 exposed to SO2-layered zinc oxide, there was increased
                                                                                 incidence of alveolar duct inflammation consisting of
                                                                                 interstitial cellular infiltrate, increased numbers of
                                                                                 macrophages, and replacement of squamous alveolar
                                                                                 epithelium with cuboidal cells. Frequency and severity of
                                                                                 lesions were greatest immediately following exposure and by
                                                                                 72 h following exposure, lesions were mild and infrequent.

                                                                                 No effects with either exposure scenario.
                                                          No effects with either exposure scenario.
                                                          Unaffected by SO2.  Increased at 24 and 72 h after exposure to
                                                          zinc oxide/SO2.
                                                          Unaffected by SO2 exposure. Functional reserve capacity,
o
o
0
H
O
o
H
W
O
O
H
hi

Diffusion capacity
for carbon
monoxide
Alveolar volume
Pulmonary
mechanics

viuii ^ajjci^iiy , oiiu luicii lung ^ajjd^iiy wcic uc^icascu iiuiii
1 to 72 h following exposure to zinc oxide/SO2.
Unaffected by SO2 exposure. Decreased by -40-50% from
1 to 24 h following exposure to zinc oxide/SO2.
Unaffected by SO2 exposure. Decreased by -10% from 1 to
24 h following exposure to zinc oxide/SO2.
Respiratory frequency, tidal volume, pulmonary resistance,
and pulmonary compliance were unaffected by either
exposure.

-------
                TABLE AX4-15 (cont'd).  EFFECTS OF SO2 LAYERED ON METALLIC OR CARBONACEOUS PARTICLES
                      Concentration
to
o
o
              SO,
     Metal (mg/m3)
   Duration
     Species
Endpoints
Interaction
Reference
to
O
o
2
o
H
O
c
o
H
W
O
V
O
HH
H
W
          1 ppm
          (2.6 mg/m3)
                                                             Author
                                                             conclusion
          1 ppm
          (2.6 mg/m3);
          head only
Zinc oxide: 1 or 2.5
(0.05 uM CMD, GSD 2.0)
Sulfate was generated at
7 and 11 ug/m3 at each
respective dose; sulfuric
acid level was reported at
21 and 33 ug/m3 at each
respective dose.
3 h/day for
5 days
Guinea pig, sex,     Pulmonary
age, and weight not  diffusing
reported,            capacity
n = 8-9/group
                                                  Ih
                                                             Bronchial
                                                             sensitivity to
                                                             acetylcholine
              Changes were identical to those
              reported in a previous study in
              which guinea pigs were exposed to
              zinc oxide alone. Sulfur
              compounds deposited on the
              surface are less important than the
              zinc oxide particle.

              No effect with exposure to 1 ppm
              SC>2 or 2.5  mg/m3 zinc oxide alone
              (data not shown by study authors).
              Significant  and dose related
              decreases on exposure days 4 and
              5 at 7 ug/m3 sulfate (20% less than
              control) and days 2-5 at 11 ug/m3
              sulfate (up to 40% less than control).

              No effect of 1 ppm SO2 or 2.8 mg/m3
              zinc oxide alone. Increased with SO2
              administered in combination with
              either zinc oxide dose. The study
              authors noted that responses were
              similar to those produced by
              200 jig/m3 sulfuric acid of similar
              particle size, thus indicating the
              importance of surface layer.
                       Amdur
                       etal.
                       (1988)

-------
                TABLE AX4-15 (cont'd). EFFECTS OF SO2 LAYERED ON METALLIC OR CARBONACEOUS PARTICLES
to
o
o
O
O
2
o
H
O
c
o
H
W
O
^
O
HH
H
W
Concentration
S02
5 ppm
(13 mg/m3);
nose only
Metal (mg/m3)
22 mg/m3 gallium
oxide (0.2 uM
volume median
Duration
2 h/day for 4 days,
followed by 2 days
without exposure,
Species
Fischer-344, male
and female,
18-19 wks old,
Endpoints
Tracheal and
large airways
morphology
Interaction
No effects observed with coexposure
to gallium oxide and SO2.
Reference
Shami et al.
(1985)
                       diameter, GSD not
                       reported), with and
                       without addition of
                       7 mg/m3
                       benzo(a)pyrene
followed by 5 more
days of exposure;
animals were evaluated
for up to 28 days
following exposure
weight not reported,
n = 2/sex/group at
each evaluation time
period
                                                                                      Pulmonary
                                                                                      morphology
                                            Cell
                                            proliferation
                                            (3H-thymidine
                                            intake) in
                                            trachea and
                                            large airways
                                    Increase numbers of non-ciliated
                                    cells in terminal bronchial epithelium
                                    was observed in the SO2/gallium
                                    oxide/benzo(a)pyrene group. Mild
                                    peribronchial and perivascular
                                    mononuclear inflammatory cell
                                    infiltrate and small hyperplastic
                                    epithelial cells in alveoli, and
                                    alveolar septal hypertrophy was
                                    observed in the SO2/gallium oxide
                                    group, with and without
                                    benzo(a)pyrene exposure; effects
                                    were more prominent with
                                    benzo(a)pyrene exposure.

                                    In the SO2/gallium oxide group:
                                    increased on days 1 and 14; basal
                                    cells were primarily labeled.  In the
                                    SO2/gallium oxide/benzo(a)pyrene
                                    group: increased on day 8.

-------
                 TABLE AX4-15 (cont'd).  EFFECTS OF SO2 LAYERED ON METALLIC OR CARBONACEOUS PARTICLES
                   Concentration
to
o
o
               SO,
                Metal (mg/m3)
                     Duration
     Species
     Endpoints
             Interaction
 Reference
           5 ppm
           (13 mg/m3);
           nose only
                                                                    Cell proliferation
                                                                    (3H-thymidine intake)
                                                                    in terminal
                                                                    bronchioles
                                                                              Types of
                                                                              3H-thymidine-labeled
                                                                              cells in the alveolar
                                                                              region
                                                                            In the SO2/gallium oxide group: increased
                                                                            on day 14; Clara cells were primarily
                                                                            labeled. In the SO2/gallium
                                                                            oxide/benzo(a)pyrene group: increased
                                                                            on day 11.

                                                                            In the SO2/gallium oxide group: type II
                                                                            cells were primarily labeled in the
                                                                            alveolar region through 14 days of
                                                                            exposure.

                                                                            In the SO2/gallium oxide/benzo(a)pyrene
                                                                            group: labeling was increased in Type II,
                                                                            Type I, and endothelial cells on day 8.
O
O
2
O
H
O
c
o
H
W
O
V
O
HH
H
W
          5 ppm
          (13 mg/m3);
          nose only
5 ppm
(13 mg/m3)
Gallium oxide:
27 mg/m3
(-0.20 uM
MMD, GSD
-1.5-2), with and
without
7.5 mg/m3 of
1-nitropyrene and
benzo[a]pyrene

0
                                 2 h/day,
                                 5 days/wk for
                                 4 wks
F344/Crl rat, male
and female,
10-11 wks old,
weight not
reported,
n = 6/sex/group
Pulmonary particle
clearance
No effect was observed with exposure to
SO2 alone; clearance was slowed only by
gallium oxide, with or without
coexposure to SO2 or the other
compounds; SO2 in combination with the
polyaromatic hydrocarbons had no effect
on clearance rate.  Study authors
concluded that toxicity was dominated by
gallium oxide.
Wolff etal.
(1989)
BAL = bronchoalveolar lavage fluid
CMD = count median diameter
GSD = geometric standard deviation
MMAD = mass median aerodynamic diameter
MMD = mass median diameter
RH = relative humidity

-------
                                         TABLE AX4-16.  EFFECTS OF SO2 AND SULFATE MIXTURES
to
o
o
O
O
2
o
H
O
c
o
H
W
O
V
O
HH
H
W
Concentration
SO2 Sulfate (mg/m3)
Acute
5 ppm Sulfate aerosol 1.5
(13.1 mg/m3); (0.5 uMMMAD,
nose only GSD 1.6)
Chronic/Subchronic
1 ppm 0
(2.62 mg/m3);
whole body
Duration

4h

5 h/day,
5 days/wk
for 4 or
8 mos; half
the animals
in the 8-mo
group were
Species

Sprague Dawley
rat, male, age not
reported, -200 g,
n = 8/group

Sprague-Dawley
rat, male, young
adult, initial
weight not
reported,
n= 12-15/data
point
Endpoints

Lung clearance of
radiolabeled tracer
particles.

Morphological
observations at
4 mos exposure in
"normal" rats
Interaction

No significant effect was observed
with the mixture of the two
compounds at 80-85% humidity.

Bronchiolar epithelial hyperplasia
and increased numbers of
non-ciliated epithelial cells were
observed in rats exposed to either
compound alone but coexposure to
both compounds did not magnify the
effects. An increase in alveolar
Reference

Mannix et al.
(1982)

Smith et al.
(1989)
                                               allowed to
                                               recover for
                                               3 mos.
1 ppm
(2.62 mg/m3)
               (NH4)2S04:
               0.5 mg/m3
               (MMAD = 0.42-0.44
               ± 0.04 urn, GSD
               2.2-2.6)
0.5 mg/m3
                                                     Morphological
                                                     observations at
                                                     4 mos exposure in
                                                     rats treated with
                                                     elastase to induce an
                                                     emphysema-like
                                                     condition
Morphological
observations at
8 mos exposure in
"normal" rats
chord length was observed in the
(NH4)2SO4 group and no further
changes were observed with
coexposure to SO2.

Bronchiolar epithelial hyperplasia
was decreased in groups exposed to
either compound alone or the
mixture of the two compounds.
A decrease in alveolar chord length
was observed in the (NH4)2SO4
group and no further changes were
observed with coexposure to SO2.

An increase in non-ciliated epithelial
cells and alveolar birefringence (an
indication of alveolar interstitial
fibrosis) was observed only in the
group exposed to (NH4)2SO4.

-------
                                      TABLE AX4-16 (cont'd).  EFFECTS OF SO2 AND SULFATE MIXTURES
                      Concentration
to
o
o
                  SO,
Sulfate (mg/m3)     Duration
Species
Endpoints
Interaction
Reference
O
O
2
O
H
O
c
o
H
W
O
^
O
HH
H
W
          Chronic/Subchronic
                                                                                Morphological
                                                                                observations at
                                                                                8 mos exposure in
                                                                                rats treated with
                                                                                elastase
                                                                                Morphological
                                                                                observations at
                                                                                12 mos exposure in
                                                                                normal rats

                                                                                Morphological
                                                                                observations at
                                                                                12 mos exposure in
                                                                                rats treated with
                                                                                elastase

                                                                                Lung function
                                                                                effects at 4 mos
                                                                                exposure in normal
                                                                                rats
                                                Lung function
                                                effects at 4 mos
                                                exposure in
                                                elastase-treated
                                                rats
                                                                   An increase in lung volume per body
                                                                   weight and emphysema incidence was
                                                                   observed in groups treated with either
                                                                   compound alone or in combination;
                                                                   alveolar chord length was increased only
                                                                   in the group exposed to the mixture of
                                                                   compounds.

                                                                   Increased alveolar chord length was
                                                                   observed only in the (NH4)2SO4 group.
                                                                   In increase in absolute lung volume was
                                                                   observed only in the group treated with
                                                                   the mixture of both compounds.
                               A decrease in residual volume was
                               observed in the SO2 group and decreased
                               quasistatic compliance was observed in
                               the SO2 group and in the  (NH4)2SO4
                               group, but the effects were not observed
                               with the mixture.

                               Ratio of residual volume/total lung
                               capacity and N2 washout was decreased
                               in the SO2 group and in the (NH4)2SO4
                               group, but the effects were not observed
                               with the mixture.

-------
                                     TABLE AX4-16 (cont'd).  EFFECTS OF SO2 AND SULFATE MIXTURES
to
o
o
                     Concentration
                  S02
Sulfate (mg/m3)    Duration
Species
Endpoints
Interaction
Reference
          Chronic/Subchronic
                                                                                 Overall            In general, pollutant effects were
                                                                                 conclusions         minimal and transient, and
                                                                                                   appeared obscured or repressed
                                                                                                   in elastase-treated groups;
                                                                                                   (NH4)2SO4 was more bioactive
                                                                                                   than SO2, with little evidence of
                                                                                                   mixture additivity (in several
                                                                                                   instances, effects seen with one or
                                                                                                   both pollutants individually were
                                                                                                   not seen with the mixture).
          GSD = geometric standard deviation
          MMAD = mass median aerodynamic diameter
O
o
2
o
H
O
c
o
H
W
O
V
O
HH
H
W

-------
                            TABLE AX4-17. EFFECTS OF ACTUAL OR SIMULATED AIR POLLUTION MIXTURES
to
o
o
                           Concentration
                  Exposed Group
                                Control Group
                                                            Duration
                                                                Species
                              Endpoints
                                              Effect
                                   Reference
oo
O
o
2
o
H
O
c
o
H
W
O
V
O
HH
H
W
Acute/Subactute

Air pollutant mixture at full
concentration (tested in two
studies): 0.35 ppm ozone,
1.3 ppm nitrogen dioxide,
2.5 ppm (6.6 mg/m3) SO2,
10 ug/m3 manganese sulfate,
500 ug/m3 ferric sulfate,
500 ug/m3 ammonium sulfate,
500 ug/m3 carbon aerosol. The
mixture was also tested at l/i and
YA concentrations. For aerosols
MMAD = 0.3-0.48 uM with
GSD = 2.6-4.6. Nose-only
exposure Compounds formed
included sulfate, nitrate,
hydrogen ion, and nitric acid.
                                          Clean air
4h
Sprague-Dawl
ey rat, male,
age not
reported,
240-280 g,
n = 6-9/group
Breathing
pattern
                                                                                       Histopathology
                                                                            Mucociliary
                                                                            clearance
Effect of full concentration mixture
in two studies: increased breathing
frequency, trend or significant
decrease in tidal volume, decreased
or unaffected oxygen consumption,
and increased or unaffected
ventilation equivalent for oxygen.
Effect of half concentration
mixture: increased min ventilation.
Quarter concentration: no
significant effects.
                                             Full concentration: Area of type 1
                                             parenchyma! lung lesions were
                                             increased in 1 of 2 experiments and
                                             area of type 2 parenchymal lung
                                             lesions were increased in both
                                             experiments. Effects were
                                             equivalent to those observed with
                                             ozone exposure alone.
                                             Half and quarter concentrations:
                                             No effects.

                                             No effect on early or late clearance
                                             of 85Kr-labeled polystyrene
                                             particles.
Mautz et al.
(1988)

-------
                       TABLE AX4-17 (cont'd).  EFFECTS OF ACTUAL OR SIMULATED AIR POLLUTION MIXTURES
                      Concentration
to
o
o
             Exposed Group
Control Group    Duration
                 Species
                              Endpoints
                                            Effect
                    Reference
O
O
2
O
H
O
c
o
H
W
O
^
O
HH
H
W
          Acute/Subacute
          2.55 ppm (6.7 mg/m )
          SO2, 0.3 ppm ozone,
          1.2 ppm nitrogen oxide,
          150 ug/m3 ferric oxide,
          130 ug/m3 nitric acid,
          2.0 uM/m3 hydrogen
          ion, and 500 ug/m3
          total Fe3+, Mn2+, and
          NH42+ combined; nose
          only
Purified air
4 h/day for
7 or
21 days
Sprague-Dawle
y rat, male, age
not reported,
200-225 g,
n= 5-13/group/
time period
Nasal epithelial injury (measured by
tritiated thymidine uptake).

Bronchoalveolar epithelial permeability
to 99mTc-diethylenetriaminepentaacetate.
                                                                                Nasal mucosal permeability to
                                                                                99mTc-diethylenetriaminepentaacetate.

                                                                                Macrophage rosette formation.
No effect at any
concentration.

No effect at either
time period.
                                                                                     No effect at either
                                                                                     time period.

                                                                                     Rosette formation
                                                                                     was decreased
                                                                                     (indicating damage
                                                                                     to Fc receptors) for
                                                                                     up to 4 days after
                                                                                     the 7-or 21-day
                                                                                     exposure;
                                                                                     magnitude of effect
                                                                                     was greater
                                                                                     following the
                                                                                     21-day exposure.
                                                                                     By day 4 after
                                                                                     exposure, numbers
                                                                                     began increasing
                                                                                     and by day 7 were
                                                                                     equivalent to
                                                                                     control values.
Phalen and
Kleinman
(1987)

-------
                        TABLE AX4-17 (cont'd).  EFFECTS OF ACTUAL OR SIMULATED AIR POLLUTION MIXTURES
                          Concentration
to
o
o
                Exposed Group
  Control Group     Duration
                Species
   Endpoints
              Effect
Reference
O
O
2
O
H
O
c
o
H
W
O
V
O
HH
H
W
          Acute/Subacute
                                                                                      Macrophage
                                                                                      phagocytic
                                                                                      activity
           Subchronic/Chronic

           Urban air: Sao Paulo, mean
           levels of air pollutants
           measured 200 m from the
           police station where rats
           were kept: 29.05 ug/m3
           (0.011ppm)SO2; 1.25ppm
           carbon monoxide,
           ll.OSppb ozone,
           35.18 ug/m3 particulates.
Rural air: Atibaia,
an agricultural
town 50 km from
Sao Paulo was
considered the
control; air
pollutant levels
were not measured.
6 mos       Wistar rat,
            male, 2 mos old,
            weight not
            reported,
            n = 14-30/group
Death
                                                                                      Respiratory
                                                                                      mechanics
                                                Mucus properties
                                                Bronchoalveolar
                                                lavage
                                                                  In rats exposed for 7 days, decreased
                                                                  activity was observed for 2 days
                                                                  following exposure.  No effects were
                                                                  observed after the 21-day exposure
                                                                  period.
37 of 69 rats housed in Sao Paulo died    Saldiva
before the end of the study and          etal.
autopsy of 10 animals identified         (1992)
pneumonia as the cause of death; 10 of
56 animals housed in Atibaia died.
                                               Nasal resistance was higher in animals
                                               housed in Atibaia.  No differences
                                               were observed for pulmonary
                                               resistance or dynamic lung elastance.

                                               In animals from Sao Paulo trachea!
                                               mucus output was lower, relative
                                               speed of tracheal mucus (as assessed
                                               by frog palate assay) was slower, ratio
                                               between viscosity and elasticity was
                                               higher for nasal mucus, and rigidity of
                                               tracheal mucus was increased.

                                               In lavage fluid from animals housed in
                                               Sao Paulo, there were increased
                                               numbers of cells, lymphocytes, and
                                               polymorphonuclear cells.

-------
                       TABLE AX4-17 (cont'd).  EFFECTS OF ACTUAL OR SIMULATED AIR POLLUTION MIXTURES
                        Concentration
to
o
o
               Exposed Group
Control Group
Duration
Species
Endpoints
Effect
Reference
>
O
O
2
O
H
O
c
o
H
W
O
V
O
HH
H
W
          Subchronic/Chronic
                                                                                       Histochemical
                                                                                       evaluation
                                                                                       Ultrastructural
                                                                                       studies
                                                                   Hyperplasia was observed in
                                                                   respiratory epithelium of rats
                                                                   housed in Sao Paulo.

                                                                   Animals housed in Sao Paulo
                                                                   had a higher frequency of cilia
                                                                   abnormalities including
                                                                   composite cilia, microtubular
                                                                   defect, vesiculation, and
                                                                   decreased microvelocity of
                                                                   luminal membrane.
Urban air: See description
for Saldiva etal. (1992)





Urban air: Sao Paulo, levels
of air pollutants measured
were: -8-50 ug/m3
(0.003-0.019 ppm) SO2,
—0.1-0.45 ppm nitrogen
dioxide, -4.8-7 ppm carbon
monoxide, and
-50-120 ug/m3 paniculate
matter.

Rural air: See
description for
Saldiva et al.
(1992)



Rural air:
Atibaia, an
agricultural town
50 km from Sao
Paulo was
considered the
control; air
pollutant levels
were not
measured.
6 mos






Four groups of rats
were housed:
3 mos in Sao
Paulo, 3 mos in
Sao Paulo followed
by 3 mos in
Atibaia, 3 mos in
Atibaia, or 6 mos
at Atibaia.

Rats were Nasal passage
from the same pathology
cohort as
Saldiva et al.
(1992);
n= 15/group

Wistar rats, Lung
male, responsiveness to
1.0-1.5 mos methacholine
old, weight not
reported,
n = 30/group




Rats housed in Sao Paulo had
increased nasal epithelium
volume, larger amounts of
mucosubstances stored in
epithelium, and more acidic
mucus secretions in lamina
propria glands.
Increased respiratory system
elastance resulting from
increased sensitivity to
methacholine in rats housed in
Sao Paulo for 3 mos compared
to all the other groups. No
exposure-related effects were
observed for respiratory system
resistance.

Lemos et al.
(1994)





Pereira et al.
(1995)









-------
                          TABLE AX4-18. EFFECTS OF METEOROLOGICAL CONDITIONS ON SO2 EFFECTS
to
o
o
to
O
O
2
o
H
O
c
o
H
W
O
V
O
HH
H
W
Concentration
S02(ppm)
0.5 or 5 ppm (1.31
or 13.1 mg/m3);
apparently
intratracheal











1.0, 2.5, or 5 ppm
(2.62, 6.55, or
13.1 mg/m3);
apparently
intratracheal




Condition
Drop in air
temperature
from 3 8 °C to
15 °C











Drop in
intratracheal
temperatures
from -35.5 °C
to -27 °C




Duration
45 min














In pre-exposure period:
15-min exposure to
warm humid air,
10-min exposure to
cold dry air, and
15-min exposure to
warm humid air. In the
SO2 exposure period:
10-min exposures to
Species
Rabbit, sex not
reported, adult,
mean 2.0 kg,
n= 5-10/group;
animals were
mechanically
ventilated.








Duncan-Hartley
guinea pigs, male,
age and weight not
reported,
n= 7-12/group,
mechanically
ventilated; animals
were
hyperventilated
Endpoints Interaction
Lung Exposure to cool air for 20 min
resistance resulted in a -54% mean increase in
lung resistance. Exposure to SO2 for
20 min increased lung resistance by
16% at 0.5 ppm and 50% at 5 ppm.
The difference in lung resistance
from warm to cold air was halved
(27%) by exposure to 0.5 ppm and
was not significant at 5 ppm. The
study authors concluded that
transient alteration in
tracheobronchial wall following
SO2 exposure may have reduced
accessibility of airway nervous
receptors to cold air.
Peak Percent decreases were significantly
expiratory greater with exposures to SO2 in dry
flow air at concentrations of 1.0 ppm
(-32.7%) and 2.5 ppm (-35.6%) than
with exposure to cold dry air (-27%);
decrease at 5 ppm SO2 in cold dry air
(-25.3%) was similar to that with
cold dry air. The effects did not
persist following exposures.
Reference
Barthelemy
etal. (1988)













Halinen et al.
(2000a)







each SO2 concentration
in cold dry air or with
cold dry air alone were
preceded and followed
by 15-min exposures to
warm humid air.
during cold air and
SO2 exposure to
simulate exercise.

-------
                        TABLE AX4-18 (cont'd). EFFECTS OF METEOROLOGICAL CONDITIONS ON SO2 EFFECTS
                 Concentration
to
o
o
SO2 (ppm)      Condition         Duration
                                                                  Species
    Endpoints
Interaction
Reference
O
o
2
o
H
O
c
o
H
W
O
V
O
HH
H
W
                                                                                 Bronchoalveolar
                                                                                 lavage
Tidal volume        Percent decreases were significantly
                   greater with exposure to SO2 in cold
                   dry air at concentrations of 1.0 ppm
                   (-22.4%) and 2.5 ppm (-28.3%) than
                   with exposure to cold dry air
                   (-18.1%); decrease at 5 ppm SO2 in
                   cold dry air (-17.8%) was similar to
                   that of cold dry air. The effects did
                   not persist following exposures.

                   The clean dry air group had
                   significantly more macrophages,
                   lymphocytes, and increased protein
                   concentration in lavage than the
                   warm humid air control.  The cold
                   dry air + SO2 group had fewer
                   macrophages than the clean dry air
                   group and higher protein
                   concentration than the unexposed
                   controls.

Histopathology      Increased incidence of eosinophilic
                   infiltration within and below tracheal
                   epithelium with exposure to cold dry
                   air or  SO2 in cold dry air.

-------
                        TABLE AX4-18 (cont'd). EFFECTS OF METEOROLOGICAL CONDITIONS ON SO2 EFFECTS
                 Concentration
to
o
o
O
O
2
o
H
O
c
o
H
W
O
V
O
HH
H
W
SO2 (ppm)      Condition         Duration
                                                                  Species
    Endpoints
           Interaction
Reference
1 ppm
(2.62 mg/m3);
apparently
intratracheal








Drop in 60 min
intratracheal
temperatures
from -37 °C
to -26 °C







Duncan-Hartley Peak expiratory
guinea pigs, male, flow
age and weight not
reported,
n = 8-9/group,
mechanically
ventilated; animals
were hyperventilated
during cold air and
SO2 exposure to
simulate exercise.

Non-significant decreases compared Halinen et al.
to baseline (4.5-10.8%) at 10 and (2000b)
20 min of exposure to cold dry air.
With exposure to SO2 in cold dry air:
decreased significantly (11.4%, i.e.,
bronchoconstriction) compared to
baseline at 10 min of exposure but
recovered from 20 to 60 min of
exposure. The effect with SO2
exposure was not statistically
significant compared to that of cold
dry air alone.
                                                                                 Tidal volume
                                                                                 Bronchoalveolar
                                                                                 lavage
Histopathology


General
conclusions
Decreased from baseline throughout
most of the exposure period with cold
dry air or SO2 in cold dry air;
response with SO2 was more shallow
than that of cold dry air alone, but
statistical significance compared to
cold dry air was obtained only at
60 min of exposure.

Decreased neutrophil numbers in the
SO2 group compared to the warm
humid air group but no significant
difference compared to the cold dry
air group.

No effect in lung or tracheobronchial
airways.

Functional effects on the lower
respiratory tract were weaker than in
the previous study with 10-min
exposures (Halinen et al., 2000a).
         GSD = geometric standard deviation
         MMAD = mass median aerodynamic density

-------
to
o
o
                             TABLE AX4-19.  IN VITRO OR EX VIVO RESPIRATORY SYSTEM EFFECTS OF SO2
                                                                  AND METABOLITES
             Concentration
    Duration
       Species
                    Effects
        Reference
O
O
2
O
H
O
c
o
H
W
O
V
O
HH
H
W
          In Vitro—Primary/Nonprimary
          0,5,10,20, 30, or
          50ppm(0, 13.1,
          26.2, 52.4, or
          131mg/m3)SO2
Ih
          0,0.1,2, 20, or
          40 mM (0, 4, 80,
          800, or 1600 ug/mL)
   min - 96 h
Fauve de Bourgogne
rabbits, 1 mo old,
tracheal epithelium
explants
Rat, Sprague-Dawley,
200-250g; sex, age,
and n not reported;
lung cells and liver
cells.

Human lung-derived
cell line, A549
Relative to control cultures, cell viability was not
reduced at 5 and 10 ppm, but was at 30 ppm (-70%)
and 50 ppm (-60%).  Ciliary beat frequency was
significantly reduced (p < 0.05) at 10-30 ppm, and
was correlated with swollen mitochondria and
depletion of cellular ATP, as well as with blebbing of
ciliated or microvilli-covered cells and with
aggregation and flattening of cilia.

This study focused on intracellular covalent reactions
of sulfite with primarily proteinaceous sulfhydryl
compounds in cells isolated from rat lung and rat
liver (for some comparative purposes), as well as in
the human lung-derived cell line, A549.  Sulfitolysis
of protein disulfide bonds results in formation of
cysteine S-sulfonate, and sulfitolysis of GSSG in
formation of GSSO3H. The latter was formed in
dose-dependent fashion upon the addition of sulfite to
A549 cells.  In addition to fibronectin and albumin,
this study identified a third sulfite-binding protein in
rat lung cytosol. GSSO3H was shown to be a potent
competitive inhibitor of GST in rat lung, liver and
A549 cells.  Results suggest that SO2 could affect
the detoxication of PAHs and other xenobiotics via
formation of GSSO3H and subsequent inhibition
of GST and enzymatic conjugation of GSH with
reactive electrophiles.
Blanquart et al. (1995)
Menzeletal. (1986)

-------
                         TABLE AX4-19 (cont'd). IN VITRO OR EX VIVO RESPIRATORY SYSTEM EFFECTS OF SO2
                                                                     AND METABOLITES
              Concentration
                           Duration
         Species
                        Effects
Reference
to
o
o
O
O
2
O
H
O
c
o
H
W
O
V
O
HH
H
W
Ex Vivo

7.5, 15,22.5, 30, or
37.5 mg/m3 (2.9, 5.7,
8.6, 11.5, or
14.3 ppm); ex vivo
expsoure of trachea
                                  30 min
Guinea pig, sex, age, and
weight not reported,
n = 4-8/group
2.5,5.0,7.5, 10.0, or
12.5 ppm (6.6, 13.1,
19.7, 26.2, or 32.8
mg/m3); ex vivo
exposure of trachea
                                  30 min
Guinea pig, sex, age, and
weight not reported,
n = 4-7/group
No remarkable morphologic abnormalities in the trachea!     Riechelmann
mucociliary system of the 2.9 ppm group, though slight       et al. (1995)
vacuolization, rare membrane blebs, and slightly widened
intercellular spaces were observed.  Abnormalities in the
5.7 and 8.6 ppm groups were similar and included loosened
contact to the basal membrane, extensive intracellular
edema and vacuolization, swollen mitochondria, polypoid
extrusions and huge blebs in the cell membrane and ciliary
membrane, widened intercellular space, and disrupted tight
junctions. Additional abnormalities in the 11.5 and
14.3 ppm groups included marked epithelial sloughing,
occasionally disrupted cell membranes and microtubules,
and frequently disrupted ciliary membranes. Tracheal
mucociliary activity was significantly decreased in all
exposure groups (from 8.7 ± 1.0 Hz [controls] to 4.0 ±1.1,
3.4 ± 2.7, 1.8 ± 2.2, 1.5 ± 1.8, and 2.0 ± 1.2 Hz in the 7.5,
15, 22.5, 30, and 37.5 mg/m3 groups, respectively).

63% decrease in tracheal mucociliary  activity at 2.5 ppm      Knorst et al.
with dose-dependent  decrease to 81% at 7.5 ppm; higher      (1994)
concentrations did not further decrease mucociliary activity.
Ciliary beat frequency decreased by 45% at 5.0 ppm with
dose-dependent decrease to 72% at  12.5 ppm. All
reductions are relative to baseline values; no effect on
controls for either parameter.
GSH = glutathione
GSSG = glutathione disulfide
GSSO3H = glutathione S-sulfonate
GST = glutathione-S-transferase
PAH = polycyclic aromatic hydrocarbons
AM = alveolar macrophages
BAL = bronchoalveolar lavage

-------
                                      TABLE AX4-20.  GENOTOXIC EFFECTS OF SO2 AND METABOLITE
               Concentration
                         Duration
   Species/System
                             Effects
Reference
to
o
o
O
O
2
O
H
O
c
o
H
W
O
^
O
HH
H
W
"Point Mutation"1
In Vitro

0 or 50 ppm (131 mg/m3)   48 h
SO2 or the equivalent
agar concentration of
SO32~, 15 ug/ml)
Cytogenetic and DNA Damage2
In Vitro

0, 20, 50 or 200 ppm (0,    1-24 h
52.4, 13 lor 524 mg/m3)
S02;

0, 0.1, 0.2 or 0.4 mM
S032~

0 or 2.5 umol HSCV per
microtiter plate well

0, 0.1, 0.2 or 0.4 mM
SO42~

0 or 10 umol MgSO4 per
tube
                                              Rat, Sprague-Dawley,
                                              female, liver enzyme
                                              preparations
Hamster, Syrian
golden, fetal lung
cells (FHLC,
gestational Day 15)

Rat, Sprague-Dawley,
male, age not
reported, ~200g,
hepatocytes

Chinese hamster
ovary cell line
transformed by SV40,
CO60 cells

Precinorm U (human
serum standard)
In vitro induction of reverse mutation in cultures of S. typhimurium strain
TA98 was not affected by incubating the bacterial-B(a)P-liver S9 enzyme
activation system in the presence of SO2/sulfite.  An ancillary finding from
the 0 ug B(a)P control exposures is that SO2/sulfite itself did not appear
mutagenic.
Toxicity and genotoxicity of SO2, suffite/bisulfite and sulfate (also
NO2/NOX) were variously assessed in several in vitro test systems. It was
noted that medium pH remained stable at [SO2] <200 ppm. Precinorm
LDH activity was substantially inhibited by 50 ppm SO2 after 1-3 h,  and
by 0.1 mM sulfite ion almost immediately, but not by 0.1 mM sulfate ion;
AST was modestly inhibited after 5 h by 200 ppm SO2; other monitored
enzymes were not affected.  While trypan blue exclusion was not affected,
SO2 cytotoxicity to FHLC was demonstrated at 20 ppm by reduced plating
efficiency; at 50 ppm, enzyme activity leaked into culture medium was
reduced only for AP and especially LDH (not other enzymes).  200 ppm
SO2 did not induce DNA damage (single-strand breaks) by itself in either
FHLC or rat hepatocytes, but did somewhat reduce that induced by
AMMN.  In hepatocytes, incubation with MgSO4 also caused a small
reduction in AMMN-induced DNA damage.  A 1-h exposure to 200  ppm
SO2 did not induce selective amplification of SV40 DNA in CO60 cells,
nor affect that induced by DMBA or B[a]P. However, while also not
affecting induction by DMBA or B[a]P, HSCV added directly to the
medium for 24 h did induce SV40 DNA  amplification on its own—authors
appear to suggest this might result from arrest of cells in mid-S phase,
which leads to DNA amplification. Thus, principal findings include
inhibition of LDH by SO2 or sulfite that could impair the cellular
energy system; such an impairment could be responsible (possibly
along with SO42~ conjugation of reactive intermediates) for the
observed inhibition of AMMN-induced DNA damage by SO2.
Further, SO2 does not appear by itself to induce DNA damage.
                                                                                         Pool-Zobel
                                                                                         et al. (1990)
                                                                                                                                        Pool et al.
                                                                                                                                        (1988a)

-------
                                 TABLE AX4-20 (cont'd).  GENOTOXIC EFFECTS OF SO2 AND METABOLITE
                  Concentration
                                    Duration
                       Species/System
                                            Effects
                                                    Reference
to
o
o
oo
O
o
2
o
H
O
c
o
H
W
O
V
O
HH
H
W
Cytogenetic and DNA Damage2
In Vitro

3 mM SO32~
          5 mM SO3  (as Na2SO3)
Cytogenetic and DNA Damage2
Acute/Subacute Exposure

0 mg/m3 (0 ppm) SO2 (+ 0 or 8
mg/kg bw SSO) or 28 mg/m3
(10.7 ppm) SO2 (+ 0, 2, 4, 6 or 8
mg/kg bw SSO); whole body
0, 14, 28, 56, or 84 mg/m3 (0,
5.35, 10.7, 21.4, or 32.1 ppm)
SO2; whole body
                                          40 min
                                          (test tube reactions)
                                1.5 h
                                (test tube reaction)
± SSO ip on Days
l-3;thenSO2for
5 day (Days 4-8),
6h/day
7 day, 4 h/day
                    dGorDNA
                    dG
Kunming mouse, male
and female, ~6 wk
old, 20-25 g,
n = 6/sex/conc.
Kunming mouse, male
and female, ~6 wk
old, 20-25 g,
n = 10/sex/conc.
                      Test tube reaction mixtures that caused sulfite to oxidize    Shi and
                      to sulfur trioxide radical (SO3~) resulted in the             Mao (1994)
                      hydroxylation of dG (8-OHdG) and the generation of
                      DNA double strand breaks.

                      Test tube reaction of sulfite ion with H2O2 shown to        Shi(1994)
                      generate OH radicals capable of hydroxylating dG to the
                      DNA damage marker, 8-OHdG. Furthermore,
                      incubation of sulfite with nitrite or various transition
                      metal ions was shown to generate sulfur trioxide anion
                      radical (SO3~).
Subacute inhalation of 28 mg/m3 SO2 induced a         Ruan et al.
significant (p < 0.001) 10-fold increase in mouse bone    (2003)
marrow MNPCE, which was partially mitigated in
dose-dependent fashion by pretreatment with SSO, a
complex natural anti-oxidant substance.  SO2
exposure also resulted in organ:bw ratios that increased
for liver and kidney, decreased for lung and spleen, and
remained unchanged for heart. Such ratio changes were
largely mitigated by SSO pretreatment.

In vivo exposure caused significantly (p < 0.01-0.001)      Meng et al.
increased frequencies of bone marrow MNPCE similarly    (2002)
in both sexes at all concentrations in a dose-dependent
manner, and with only minimal cytotoxicity at the
3 highest concentrations. The level of MNPCE (%) even
at the low SO2 cone, was triple that of the control value.
Thus, subacute inhalation of SO2 at noncytotoxic
concentrations (though still notably higher than most
human exposures) was clastogenic in mice.

-------
                                 TABLE AX4-20 (cont'd). GENOTOXIC EFFECTS OF SO2 AND METABOLITE
             Concentration
                       Duration
    Species/System
                             Effects
 Reference
to
o
o
O
O
2
O
H
O
c
o
H
W
O
V
O
HH
H
W
Cytogenetic and DNA Damage
Acute/Subacute Exposure
          0, 14, 28, 56, or
          84 mg/m3 (0, 5.35,
          10.7, 21.4, or
          32.1ppm)SO2;
          whole body
                     7 day, 6 h/day
Kunming mouse, male
and female, ~5 wk old,
18-20 g,
n = 6/sex/conc.
          0 or 50 ppm
          (131 mg/m3) SO2
                     2wk,
                     7 day/wk,
                     24 h/day
Rat, Sprague-Dawley,
female, 4 mo old, wt
not reported, n = 5 per
group
Following in vivo exposure to SO2, it was shown by the single cell gel
electrophoresis (comet) assay that such exposure induced significant
(p <.001-.05) dose-dependent DNA damage (presumed mostly to be
single-strand breaks and alkali-labile sites) in cells isolated from brain,
lung, liver, intestine, kidney, spleen, and testicle, as well as in
lymphocytes, and beginning at the lowest concentration (except male
intestine—lowest response at 28 mg/m3).  Results demonstrate that SO2,
can cause systemic DNA damage in many organs, not just the lung.
Authors note that potential occupational exposures and the fact that
the obligate nose-breathing mouse removes ~95% of inhaled SO2 in its
nasal passages make this experimental concentration range relevant
to possible human exposures.

Assessments were conducted on isolated primary lung and liver cells, or
on blood serum. In vivo SO2 exposure did not affect viability (trypan blue
exclusion) of cells either immediately after isolation or after 1 h incubation
with 1% DMSO (used for enzyme leakage assays). In contrast to controls,
hepatocytes from SO2-exposed rats released no LDH activity into
DMSO-medium after 1 h, and AST activity was reduced.  Other enzyme
(AP, ALT, GT) activity releases were not affected in lung cells, and none
were in hepatocytes.  In blood serum, the only effect was a marked
increase in LDH activity. The only significant (p < 0.001-0.01) exposure
effects on lung or liver activities (in x 9000 g supernatants of cell
homogenates) of xenobiotic metabolizing enzymes (AHH, NDMA-D,
GST) were elevated NDMA-D in the liver and reduced GST in the lung.
Single-strand DNA breakage induced by three nitroso compounds
(AMMN, NDMA, NMBzA) was reduced in hepatocytes from
SO2-exposed rats. Authors discuss possible mechanisms for the observed
effects, and note they are similar to in vitro effects reported elsewhere (see
above, Pool etal., 1988a).
Meng et al.
(2005b)
Pool et al.
(1988b)

-------
                                     TABLE AX4-20 (cont'd).  GENOTOXIC EFFECTS OF SO2 AND METABOLITE
                    Concentration
                                       Duration
  Species/System
                           Effects
 Reference
to
o
o
O
O
2
O
H
O
c
o
H
W
O
V
O
HH
H
W
Cytogenetic and DNA Damage2
Subchronic/chronic
0, 0.2 mL C, or
{0.2 mL DEP+C ± [4 ppm
(10.48 mg/m3) SO2 or 6 ppm
(11.28 mg/m3) NO2 or 4 ppm
SO2 + 6 ppm NO2]}; whole body

[Note: 0.2 mL C = 1 mg; 0.2 mL
DEcCBP=lmgC + 2.5mg
DEP)]
                                               SO2 and/or NO2:
                                               10 mo, 16 h/day

                                               Cor DEP+C:
                                               4 wk, once/wk
                                               by intratracheal
                                               infusion
Rat, SPF F344/M,
male, 6 wk old, wt
not reported,
n= 23-30 per group
in 6 groups
Purpose was to study effects of DEP on rat lung tumorigenesis
and possible tumor promoting effects of SO2 or NO2 singly or
together.  [See Table AX4-17 for tumor-related effects.]  DEP
extract-DNA adducts were found only in the three
gas-exposed groups.  Chromatograms revealed two different
adducts, one of which appears somewhat more abundant with
SO2 coexposure, the other substantially more so with NO2;
combined coexposure of both gases with DEP+C produced an
adduct chromatogram appearing to be a composite of those for
the individual gases.  Thus, SO2 and NO2 appear capable of
promoting the genotoxicity of DEP extract, though
perhaps not in identical fashion.
Ohyama
etal.
(1999)
           'Encompasses classical mutant selection assays based upon growth conditions under which mutants (or prototrophic revertants), but not the wild type (or auxotrophic) population treated with the test
           agent, can successfully grow (e.g., "Ames test", CHO/HGRPT or mouse lymphoma L5178Y/TK mammalian cell systems, various yeast and Drosophila systems, etc.); while most viable mutation events
           detected in these assays are typically "point" mutations (DNA base substitutions, small deletions or frameshifts, etc.), some may involve larger losses/rearrangements of genetic material.

           2Encompasses CA, induction of MN or SCE, aneuploidy/polyploidy, DNA adduct and crosslink formation, DNA strand breakage, etc.
AHH = aryl hydrocarbon hydroxylase
AP = alkaline phosphatase
AMMN = N-nitroso-acetoxymethylmethylamine
ALT = alanine-amino-transferase
AST = aspartate-amino-transferase
B[a]P = benzo[a]pyrene
bw = body weight
C = carbon or carbon black particles
CA = chromosome aberrations
DEcCBP = DEP extract coated carbon black particles
DEP+C = diesel exhaust particle extract adsorbed to C
DMBA = 7, 12-dimethylbenzanthracene
DMSO = dimethyl sulfoxide
dG = 2'-deoxyguanosine
                        8-OHdG = 8-hydroxy-2'-deoxyguanosine
                        FHLC = fetal hamster lung cells
                        GT = y-glutamyltransferase
                        GST = glutathione-S-transferase;
                        LDH = lactate dehydrogenase
                        MN = micronuclei
                        MNPCE = micronucleated PCE
                        NDMA = N-nitrosodimethylamine
                        NDMA-D = N-nitrosodimethylamine demethylase
                        NMBzA = N-nitrosomethylbenzylamine
                        PCE = polychromatic erythrocytes
                        SSO = seabuckthorn seed oil
                        SCE = sister chromatid exchanges
                        SV40 = simian virus 40

-------
                                     TABLE AX4-21.  LIVER AND GASTROINTESTINAL EFFECTS OF SO2
             Concentration
                          Duration
                          Species
                                                   Effects
                                                               Reference
to
o
o
O
O
2
O
H
O
c
o
H
W
O
^
O
HH
H
W
          Subacute/Subchronic Exposure
22, 56, orll2mg/m3
(7.86, 20, or 40 ppm
per author
conversion); whole
body
          22, 64, or 148 mg/m3
          (8.4, 24.4, or
          56.5 ppm); whole
          body

          14, 28, or 56 mg/m3
          (5.35, 10.70, or
          21.40 ppm); whole
          body
          14, 28, or 56 mg/m3
          (5.35, 10.70,
          or 21.40 ppm); whole
          body
6 h/day for 7 days
Kunming albino mouse,
male and female, 5 wks
old, 19 ± 2 g,
n = 6/sex/subgroup
                      6 h/day for 7 days   Kunming-strain mice,
                                        male, age not reported,
                                        18-20 g,n=10/group
                      6 h/day for 7 days   Wistar rat, male, age not
                                        reported, 180-200 g,
                                        n = 6/group in 4 groups
                      6 h/day for 7 days   Wistar rat, male, age not
                                        reported, 180-200 g,
                                        n = 6/group in 4 groups
Effects observed in stomach (concentration of effect) included:        Meng et al.
increase in SOD activity (7.86 ppm, males only) and TEARS level     (2003c)
(>7.86 ppm) and decreases in SOD (>20 ppm, males only) and GPx
activities (>20 ppm, males only) and GSH level (40 ppm). Effects
observed in intestine were increases in catalase activity (>20 ppm in
males, 40 ppm in females) and TEARS level (>20 ppm) and
decreases in SOD (>7.86 ppm) and GPx (>20 ppm) activities and
GSH level(>7.86 ppm).

No effects were observed in the liver at 22 or 64 mg/m3. GST and     Wu and
glucose-6-phosphate dehydrogenase activities and GSH level were     Meng
decreased at 148 mg/m3.                                         (2003)
                                          Significant and concentration-dependent changes in mRNA (mid and   Bai and
                                          high concentrations) and protein expression (all concentrations)       Meng
                                          included increases for bax and p53 apoptosis-promoting genes, and    (2005b)
                                          decrease for bcl-2 apoptosis-repressing gene. Authors speculated
                                          potential impact on human apoptosis-deficient diseases.

                                          SO2 caused significant concentration-dependent reductions in liver     Qin and
                                          enzyme activities and gene expression for CYP1A1 and CYP1A2.      Meng
                                          Effects were seen at the mid and high concentrations (only high for    (2005)
                                          CYP1A1  enzyme activity), but not the low.  Authors speculate that
                                          underlying mechanisms may involve oxidative stress and/or cytokine
                                          release, and may represent an adaptive response to minimize cell
                                          damage.

-------
                                 TABLE AX4-21 (cont'd). LIVER AND GASTROINTESTINAL EFFECTS OF SO2
              Concentration
                         Duration
                        Species
                                                     Effects
                                                                Reference
to
o
o
to
O
o
2
o
H
O
c
o
H
W
O
V
O
HH
H
W
           Subacute/Subchronic Exposure
5 or 10ppm(13.1 or
26.2 mg/m3); whole
body
5, 50, or 100 ppm
(13.1, 131, or
262 mg/m3); whole
body

286 mg/m3
(100 ppm); whole
body Units were
incorrectly reported as
ug/m3 in the study but
were corrected
according to
information provided
by study author
24 h/day for
15 days
                                 5 h/day for
                                 7-28 days
5 h/day for
28 days
Sprague-Dawley CD rat,
male, age not reported,
250-275 g, n = 9/subgroup
Wistar rat, male, 7 wks
old, weight not reported,
n = 4-5/treatment group,
8 controls

Wistar rat, male, 7 wks
old, weight not reported,
n=4-16
Subjects were rats fed standard diet (normal) or high cholesterol     Lovati et al.
diet, and rats with streptozotocin-induced diabetes fed standard      (1996)
diet. SO2 (> 5 ppm) elevated plasma triglycerides in normal and
hypercholesterolemic groups, while 10 ppm lowered plasma high
density lipoprotein cholesterol in hypercholesterolemic rats. In
diabetic rats, 10 ppm SO2 lowered triglycerides and free fatty
acids without affecting high density lipoprotein cholesterol or total
cholesterol. In the liver, SO2 elevated triglycerides in normal and
hypercholesterolemic groups (at 10 ppm), but lowered it in diabetic
rats (at >5 ppm); esterified cholesterol was elevated in normal rats
(at 10 ppm), but lowered in diabetic rats (at > 5ppm),  and free
cholesterol was unchanged in all groups. In normal rats,
triglycerides secretion rate was inhibited by 10 ppm SO2. SO2
caused several changes in plasma apolipoprotein composition in
normal and hypercholesterolemic groups, but not in diabetic rats.
Leukotriene parameters were not affected. Thus, in each rat
model, inhalation of SO2 at levels without overt effects affected
plasma and tissue lipid content.  Specific effects varied
according to diet or diabetes.

GSH was depleted in the liver at 5 and 100 ppm but not at 50 ppm.   Langley-Evans
With respect to GSH-related enzymes, exposure to  5 ppm           et al. (1996)
decreased GRed and GST activity in the liver. Exposure to 50 ppm
did not affect liver GST, but decreased liver GRed and GPx.

Adult rats exposed to air or SO2 were born to dams fed diets with    Langley-Evans
varying casein contents (180 [control], 120, 90 or 60 g/kg) during    et al. (1997);
gestation.  In the liver,  SO2 exposure elevated GSH level in the      Langley-Evans
120 g/kg dietary group but lowered it in the 60 g/kg dietary group.    2007
SO2 did not affect liver GST in any group. SO2 increased GCS
levels in the 180 and 90 g/kg groups, GPx in the 60 g/kg group,
and GRed in the 120 and 90 g/kg groups. This study provides
information for an extremely high concentration level but is being
acknowledged here with the unit corrected to verify that a
low-concentration level study was not missed.

-------
                                  TABLE AX4-21 (cont'd).  LIVER AND GASTROINTESTINAL EFFECTS OF SO2
to
o
o
Concentration Duration
Subacute/Subchronic Exposure
10 or 30 ppm (26.2 or 6 h/day,
78.6 mg/m3); whole ~5 days/wk for
body 21 wks (total of
99 days)
Species

Sprague-Dawley CD
rat, male, 8 wks old,
weight not reported,
n = 70/group in
3 groups (inhalation
series)
Effects

No effects on relative liver weight or histopathology were found.
Reference

Gunnison
etal.
(1987)
           10 ppm (26.2 mg/m3);
           whole body
1 h/day, 7 days/wk
for 6 wks
           10 ppm (26.2 mg/m3);
           whole body
1 h/day, 7 days/wk
for 6 wks
Swiss Albino rat, male,
3 mos old, weight not
reported, n = 10/group
Rat, male, 3 mos old,
weight not reported,
n = 10/group in 4
groups
Effects were compared in non-diabetic rats, non-diabetic rats          Agar et al.
exposed to SO2, alloxan-induced diabetic rats, and diabetic rats        (2000)
exposed to SO2.  SO2 increased blood glucose in all groups, but did
not affect total cholesterol, high density lipoprotein cholesterol, low
density lipoprotein cholesterol, very low density lipoprotein
cholesterol, or triglyceride levels in either normal or diabetic rats.

Effects compared in normal rats and rats with alloxan induced         Kuciikatay
diabetes. Among the significant effects observed, SO2 exposure       et al.
enhanced the body weight loss seen in the diabetic group, but did      (2003)
not affect body weight gain in the control group. SO2 elevated blood
glucose levels in both controls and diabetics, but lowered
triglycerides only in diabetics. Cholesterol parameters were not
affected.
O
O
2
O
H
O
c
o
H
W
O
V
O
HH
H
W
                                                             GST = glutathione S-transferase
                                                             GT = y-glutamyltranspeptidase
                                                             SOD = Cu,Zn-superoxide dismutase
                                                             TEARS = thiobarbituric acid-reactive substances

-------
                                                    TABLE AX4-22.  RENAL EFFECTS OF SO2
to
o
o
O
O
2
O
H
O
c
o
H
W
O
V
O
HH
H
W
Concentration
22, 64, or 148 mg/m3 (8.4,
24.4, or 56.5 ppm)
Duration
6 h/day for 7 days
Species
Kunming-strain mice,
male, age not reported,
18-20 g, n= 10/group
Effects
GST was decreased in the kidney at 64 and
148 mg/m3 and glucose-6-phosphate dehydrogenase
activity was decreased at 148 mg/m3. Kidney GSH
levels were reduced at all exposure levels.
Reference
Wu and Meng
(2003)
          5, 50, or 100 ppm (13.1, 131,   5 h/day for 7-28 days   Wistar rat, male, 7 wks     GSH was depleted in the kidney in the 5 and 100 ppm  Langley-Evans
          or262mg/m3)                                    old, weight not reported,    groups but not in the 50 ppm group.  No effects were   etal. (1996)
                                                          n = 4-5/treatment group,    observed for other GSH-related enzymes.
                                                          8 controls

-------
                                  TABLE AX4-23. LYMPHATIC SYSTEM EFFECTS OF SO2 AND SO2 MIXTURE
               Concentration
                             Duration
                               Species
                                                       Effects
                                                           Reference
to
o
o
           Subchronic/Chronic Exposure
1 ppm (2.62 mg/m3);
whole body
           13.2 mg/m3 (5.0 ppm)
           SO2+1.04 mg/m3
           ammonium
           sulfate + 0.2 mg/m3
           (0.10 ppm) ozone;
           whole body
5 h/day, 5 days/wk
for 4 mos.
                         5 h/day, 5 days/wk
                         for up to 103 days
Sprague-Dawley rat, male,
young adult, initial weight
not reported, n= 12-15/data
point

CD1 mice, female, 3-4 wks
old, weight not reported,
n = 360/group total
(14-154/group in each assay)
No significant effects were reported for spleen weight or
mitogen-induced activation of peripheral blood lymphocytes
or spleen cells (data not shown by study authors).


Cytostasis of MBL-2 leukemia target cells by peritoneal
macrophage was increased in groups exposed to ozone alone
or a mixture of the three compounds but was significantly
higher with the mixture than with ozone alone at a
macrophage:target cell ratio of 10:1; no significant effects
were observed with macrophage:target cell ratio of 20:1.
A reduction in splenic lymphocyte blastogenesis in response
to phytohemagglutinin and concanavalin A occurred after
exposure to ozone alone, but increased response occurred
after exposure to the mixture; no response to alloantigen
occurred after exposure to ozone alone but increased
response occurred after exposure to mixture; there were  no
effects on S. typhosa lipopolysaccharide with either exposure
scenario.
Smith et al.
(1989)
                                                                                                             Aranyi
                                                                                                             etal.
                                                                                                             (1983)
O
O
2
o
H
O
c
o
H
W
O
V
O
HH
H
W
 B(a)P = benzo(a)pyrene
 GCS = y-glutamylcysteine synthetase
 GPx = glutathione peroxidase
 GRed = glutathione reductase
 GSH = glutathione
 GSH = glutathione
 GST = glutathione-S-transferase
 GPx = glutathione peroxidase
 GSH = glutathione
 SOD = superoxide dismutase
 TEARS = thiobarbituric acid-reactive substances
                                                                                       GST = glutathione S-transferase
                                                                                       GT = y-glutamyltranspeptidase
                                                                                       SOD = Cu,Zn-superoxide dismutase
                                                                                       TEARS = thiobarbituric acid-reactive substances

-------
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 9    Halinen, A. I.; Salonen, R. O.; Pennanen, A. S.; Kosma, V. M. (2000a) Combined respiratory
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15    Heinrich, U.; Mohr, U.; Fuhst, R.; Brockmeyer, C. (1989) Investigation of a potential
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      September 2007                            AX4-68   DRAFT-DO NOT QUOTE OR CITE

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40          423-428.
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1   Yargi90glu, A.; Agar, S.; Gumus.lu, S.; Bilmen, S.; Oguz, Y. (1999) Age-related alterations in
2          antioxidant enzymes, lipid peroxide levels, and somatosensory-evoked potentials: effect
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4   Yargi90glu, P.; Gumus.luoriob, S.; Agar, A.; Korgun, D. K.; Kii9iikatay, V. (2001) Effect of
5          sulfur dioxide inhalation on erythrocyte antioxidant status, food intake, and lipid
6          peroxidation during aging. Arch. Environ. Health 56: 53-57.
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   AX5. CHAPTER 5 ANNEX - EPIDEMIOLOGICAL
STUDIES OF HUMAN HEALTH EFFECTS ASSOCIATED
  WITH EXPOSURE TO AMBIENT SULFUR OXIDES
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                     TABLE AX5.1 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                                 RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
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Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean SO2 Levels Copollutants Considered
Findings &
Interpretation
Effect Estimates
(95% CI)
UNITED STATES (cont'd)
           Schildcrout et al. (2006)
           Albuquerque, NM;
           Baltimore MD;
           Boston MA;
           Denver, CO;
           San Diego, CA;
           Seattle, WA;
           St. Louis, MO;
           Toronto, Ontario, Canada
           Novl993-Septl995
Meta-analysis of 8 panel
studies with 990 children of
the Childhood Asthma
Management Program
(CAMP), during the 22-mo
prerandomization phase to
investigate effects of
criteria pollutants on
asthma exacerbations (daily
symptoms and use of
rescue inhalers). Poisson
regression and logistic
regression models used in
analyses. Within city
models controlled for day
of wk, ethnicity, annual
family income, flexible
functions of age and log-
transformed sensitivity to
the methacholine  challenge
using natural splines with
knots fixed at 25th, 50th,
and 75th percentiles.  Also
controlled for confounding
due to seasonal factors. All
city-specific estimates
included in calculations of
study-wide effects except
Albuquerque where SO2
data were not collected.
24-h avg SO2:
Median (10th, 25th, 75th,
90th percentile):

Albuquerque: NA

Baltimore: 6.7 ppb
(3.2,4.7,9.8,14.2)

Boston: 5.8 ppb
(2.7,3.7,9.1,14.1)

Denver: 4.4 ppb
(1.2,2.5,6.7,9.5)

San Diego: 2.2 ppb
(1.2,1.7,3.1,4.4)

Seattle: 6.0 ppb
(3.7,4.7,7.5,9.5)

St. Louis: 7.4 ppb
(3.9,5.3,10.7,13.6)

Toronto:  2.5 ppb
(0.2,1.0,4.8,8.8)
O3(-0.03 
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            TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

                              RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
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Reference, Study
Location, & Period
Outcomes, Design,
& Methods Mean SO2 Levels
Findings &
Copollutants Considered Interpretation
Effect Estimates
(95% CI)
UNITED STATES (cont'd)
Schwartz etal. (1994)
Watertown, MA
(Apr-Aug 1985);
Kingston-Harriman, TN
(Apr-Aug 1986);
St. Louis, MO;
(Apr-Aug 1986);
Steubenville, OH;
(Apr-Aug 1987);
Portage, WI;
(Apr-Aug 1987);
Topeka, KS
(Apr-Aug 1988)












Longitudinal study of 1 ,844 24-h mean SO2 :
children in grades 2-5 from Median: 4.1 ppb
the Six Cities Study to IQR: 1 .4, 8.2
examine the effects of PM Max' 819
and SOX on respiratory
health. Daily diaries
completed by parents,
recording symptoms, such
as cough, chest pain,
phlegm, wheeze, sore
throat, and fever. Logistic
regression models adjusting
for aurocorrelation were
used for the analysis. To
examine possible non-
linearity in the relationship,
smooth functions of the air
pollution variables were fit
using GAM and the
significance of the
deviation from linearity
was tested.




O3 (r = -0.09) SO2 associated with
NO2 (r = 0. 5 1 ) incidence of cough and
PM10 (r = 0.53) lower respiratory
PM (r = 0 55) symptoms. Local smooth
PM2" sulfur (r = 0.50) sho^ed mf ease,d co^h
TT+ / _ Q 93 \ incidence for only above a
4-day avg of 20 ppb (less
than 5% of data). Test for
nonlinearity was
significant (p = 0.002).
No increase in incidence
of lower respiratory
symptoms was seen until
24-h avg SO2
concentrations exceeded
22 ppb.

ORs for cough and lower
respiratory symptoms
related to were
substantially reduced after
adjustment for PM10,
suggesting the SO2
associations might be
confounded by particles.

OR for cough incidence
associated with 10-ppb
increase in 4-day avg SO2
concentration:
Single-pollutant model:
1.15(1.02,1.31)
SO2 with PM10 model:
1.08(0.93,1.25)
SO2 with O3 model'
1.15 (1.01, 1.31)
SO2 with NO2 model:
i no (r\ 0/1 i "?ru
1 AJy (U.V^t, 1 . J\))

OR for lower respiratory
symptoms associated with
10-ppb increase in 24-h
avg SO2 concentration:

Single-pollutant model:
1.28(1.13,1.46)
SO2 with PM10 model:
Not presented. Stated as
not statistically
significant.

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                    TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                               RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
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HH
H
W
Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean SO2 Levels
Copollutants
Considered
Findings &
Interpretation
Effect Estimates
(95% CI)
UNITED STATES (cont'd)
Delfino et al. (2003)
Los Angeles, CA
Novl999-Jan2000










Panel study of 22 Hispanic
children with asthma aged
10 to 16 yrs. Participants
performed twice-daily PEF
measurements and filled out
symptom diaries. Analyses
of symptoms conducted using
GEE with exchangeable
correlation. Linear mixed
model used for PEF analyses.
GEE models controlled for
respiratory infections (data
available for 20 subjects) and
temperature.


l-hmaxSO2:
7.0 ppb (SD 4.0)
IQR: 4.0

8-h max SO2:
4. 6 ppb (SD 3.0)
IQR: 2.5







O3(r=-0.19)
N02(r=0.89)
CO (r = 0.69)
PM10
(r=0.73)
EC (r= 0.87)
OC(r = 0.83)
VOCs
V V_/v_.o






NoneoftheVOCsor
gaseous pollutants
associated with PEF.

Current-day, but not
previous-day, SO2
concentrations
associated with symptom
score >1 and>2.






OR for symptom score
>1 per IQR increase in
S02:
1-hmax SO2:
LagO: 1.31
(1.10,1.55)
Lagl: 1.11
(0.91,1.36)

8-h max SO2:

LagO: 1.23
(1.06,1.41)
T I 111
Lagl: 1.11
(0.97, 1.28)

OR for symptom
score >2 per IQR
increase in SO2:

1-hmax SO2:
LagO: 1.37
(0.87,2.18)
Lagl: 0.76
(0.35, 1.64)


8-h max SO2:
LagO: 1.36
(1.08, 1.71)
Lagl: 0.91
(0.51, 1.60)
           Neasetal. (1995)
           Uniontown, PA
           Summer 1990
Panel study of 83 fourth and
fifth grade students in
Uniontown, Pennsylvania.
Participants reported twice-
daily PEF and the presence of
cold, cough, or wheeze.
During the summer of 1990,
there were 3,582 child-days.
PEF analyzed with
autoregressive linear
regression model that
included a separate intercept
for evening measurements,
trend, temperature and 12-h
avg air pollutant
concentration, weighted by
the number of hours child
spent outdoors during the
previous 12 h.
12-h avg SO2:
10.2 ppb
Max: 44.9
IQR: 11.1

Daytime 12-h avg
SO2 (8 a.m.-8 p.m.):
14.5 ppb

Overnight 12-h avg
SO2(8p.m.-8a.m.):
5.9 ppb
PM10
PM25
03
total sulfate
particles
particle-strong
acidity
(r = 0.44)
Incidence of new
evening cough episodes
significantly associated
with the preceding
daytime 12-h avg SO2.
Mean deviation in PEF
not associated with SO2.
Effects associated with 10-ppb increase in
12-h avg SO2:

Change in mean deviation in PEF:
-0.63 L/min(-1.33, 0.07)

OR for evening cough: 1.19 (1.00, 1.42)

Concentration weighted by proportion of
hours spent outdoors during  prior 12 h:

Change in mean deviation in PEF:
-1.25 L/min (-2.75, 0.25)

OR for evening cough: 1.53 (1.07,2.20)

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                   TABLE AX5.1 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                              RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Copollutants
Mean SO2 Levels Considered
Findings &
Interpretation
Effect Estimates
(95% CI)
UNITED STATES (cont'd)
Newhouse et al. (2004)
Tulsa, OK
Sep-Oct 2000









Panel study of 24 patients aged 9 to 64 yrs
with physician-diagnosed asthma. Subjects
performed twice-daily PEF (morning and
evening) measurements, and recorded
medications taken and symptoms. Simple
linear regression, forward stepwise multiple
regression and correlation analysis
performed. Multiple regression analyses
used to develop predictive models for other
environmental factors. Analyses produced
complex models with different predictor
variables for each symptom.
24-h avg SO2: PM25
0.01 ppm CO
Range: 0.00,0.02 O3
pollen
fungal spores







Of the atmospheric
pollutants, avg and max
O3 were most significant
factors that influenced
symptoms. Quantitative
results not provided for
S02.

Avg or max SO2 found to
be negative predictors of
asthma in subgroup
analyses of women and
Not quantitatively useful.











          Ross et al. (2002)         Panel study of 59 asthmatic subjects aged
          East Moline, IL          5 to 49 yrs. Analysis based on 40 subjects,
          May-Oct 1994           due to withdrawal or failure to provide
                                 requested health data. Study assessed the
                                 effect of single and combined exposures to
                                 air pollutants and airborne allergens on PEF,
                                 symptom scores and medication use
                                 frequency. Multivariate linear-regression
                                 models with 1 st order autoregression used
                                 for analysis of daily means of mean -
                                 standardized PEF, symptom scores and
                                 asthma medication use; logistic regression
                                 used for dichotomized data for symptom
                                 score and medication use, log-linear models
                                 for log-transformed symptom scores and
                                 medication use frequency.
                                                                        24-h avg SO2:
                                                                        3.4ppb(SD3.1)
                                                                        Median: 2.8
                                                                        IQR:  2.4
                                                                        Range: 0,27.3
PM10
03
NO2
pollen
fungi
nonsmokers and rhinitis in
all patients. Avg SO2 also
negative predictor of
evening PEF.

No associations observed
with SO2.
No effect estimates provided.

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             TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

                              RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
to
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Reference, Study
Location, & Period
Outcomes, Design,
& Methods Mean SO2 Levels
Copollutants Findings &
Considered Interpretation
Effect Estimates
(95% CI)
EUROPE
Boezenetal. (1998)
Amsterdam and
Meppel, the
Netherlands
winter of 1993-1994































Panels study of 1 89 adults (48 to 24-h avg SO2
73 yrs) with and without chronic
respiratory symptoms in urban and Urban
rural areas to investigate whether Mean: 11.8ug/m3
bronchial hyperresponsiveness and Range: 2.7,33.5
PEF variability can be used to
identify subjects who are susceptible Rural
to air pollution. Spirometry and Mean: 8.2
methacholine challenge were Range: 0.8,41.5
performed and subjects with a fall in
FEY] of 20% or greater were
considered BHR. Subjects
performed twice-daily peak flow for
3 mos. A subject's basal PEF
variability was calculated over an
8-day period with low air pollution.
PEF variability was expressed as
(highest PEF-lowest PEF/mean) or
amplitude % mean (ampl%mean)
PEF. After calculation of the daily
PEF variability, the number of days
where the ampl% mean was greater
than 5% was determined. This
resulted in two groups of subjects;
those with ampli%mean PEF of 5%
or less every day in the 8-day period,
and those with an ampl%mean PEF
greater than 5% on at least 1 day.
Effects of air pollutants on
prevalence of symptoms assessed
with logistic regression models that
adjusted for autocorrelation of the
residuals, daily min temp, time trend
and weekends/holidays.


PM10 No association
BS between SO2 and
NO2 respiratory symptoms
in subjects with no
BHR, BHR at < cum
2.0 methacholine or
BHR at < cum
1 .0 methacholine. In
subjects with
ampl%mean PEF > 5%
and those with
ampli%mean
PEF > 5% for > 33%
of days, SO2 was
associated with the
prevalence of phlegm.




















Odds ratio (per 40 ug/m3 SO2)
Subjects with no BHR
URS: 0.86(0.73,1.03)
LRS: 1.15(0.90,1.46)

Cough: 1.01 (0.84,1.21)
Phlegm: 1.01(0.86,1.20)
BHR at < cum 2.0

Methacholine
URS: 1.11(0.78,1.56)
LRS: 1.03(0.72,1.47)

Cough: 0.89(0.66,1.19)
Phlegm: 1.03(0.78,1.37)
BHR at < 1.0

Methacholine
URS: 1.02(0.65,1.61)
LRS: 0.96(0.63,1.47)
Cough: 0.96(0.64,1.44)
Phlegm: 1.00(0.68,1.46)

AmpP/omeanPEF <5%
URS: 0.82(0.62,1.08)
LRS: 1.38(0.93,2.03)

Cough: 0.72(0.52,0.98)
Phlegm: 0.79(0.59,1.05)

AmpP/omean PEF > 5%
URS: 1.04(0.88,1.23)
LRS: 1.14(0.96,1.36)

Cough: 1.07(0.90,1.26)
Phlegm: 1.23(1.05,1.43)

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                    TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                                RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
             Reference, Study
            Location, & Period
                            Outcomes, Design,
                               & Methods
  Mean SO2 Levels
   Copollutants
    Considered
     Findings &
   Interpretation
         Effect Estimates
            (95% CI)
to
o
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EUROPE (cont'd)
           Boezenetal. (1998)
           (cont'd)
                                                                                                                    Ampl%mean PEF > 5%, >33% of
                                                                                                                    days
                                                                                                                    URS:  1.10(0.85,1.41)
                                                                                                                    LRS:  1.14(0.91,1.42)

                                                                                                                    Cough: 1.14(0.89,1.47)
                                                                                                                    Phlegm:  1.36(1.14,1.63)
X
10% morning PEF decrease
LagO:  1.09(0.89,1.34)
Lagl:  1.00(0.81,1.23)

>10% evening PEF decrease
LagO:  1.060.86,1.30)
Lagl:  0.83(0.68,1.02)

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                   TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                            RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
            Reference, Study
           Location, & Period
                         Outcomes, Design,
                            & Methods
Mean SO2 Levels
Copollutants
 Considered
 Findings &
Interpretation
Effect Estimates
   (95% CI)
to
o
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EUROPE (cont'd)
X
H
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          Boezenetal. (1999)
          (cont'd)
                                                                                                         NO BHR and low IgE (n = 167)
                                                                                                         LRS
                                                                                                         LagO: 1.12(0.76,1.66)
                                                                                                         Lagl: 0.61(0.39,0.94)

                                                                                                         URS
                                                                                                         LagO: 1.01(0.89,1.13)
                                                                                                         Lagl: 1.08(0.96,1.22)

                                                                                                         >10 morning PEF decrease
                                                                                                         LagO: 1.02(0.89,1.16)
                                                                                                         Lagl: 1.00(0.87,1.15)

                                                                                                         >10% evening PEF decrease
                                                                                                         LagO: 1.10(0.97,1.25)
                                                                                                         Lagl: 1.06(0.93,1.21)

                                                                                                         With BHR and low IgE (n = 67)
                                                                                                         LRS
                                                                                                         LagO: 0.72(0.41,1.28)
                                                                                                         Lagl: 1.03(0.56,1.91)

                                                                                                         URS
                                                                                                         LagO: 0.82(0.62,1.09)
                                                                                                         Lagl: 0.84(0.64,1.12)

                                                                                                         >10% morning PEF decrease
                                                                                                         LagO: 0.74(0.51,1.07)
                                                                                                         Lagl: 0.96(0.67,1.37)

                                                                                                         >10% evening PEF decrease
                                                                                                         LagO: 1.23(0.88,1.73)
                                                                                                         Lagl: 1.32(0.96,1.82)

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                   TABLE AX5.1 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                            RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
            Reference, Study
           Location, & Period
                          Outcomes, Design,
                             & Methods
Mean SO2 Levels
Copollutants
 Considered
 Findings &
Interpretation
Effect Estimates
   (95% CI)
to
o
o
EUROPE (cont'd)
X
(Si
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o
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6
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o
H
O
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W
O
O
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H
W
          Boezenetal. (1999)
          (cont'd)
                                                                                                          With BHR and low IgE (n = 67)
                                                                                                          LRS
                                                                                                          LagO:  0.72(0.41,1.28)
                                                                                                          Lagl:  1.03(0.56,1.91)

                                                                                                          URS
                                                                                                          LagO:  0.82(0.62,1.09)
                                                                                                          Lagl:  0.84(0.64,1.12)

                                                                                                          >10% morning PEF decrease
                                                                                                          LagO:  0.74(0.51,1.07)
                                                                                                          Lagl:  0.96(0.67,1.37)

                                                                                                          >10% evening PEF decrease
                                                                                                          LagO:  1.23(0.88,1.73)
                                                                                                          Lagl:  1.32(0.96,1.82)

                                                                                                          No BHR and high IgE (n = 104)
                                                                                                          LRS
                                                                                                          LagO:  1.44(1.17,1.77)
                                                                                                          Lagl:  1.28(1.00,1.64)
                                                                                                          Lag 2:  (1.38(1.08,1.77)
                                                                                                          5-day mean: 2.49(1.54,4.04)

                                                                                                          URS
                                                                                                          LagO:  0.98(0.84,1.14)
                                                                                                          Lagl:  1.010.87,1.18)

                                                                                                          >10% morning PEF decrease
                                                                                                          LagO:  0.92(0.79,1.08)
                                                                                                          Lagl:  1.03(0.89,1.21)

                                                                                                          >10% evening PEF decrease
                                                                                                          LagO:  1.00(0.85,1.17)
                                                                                                          Lagl:  1.05(0.90,1.23)

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             TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

                              RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
to
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HH
H
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Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean SO2 Levels
Copollutants Findings &
Considered Interpretation
Effect Estimates
(95% CI)
EUROPE (cont'd)
Boezen et al. (2005)
Meppel, Nunspeet,
Amsterdam, The
Netherlands
two winters 1993-1995































Panel study of 327 elderly patients
(50 to 70 yrs) to determine
susceptibility to air pollution by
airway hyperresponsiveness (AHR),
high total immunoglobulin (IgE), and
sex. Methacholine challenges were
performed and subjects with greater
than or equal to 20% fall in FEVj after
inhalation of up to 2.0 mg
methacholine were considered AHR+.
Subjects with total serum IgE > 20
kU/L were defined as high total IgE
(IgE+). Twice daily PEF
measurements and daily symptoms
recorded for 3 mos. Data analysis
performed using logistic regression
with modeling of first-order
autocorrelation in the residuals that
adjusted for daily minimum
temperature, time trend,
weekend/holidays and influenza
incident for the rural and urban areas
and the two winters separately.
Subjects were classified as IgE+
AHR+, IgE+ AHR- , IgE- AHR+ or
IgE- AHR+. Examined effects of
pollutants on the same day, Lag 1, Lag
2 and the 5-day mean concentration of
Lag 0 to Lag 4 preceding that day.
Groups that had effect estimates for
PMio, BS, SO2, and NO2 that were
outside the 95% CI of the effect
estimates for the AHR-/IgE- (control
group) were considered to have
increased susceptibility to air
pollution.
24-h mean SO2
(ug/m3) in winter

Winter 1993/1 994
Urban:
Mean: 11.8 ug/m3
Median: 10.2
Range: 2.7,33.5
Rural:
Mean: 8.2
Median: 4.4
Range: 0.8,41.5

Winter 1994/1 995
Urban:
Mean: 8.3
Median: 7.4
Range: 0.6,24.4
Rural:
Mean: 4.3
Median: .7
Range: 0.5, 17.0














PM10 No consistent
BS associations between
NO2 the prevalence of LRS
or > 10% fall in
evening PEF and air
pollution in any of the
four groups. In the
AHR+/IgE group, the
prevalence of URS
was associated with
SO2 at 1 day Lag, and
the prevalence of
>10% fall in morning
PEF with SO2 at Lag
l,Lag2 and 5-day
mean (avg of Lag 0 to
Lag 4). For females
who were AHR+/IgE+,
the prevalence of
> 10% fall in PEF was
associated with SO2
Lag 1 , Lag 2 and 5-day
mean. In subjects with
AHR-/IgE+ the
prevalence of URS
was associated with
SO2 the previous day
and the mean of Lag 0
to Lag 4. The effect
estimate was outside
the 95% CI of





Odds ratio (per 10 ug/m3 SO2)
AHR-/IgE-
URS
LagO: 0.99(0.93,1.05)
Lagl: 1.02(0.97,1.08)

Cough:
LagO: 1.03(0.98,1.08)
Lagl: 0.97(0.93,1.02)

>10% fall in morning PEF
Lagl: 1.00(0.92,1.08)

AHR-/IgE+
URS LagO: 0.98(0.92,1.03)
Lagl: 1.07(1.01,1.12)
5-day mean 1.15 (1.02, 1.29),
OR outside 95% CI of control group

Cough:
LagO: 1.01(0.95,1.07)
Lagl: 1.02(0.96,1.08)

>10 % fall in morning PEF
Lagl: 1.00(0.92,1.08)
AHR+/IgE-
LagO: 1.05(0.94,1.17)
Lagl: 1.07(0.96,1.19)

Cough:
LagO: 1.03(0.95,1.12)
Lagl: 1.01(0.93,1.09)





-------
                   TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                              RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
            Reference, Study
           Location, & Period
                           Outcomes, Design,
                              & Methods
Mean SO2 Levels
Copollutants
 Considered
 Findings &
Interpretation
Effect Estimates
   (95% CI)
to
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EUROPE (cont'd)
X
(Si
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          Boezen et al. (2005)
          (cont'd)
                                                                                         The estimate for the
                                                                                         control group
                                                                                         AHR-/IgE-. No
                                                                                         consistent positive
                                                                                         associations found
                                                                                         between prevalences
                                                                                         ofURS, cough or
                                                                                         >10% fall in morning
                                                                                         PEF and air pollutants
                                                                                         in subjects with
                                                                                         AHR+/IgE- or
                                                                                         AHR-/IgE-. Based
                                                                                         on results of the study,
                                                                                         authors conclude that
                                                                                         subjects with
                                                                                         AHR+/IgE+ were the
                                                                                         most responsive to air
                                                                                         pollution.
                                                          >10 % fall in morning PEF
                                                          Lagl: 0.99(0.87,1.12)
                                                          5-day mean:  0.78(0.61,0.98),
                                                          OR outside 95% CI of control group
                                                          AHR+/IgE+
                                                          LagO: 1.06(0.97,1.15)
                                                          Lagl: 1.13(1.05,1.23)

                                                          Cough:
                                                          LagO: 1.02(0.94,1.11)
                                                          Lagl: 1.02(0.94,1.10)
                                                          >10 % fall in morning PEF
                                                          Lagl: 0.99(0.87,1.12)
                                                          AHR+/IgE+

                                                          URS
                                                          LagO: 1.06(0.97,1.15)
                                                          Lagl: 1.13(1.05,1.23),
                                                          OR outside 95% CI of control group

                                                          Cough:
                                                          LagO: 1.02(0.94,1.11)
                                                          Lagl: 1.02(0.94,1.10)

                                                          >10 % fall in morning PEF
                                                          Lagl: 1.15(1.04,1.27),
                                                          OR outside 95% CI of control group
                                                          Lag 2:  1.18(1.07,1.30),
                                                          OR outside 95% CI of control group
                                                          5-day mean : 1.26 (1.07, 1.49),
                                                          OR outside 95% CI of control group

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                    TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                                RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
            Reference, Study
            Location, & Period
                             Outcomes, Design,
                                 & Methods
                                                                    Mean SO2 Levels
 Copollutants
  Considered
      Findings &
    Interpretation
        Effect Estimates
           (95% CI)
to
o
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EUROPE (cont'd)
X
          Cuijpersetal. (1994)
          Maastricht, the
          Netherlands
          Nov-Dec 1990
          (baseline)
          Aug 8-16
          (smog episode)
                      The effects of exposure to summer
                      smog on respiratory health were
                      studied in 535 children (age
                      unspecified).  During a smog
                      episode, 212 children were randomly
                      chosen to be reexamined for lung
                      function and symptoms.  Only 112 of
                      the children had adequately
                      completed summer questionnaires
                      and were used for the symptom
                      analysis.  Lung function
                      measurements made with forced
                      oscillation technique were available
                      for 212 children and valid spirometry
                      was available for 208 children.
                      Corrected baseline lung function
                      compared using paired t test and
                      difference in the prevalence in
                      symptoms during baseline and
                      episode compared.
                                                                  24-h avg SO2

                                                                  Baseline 55 |ig/m3
                                                                  Summer episode
                                                                  23 ng/m
N02
BS
03
PM10
Acid aerosol
IT
Small decrements in
FEV] and FEF25_75 found
in the 212 children
during the episode
compared to baseline.
However, there was also
a significant decrease in
resistance parameters.
No increases observed in
the prevalence of acute
respiratory symptoms.
Change in lung function and
impedance between baseline and
smog episode:

FEVj: -0.032 L (SD 0.226),
p< = 0.05
FEF25.75:  -0.086 L/s (SD 0.415),
p< = 0.01
Resistance at 8 Hz: - 0.47 cm H2O
(L/s)
(SD1.17),p< = 0.05
H
6
o

o
H
O
o
H
W
O
O
HH
H
W
          Hoek and Brunekreff
          (1995)
          Deurne and
          Enkhuizen, The
          Netherlands
          Mar-Jul 1989
                      Panel study of 300 children
                      (7-11 yrs) to examine the effects of
                      photochemical air pollution on acute
                      respiratory symptoms.  Occurrence
                      of respiratory symptoms recorded by
                      parents in daily diary. Symptoms
                      included cough, shortness of breath,
                      upper and lower respiratory
                      symptoms, throat and eye irritation,
                      headache and nausea. Association of
                      symptom prevalence and incidence
                      assessed using first order
                      autoregressive, logistic regression
                      model.
                                                                  Daily concentration
                                                                  ofSO2<43|ig/m3
03
PM10
SO42
Same day concentrations
ofSO2andNO2not
associated with symptom
prevalence.
No effect estimates for SO2
provided

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to
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             TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

                              RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean SO2 Levels
Copollutants Findings &
Considered Interpretation
Effect Estimates
(95% CI)
EUROPE (cont'd)
Koppetal. (1999)
Two towns in Black
Forest, Germany
Villingen and
Freudenstadt
Mar-Octl994












Panel study of 170 children
(median age 9. 1 yrs) to
investigate nasal inflammation
and subsequent adaptation after
ambient ozone exposures. Nasal
lavage was sampled over 1 1 time
points, and skin prick tests
performed. Nasal lavage samples
were analyzed for eosinophil
cationic protein, albumen, and
leukocytes as markers of nasal
inflammation. To avoid
confounding with allergens, the
study population was restricted to
only children with no positive
reaction to any of the tested
inhalant allergens. GEE used in
analysis.
Mean SO2 (mg/m3)

Villingen
Mean: 3
5%: 0
95%: 9

Freudenstadt
Mean: 3
5%: 0
95%: 9







O3, NO2, TSP, PM10 Results for only O3.
Authors noted that
since there were very
low concentrations of
NOX and SO2, the
confounding effects of
these components in
ambient air were
negligible.

Eosinophil cationic
protein and leukocyte
levels peaked after the
first increase in
ambient ozone levels.





















H

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             TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

                              RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
to
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o
X
H

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O
HH
H
W
Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean SO2 Levels
Copollutants Findings &
Considered Interpretation
Effect Estimates
(95% CI)
EUROPE (cont'd)
Peters etal. (1996)
Erfurt and Weimar,
former German
Democratic Republic;
Sokolov, Czech
Republic
Sept 1990 to June
1992





















Panel study of 102 adult
(32 to 80 yrs) and 155 children
(7 to 15 yrs) with asthma from
the former German Democratic
Republic and Czech Republic to
investigate the acute effects of
winter type air pollution on
symptoms, medication intake and
PEF. Used regression analyses
and distributed Lag models.




















Winter 1990/1 991

Erfurt
Mean: 125 ug/m3,
Max: 564 ug/m3,
IQR: 113 ug/m3

Weimar
Mean: 236 ug/m3,
Max: 1018 ug/m3,
IQR: 207 ug/m3

Sokolov
Mean: 90 ug/m3,
Max: 492 ug/m3,
IQR: 94 ug/m3

Winter 199 1/1 992
Tnrfnrf
HIILU I
Mean: 96 ug/m3,
Max: 462 ug/m3,
IQR: 80 ug/m3
Weimar
Mean: 153 ug/m ,
Max: 794 ug/m3,
IQR: 130 ug/m3
Sokolov
Mean: 71 ug/m3,
Max: 383 ug/m3,
IQR: 66 ug/m3
TSP, 5-day mean
PM10, concentration of SO2
SO4j associated with PEF
PSA (particle strong and symptoms in
acidity) children (combined
analysis from former
German Democratic
Republic and Czech
Republic).
Correlation coefficient
between SO2 and TSP
in Erfurt was r = 0.8,
0.9 during both winters
and in Weimar during
the first winter.


Correlation with TSP
in Sokolov and in
Weimar during the
second winter was
r= 0.4, 0.5.










Combined analysis for children

Change in PEF
Concurrent day 0.18 (-0.44, 0.09) per
133 ug/m3
5-day mean -.90 (-1.35, -0.46) per
128 ug/m3

Change in symptom score
Concurrent day -0.1 (-5.9, 5. 7) per
133 ug/m3
5-day mean 14.7 (0.8, 28.6) per
128 ug/m3
Combined analysis for adults

Change in PEF
Concurrent day -0.20 (-0.53, 0.12) per
133 ug/m3
5-day mean -0.28 (-0.72, 0.16) per
128 ug/m3












-------
                     TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                                RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
             Reference, Study
            Location, & Period
                            Outcomes, Design,
                               & Methods
  Mean SO2 Levels
   Copollutants
    Considered
     Findings &
    Interpretation
         Effect Estimates
             (95% CI)
to
o
o
EUROPE (cont'd)
X
           Pinter etal. (1996)
           Tata Area, Hungary
           winter mos between
           Dec 1993-Mar 1994
                      Longitudinal (children <14 yrs)
                      and cross-sectional study (9 to
                      11 yrs) to examine air pollution
                      and respiratory morbidity in
                      children. In the longitudinal
                      prospective study, respiratory
                      morbidity was evaluated daily
                      and on a weekly basis. In cross-
                      sectional study, anthropometric
                      parameters, physical status, pulse
                      and blood pressure, lung function
                      parameters, eosinophils in the
                      nasal smear, hematological
                      characteristics and urinary
                      excretion of some metabolites
                      were examine and measured.
                      Anova and linear regression used
                      in analysis.
Mean SO2 exceeded
the limit of yearly
avg 150 ug/m3

Daily peaks reached
as high as 450 ug/m3

No specific values
given
NO,
Significant correlation
between SO2 levels and
acute daily respiratory
morbidity, but no
correlation with
weekly incidence.
Authors stated that in
the cross-sectional
study, almost all health
parameters were
impaired but no results
were shown.
Results only provided in graph. No
p-values provided
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                TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                        RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
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Reference, Study
Location, & Period
Outcomes, Design, Copollutants
& Methods Mean SO2 Levels Considered
Findings &
Interpretation
Effect Estimates
(95% CI)
EUROPE (cont'd)
Roemeretal. (1993)
Wageningen and
Bennekom,
Netherlands
















Panel of 73 children (mean age Daily concentrations NO2
9.3 yrs, range 6 to 12 yrs) with of SO2 shown in PM10
chronic respiratory symptoms to graph gg
investigate effects of winter air
pollution on lung function, Highest 24-h avg
symptoms and medication use. concentration SO2:
Subjects performed twice-daily 105 ng/m3
PEF measurements, largest of
three PEF readings used in
regression analysis. Both
incidence and prevalence of
symptoms analyzed, using
logistic regression.







Positive association
between incidence of
phlegm and runny nose
with SO2 on the same
day. Significant
association also found
between evening PEF
and SO2 on, the same
day, previous day and
1 wk (avg of same day
and 6 days before).
The use of
bronchodilators also
associated with SO2.

Correlation with
copollutants:
N02: r=0.26
PM10: r = 0.65
BS: r = 0.63
Mean of individual regression
coefficient

Morning PEF
Same day: -0.021(0.024)
Lagl: -0.024(0.031)
Wk: -0.50(0.069)

Evening PEF
Same day: -0.048 (0.018) p< 0.05
Lagl: -0.039 (0.021) p< 0.10
Wk: -0.110(0.055)p<0.05

Prevalence of symptoms
(per 50 ng/m3 SO2)

Asthma attack
Same day: 0.008(0.012)
Lagl: 0.016(0.011)
1 wk: 0.058(0. 027) p< 0.05
                                                                                                        Wheeze
                                                                                                        Same day:  0.033 (0.17) p< 0.10
                                                                                                        Lagl: 0.042 (0.016) p< 0.05
                                                                                                        Wk: 0.069 (0.032) p< 0.05

                                                                                                        Waken with symptoms
                                                                                                        Same: day 0.033 (0.019) p< 0.10
                                                                                                        Lagl: 0.032 (0.018) p< 0.10
                                                                                                        Wk: 0.058(0.045)

                                                                                                        Shortness of breath
                                                                                                        Same: day 0.029 (0.016) p< 0.10
                                                                                                        Lagl: 0.016(0.015)
                                                                                                        Wk: 0.044(0.035)

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                     TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                                 RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
            Reference, Study
            Location, & Period
                           Outcomes, Design,
                              & Methods
                                Mean SO2 Levels
                      Copollutants
                       Considered
 Findings & Interpretation
         Effect Estimates
            (95% CI)
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EUROPE (cont'd)
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           Roemeretal. (1993)
           (cont'd)
Roemeretal. (1998)
14 European Centers:
Umea, Sweden;
Malmo, Sweden;
Kuopi, Finland;
Oslo, Norway;
Amsterdam, The
Netherlands;
Berlin, Germany;
Katowice, Poland;
Cracow, Poland;
Teplice, Czech
Republic;
Prague, Czech
Republic; Budapest,
Hungary;
Pisa,Italy;
Athens, Greece
Winter 1993-1994
Multicenter panel study of the
acute effects of air pollution on
respiratory health of
2010 children (aged 6 to 12 yrs)
with chronic respiratory
symptoms. Results from
individual centers were reported
by Kotesovec et al. (1998),
Kalandidi et al. (1998), Haluszka
etal. (1998),Forsbergetal.
(1998), Clench-Aas etal. (1998),
and Beyer etal. (1998).
Calculated effect estimates of air
pollution on PEF or the daily
prevalence of respiratory
symptoms and bronchodilator use
from the panel-specific effect
estimates
Range: -2.7 |ig/m3
(Umea, urban),
113.9ng/m3
(Prague, urban)
                                                                                   PM10,
                                                                                   BS
No clear associations between
PMio, BS, SO2j or NO2 and
morning PEF, evening PEF,
prevalence of respiratory
symptoms, or bronchodilator
use could be detected.

Previous day PM10 was
negatively associated with
evening PEF, but only in
locations where BS was high
compared to PM10
concentrations.

No consistent differences in
effect estimates between
subgroups based on urban
versus suburban,
geographical location or
mean levels of PM10, BS,
SO2, andNO2.
                                                                                                                    Cough
                                                                                                                    Same day 0.018 (0.025)
                                                                                                                    Lagl: 0.012(0.023)
                                                                                                                    Wk 0.072 (0.066)

                                                                                                                    Runny nose
                                                                                                                    Same day 0.070 (0.026) p < 0.05
                                                                                                                    Lagl: -0.11(0.025)
                                                                                                                    Wk 0.153 (0.074) p< 0.05

                                                                                                                    Phlegm
                                                                                                                    Same day 0.011(0.022)
                                                                                                                    Lagl: 0.014(0.020)
                                                                                                                    Wk-0.005 (0.056)
Combined effect estimates with 95%
CI of air pollution on PEF

Morning
LagO: 0.2 (-0.2, 0.6)
Lagl: 0.2 (-0.2, 0.6)
Lag 2: 0.6(0.2,1.0)
7-day mean 0.6 (-1.3, 2.5)

Afternoon
LagO: 0.1 (-0.3, 0.5)
Lagl: 0.0 (-0.4, 0.4)
Lag 2: 0.1 (-0.4, 0.6)
7-day mean 0.2 (-0.5, 0.9)

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             TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

                               RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
Reference, Study
Location, & Period
Outcomes, Design,
& Methods Mean SO2 Levels
Copollutants Findings &
Considered Interpretation
Effect Estimates
(95% CI)
EUROPE (cont'd)
Taggartetal. (1996)
Runcorn and Widnes
in NW England
Jul-Sep 1993











Panel study of 38 nonsmoking 24-h avg SO2
asthma subjects (18 to 70 yrs) to Max: 103.7 ug/m
investigate the relationship
between asthmatic bronchial
hyperresponsiveness and
pulmonary function (PEF, FEVi,
FVC) and summertime ambient
air pollution. Used univariate
nested (hierarchical) analysis of
variance to test hypothesis that
BHR or spirometry
measurements varied with air
pollution levels. Analysis was
limited to within- subject variation
of(BHR,FEVl5orFVC).
NO2 No association
O3 between SO2 and FEVj
smoke or FVC.

Changes in BHR
correlated significantly
with changes in 24-h
mean SO2, NO2, and
smoke.

Correlation with
copollutants:
O3: r= 0.13

NO2: r — 0.65
Smoke: r=0.48
Percentage change in BHR per 10 ug/m3 SO2

24-h mean SO2 -6.3 % (- 13.6, 0.6)
48-h mean -2.9 % (- 12.8, 8.2)
24-h Lag 7.4% (-4. 5, 20. 8)










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             TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

                              RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
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Reference, Study Outcomes, Design, Copollutants Findings &
Location, & Period & Methods Mean SO2 Levels Considered Interpretation
Effect Estimates
(95% CI)
EUROPE (cont'd)
Ward et al. (2002) Panel study of 162 children 24-h avg SO2 NO2
Birmingham and (9 yrs at time of enrollment) O3
Sandwell, England from two inner city Winter: PM10
Jan-Mar 1997 locations to investigate the Jan 13-Mar 10, jj+
May -Jul 1997 association between 1997 pi-
ambient acid species with Median: 5. 4 ppb „„,
PEF and symptoms. Daily Range: 2, 1 8 ppb
symptoms and twice-daily HJNO3
"MTT
peak flow measurements Summer'
were recorded over 8 wk May 19- July 14, NH/t
periods in the summer and 1997 NO3
winter. 39 of the children Median: 4.7 ppb SO42~
reported wheezing in the Range: 2, 10 ppb
past 12 mos. Linear
regression used for PEF and
logistic regression for
symptoms.
















In the summer,
changes in
morning PEF were
associated with
SO2 at 3-days lag
and the 7-day
mean SO2.
Prevalence of
cough associated
with SO2 on the
same day.
In the winter SO2
was only
associated with
symptom of
feeling ill on the
same day.















24-h avg SO2 (per 4.0 ppb in winter; per 2.2 ppb in summer)
Data also available for 3-,4-,

Change in PEF (L/min)
Morning- Lag 0-day
Winter
-0.60 (-2.51, 1.32)
Summer
0.91 (-0.95, 2.78)
Afternoon- Lag 0-day
Winter
-0.32 (-2.71, 2.04)
Wummer
-0.89 (-2. 61, 0.83)

Odds ratio for symptoms
Cough-Lag 0-day
Winter
0.92(0.81,1.05)
Summer
1.08(1.02,1.15)
Ill-Lag 0-day
Winter
1.09(1.01,1.18)
Summer
1.05(0.96,1.14)
Shortness of breath-
Lag 0-day
Winter
1.02(0.93,1.13)
Summer
0.98(0.87,1.10)
and 7-day Lag


Morning- Lag 1-day
Winter
0.08 (-1.67,1. 86)
Summer
0.29 (-1.56, 2.14)
Afternoon- Lag 1-day
Winter
-0.88 (-2.87, 1.10)
Summer
-0.02 (-1.68, 1.65)


Cough-Lag 1-day
Winter
1.00(0.87,1.15)
Summer
1.04(0.97,1.11)
Ill-Lag 1-day
Winter
1.03(0.95,1.11)
Summer
1.02(0.94,1.12)
Shortness of breath-
Lag 1-day
Winter
1.00(0.90,1.09)
Summer
1.00(0.89,1.13)

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               TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

                                     RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
Reference, Study Outcomes, Design, Mean SO2 Copollutants Findings & Effect Estimates
Location, & Period & Methods Levels Considered Interpretation (95% CI)
EUROPE (cont'd)
Ward et al. (2002)
(cont'd)



Wake at night with cough-
Lag 0 day
Winter
1.00(0.91,1.10)
Summer
1.00(0.87,1.14)
Wheeze- Lag 0 day
Winter
0.96, (0.85, 1.07)
Summer
1.05(0.92,1.19)
Wake at night with cough-
Lag 1 day
Winter
1.05(0.96,1.15)
Summer
1.02(0.89,1.16)
Wheeze-Lag 1 day
Winter
0.96(0.86,1.07)
Summer
1.00(0.88,1.13
Summer change in PEF 2.7 (1.03, 4.38)

per2.2ppbSO2

Lag 3 days (p < 0.05)



Summer change in PEF 6.83 (0.98, 12.69)

per2.2ppbSO2

Lag 0-6 days (p < 0.05)
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             TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

                              RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
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W
Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean SO2 Copollutants Findings &
Levels Considered Interpretation
Effect Estimates
(95% CI)
EUROPE (cont'd)
van der Zee etal. (1999)
Netherlands, 3 winters
from 1992 to 1995
Rotterdam and
Bodegrven/Reeuwijk
(1992-1993)
Amsterdam and Meppel
(1993-1994)
Amsterdam and
Nunspeet (1994-1995)

























Panel study of
633 children (aged 7 to
1 1 yrs) with and without
chronic respiratory
symptoms, living in
urban and nonurban
areas in the Netherlands.
Volunteers measured
daily PEF and reported
the occurrence of
respiratory symptoms
and bronchodilator use
in a diary. Association
between air pollution
and decrements in PEF,
symptoms and
bronchodilator use
evaluated with logistic
regression models that
adjusted for first order
autocorrelation, min
daily temperature, day of
wk, time trend,
incidence of influenza
and influenza-like
illness.









Median and max PM10 The correlation between
24-h mean Black smoke SO2 and PM varied from
concentration Sulfate 0.5 to 0.8 during first
(ug/m3) N02

1992-1993
Urban 23 (152);
Nonurban 8.9
(43)

1993-1994
Urban 1 1 (34);
Nonurban 5.0
(42)

1994-1995
Urban 6.0 (24);
Nonurban 3.6
(17)
















two winters. Correlation
with NO2 about 0.50.

In the urban areas, SO2
was associated with
>10% decrements in
evening PEF, LRS and
use of bronchodilator in
children with symptoms.
Most consistent
associations found with
PMio, BS, and sulfate.
No association found
between SO2 and
prevalence of URS,
cough, phlegm, and
>10% decrements in
morning PEF. In the
nonurban areas, no
associations found with
SO2. In children without
symptoms, no consistent
associations with SO2.
Authors concluded that
children with symptoms
are more susceptible to
particulate air pollution
effects and that use of
medication for asthma
did not prevent the
adverse effects of PM in
children with symptoms.
Odds ratio (per 40 ug/m3 SO2)
Children with symptoms
Urban areas
Evening PEF
LagO: 1.32(0.96,1.80)
Lagl: 0.83(0.60,1.14)
Lag 2: 1.67(1.28,2.19)

Symptoms of lower
respiratory tract
LagO: 1.35(1.01,1.79)
Lagl: 1.23(0.93,1.64)

Symptoms of upper
respiratory tract
LagO: 0.97(0.82,1.14)
Lagl: 1.10(0.94,1.28)



Cough
LagO: 0.90(0.77,1.05)
Lagl: 1.12(0.96,1.30)

Use of bronchodilator
LagO: 0.92(0.72,1.18)
Lagl: 1.45(1.13,1.86)







Nonurban areas
Evening PEF
LagO: 1.20(0.91,1
Lagl: 0.89(0.68,1


Symptoms of lower
respiratory tract
Lag 0: 0.91 (0.69, 1
Lagl: 0.91(0.69,1

Symptoms of upper
respiratory
LagO: 0.94(0.81,1
Lagl: 0.97(0.83,1
5-day mean:
0.67 (0.47, 0.94)

Cough
LagO: 1.08(0.94,1
Lagl: 0.98(0.85,1



.58)
.17)




.19)
.22)



.09)
.13)




.23)
.12)

Use of bronchodilator
Lag 0: 0.86 (0.59, 1
Lagl: 1.18(0.80,1







.25)
.74)








-------
      ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^=
3          Reference, Study        Outcomes, Design,        Mean SO2     Copollutants       Findings &                   Effect Estimates
n>         Location, & Period           & Methods            Levels      Considered      Interpretation                    (95% CI)
K>       EUROPE (cont'd)	
O       van der Zee etal. (1999)                                                                              Odds ratio (per 40 ng/m3 SO2)
         (cont'd)                                                                                           Children without symptoms

                                                                                                     Urban areas          Nonurban areas
                                                                                                 Evening PEF           Evening PEF
                                                                                                 LagO:  1.13(0.88,1.47)   LagO:  1.10(0.87,1.39)
                                                                                                 Lagl:  1.16(0.90,1.50)   Lagl:  1.07(0.85,1.35)

                                                                                                 URS                 URS
                                                                                                 LagO:  0.92(0.76,1.11)   LagO:  1.07(0.92,1.25)
                                                                                                 Lagl:  1.10(0.91,1.34)   Lagl:  0.85(0.72,1.00)
                                                                                                 Lag 2:  0.83(0.70,0.99)

                                                                                                 Cough                Cough
^                                                                                               LagO:  0.93(0.78, 1.11)   Lag 0:  0.86 (0.76, 0.97)
X	Lag 1:  1.02 (0.84, 1.23)   Lag 1:  0.95 (0.83, 1.08)

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             TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

                              RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
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Reference, Study Outcomes, Design,
Location, & Period & Methods
Mean SO2 Copollutants
Levels Considered Findings & Interpretation
Effect Estimates
(95% CI)
EUROPE (cont'd)
van der Zee (2000) Panel study of 489 adults
Netherlands, (aged 50 to 70 yrs) with
3 winters from and without chronic
1992 to 1995 respiratory symptoms,
Rotterdam living in urban and
1992-1993 nonurban areas in the
Netherlands. Volunteers
measured daily PEF and
reported the occurrence of
respiratory symptoms and
bronchodilator use in a
diary. Association
between air pollution and
decrements in PEF,
symptoms and
bronchodilator use
evaluated with logistic
regression models that
adjusted for first order
autocorrelation, min daily
temperature, day of wk,
time trend, incidence of
influenza and influenza-
like illness.












Median PM10
(max) cone BS
Sulfate
1992/1993: NO2
Urban 25
(61) ue/m3
V / r^fo
1993/1994
Urban 11
(34) NQ/rn
\ / r-& ?
Nonurban
5.0
(42) ug/m3

1994/1995
Urban 6.0
(24),
Nonurban
1 f.
J.D
(17) ug/m3















Among symptomatic adults
living in urban areas, the
prevalence of >20%
decrement in morning PEF
was associated with SO2.
Moreover, there were no
associations found with
prevalence of
bronchodilator use, LRS,
>10% decrement in
morning PEF and >10% and
>20% decrement in evening
PEF.

In the nonurban areas, there
was no consistent
association between air
pollution and respiratory
health. In the
nonsymptomatic adults, no
consistent associations
observed between health
effects and air pollutants,
but a significant and
positive association was
observed with URS in the
nonurban area at 1 day Lag.

Range of Spearman
correlation coefficients
between 24-h avg cone SO2
and copollutants :
PM10: 0.31,0.78
BS: 0.21,0.75
Sulfate: 0.29,0.69
NO2: 0.47,0.51
Odds ratio (per 40 ug/m3 SO2)
symptomatic adults
In urban areas In nonurban areas
> 1 0% decline in PEF > 1 0 % decline in PEF
Morning
LagO: 0.86(0.60, 1.23)
Lagl: 0.97(0.68,1.39)

>20% decline in PEF
Morning
LagO: 1.33(0.66,2.71)
Lagl: 1.98(1.03-3.79)

LRS
LagO: 1.01(0.84,1.20)
Lagl: .97(0.82,1.16)

5-day mean:
0.71 (95% CI: 0.53 to
0.95)

URS
LagO: 1.15(0.97,1.37)
Lagl: 1.06(0.90,1.26)

Bronchodilator use
LagO: 1.09(0.93,1.28)
Lagl: 1.05(0.89,1.24)
Lag 2: 0.85(0.72,0.99)





Morning
LagO: 79(0.48,1.29)
Lagl: 1.08(0.68,1.72)

>20% decline in PEF
Morning
LagO: 0.79(0.22,2.88)
Lagl: 71(0.13,4.02)

LRS
LagO: 1.11(0.94,1.30)
Lagl: 1.04(0.88,1.22)




URS
LagO: 0.97(0.79,1.20)
Lagl: 1.20(0.98,1.47)

Bronchodilator use
LagO: 1.04(0.91,1.18)
Lagl: 1.08(0.95,1.22)







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                  TABLE AX5.1 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                           RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
          Reference, Study Location,
                  & Period
                         Outcomes, Design,
                            & Methods
Mean SO2
  Levels
Copollutants
 Considered
 Findings &
Interpretation
Effect Estimates
   (95% CI)
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          van der Zee (2000) (cont'd)
                                                                                                     Nonsymptomatic adults
                                                                                               Urban areas             Nonurban areas
                                                                                                  > 10% decline in PEF
                                                                                                  Morning
                                                                                                  LagO: 0.77(0.39,1.52)
                                                                                                  Lagl: 0.94(0.51,1.73)
                                                                                                  URS
                                                                                                  LagO: 1.10(0.81,1.48)
                                                                                                  Lagl: 1.23(0.92,1.65)
                                                                                                                 > 10% decline in PEF
                                                                                                                 Morning
                                                                                                                 LagO: 2.12(0.98,4.62)
                                                                                                                 Lagl: 0.87(0.38,1.99)
                                                                                                                 Lag 2: 0.13(0.04,0.36)
                                                                                                                 5-day mean:
                                                                                                                 0.03 (0.00, 0.24)

                                                                                                                 URS
                                                                                                                 LagO: 0.73(0.49,1.07)
                                                                                                                 Lagl: 1.71(1.18,2.46)
                                                                                                                 Lag 2: 0.65(0.44,0.97)
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                    TABLE AX5.1 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                              RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
Reference, Study
Location, & Period
Outcomes, Design,
& Methods

Mean SO2 Levels
Copollutants
Considered
Findings &
Interpretation
Effect Estimates
(95% CI)
EUROPE (cont'd)
Desqueyroux et al.
(2002)
Paris, France
Nov 1995-Nov 1996






Panel study of 60 patients with
moderate to severe physician-
diagnosed asthma (mean age
55 yrs). Asthma attacks were
noted by physician at each
consultation (regular or
emergency). Asthmatic
attacks defined as need to
increase twofold the dose of
beta2 agonist.
24-h avg SO2

Summer 7 (5) ug/m3
Range: 2,27

Winter 19 (12) ug/m3
Range: 3, 81



PM10
N02
03







No association
between asthma
attacks and SO2 for
any Lag or season.






Mean 24-h SO2 (per 10 ug/m3)
OR on incident of asthma attacks

Lagl: day 0.98 (0.76, 1.27)
Lag 2: day 0.92 (0.72, 1.19)
Lag 3: day 1.01(0.82,1.23)
Lag 4: day 1.01(0.86,1.19)
Lag 5: day 1.05(0.85,1.29)

Cumulative exposure mean (-1 to -5 days)
          Forsberg et al. (1993)   Panel study of 31 asthmatic     24-h avg SO2 (ug/m3)  NO2, BS
Pitea, Northern
Sweden
March to April
patients (9 to 71 yrs) to assess
relationship between daily
occurrence of asthma
symptoms and fluctuations in
air pollution and
meteorological conditions.
Subjects recorded symptoms
(shortness of breath,
wheezing, cough, and phlegm)
for 14 consecutive days.
Mean: 5.7
Range:  1.3, 12.9
No significant
association observed
withSO2. Positive
association between
severe shortness of
breath and black
smoke.

Correlation with
copollutants:
NO2: r=0.24
BS: r = 0.70
0.99(0.76,1.30)

Regression coefficient and 90% CI

Subjects with shortness of breath (n = 28)
0.0345 (-0.49, 0.118)

Subjects with 5 or more incident episodes of
severe shortness of breath (n = 10)
-0.0266 (-0.140, 0.087)

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             TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

                              RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
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Reference, Study Outcomes, Design, Copollutants Findings &
Location, & Period & Methods Mean SO2 Levels Considered Interpretation
Effect Estimates
(95% CI)
EUROPE (cont'd)
Higginsetal. (1995) Panel study of 75 patients with Maximum 24-h SO2 O3 The amplitude % mean
United Kingdom physician diagnosed asthma or 117ug/m3
chronic bronchitis (mean age
50, range 18to82yrs)to
determine if air pollution
affects respiratory function
and symptoms. Subjects
asked to keep symptom
records and perform PEF for
28 days. PEF values recorded
every 2 h beginning at 02.00
our each day. Methacholine
challenge performed on each
subjects. Those with PM20
FEVj of<12.25 umol were
considered as methacholine
reactors. PEF variability was
calculated as the amplitude %
mean: (highest-lowest PEF
value/mean) x 100. 75 patients
had PEF records,
65 completed symptom
questionnaires.
NO2 was significantly
associated with
increasing levels of
SO2, on the same day
for all subjects and
among reactors. Mean
daily PEF and
minimum PEF
associated with SO2
among reactors only.
Significant
associations also
observed with wheeze
and SO2 on the same
day, at 24-h Lag, and
48-h Lag for all
subjects and meta-
choline reactors; and
with bronchodilator
use for all subjects at
24-h Lag.

Regression coefficient per 10 ug/m SO2
All subjects
Mean PEF (L/min)
SciinG dciy
-0.021 (0.031)
24-h Lag
0.003 (0.033)
48-h Lag
0.021 (0.032)

Minimum
PEF(L/min)
Same day
-0.062(0.039)
24-h Lag
-0.048(0.041)
48-h Lag
-0.001 (0.040)




Reactors
Mean PEF (1/min)
SciiTiG dciy
-0.087(0.054)
24-h Lag
-0.44(0.058)
48-h Lag
0.012(0.057)

Minimum
PEF(L/min)
Same day
-0.168(0.071)
24-h Lag
-0.078(0.076)
48-h Lag
-0.026(0.075)





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             TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

                              RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
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Reference, Study Outcomes, Design, Copollutants Findings & Effect Estimates
Location, & Period & Methods Mean SO2 Levels Considered Interpretation (95% CI)
EUROPE (cont'd)
Higgins et al. (1995) Amplitude
(cont'd) (% mean)
Same day:
0.167(0.072)
24-h Lag 0.191 (0.76)
48-h Lag 0.022 (0.075)
Wheeze
Same day:
1.14(1.03,1.26)
24-h Lag
1.22(1.09,1.37)
48-h Lag
1.14(1.02,1.27)
Dyspnoea
Same day:
1.03(0.94,1.14)
24-h Lag
1.07(0.96,1.18)
48-h Lag
0.94(0.85,1.05)
Cough
Same day:
1.03(0.95,1.12)
24-h Lag
1.04(0.95,1.13)
48-h Lag
1.02(0.94,1.12)
Amplitude
(% mean)
Same day:
0.157(0.120)
24-h Lag 0.083 (0.127)
48-h Lag 0.005 (0.126)
Wheeze
Same day:
1.26(1.08,1.47)
24-h Lag
1.57(1.30,1.89)
48-h Lag
1.24(1.06,1.45)
Dyspnoea
Same day:
1.04(0.90,1.20)
24-h Lag
1.17(1.00,1.37)
48-h Lag
1.03(0.89,1.20)
Cough
Same day:
1.09(0.96,1.24)
24-h Lag
1.05(0.91,1.20)
48-h Lag
1.00(0.87,1.15)

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             TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

                              RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
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Reference, Study Outcomes, Design, Copollutants Findings & Effect Estimates
Location, & Period & Methods Mean SO2 Levels Considered Interpretation (95% CI)
EUROPE (cont'd)
Higgins et al. (1995) Throat symptoms
(cont'd) Same day:
1.01(0.92,1.11)
24-h Lag
1.00(0.91,1.10)
48-h Lag
0.96(0.87,1.06)
Eye symptoms
Same day:
1.08(0.97,1.20)
24-h Lag
1.11(0.99,1.24)
48-h Lag
1.10(0.99,1.21)
Bronchodilator use
Same day
1.11(0.97,1.26)
24-h Lag
1.16(1.01,1.34)
48-h Lag
1.12(0.98,1.27)
Throat symptoms
Same day:
1.06(0.92,1.21)
24-h Lag
1.06(0.91,1.23)
48-h Lag
1.01(0.87,1.17)
Eye symptoms
Same day:
1.19(1.01,1.40)
24-h Lag
1.21 (1.01,1.45)
48-h Lag
1.08(0.91,1.28)
Bronchodilator use
Same day
1.18(0.99,1.42)
24-h Lag
1.23(1.02,1.50)
48-h Lag
1.31 (1.09,1.58)

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                    TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                                RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
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Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean SO2 Levels
Copollutants
Considered
Findings & Interpretation
Effect Estimates
(95% CI)
EUROPE (cont'd)
           Hoek and Brunekreff
           (1993)
           Wageningen,
           The Netherlands
Panel study of 112 children
(7 to 12 yrs, non-urban) to
assess effects of winter air
pollution pulmonary function
and respiratory symptoms.
Parents filled out symptom
diary that was turned in every
2 wks. Pulmonary function
test performed by technician
every 3 wks.  Additional
pulmonary function tests
performed when SO2 was
predicted to be higher than
125 ug/m3 orNO2 >90  ug/m3.
Daily concentrations
presented in graph;

Highest 24-h avg
cone SO2: 105 ug/m3
(air pollution
episode)
o, BS, NO2  During the winter episode,
           pulmonary function of
           schoolchildren was significantly
           lower than baseline. Significant
           negative associations between SO2
           and FVC, FEVj and MMEF. No
           significant associations found with
           prevalence of respiratory
           symptoms. Authors noted that it is
           not clear which components of
           episode mix responsible for
           association and that the
           concentrations of acid aerosol and
           SO2 were too low for direct effects
           to be likely. SO2 moderately
           correlated with PM10 (r = 0.69)
           and black smoke (r = 0.63) but not
           NO2 (r = 0.28).
Mean of individual regression
slopes and SE

FVC
Same day -0.55 (0.10), p < 0.05
Lagl: -0.74 (0.15) p< 0.05
1 wk-0.94 (0.20) p< 0.05

FEVj
Same day -0.51 (0.09) p < 0.05
Lagl: -0.21 (-0.63) p< 0.05
1 wk-0.78 (0.18) p< 0.05

PEF
Same day-0.64 (-0.44)
Lagl: -0.21(0.63)
1 wk-0.34 (0.81) p< 0.05

MMEF
Same day-0.54 (0.20)
Lagl: -0.40(0.29)
Iwk-0.61 (0.37)

Prevalence of acute respiratory
symptoms
regression coefficient from time-
series model and SE

Cough
Same day 0.02(0.18)
Lagl: -0.14(0.19)
Iwk 0.13 (0.76)

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                   TABLE AX5.1 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                              RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
            Reference, Study
           Location, & Period
                         Outcomes, Design,
                            & Methods
 Mean SO2 Levels
 Copollutants
 Considered
   Findings & Interpretation
       Effect Estimates
          (95% CI)
to
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EUROPE (cont'd)
          Hoek and Brunekreff
          (1993) (cont'd)
                                                                                                                 Upper respiratory symptoms
                                                                                                                 Same day 0.12 (0.16)
                                                                                                                 Lagl: -0.02(0.17)
                                                                                                                 1 wk -0.24 (0.76)
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          Lagorio et al. (2006)
          May 24 to June 24,
          1999 and Nov 18 to
          Dec 22, 1999
          Rome, Italy
                     Panel study of 29 patients with
                     either COPD (n = 11, mean
                     age 67 yrs), asthma (n = 11,
                     mean age 33 yrs) or ischemic
                     heart disease (n = 7, mean age
                     63 yrs) to evaluate whether
                     daily levels of air pollutants
                     have a measurable impact on
                     lung function in adults with
                     preexisting lung  or heart
                     disease.
24-h mean SO2
Spring mean 4.7
SD1.8
Winter mean 7. 9
SD2.2
Overall mean 6.4
SD2.6
PM2.5
PM10-2.5
PM10
CD
Cr
FE
NI
PB
PT
V
Zn
N02
CO
03
Because avg 24-h concentrations
of SO2 were low and showed little
variability, SO2 was not
considered in the analysis

Correlation with copollutants:
PM25: r=0.34
PM10.2.5: r= -0.16
PM10: r = 0.21
NO2: r=0.01
03:  r=-0.61
CO:  r=0.65
Lower respiratory symptoms
Same day 0.06 (0.26)
Lagl: -0.11(0.29)
1 wk -0.54 (0.92)

Any respiratory symptoms
Same day 0.01 (0.13)
Lagl: -0.03(0.13)
1 wk -0.11(0.60)

No data available

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                    TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                                RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
             Reference, Study
            Location, & Period
                          Outcomes, Design,
                             & Methods
Mean SO2 Levels
 Copollutants
 Considered
Findings & Interpretation
Effect Estimates
   (95% CI)
to
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EUROPE (cont'd)
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           Neukirchetal. (1998)
           Paris, France
           Novl5, 1992 to
           May 9, 1993
                      Panel study of
                      40 nonsmoking, mild to
                      moderate asthmatics (16 to
                      70 yrs, mean 46) to examine
                      the short-term effects of
                      winter air pollution in asthma
                      symptoms and three daily
                      peak flow measurements.
                      Patients were followed for
                      23wks. Used GEE models
                      that controlled for
                      autocorrelation of responses,
                      weather, and time trends.
                      Analysis conducted on entire
                      study population and for
                      subgroup of subjects who took
                      inhaled B2 agonists as needed.
                      Assessed air pollution effect
                      on both incident and
                      prevalence of symptoms,
                      Z-transformed morning PEF
                      and daily PEF variability.
24-h avg SO2

Mean: 21.7
(13.5) ug/m3
Range: 4.4, 83.8
NO2, PM13,      Significant effects on
Black smoke    incidence and prevalence of
               symptoms. Effects at Lag
               days 3-6 and weekly avg
               exposures. Based on group
               avgPEFof4071/min,a
               50 ug/m  increase SO2 caused
               a maximum decrease in
               morning PEF of 5.5%.

               Correlation with copollutants:
               NO2: r=0.54
               PM13: r = 0.83
               BS: r = 0.89
                          24-h avg SO2 (per 50 ug/mj)

                          Odds ratio:  all subjects
                          Incident episodes:

                          Wheeze:
                          Lag 5:  1.66(1.01,2.70)

                          Nocturnal cough:
                          Lag 3:  1.60(0.98,2.62)
                          Lag 4:  1.71(0.86,3.40)
                          Lag 6:  1.72(1.16,2.55)

                          Respiratory infections:
                          Lag 3:  3.14(1.30,7.59)
                          Lag 4:  2.70(1.36,5.37)
                          Lag 5:  2.79(0.95,8.21)
                          Wk: 8.52(1.20,60.5)

                          Odds ratio:  all subjects
                          Prevalent episodes:
                          Wheeze:
                          Lag 5:  1.35(1.01,1.81)
                          Lag 6:  1.39(1.04,1.87)
                          Wk: 1.64(0.91,2.94)

                          Nocturnal cough:
                          Lag 6:  1.34(1.00,1.79)

                          Shortness of breath:
                          Wk: 1.56(1.06,2.32)
                          Respiratory infections:
                          Lag 4:  2.40(1.33,4.33)
                          Lag 5:  2.72(1.67,4.44)
                          Lag 6:  2.94(1.80,4.79)
                          Wk: 6.30(1.31,30.2)

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                   TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                             RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
            Reference, Study
           Location, & Period
Outcomes, Design,
   & Methods
                                                 Mean SO2
                                                   Levels
Copollutants
 Considered
Findings & Interpretation
Effect Estimates
   (95% CI)
to
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EUROPE (cont'd)
          Neukirchetal. (1998)
          (cont'd)
                                                                                                       Odds ratio: Subjects taking B2 agonists
                                                                                                       Incident episodes:

                                                                                                       Asthma attacks:
                                                                                                       Lag 6:  2.19(0.91,5.29)

                                                                                                       Wheeze:
                                                                                                       Lag 5:  1.84(1.13,3.00)

                                                                                                       Nocturnal cough:
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                                                                                                       Lag 3: 2.41(1.47,3.93
                                                                                                       Lag 4: 2.35(0.88,6.26)
                                                                                                       Lag 6: 1.86(1.14,3.04)

                                                                                                       Odds ratio: Subjects taking B2 agonists
                                                                                                       Prevalent episodes:

                                                                                                       Asthma attacks:
                                                                                                       Lag 5: 1.88(0.95,3.73)
                                                                                                       Lag 6: 2.82(1.57,5.07)

                                                                                                       Wheeze:
                                                                                                       Lag 5: 1.51(1.02,2.23)
                                                                                                       Lag 6: 1.57(1.06,2.32)

                                                                                                       Nocturnal cough:
                                                                                                       Lag 3: 1.73(1.06,2.82)
                                                                                                       Lag 4: 2.28(1.27,4.11)
                                                                                                       Lag 5: 1.91(1.17,3.12)
                                                                                                       Lag 6: 1.91(1.17,3.12)

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      ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^=^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^=
3         Reference, Study        Outcomes, Design,        Mean SO2     Copollutants                                     Effect Estimates
n>        Location, & Period          & Methods             Levels       Considered    Findings & Interpretation               (95% CI)
K>       EUROPE (cont'd)	
O       Neukirchetal. (1998)                                                                              Shortness of breath:
         (cont'd)                                                                                       Lag 4: 1.81(1.22,2.67)
                                                                                                      Lag 5: 1.65(1.11,2.44)
                                                                                                      Lag 6: 1.61(1.20,2.16)
                                                                                                      Wk: 3.03(1.26,7.33)

                                                                                                      Regression coefficients of the effects and
                                                                                                      SE (per 1 |ig/m3)

                                                                                                      Z-transformed morning PEF
                                                                                                      Lag 5: -0.450 (0.138) p = 0.001
                                                                                                      Lag 6: -0.337 (0.164) p = 0.03

                                                                                                      PEF daily variability
>                                                                                                    Lag 2: 0.025 (0.013) p = 0.05
X
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                    TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                               RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
             Reference, Study
            Location, & Period
                          Outcomes, Design,
                             & Methods
  Mean SO2
    Levels
 Copollutants
 Considered
  Findings & Interpretation
           Effect Estimates
              (95% CI)
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           Peacock et al. (2003)
           Southern England
           Nov 1,1996 to Feb 14,
           1997
                      Panel study of 177 children
                      (mean age 10.7 yrs, range 7 to
                      13) from three schools (two
                      urban and 1 rural location) to
                      investigate effects of winter
                      air pollution on respiratory
                      function. Children were
                      followed for 13 wks.  Used
                      two sources of air pollution in
                      the rural area, one that was
                      "locally validated" and the
                      other "nationally validated".
24-h avg SO2
(Ppb)

Rural
(nationally
validated)
Mean 5.1(4.7)
Range 0.0, 35.6

Rural
(locally
validated)
Mean 5.4 (5.1)
Range 0.0, 39.1

Urban 1
Mean 6.0 (6.0)
Range 0.5, 32.5
03
N02
PM10
S04
No statistically  significant
association between winter SO2
andPEFR,

0.70% decline in PEFR for a
10-ppb increase in the five-day
mean concentration of SO2
(community monitor)
24-h avg SO2
change in PEF per 1 ppb SO2 - community
monitor
LagO: 0.05 (-0.05, 0.16)
Lagl: -0.04 (-0.13, 0.06)
Lag 2: -0.08 (-0.19, 0.04)
Mean (0-4) -0.23 (-0.65, 0.18)

Change in PEF per 1 ppb SO2 - local
LagO: -0.01 (-0.10, 0.07)
Lagl: 0.02 (-0.05, 0.10)
Lag 2: -0.09 (-0.18, 0.01)
Mean (0-4) -0.09 (-0.25, 0.07)

Odds of 20% decrement in PEF below
the median-all children
Lag 00.987 (0.958, 1.017)
Lagl 1.007(0.986,1.030)
Lag 2 0.992 (0.963, 1.023)
Mean (0-4) 0.972 (0.887, 1.066)

Odds of 20% decrement in PEF below
the median-wheezy children
Lag 00.981 (0.925, 1.041)
Lag 10.999 (0.957, 1.042)
Lag 2 0.995 (0.939 1.054)
Mean (0-4) 1.019 (0.890 to 1.167)

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                    TABLE AX5.1 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                                RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
            Reference, Study
            Location, & Period
                                      Outcomes, Design,
                                         & Methods
   Mean SO2
    Levels
 Copollutants
 Considered
  Findings & Interpretation
           Effect Estimates
              (95% CI)
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           EUROPE (cont'd)
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          PonkaA. (1990)
          Helsinki, Finland 1991
                                 Survey study to compare
                                 weekly changes in ambient
                                 SO2, NO2, and temperature
                                 and the incidence of
                                 respiratory diseases, and
                                 absenteeism for children in
                                 day-care centers and schools
                                 and for adults in the work
                                 place during a 1-yr period
                                 (1987).
Mean weekly
concentration of
S02 (ug/m3)
Mean: 21.1
SD= 11.7
Median:  17.0
Range: 9,61.5

Mean of daily
max
Mean: 53
SD = 20.8
Median: 48
Range: 25.9,
130.3
N02
Mean SO2 concentration
correlated with the incidences
of URI and tonsillitis reported
from health centers.  SO2 also
correlated with absenteeism
due to febrile illness among
children in day care centers and
adults. When comparing
incidences during the low and
high levels of SO2, the number
of cases of URI and tonsillitis
reported from health centers
increased as well as
absenteeism. After
standardization for temperature,
the only difference that was
statistically significant was the
occurrence of URI diagnosed at
health centers. Frequency of
URI was 15% higher during
high levels of SO2 compared to
low.
Statistical significance (p) of product
moment correlation coefficients
(correlation coefficient) between SO2 and
respiratory disease and absenteeism

Respiratory tract infections diagnosed at
health centers:
URI SO2 arithmetic mean p < 0.001
(0.553)
SO2 mean of daily maximums:  p = 0.0012
(0.437)

Tonsillitis
Arithmetic mean: 0.0098 (0.355)
Mean of daily maximums: NS

Absenteeism due to febrile illness:
Day care centers
SO2 arithmetic mean: p = 0.012 (0.404)
Mean of daily maximums: p = 0.048
(0.323)
                                                                                                                          School children
                                                                                                                          SO2 arithmetic mean: NS
                                                                                                                          Mean of daily maximums:
                                                                                                                                                  NS
                                                                                                                          Adults
                                                                                                                          SO2 arithmetic mean: p < 0.0001 (0.644)
                                                                                                                          Mean of daily maximums: p < 0.0001
                                                                                                                          (0.604)
                                                                                                                          No significant correlation between SO2 and
                                                                                                                          URI, tonsillitis, otitis, or LRI in day care
                                                                                                                          center children

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                   TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                            RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
            Reference, Study
           Location, & Period
                         Outcomes, Design,
                            & Methods
Mean SO2
  Levels
Copollutants
 Considered
Findings & Interpretation
Effect Estimates
   (95% CI)
to
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X
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          PonkaA. (1990)
          (cont'd)
                                                                                                       Statistical significance of weekly
                                                                                                       frequency of respiratory tract disease and
                                                                                                       absenteeism during low and high levels of
                                                                                                       S02:
                                                                                                       Respiratory infections diagnosed at health
                                                                                                       centers: URI
                                                                                                       SO2 arithmetic mean: p< 0.001
                                                                                                       Mean of daily max: p = 0.0005

                                                                                                       Tonsillitis
                                                                                                       SO2 arithmetic mean: 0.0351
                                                                                                       SO mean of daily max:  NS

                                                                                                       Absenteeism due to febrile illness
                                                                                                       Day care center children: p = 0.0256
                                                                                                       School children: p = 0.0014
                                                                                                       Adults:  p = 0.0005
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             TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

                               RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
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Reference, Study
Location, & Period
Outcomes, Design, Copollutants Findings &
& Methods Mean SO2 Levels Considered Interpretation
Effect Estimates
(95% CI)
EUROPE (cont'd)
Segalaetal. (1998)
Paris, France
Novl5, 1992 to
May 9, 1993
















Panel study of 84 children (7 to SO2 mean (SD): NO2
1 5 yrs) with physician 21.7 (13.5) ng/m3 PM13
diagnosed asthma to examine gg
the effects of winter air Range' (44
pollution on childhood asthma. gg g\ ue/m3
For 25 wks, parents recorded
the presence or absence of
asthma attacks, upper or lower
respiratory infections with
fever, the use of supplementary
inhaled B2 agonist, the severity
of symptoms (wheeze,
nocturnal cough and shortness
of breath). Children also
recorded PEF three times a day.
GEE models adjusted for age,
sex, weather and time trend.
Investigated effects of SO2 at
0 to 6 day Lags.








SO2 associated with
both incident and
prevalent episodes
of asthma, use of
supplementary beta
2 agonist, incident
episodes of
nocturnal cough,
prevalent episodes
of shortness of
breath and
respiratory
infection.
Correlation with
copollutants:
MM • r — H ^A
1NW2. I — U.J^I
T>TV /r n A "3
PM13: r- 0.43
Re. r — n QQ
IJO. I — U.O:7







OR per 50 ug/m3 SO2

(Only effects at 0 and 1-days Lag shown below unless
statistically significant)

Incident episodes:
Mild asthmatics (n = 43)
Asthma'
LagO: OR 2.86 (1.31, 6.27)
Lagl: 2.45(1.01,5.92)
Wheeze:
LagO: 1.47(0.90,2.41)
Lagl: 1.27(0.48,3.38)
Nocturnal cough:
Lag 3: 1.93(1.18,3.15)
Lag 4: 2.12(1.43,3.13)


Respiratory infections
Lagl: 1.52(0.38,5.98)






Prevalent episodes
Mild asthmatics (n = 43)
Asthma'
LagO: 1.71(1.15,2.53)
Lagl: 1.55(0.86,2.78)
Wheeze:
Lag 4: 1.48(0.90,2.41)

Shortness of breath :
Lagl: 1.36(0.92,2.01)
Lag 2: 1.45(0.98,2.14)
Lag 3: 1.52(1.03,2.25)
Lag 4: 1.51(1.02,2.24)
Respiratory infections:
LagO: 1.58(0.72,3.46)
Lagl: 1.91(0.79,4.62)
Lag 2: 2.13(0.97,4.67)
Lag 3: 2.09(1.05,4.15)
Lag 4: 2.05(1.14,3.68)

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                  TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                           RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
          Reference, Study
         Location, & Period
                         Outcomes, Design,
                            & Methods
Mean SO2
 Levels
Copollutants
 Considered
 Findings &
Interpretation
Effect Estimates
   (95% CI)
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EUROPE (cont'd)
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          Segalaetal. (1998)
          (cont'd)
                                                                                                 Beta2 agonist:    Beta2 agonist:
                                                                                                 Lag 4: 1.63      Lag 4: 2.02(1.02,4.01)
                                                                                                 (1.00,2.66)      Lag 5: 1.96(0.99,3.88)
                                                                                                 Moderate asthmatics (n = 41)
                                                                                                 Statistically significant (only) prevalent
                                                                                                 episodes:
Beta2 agonist:
LagO: 3.67(1.25,10.8)
Lagl: 4.60(2.10,10.1)
Lag 2: 7.01(3.53,13.9)
Lag 3: 4.74(1.96,11.5)
Timonen and Panel study of 169 children (7 to 12 yrs)
Pekkanen (1 997) with asthma or cough symptoms living in
Kuopio, Finland urban and suburban areas of Kuopio,
1 994 Finland to determine association between
air pollution and respiratory health. In
the urban areas there were 39 asthmatics
and 46 with cough only; in the suburban
areas there were 35 asthmatics and 49
with cough who were included in the
final analysis. Twice daily PEF and daily
symptoms were recorded for 3 mos. First
order autoregressive models used to
assess associations between air pollutants
and PEF and logistic regression models
used for symptom prevalences and
incidences. Analysis conducted on daily
mean PEF deviations. Mean morning or
evening PEF calculated for each child
was subtracted from the daily value of
morning or evening PEF. The daily
deviations were then Avgd to obtain daily
mean PEF deviation for morning or
evening PEF.
Avg daily PM10
SO2 (ng/m3) BS
NO2
Urban area:
Mean: 6.0
25th
percentile: 2.6
50th
percentile: 3.6
75th
percentile:
7.1
Max: 32










Among children with
cough only, morning and
evening deviations in
PEF in the urban panel
was negatively
associated with SO2.
SO2 was also associated
with an increase in the
incidence of URS in
children with cough only
in the urban area. When
excluding the three
highest SO2 days, these
effects were no longer
statistically significant.
No associations found
between SO2 and
morning or evening PEF
or respiratory symptoms
in children with cough
only in the suburban
panel.

Correlation coefficient with SO2:

PM10r=0.21
BSr = 0.20
N02 r = 0.22
Regression coefficient
S02)

Morning PEF
deviations
Children with cough
alone
LagO: -0.229
(0.608)
Lag 1: -1.38(0.564)
Lag 2: -0.683
(0 523)
V -^ ±*~* f
4-day mean:
-1.28(0.633)








(SE)(perlO|ig/m3


Evening PEF
deviations
Children with
cough alone
LagO: -1.84
(0.673)
Lag 1: -0.144
(0.711)
Lag 2: -0.291
(0613)
V /
4-day mean:
-0.878(0.868)




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                TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                     RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
Reference, Study Outcomes, Design,
Location, & Period & Methods
Mean SO2 Copollutants Findings &
Levels Considered Interpretation
Effect Estimates
(95% CI)
EUROPE (cont'd)
Timonen and
Pekkanen(1997)
(cont'd)



Correlation with
copollutants (urban
area):
PM10: r = 0.21
BS: r = 0.20
N02: r=0.22



Asthmatic
LagO: 0.198(0.804)
Lagl: 0.382(0.789)
Lag 2: 0.648(0.715)
4 day mean:
1.39(1.14)
Odds ratio (per
10 ng/m3)
URS
Lagl: 1.46(1.07,
2.00)
Lag 2: 1.46(1.14,
1.87)
4-day mean: 1.55
(1.08,2.24)
Asthmatics
LagO: 1.28(0.711)
Lagl: 0.575(0.727)
Lag 2: 0.819(0.642)
4-day mean:
1.34(1.05)



                                                                                           Odds ratio when
                                                                                           excluded 3 highest
                                                                                           SO2 days (no 95% CI
                                                                                           provided, but effects
                                                                                           were not significant)
                                                                                           Lagl: 1.13
                                                                                           Lag 2: 1.46
                                                                                           4-day mean: 1.12

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                   TABLE AX5.1 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                             RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Copollutants
Mean SO2 Levels Considered
Findings &
Interpretation
Effect Estimates
(95% CI)
LATIN AMERICA
Pino et al. (2004)
Santiago, Chile
1995-1997









Cohort study of 492 infants recruited at
4 mos of age and followed through the
first yr of life to determine the association
between air pollution on wheezing
bronchitis.







Mean concentration PM2 5
ofSO2(ppb) NO2

Mean: 11.6
SD=8.1
Median: 10.0






No consistent
association was found
between the 24-h avg
SO2 and risk of
wheezing bronchitis.
However, after a
7-day lag, a 10-ppb
increase in the 24-h
avg SO2 was
associated with a 2 1 %
increase in risk of
wheezing bronchitis.
Increase in wheezing bronchitis
(95%CI)perlOppbSO2

21% (8, 39%)








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Romieuetal. (1996)
Mexico City, Mexico
April-Jul 1991
Nov 1991-Feb 1992
Panel study of 71 mildly asthmatic
children (5 to 13 yrs) to assess the
relationship between air pollution and
childhood asthma exacerbation.  Children
measured PEF three times daily and
recorded daily symptoms and medication
use. Examined both incidence and
prevalence of symptoms. Lower
respiratory symptoms, cough, phlegm,
wheeze, and/or difficulty breathing.
24-h avg SO2 (ppm)
Mean: 0.09
SD = 0.05
Range:  0.02,0.20
03
PM10
PM2.5
NO2
SO2 concentrations
were not related to
changes in PEF or
respiratory symptoms
Change in PEF per 10-ppb
increase in SO2
0.26 (-0.35, 0.88,1.01) L/min

Odds ratio per 10 ppb SO2
Coughing: 0.96(0.92,1.01)
Lower respiratory symptoms:
0.97(0.94,1.01)

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                   TABLE AX5.1 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                              RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean SO2 Levels
Copollutants
Considered
Findings &
Interpretation
Effect Estimates
(95% CI)
ASIA
Chen etal. (1999)
Three towns in Taiwan:
Sanchun, Taihsi, Linyuan
May 1995-Jan 1996








Cross-sectional panel study of 895
children (8 to 13 yrs) to evaluate the
short-term effect of ambient air pollution
on pulmonary function. Single and
multipollutant models adjusted for sex,
height, BMI, community, temperature,
and rainfall. Examined 1, 2, and 7-day
lag effects.




Peak concentrations
ofS02

Range: 0, 72.4 ppb
Day-time avg and
1-day lag
SO2 correlated with
PM10 (r = 0.68)
SO2 correlated with
NO2(r = 0.71)


CO
N03
PM10
NO2








Daytime peak SO2 at 2
days lag significantly
associated with FVC
using the single-
pollutant model.
Association also
observed with NO2
and CO with FVC.
No PM10 effects.
Only O3 effects
significant in
multipollutant models.
Change in FVC (mL) daytime
avg SO2
Lag 1: -3.18(1.80)
Lag 2: -2.70(1.49)
Lag 7: 0.61 (2.59)
Daytime peak SO2
Lag 1: -0.91 (0.73)
Lag 2: -1.27 (0.59), p< 0.05
Lag 7: -1.05(1.29)

Change in FEV! (mL)
daytime avg SO2
                                                                                            Lag 1: -1.95(1.69)
                                                                                            Lag 2: -1.12(1.41)
                                                                                            Lag 7: -1.48(2.44)

                                                                                            Daytime peak SO2
                                                                                            Lag 1: -0.57(0.68)
                                                                                            Lag 2: -0.64(0.56)
                                                                                            Lag 7: -1.96(1.22)
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          Xuetal. (1991)
          Beijing, China
          Three areas:  industrial,
          residential and suburban
          (control)
          August 1986
Cross sectional survey of 1140 adults
(40 to 69 yrs) who had never smoked
living in three areas of Beijing, to
determine respiratory health effects of
indoor and outdoor air pollution. A
trained interviewer obtained pulmonary
function measurements and determined
history of chest illnesses, respiratory
symptoms, cigarette smoking,
occupational exposure, residential history,
education level and type of fuel used for
cooking and heating.
Annual mean
concentration of SO2
(ug/m3)
Residential:  128
Industrial: 57
Suburban: 18
                                                                                        TSPM
An inverse linear
association found
between Ln outdoor
SO2 and FEVj and
FVC after adjusting
for age, height and
Regression estimate and standard
error
per Ln SO2 (ug/m3)

Height-adjusted FEVj (mL):
-35.6(17.3)

Height-adjusted FVC (mL):
-131.4(18.8)

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                   TABLE AX5.1 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                              RESPIRATORY MORBIDITY IN FIELD/PANEL STUDIES
Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Copollutants
Mean SO2 Levels Considered
Findings &
Interpretation
Effect Estimates
(95% CI)
ASIA (cont'd)
Park et al. (2002)
Seoul, Korea
Mar 2, 1996 to
Dec 22, 1999


Time series analysis of school
absenteeism due to illness and air
pollution in one elementary school in
Seoul. School located in area with heavy
traffic. Avg enrollment in 1996 was
1,264.


24-h avg SO2 PM10
N02
Mean:9.19ppb CO
SD=4.61 o
Range: 2.68,28.11 3
SO2 correlated with
CO (r = 0.67)

SO2, PM10j and O3
associated with illness
related school
absenteeism. SP2 and
O3 are protective for
non-illness related
absences.

Relative risk per IQR SO2
(5.68ppb)
Total absences:
1.03(1.02,1.05)
Non-illness related absences:
0.95(0.92,0.99)
Illness related absences:
1.09(1.07,1.12)
2-pollutant model with O3:
1.10(1.08,1.13)
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          Park et al. (2005a)
          Korea
          March to June 2002
Panel study of 69 patients (16 to 75 yrs)
diagnosed with asthma by bronchial
challenge or by bronchodilator response.
Patients recorded twice-daily PE,
symptoms at the end of each day (cough,
wheeze, chest tightness, shortness of
breath, sputum changes and the next
morning, night awakenings). During the
study period, 14 Asian dust days were
identified. GEE and generalized additive
Poisson regression model used in
analysis.
Daily avg SO2

Control days:
0.0069 (0.0019) ppm
Dust days:
0.0052 (0.0010) ppm
PM10
N02
CO
03
During the dust days,   Relative risk based on Poisson
SO2 levels were
significantly lower
compared to control
days. SO2 had no
significant effect on
PEF variability or
night symptoms.
log-linear regression analysis

PEF variability (>20%)
0.76(0.37,1.56)
Night symptoms:
0.98(0.59,1.51)

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                TABLE AX5.2. ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

            EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
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Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels &
Monitoring Stations
Copollutants &
Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change &
Confidence Intervals (95%)
UNITED STATES
Jaffe et al. (2003)
3 cities, Ohio, United
States (Cleveland,
Columbus, Cincinnati)
Period of Study:
7/91-6/96















ED Visits
Outcome (ICD9):
Asthma (493)
Age Groups
Analyzed:
5-34
Study design: Time
series
N: 4,416
Statistical analyses:
Poisson regression
using a standard
GAM approach
Covariates: City, day
ofwk, wk, yr,
minimum
temperature, overall
trend, dispersion
parameter
Season: June to Aug
only
Dose-response
investigated: Yes
Statistical package:
NR
Lag: 0-3 days
24-h avg:

Cincinnati: 35.9(25.1)
ug/m3
Range: 1.7, 132
Cleveland: 39.2(25.3)
ug/m3
Range: 2.6, 167
Columbus: 11.1
(8.5) ug/m3
Range: 0,56.8













Cincinnati:
PM2.5;r = 0.31
NO2; r = 0.07
O3;r=0.14
Cleveland:
PM2 5; r = 0.29
N02; r = 0.28
O3; r = 0.26
Columbus:
PM2.5; r = 0.22
wn • r — NT?
1NW2, 1 — IN IX
O3; r = 0.42











Wide confidence intervals
for data from Cleveland
and Columbus make these
data not significant and
unstable. Only data for
Cincinnati was considered
statistically significant and
demonstrated a
concentration response
function that was positive.
No multipollutant models
were utilized.













Increment: 50 ug/m

Cincinnati: 35% [9, 21] lag 2



Cleveland: 6% [-7, 21] lag 2
Columbus: 26% [-25, 213] lag 3
All cities: 12% [1,23]
Attributable risk from SO2
increment:
Cincinnati: 4.2%
Cleveland: 0.66%
Columbus: 2.94%





























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               TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

              EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels & Copollutants
Monitoring Stations & Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change &
Confidence Intervals (95%)
UNITED STATES (cont'd)
Moolgavkar* et al.
(1997)
United States:
Minneapolis-St. Paul;
Birmingham

Period of Study:
1986-1991










Hospital Admissions
Outcomes (ICD 9
codes): COPD including
asthma
(490-496), Pneumonia
(480-487)
Age groups analyzed:
65+
Study design: Time
series
Statistical analyses:
Semi-parametric Poisson
regression, GAM
Covariates: day of wk,
season, temporal trends,
temperature
Statistical package:
SPlus

Lag: 0-3 days

SO2 24-h avg (ppb):
Minneapolis:
PM2.5; r = 0.08
Minneapolis:
Mean: 4.82
10th: 1.9
25th: 2.66
50th: 4.02
75th: 6.0
90th: 8.5

Birmingham:
Mean: 6.58
10th: 2.2
25th: 3.7
50th: 6.0
75th: 8.6
90th: 11.6



NO2; r :
CO;r =
O3;r =

= 0.09
0.07
-0.12

Birmingham:
PM2.5;r = 0.17
CO; r= 0.16
03;r =









0.02









SO2 with NO2 and PM2 5
were associated with
hospital admissions.
Evidence of mixture
effects was found. No
single-pollutant was
more important than the
other for respiratory
admissions. Each
pollutant was associated
with admissions except
CO.

Consideration of four
pollutants together
showed the strongest
association with ozone.
No pollutant other than
O3 was stable in its
association with hospital
admissions.
Increment: 3.5 ppb


Sum of Pneumonia and COPD
1.6% [-0.1, 3. 3] lag 2

Pneumonia Only
Minneapolis:
65+ 0.9% [-1.1, 2.9] lag 2 20 df
0.5% [-1.5, 2.5]
lag2130dfS








                                                                        No effects were reported

                                                                        for Birmingham.

                                                                        Positive results were

                                                                        only observed in

                                                                        Minneapolis.

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              TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

             EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels & Copollutants
Monitoring Stations & Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change &
Confidence Intervals (95%)
UNITED STATES (cont'd)
Moolgavkar (2000)
Reanalysis (2003)
Multicity, United States:
Chicago, Los Angeles,
Maricopa County,
(Phoenix)
Period of Study:
1987-1995










Hospital Admissions
Outcomes (ICD 9 codes):
COPD including asthma
(490-496)
Age groups analyzed:
0-19,20-64,65+
(LA only)
Study design: Time series
Statistical analyses:
Poisson regression, GAM
Covariates: Day of wk,
temporal trends,
temperature, relative
humidity
Lag: 0-5 days




Chicago:
Median: 6 ppb
25th: 4
75th: 8
Range: 0.5,36

Los Angeles:
Median: 2 ppb
25th' 1

75th: 4
Range: 0, 16

Maricopa:
Median: 2 ppb
25th: 0.5
75th: 4
Range: 0, 14

Chicago:
PM2.5; r = 0.42
CO; r= 0.35
NO2; r = 0.44
03;r=0.01

Los Angeles:
PM2.5; r = 0.42
PM • r = o 41

CO; r= 0.78
NO2; r = 0.74
03; r= -0.21

Maricopa:
PM2.5;r = 0.11
CO; r= 0.53
NO2; r = 0.02
O3;r=-0.37
In Los Angeles there
was a significant
association with and
hospital admissions
for COPD.

SO2 may be acting as
a surrogate for other
pollutants since
heterogeneous
responses found in
different cities are
inconsistent with a
cause-effect model.





Increment:

COPD, >65
Chicago lag
LA lag 0: 2
LA lag 0: 1
GAM- 100
LA lag 0: 1
NS-100










10 ppb

yrs
0: 4.87(t=3.18)GAM-100
.84 (t= 13.32) GAM-30
.80(1=9.60)
.78 ( t = 7.72)










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              TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

             EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
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Reference, Study Outcomes, Design,
Location, & Period & Methods
Mean Levels & Monitoring Copollutants Method, Findings,
Stations & Correlations Interpretation
Effects: Relative Risk or % Change &
Confidence Intervals (95%)
UNITED STATES (cont'd)
Schwartz (1995)
New Haven, CT
Tacoma, WA
United States

Period of Study:
1988-1990













Hospital Admissions
Outcomes
(ICD9codes): All
respiratory admissions
(460-519)
Age groups analyzed:
>65
Study design:
Time series
Ni "3 A *7n
: 13,470
Statistical analyses:
Poisson regression, log
linear regression using
GLM and GAM
Covariates: dewpoint,
temp, long-term trends,

days of wk
Statistical package:
S- Plus
T n i
Lag: 0-1





24-h avg PM2.5
New Haven O3
Mean 78 ug/m3 (29.8 ppb)
10th: 23
25th: 35
50th: 78
75th: 100
90th: 159

Tacoma 44 ug/m3 (16.8 ppb)
10th: 15
25th: 26
50th: 40
75th: 56
90th: 74










In New Haven, risk
associated with SO2
was not affected by
inclusion of PM2 5 in
the model and the
effect of PM2 5 was
not strongly affected
by inclusion of SO2.
This suggests that in
New Haven, SO2 and
PM2 5 acted
independently.
In Tacoma
2-pollutant model
analysis showed risk
associated with SO2

was attenuated by
PM25. This
suggested risks
associated with SO2
and PM2 5 were not
independent.
Possible SO2 acts as a
surrogate for PM2 5 in
this city.
Increment: 50 ug/m3

New Haven, CT
RR= 1.03 [CI 1.02,1.
p< 0.001
or 18. 8 ppb


05], lag 0-1

2-pollutant model with PM2 5:
RR = 1.04 [CI 1.02, 1.06] p < 0.001
Tacoma, WA

RR = 1.06 [CI 1.01, 1.12], lag 0-1
p>0.02
2-pollutant model with PM2 5:
RR = 0.99 [CI 0.93, 1.06] p > 0.5























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       TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY

                   DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
to
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Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels & Copollutants
Monitoring Stations & Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
UNITED STATES (cont'd)
Wilson et al. (2005)
Multicity, United
States
(Portland, ME and
Manchester, NH)
Period of Study: 1996-
2000 (Manchester)
1998-2000 (Portland)
















ED Visits
Outcomes
(ICD9codes): All
respiratory
(460-519);
Asthma (493)
Age groups analyzed:
0-14yrs; 15-64yrs;
>65 yrs
Study design: Time
series
Statistical analyses:
Multiple regression
analysis standard GAM
with more stringent
criteria parameters
Covariates:
Time-trend, season,
influenza, temperature,
humidity, precipitation
Stat package:
S-Plus
Lag: 0-2




SO2 1-h max: Mean, (SD) O3
(Ppb) PM2.5

Portland
Allyr: 11.1(9.1)
Winter: 17.1 (12.0)
Spring: 10.0(7.1)
Summer: 9.1 (8.0)
Fall: 9.7(7.1)

Manchester
Allyr: 16.5(14.7)
Winter: 25.7(15.8)
Spring: 14.8(12.0)
Summer: 10.6(15.1)
Fall: 14.6(11.1)










Elevated levels of
SO2 were positively
associated with
elevated respiratory
and asthmatic ER
visits. The
significance of these
relationships is not
sensitive to analytic
or smoothing
techniques.















Increment: 6.3 ppb (IQR) for Portland; IQR
for Manchester

Portland:
All respiratory
All ages RR 1.05 [1.02, 1.07] lag 0
0-14 yrs RR 0.98 [0.93, 1.02] lag 0
15-64 yrs RR 1.06 [1.03, 1.09] lag 0
>65 yrs RR 1.10 [1.05, 1.15] lag 0
Asthma
All ages RR 1.06 [1.01, 1.12] lag 2
0-14 yrs RR 1.03 [0.93, 1.15] lag 2
15-64 yrs 1.07 [1.01, 1.15] lag 2
>65 yrs RR 1 .07 [0.90, 1 .26] lag 2

Manchester:
All respiratory
All ages RR 1.01 [0.99, 1.02] lag 0
0-14 yrs RR 1.00 [0.96, 1.04] lag 0
15-64 yrs RR 1.00 [0.98, 1.03] lag 0
>65 yrs RR 1.04 [0.97, 1.11] lag 0
Asthma
All ages RR 1.03 [0.98, 1.09] lag 2
0-14 yrs RR 1.11 [0.98, 1.25] lag 2
15-64 yrs 1.02 [0.96, 1.08] lag 2
>65 yrs RR 1 .06 [0.83, 1 .36] lag 2

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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

            EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design, & Mean Levels &
Methods Monitoring Stations
Copollutants Method, Findings,
& Correlations Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
UNITED STATES (cont'd)
Gwynn* et al. (2000)
Buffalo, NY
United States

Period of Study:
1988-1990

Days: 1,090












Hospital Admissions 24-h avg SO2 (ppb):
Outcomes (ICD 9 Min: 1.63
codes): Respiratory 25th: 8.4
admissions: Acute Mean: 12.2
bronchitis/bronchiolitis 75th- 154
(466); Pneumonia M'. 37y
(480-4860); COPD and
Asthma
(490-493, 496)
Age groups analyzed:
6
Study design:
Time series
N: 24,
Statistical analyses:
Poisson regression
with GLM and GAM
Covariates: season,
day of wk, holiday,

temperature, relative
humidity
Lag: 0-3 days
If r = 0.06 Significant
SO42~ r = 0. 1 9 associations observed
PM2 5 r = 0. 1 9 between several
O r = 0 02 pollutants and
TVTQ - o % various health-effect
rr>2 -nil outcomes make it
V_/\J r U. 1 1 Jm£~£- 1j_ j_
COHr-019 difficult to
COM r- 0.1 9 discriminate the
influence of a single-
pollutant. This is
likely the a result of
the relatively high
intercorrelations
among the various
pollutants, as well as
the possible
interactive role of
several pollutants in
the reported
associations.



Increment: 25. 5, 7.0 ppb
(Max-Mean; IQR)

SO2 alone:
Max-Mean RR 1.096 (t = 3.05) lag 0
IQR RR1. 025 (t= 3.05) lag 0














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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

             EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels & Copollutants Method, Findings,
Monitoring Stations & Correlations Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
UNITED STATES (cont'd)
Lin et al. (2004a)
New York (Bronx
County), United States

Period of Study:
6/1991-12/1993






Hospital Admissions
Outcomes (ICD 9
codes): Asthma (493)
Age groups analyzed: 0-
14
Study design:
Case-control
N: 2,629 cases; 2,236
controls
Statistical analyses:
logistic regression
Covariates: Race and
ethnicity, age, gender,
season
Statistical package:
Lag: 0,1,2,3,0-3
Cases:
24-havg: 16.78 ppb
50th: 13.72
Range: 2.88,66.35
Controls:
24-havg: 15. 57 ppb
50th: 13.08
Range: 2.88,66.35

Quartile Concentrations
(ppb) :
Ql : 2.88,8.37
Q2: 9.37, 13.38
Q3: 13.5,20.91
Q4: 20.21,66.35
Odds ratios for risk
of hospitalization for
asthma increased
with each quartile of
SO2 concentration.

Lag 1,2, or 3 all
showed a
concentration
response that was
positive for odds
ratio as each quartile
was compared to the
total exposure group
(trend p> 0.001).

Quartile (24-h avg)
Q2 OR 1.26 lag 3
Q3 OR 1.45 lag 3
Q4 OR 2. 16 [1.77, 2.65] lag 3

Quartile (1-h max)
Q4 OR 1.86 [1.52, 2.27] lag 3

For a 4-ppb increase in SO2
(24-h avg)
RR 1.07 [1.04, 1.11]


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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

             EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design, Mean Levels & Copollutants Method, Findings,
& Methods Monitoring Stations & Correlations Interpretation
Effects: Relative Risk or % Change &
Confidence Intervals (95%)
UNITED STATES (cont'd)
Michaud et al. (2004)
Hilo, Hawaii
2/21/1997-5/31/2001
















ED Visits 1-hmax: PMi
Outcomes (ICD 9 1 .92 (12.2) ppb
codes): COPD(490- Range: 0.0,447
496); Asthma (493,
495); bronchitis (490, 24 h avg-
491), other COPD L97 (7.12)ppb
(492,494,496) ^ Q ^ 5
Age groups analyzed:
All
Study design: Time
series
Statistical analyses:
Exponential
regression models
Covariates: temporal
variables, day of wk,
meteorology
Stat package: Stata,
SAS
Lag: 0,1, 2,3 days

The lack of organic
carbon shows the pure
SO2 effect
uncontaminated by
vehicle emissions.

Asthma is associated
with Vog, but Vog is not
a major cause of asthma
in Hawaii. The strongest
association was with the
mo oftheyr.

Admission for asthma
and respiratory
conditions was higher in
the winter compared to
the summer, based on
admission per day
(observational- not
statistical analysis).
Increment: 10 ppb

COPD
RR 1.04 [0.99, 1.09] lag
RR 1.04 [1.00, 1.09] lag
RR 1.07 [1.03, 1.11] lag
Asthma
RR1.01 [1.00, 1.10] lag
RR 1.02 [1.03, 1.12] lag
RR 1.02 [1.03, 1.12] lag
Bronchitis
RR1.01 [0.93, 1.13] lag
RR 0.99 [0.88, 1.05] lag
RR1.01 [1.00, 1.14] lag
Other COPD
RR 1.00 [0.78, 1.23] lag
RR 0.96 [0.62, 1.11] lag
RR 0.98 [0.75, 1.16] lag





;1
;2
;3

;i
;2
;3

;i
;2
;3

;i
;2
;3


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          TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY
                          DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels &
Monitoring Stations
Copollutants
& Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change &
Confidence Intervals (95%)
UNITED STATES (cont'd)
Peel et al. (2005)
Atlanta, GA, United
States

Period of Study:
1/93-8/2000



ED Visits
Outcome(s) (ICD 9):
All respiratory (460-6,
477, 480-6, 480-6, 490-
3, 496); Asthma (493);
COPD(491-2,496);
Pneumonia (480-486);
Upper Respiratory
Infection (460-6, 477)
Age groups analyzed:
All
Study design: Time
series
1-hmax: 16.5
(17.1) ppb
10th%: 2.0
90th%: 39.0





03
N02
CO
PM2.5

Evaluated
multipollutant models
(data not shown)



Estimates from
distributed lag
models (0-13 days)
tend to be higher than
for 3-day moving
avg. Positive
associations for URI
and COPD with SO2
were noted for
unconstrained lags
(0-1 3 days) that
covered the previous
two weeks of
Increment: 20 ppb

All respiratory
RR 1.008 [0.997, 1.019] lag 0-2, 3-day
moving avg
Upper Respiratory Infection (URI)
RR 1.010 [0.998, 1.024] lag 0-2, 3-day
moving avg
Asthma
All: 1.001 [0.984, 1.017] lag 0-2, 3-day
moving avg
Pneumonia
                              N: 484,830
                              # of Hospitals: 31
                              Statistical analyses:
                              Poisson Regression,
                              GEE, GLM, and GAM
                              (data not shown for
                              GAM)
                              Covariates:  Day of wk,
                              hospital entry/exit,
                              holidays, time trend;
                              season, temperature, dew
                              point temperature
                              Statistical package:
                              SAS, S-Plus
                              Lag:  0 to 7 days. 3 day
                              moving avgs.
                                                                                          exposure.
                                                                                                            RR 1.003 [0.984, 1.023] lag 0-2, 3-day
                                                                                                            moving avg
                                                                                                            COPD
                                                                                                            RR 1.016 [0.985, 1.049] lag 0-2, 3-day
                                                                                                            moving avg

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                    TABLE AX5.2 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                   EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
             Reference, Study
            Location, & Period
                        Outcomes, Design,
                           & Methods
    Mean Levels &
  Monitoring Stations
    Copollutants
   & Correlations
 Method, Findings,
   Interpretation
 Effects: Relative Risk or % Change &
      Confidence Intervals (95%)
to
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UNITED STATES (cont'd)
>
X
          Schwartz etal. (1996)
          Cleveland, OH

          Period of Study:
          1988-1990
                      Hospital Admissions
                      Outcomes (ICD 9
                      codes): All respiratory
                      disease
                      Age groups analyzed:
                      >65
                      Study design: Time
                      series
                      Statistical analyses:
                      Poisson regression
                      Covariates: Season,
                      temperature, day of wk
                      Statistical package:
                      Lag: 0-1
24-h avg: 35 ppb
10th: 13
25th: 20
50th: 31
75th: 45
90th: 61
PM2.5
03
Significant
associations were
seen for PM2 5 and
O3, with somewhat
weaker evidence for
S02.
Increment:  100 ug/m

RR 1.03 [0.99, 1.06] lag 0-1
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                     TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                    EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
             Reference, Study
             Location, & Period
                           Outcomes, Design,
                              & Methods
    Mean Levels &
  Monitoring Stations
                   Copollutants
                  & Correlations
                  Method, Findings,
                    Interpretation
                     Effects: Relative Risk or % Change &
                          Confidence Intervals (95%)
to
o
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UNITED STATES (cont'd)
>
X
           Sheppard et al. (1999)
           Reanalysis (2003)
           Seattle, WA, United
           States

           Period of Study:
           1987-1994
                       Hospital Admissions
                       Outcomes (ICD 9 codes):
                       Asthma (493)
                       Age groups analyzed: <65
                       Study design:  Time series
                       N:  7,837
                       # of hospitals: 23
                       Statistical analyses: Poisson
                       regression with adjustment
                       for auto-correlation.
                       Covariates:
                       Statistical package: S-Plus
                       Lag: 0,1,2,3
24-h avg:  8 ppb
IQR: 5 ppb
10th:
25th:
50th:
75th:
90th:
3.0
5.0
8.0
10.0
13.0
PM2.5;r = 0.31
PM2.5; r = 0.22
O3;r=0.07
CO; r= 0.24
Sources of SO2
adjacent or near to
monitoring site. Low
concentrations. No
association with SO2
for asthma but
positive association
for appendicitis.
Increment:  5 ppb (IQR)

GAM with stricter criteria:
1.0% [-2.0, 3.0] lag 0

GLM with natural spline
smoothing:
0.0% [-3.0, 4.0] lag 0
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                     TABLE AX5.2 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                    EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
              Reference, Study
             Location, & Period
    Outcomes, Design,
        & Methods
    Mean Levels &
  Monitoring Stations
  Copollutants
 & Correlations
 Method, Findings,
   Interpretation
 Effects:  Relative Risk or % Change &
      Confidence Intervals (95%)
to
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           CANADA
>
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           Bates etal. (1990)
           Vancouver Region, BC,
           Canada
           Period of Study:
           7/1/1984-10/31/1986
ED Visits
Outcome(s) (ICD 9): Asthma
(493);
Pneumonia (480-486);
Chronic bronchitis
(491,492,496);
Other respiratory (466)
Age groups analyzed:
All; 15-60
Study design:
# of Hospitals: 9
Statistical analyses: Pearson
correlation coefficients were
calculated between asthma
visits and environmental
variables
Season:
Warm (May-Oct);
Cool (Nov-Apr)
Covariates: NR
Statistical package: NR
Lag:  0,1,2
May-Oct
SO2l-hmax:
Range: 0.0137,0.0151
ppm

Nov-Apr
Range: 0.012,
0.0164 ppm
                                                            Number of stations:  11
May-Oct.
03; r = 0.23
NO2; r = 0.67
CoH; r = 0.34
SO4; r = 0.46

Nov-Apr
03; r = 0.47
NO2; r = 0.61
CoH; r = 0.64
S04; r = 0.54
SO2 effects depend
on the season. In the
summer a rise in
ambient SO2 levels
was seen to coincide
with a rise in
respiratory related
hospital admissions.
Correlation Coefficients:
Warm Season (May-Oct)
Asthma (15-60 yrs)
r= 0.118 lag 0 p<0.01
r= 0.139 lag 1
Respiratory (15-60 yrs)
r= 0.134 lag 0 p< 0.001
r = 0.164 lag 1 p< 0.001
Cool Season (Nov-Apr)
Respiratory
1-14 yrs
r= 0.205 lag 0 p< 0.001
r= 0.234 lag 1 p< 0.001
r= 0.234 lag 2 p< 0.001
15-60 yrs
r= 0.180 lag 0 p< 0.001
r= 0.214 lag 1 p< 0.001
r= 0.215 lag 2 p< 0.001
>61 yrs
r= 0.257 lag 0 p< 0.001
r= 0.308 lag 1 p< 0.001
r= 0.307 lag 2 p< 0.001
Asthma (>61 yrs)
r = 0.125 lag 0 p< 0.001
r = 0.149 lag 1 p< 0.001
r= 0.148 lag 2 p< 0.001
Total ER admissions (>61 yrs)
r =0.13 lag 1 p<0.01
r= 0.13 lag 2 p<0.01

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                     TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                    EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
             Reference, Study
             Location, & Period
                           Outcomes, Design,
                              & Methods
    Mean Levels &
  Monitoring Stations
  Copollutants
 & Correlations
 Method, Findings,
   Interpretation
  Effects:  Relative Risk or % Change
     & Confidence Intervals (95%)
to
o
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CANADA (cont'd)
>
X
           Burnett etal. (1997a)
           16 cities
           Canada

           Period of Study:
           4/1981-12/1991

           Days: 3,927
                      Hospital Admissions
                      Outcomes (ICD 9 codes): All
                      respiratory admissions
                      (466, 480-6, 490-4, 496)
                      Study design: Time series
                      N: 720,519
                      # of hospitals:  134
                      Statistical analyses: random
                      effects relative risk regression
                      model
                      Covariates:  Long-term trend,
                      season, day of wk, hospital,
                      Statistical package: NR
                      Lag:  0, 1,2 day
l-hmaxSO2(ppb)
Mean: 14.4
SD = 22.2
25th: 3
50th: 10
75th: 19
95th: 45
99th: 97
O3r=0.04
CO
N02
COH
Control of SO2
reduced but did not
eliminate the ozone
association with
respiratory hospital
admissions.
Increment:  lOppb

Single-pollutant
SO2 and respiratory admissions,
p = 0.134

Multipollutant model (adjusted for CO, O3,
NO2, COH, dew point):
RR 1.0055 [0.9982, 1.0128] lag 0
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Study design: Time series
N: 1,163
1-h max SO2 (ppb)
Mean: 38.1
Range: 0,390
95th 110
O3; r = 0.04
NO2;r=-0.03
SO42~; r = 0.23
TSP;r=0.16
SO2 did not affect the Increment: NR
rate of asthma ED
visits when O3 was SO2 + O3: (3 = - 0.0030 (0.0027) lag 0
included in the
model.
                           # of Hospitals: 2
                           Statistical analyses: SAS
                           NLIN (Equivalent to Poisson
                           GEE)
                           Covariates:  Day of wk, long-
                           term trends,
                           Season: Summers only
                           (May-Sep)
                           Dose-response investigated?:
                           Yes
                           Statistical package: SAS
                           Lag: 0-3 days
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              TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

             EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels &
Monitoring Stations
Copollutants
& Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
CANADA (cont'd)
Stieb* et al. (2000)
Saint John, New
Brunswick, Canada

Period of Study:
Retrospective:
7/92-6/94
Prospective:
7/94-3/96












ED Visits
Outcome(s): Asthma; COPD;
Respiratory infection
(bronchitis, bronchiolitis,
croup, pneumonia);
All respiratory ICD9 codes:
NR
Age groups analyzed: All
Study design: Time series
N: 19,821
Statistical analyses: Poisson
regression, GAM
Covariates: Day of wk,
selected weather variables in
each model
Seasons: All yr, summer only
Dose-response investigated:
VV,o
i es
Statistical package: S-Plus
Lag: all yr = 0; summer
only = 0-3
24-h avg:
Annual mean: 6.7
(5.6) ppb
95th: 18.0
Max: 60.0
Warm season mean: 7.6
(5 .2) ppb
95th: 18.0
Max: 29.0

1-hmax:
Annual mean: 23.8(21.0)
,
ppD
95th: 62.0
Max: 161.0
Warm season mean: 25.4
(17.8) ppb
95th: 62.0
Max: 137.0


CO; r= 0.31
O3;r=0.10
NO2; r = 0.41
TRS;r=0.08
PM2 5; r = 0.36
PM2.5;r = 0.31
If; r = 0.24
SO42~; r = 0.26
COH;r = 0.31
H2S;r= -0.01

.Assessed

multipollutant
models







Non-linear effect of
SO2 on summertime
respiratory visits
observed and log
transformation
strengthened the
association.














Increment: 23.8 ppb (mean)
1-hmax:
Respiratory visits: 3. 9% lag 5
May to Sept: 3. 9% lag 0-3

Multipollutant model (SO2, O3, NO2)
Allyr: 3.7% [1.5, 6.0] lag 5

Multipollutant model (In (NO2), O3, SO2
COH)
May to Sept: 3.9% [1.1, 6.7] lag 0-3










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                       TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                      EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
             Reference, Study
            Location, & Period
                          Outcomes, Design,
                              & Methods
    Mean Levels &
  Monitoring Stations
  Copollutants
 & Correlations
   Method, Findings,
    Interpretation
 Effects:  Relative Risk or % Change &
      Confidence Intervals (95%)
to
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CANADA (cont'd)
X
(Si
 I
ON
O
           Burnett etal. (1997b)
           Toronto, Canada
           Period of Study:
           1992-1994
                     Hospital Admissions
                     Outcomes
                     (ICD 9 codes): Respiratory
                     tracheobronchitis (480-6),
                     COPD(491-4,496)
                     Study design: Time series
                     Statistical analyses: Poisson
                     regression, GEE, GAM
                     Covariates:  Temperature, dew
                     point temperature, Long-term
                     trend, season, influenza, day of
                     wk
                     Seasons:  Summers only
                     Lag: 0,1,2,3,4 days
MeanSO2: 7.9 ppb
CV: 64
Range:  0,26
5th: 1
25th: 4
50th: 7
75th: 11
95th: 18

Number of Stations: 6-
11
CO; r = 0.37
H+;r=0.45
SO4; r = 0.42
TP;r = 0.55
FP;r = 0.49
CP; r = 0.44
COH; r = 0.50
O3;r = 0.18
NO2; r = 0.46
Risks of hospitalization
for respiratory disease
were summed for O3,
NO2)andSO2atll%
increase in admissions.
The proportion
associated with the
single-pollutant SO2 was
3.6%. CoHwasthe
strongest predictor of
hospitalization indicating
particle associated
pollutants are
responsible for effects
and outcomes measured.
Increment:  4.00 ppb (IQR)

Respiratory-percent increase
4.0% (t = 4.14) lag 0

Copollutant and multipollutant
models RR
(t-statistic):
S02,COH: 1.012(1.10)
SO^Lf: 1.022(1.96)
SO2, SO4: 1.021(1.93)
S02,TP: 1.021(1.72)
S02,FP: 1.022(1.92)
SO2, CP: 1.023(2.03)
S02,03,N02:  1.019(1.64)
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              TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

             EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
to
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Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels & Copollutants
Monitoring Stations & Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change &
Confidence Intervals (95%)
CANADA (cont'd)
Burnett etal. (1999)
Metro Toronto, Canada

Period of Study:
1980-1994




















Hospital Admissions
Outcomes (ICD 9 codes):
Asthma (493); obstructive
lung disease (490-2, 496);
Respiratory infection
(464, 466, 480-7, 494)
Study design: Time series
Statistical analyses:
Poisson regression model
with stepwise analysis
Covariates: Long-term
trends, season, day of wk,
dciilv in3.xirrru.iTi
temperature, daily
minimum temperature,
daily avg dew point
temperature, daily avg
relative humidity
Statistical package: S-
Plus, SAS
Lag: 0,1, 2 days,
cumulative







24-hmean: 5.35ppb, PM2.5;r=0.46
CV=110; PM2.5_2.5; r = 0.28
5th: 0 PM2.5;r=0.44
25th: 1 CO; r= 0.37
50th: 4 NO2;r = 0.54
75th: 8 03;r = 0.02
95th: 17
inntiv «7
1 VJVJLll. J I
Number of stations: 4

















The percent hospital
admissions associated
with SO2 increased for:
asthma, COPD, and
respiratory infection.
However, in
multipollutant models
significant increases
were only seen in
asthma and respiratory
infection

SO2 effects could be
largely explained by
other variables in the
pollution mix as
demonstrated by the
Multipollutant model.

The greatest
contribution of SO2 is
to respiratory infection.
However, overall SO2
is a small factor in total
hospitalization
response.



Increment: 5.35 ppb (Mean)

Single-pollutant model percent increase (t
statistic)
Asthma: 1.01% (1.76) lag 0-2
OLD 0.03% (0.05) lag 0-1
Respiratory infection: 2.40% (5.04) lag 0-
2

Multipollutant model percent
increase (SE)
A tV,
Astnma:
SO2 + CO + O3: 0.89%
/CT7 ,*• T\
(SE < 2)
S02 + CO + 03 + PM2.5: 0.69%
(SE < 2)
SO2+CO + O3 + PM25_25: 0.16%
(SE < 2)
S02 + CO + 03 + PM2 5: 0.76%
(SE<2)
Respiratory infection:
SO2 + NO2 + O3: 1.85%
SO2 + NO2 + O3 + PM2 5: 0.67
(SE < 2)
S02 + N02 + 03 + PM25_25: 1.71
(SE > 3)
S02 + N02 + 03 + PM25: 1.00
(SE>2)

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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

            EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design, &
Methods
Mean Levels & Copollutants Method, Findings, Effects: Relative Risk or % Change &
Monitoring Stations & Correlations Interpretation Confidence Intervals (95%)
CANADA (cont'd)
Burnett* etal. (2001)
Toronto, Canada

Period of Study:
1980-1994















Hospital Admissions
Outcomes (ICD 9 codes):
Croup (464.4), pneumonia
(480-486), asthma (493),
acute
bronchitis/bronchiolitis
(466)
Age groups analyzed:
<2yrs
Study design: Time series

Statistical analyses:
Poisson regression with
GAM
Covariates: Temporal
trend, day of wk,
temperature, relative
humidity
Statistical package:
S-Plus
Lag: 0-5 days
l-hmaxSO2(ppb) O3;r=0.39
Mean: 11.8 SO2
CV: 93 CO
5th: 0 PM2.5
25th: 5 PM2.5_2.5
50th: 10
75th: 15
95th: 32
99th: 55
100th: 110


Number of stations: 4







SO2 had the smallest Increment: NR
effect on respiratory
admissions of all All respiratory admissions:
pollutants considered. single-pollutant:
Percent increase: 3. 1% (t = 1
lag 3





.900)


Multipollutant (adjusted for O3):
Percent increase: 1.21% (t =
1 "5
lag 3










0.67)











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                TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

               EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design, Mean Levels &
& Methods Monitoring Stations
Copollutants
& Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
CANADA (cont'd)
Fung et al. (2006)
Vancouver, BC,
Canada

Period of Study:
6/1/95-3/31/99









Hospital Admissions SO2 24-h avg:
Outcomes (ICD 9 codes): All Mean: 3.46ppb
respiratory hospitalizations SD=1.82
(460-519) iQR: 2.50ppb
Age groups analyzed: 65+ Range: 0.00,12.50
Study design: (1) Time series
(2) Case-crossover, (3) DM-
models (Dewanji and
Moolgavkar, 2000, 2002)
N- 40 974
Statistical analyses: (1)
Poisson, (2) conditional
logistic regression, (3) DM
method-analyze recurrent
data in which the occurrence
of events at the individual
level over time is available
Covariates: Day of wk
Statistical package: S-Plus
andR
Lag: Current day, 3 and
5 day lag
CO; r= 0.61
COH; r = 0.65
NO2;r = 0.57
PM2.5;r=0.61
PM2.5; r = 0.42
PM2.5_2.5; r = 0.57
03;r=-30.35








No significant
association was found
between hospital
admissions and current
day SO2 levels (lag 0).
Significant
associations were
found with SO2 using a
3,5, and 7 day moving
avg, with the strongest
association observed
with a 7 day lag. The
DM method produced
slightly higher relative
risks compared to the
Time series and case
crossover results.






Increment: 2.5ppb(IQR)

NO2 Time series
RR 1.0 13 [0.997, 1.028] lag 0
RR 1.030 [1.010, 1.051] lag 0-3
RR 1.032 [1.008, 1.056] lag 0-5
RR 1.031 [1.003, 1.060] lag 0-7
NO2 Case-crossover
RR 1.0 10 [0.992, 1.027] lag 0
RR 1.028 [1.005, 1.050] lag 0-3
RR 1.030 [1.004, 1.057] lag 0-5
RR 1.028 [0.998, 1.058] lag 0-7
NO2 DM model
RR 1.0 13 [0.998, 1.027] lag 0
RR 1.034 [1.015, 1.053] lag 0-3
RR 1.039 [1.016, 1.061] lag 0-5
RR 1.044 [1.018, 1.070] lag 0-7

DM method produced slightly
higher RR estimates on O3, SO2 and
PM2 5 compared to time-series and
                                                                                                case-crossover, and slightly lower

                                                                                                RR estimates on COH, NO2, and PM2.5,

                                                                                                though the results were not significantly

                                                                                                different from one another.

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                    TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                   EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
             Reference, Study
            Location, & Period
                       Outcomes, Design,
                          & Methods
    Mean Levels &
  Monitoring Stations
  Copollutants
 & Correlations
   Method, Findings,
     Interpretation
 Effects: Relative Risk or % Change &
      Confidence Intervals (95%)
to
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CANADA (cont'd)
          Kestenetal. (1995)
          Toronto, ON, Canada
          Period of Study:
          1991-1992
                     ED Visits
                     Outcome(s) (ICD 9):
                     Asthma (493)
                     Age groups analyzed:
                     Study design: Time
                     series
                     N: 854
                     # of Hospitals:  1
                     Statistical analyses:
                     Auto regression
                     Statistical package: SAS
                     Lag:  1 or 7
SO2 24-h avg

No data was provided
for concentration or for
correlation with other
pollutants.
N02
03
API (TRS, CO,
TSP)
X
Fit of an auto-regression
model with covariates
linked to same day gave
no evidence of association
between asthma and SO2.

Despite multiple attempts
to correlate individual or
combinations of pollutants
with air quality indices, no
association was found
between ER visits for
asthma and ambient daily,
weekly, or monthly levels
ofSO2,NO2, orO3.
No relative risks were provided.
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                  TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                  EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
to
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H
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Reference, Study Outcomes, Design, Mean Levels & Copollutants Method, Findings,
Location, & Period & Methods Monitoring Stations & Correlations Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
CANADA (cont'd)
Lin etal. (2003) Hospital Admissions SO2 24-h avg: 0.36 ppb CO; r= 0.37
Toronto, ON Outcomes (ICD 9 SD = 5.90 NO2;r=0.54
codes): Asthma Range: 0,57.00 PM25;r = 0.44
Period of Study: (493) 25th: 1.00 O3;r=-0.01
1981-1993 Age groups analyzed: 50th: 4.00 PM25T = 046
6-12 75th: 8.00 PM25'25;
Study design: Bi- r = 0 28 '
directional case- Number of Stations: 4
crossover
N: 7,319
Statistical analyses:
Conditional logistic
regression
Covariates: Daily
maximum and
minimum
temperatures and avg
relative humidity
Lag: Cumulative lag
f i *7 J,,, 7C,
oi I- / days.
SO2 is positively Increment: 7 ppb (IQR)
associated with
asthma Boys 6-12 yrs; Girls 6-12 yrs
hospitalizations, Lag Q. OR 1.00 [0.95, 1.05]; 1.
although the m
relationship varies T
in boys and girls. TQ
La
[0.
La
[0.
La
[1.
La
[1.
La
[1-

97,1.
gO-1
95,1.
gO-2
95,1.
gO-3
98,1.
gO-4
00,1.
gO-5
02,1.
gO-6
04,1.

,11]
: ORO.
,13]
: ORO.
,16]
: ORO.
,22]
: ORO.
,28]
: ORO.
,34]
: ORO.
,39]


,99

,98

,96

,95

,93

,93



[0.

[0.

[0.

[0.

[0.

[0.


Multipollutant model
Br
IVS 6-
1 9 vrs' '

k(

93,

90,

87,

86,

83,

83,



1.06];

1.06];

1.05];

1.05];

1.03];

1.04];


with PM2
S-1 >
' vrs
04

1.04

1.05

1.09

1.13

1.17

1.20


.5-2.5 and PM2 5

                                                                                                   Lag 0:  OR 0.98 [0.93, 1.04]; 1.06 [0.98, 1.14]
                                                                                                   Lag 0-1: OR 0.99 [0.91, 1.06]; 1.03
                                                                                                   [0.93,1.14]
                                                                                                   Lag 0-2: OR 0.96 [0.88, 1.05]; 1.04
                                                                                                   [0.92,1.17]
                                                                                                   Lag 0-3: OR 0.95 [0.85, 1.05]; 1.08
                                                                                                   [0.95, 1.23]
                                                                                                   Lag 0-4: OR 0.94 [0.84, 1.06]; 1.12
                                                                                                   [0.97, 1.29]
                                                                                                   Lag 0-5: OR 0.91 [0.80,1.04]; 1.18 [1.00, 1.38]
                                                                                                   Lag 0-6: OR 0.91 [0.80,1.04]; 1.28 [1.08, 1.51]

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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

             EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
to
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Oi
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Reference, Study
Location, & Period
Outcomes, Design, &
Methods
Mean Levels &
Monitoring Stations
Copollutants Method, Findings,
& Correlations Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
CANADA (cont'd)
Lin* et al. (2004b)
Vancouver, BC
Canada

Period of Study:
1987-1998
















Hospital Admissions
Outcomes (ICD 9
codes):
Asthma (493)
Age groups analyzed:
6-12
Study design: Time
series
N: 3,754(2,331 male,
1 423 female)
Statistical analyses:
Semi-parametric
Poisson regression
with GAM (with
default and more
stringent criteria)
Covariates: Trend, day
of wk,
Statistical package: S-
Plus
Lag: Cumulative
1-7 day



24-h avg SO2 (ppb)
Mean: 4.77
SD = 2.75
Min: 0
25th: 2.75
50th: 4.25
75th: 6.00
Max: 24.00


Number of stations: 30













CO; r = 0.67 Results presented are
NO2; r = 0.67 default GAM, but
Q • r = -0 10 authors state that use
pjyj . r_ of natural cubic
pAyr ' _ splines with a more
stringent
convergence rate
produced similar
results
















Increment: 3. 3 ppb (I QR)

Boys 6-12 yrs by SES status: Low; High
Lag 0 RR 1.02[0.94, 1.10]; 1.03 [0.95, 1.12]
Lag 0-1 RR 1.03 [0.94, 1.13]; 1.06 [0.96, 1.17]
Lag 0-2 RR 1.03 [0.93, 1.15]; 1.06 [0.95, 1.18]
Lag 0-3 RR 1.01 [0.90, 1.13]; 1.04 [0.92, 1.17]
Lag 0-4 RR 0.98 [0.88, 1.10]; 1.02 [0.90, 1.14]
Lag 0-5 RR 0.97 [0.86, 1.10]; 1.02 [0.89, 1.16]

Lag 0-6 RR 0.98 [0.86, 1.12]; 1.05 [0.91, 1.21]
Girls 6-12 yrs by SES status: Low; High
Lag 0 RR 1.05 [0.95, 1.16]; 1.07 [0.96, 1.19]
Lag 0-1 RR 1.11 [0.99, 1.25]; 1.07 [0.94, 1.21]
Lag 0-2 RR 1.11 [0.97,1.26]; 1.07 [0.93, 1.23]
Lag 0-3 RR 1.18 [1.02, 1.36]; 1.02 [0.87, 1.19]
Lag 0-4 RR 1.18 [1.02, 1.35]; 0.99 [0.85, 1.15]
Lag 0-5 RR 1.19 [1.01, 1.40]; 0.95 [0.80, 1.13]
Lag 0-6 RR 1.15 [0.97, 1.36]; 0.98 [0.81, 1.17]

Multipollutant model (adjusted for NO2)
Girls, Low SES:
1.17 [1.00, 1.37] lag 0-3
1.19 [1.00, 1.42] lag 0-5

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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

            EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
to
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Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels & Copollutants
Monitoring Stations & Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
CANADA (cont'd)
Lin etal. (2005)
Toronto, ON, Canada

Period of Study:
1998-2001














Hospital Admissions
Outcomes (ICD 9
codes): Respiratory
infections (464,466, 480-
487)
Age groups analyzed: 0-
14
Study design: Case-
crossover
N: 6,782
# of Hospitals:
Statistical analyses:
Conditional logistic
regression
Covariates:
Statistical package: SAS
8.2
Lag: 0-6 days





24-h avg: PM2.5; r = 0.47
Mean: 4.73 ppb PM2 5_2 5; r = 0.29
SD = 2.58 ppb PM2.5;r = 0.48
Range: 1.00,19.67 CO;r=0.12
25th: 3.00 NO2;r=0.61
50th: 4.00
75th: 6.00
Number of monitors: 5













Asthma hospitalization
for boys was
associated with SO2
before the adjustment
for fine and coarse PM.
Asthma hospitalization
for girls was not
associated with SO2 for
any lag.














Increment: 3 ppb (IQR)

Unadjusted Boys only:
OR 1.06 [0.97, 1.1 6] lag 0-3
OR 1.02 [0.92, 1.1 3] lag 0-5
Girls only:
OR 1.05 [0.94, 1.1 6] lag 0-3
OR 1.07 [0.95, 1.21] lag 0-5
Boys and Girls
OR 1.06 [0.99, 1.1 3] lag 0-3
OR 1.04 [0.96, 1.1 3] lag 0-5

Adjusted Boys only:
OR 1.11 [1.01, 1.21] lag 0-3
OR 1.08 [0.97, 1.21] lag 0-5

Girls only:
OR 1.07 [0.96, 1.1 9] lag 0-3
OR 1.12 [0.98, 1.28] lag 0-5
Boys and Girls
OR 1.10 [1.02, 1.18] lag 0-3
OR 1.10 [1.01, 1.20] lag 0-5

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                  TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                 EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
            Reference, Study
            Location, & Period
                      Outcomes, Design,
                         & Methods
  Mean Levels &
Monitoring Stations
 Copollutants
& Correlations
Method, Findings,
  Interpretation
Effects: Relative Risk or % Change
  & Confidence Intervals (95%)
to
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CANADA (cont'd)
          Linetal. (2005) (cont'd)
                                                                                                Multipollutant model with PM2 5 and PM2;
                                                                                                Boys only:
                                                                                                OR 1.02 [0.90, 1.15] lag 0-3
                                                                                                OR 0.99 [0.85, 1.16] lag 0-5
                                                                                                Girls only:
                                                                                                OR 1.09 [0.0.94, 1.26] lag 0-3
                                                                                                OR 1.07 [0.90, 1.28] lag 0-5
                                                                                                Boys and Girls
                                                                                                OR 1.05 [0.95, 1.15] lag 4
                                                                                                OR 1.03 [0.91, 1.16] lag 6
X
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                   TABLE AX5.2 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                  EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
to
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Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels &
Monitoring Stations
Copollutants
& Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
CANADA (cont'd)
Luginaah et al. (2005)
Windsor, ON, Canada

Period of Study:
4/1/95-12/31/00






Hospital Admissions
Outcomes (ICD 9
codes): Respiratory
admissions
(460-519)
Age groups analyzed:
0-14,
15-64, 65+, all ages
Study design:
(1) Time series and (2)
case-crossover
SO2 mean 1 h
Max: 27.5 ppb,
SD= 16.5;
Range: 0, 129
IQR:

Number of stations: 4




NO2; r = 0.22
CO; r=0.16
PM2.5; r = 0.22
COH;r = 0.14
O3;r=-0.02
TRS;r=0.13





The effect of SO2 on
respiratory
hospitalization varies
considerably,
especially at low
levels of exposure.





Increment: 19.25 ppb (IQR)

Time-series, females; males
All ages, 1.041 [0.987, 1.098]; 0.953
[0.900, 1.009] lag 1
0-14 yrs, 1.111 [1.011, 1.221] ; 0.952
[0.874, 1.037] lag 1
15-65 yr, 1.031 [0.930, 1.144] ; 0.971
[0.845, 1.15] lag 1
65+ yr, 1.030 [0.951, 1.115] ; 0.9409
[0.860, 1.029] lag 1
N: 4,214
# of Hospitals: 4
Statistical analyses:
(1 )Poisson regression,
GAM with natural
splines (stricter
criteria), (2)
conditional logistic
regression with Cox
proportional hazards
model
Covariates:
Temperature,
humidity, change in
barometric pressure,
day of wk
Statistical package: S-
Plus
Lag:  1,2,3 days
Case-crossover, females; males
All ages, 1.047 [0.978, 1.122]; 0.939
[0.874, 1.009] lag 1
0-14 yrs, 1.119 [0.995, 1.259] ; 0.923
[0.831, 1.025] lag 1
15-65 yr, 1.002 [0.879, 1.141]  ; 0.944
[0.798, 1.116] lag 1
65+yr, 1.020 [0.924, 1.126] ; 0.968
[0.867, 1.082] lag 1

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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

             EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design, Mean Levels &
& Methods Monitoring Stations
Copollutants Method, Findings,
& Correlations Interpretation
Effects: Relative Risk or % Change &
Confidence Intervals (95%)
CANADA (cont'd)
Villeneuve et al., 2006
Toronto, ON, Canada

Period of Study:
1995-2000
Days: 2,190














GP Visits 24-havg: 4.7 ppb
Outcome(s) (ICD9): SD = 2.8
Allergic Rhinitis (177) IQR: 3.2 ppb
Age groups analyzed: Range: 0, 24.8
^65 Number of stations: 9
Study design: Time series
N: 52,691
Statistical analyses:

GLM, using natural
splines (more stringent
criteria than default)
Covariates: Day of wk,
holiday, temperature,
relative humidity,
aero-allergens
Season: All Yr;
Warm, May-Oct;
Cool, Nov-Apr
Statistical package:
S-Plus
Lag: 0-6
NO2 There were positive
O3 associations between
CO allergic rhinitis and
pjyj SO2 for exposures
r>A , occurring on the
rlvl2 5-25 ,
same day as
physician visits, but
only during the
winter time












Increment: 10.3 ppb (IQR)

All results estimated from Stick Graph:

All Yr:
Mean increase: 1.7% [-0.4, 2.8] lag 0
\Vcinrr

Mean increase: 0.3% [-1.9, 2.5] lag 0

Cool:
Mean increase: 1 . 9% [- 0.2, 4. 1 ] lag 0








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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

            EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels & Copollutants
Monitoring Stations & Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
CANADA (cont'd)
Yang et al. (2003a)
Vancouver, Canada

Period of Study:
1986-1998

Days: 4748






Hospital admissions
outcomes (ICD 9 codes):
All respiratory
admissions (460-519)
Study design:
Case-crossover
Age groups analyzed:
<^"5 -^£\^
<-J, >OJ
Statistical analyses:
conditional logistic
regression
Statistical package: NR
Lag: 0-5 days
24-h avg SO2 (ppb): CO
Mean: 4.84 NO2
SD = 2.84 03;r=-0.37
5th: 1.50 COH
25th: 2.75
50th: 4.25
75th: 6.25
100th: 24.00
IQR: 3.50

Number of stations: 30


SO2 showed the
weakest effect among
children and the
second weakest effect
among older adults
when compared to all
other pollutants
considered in the

study.




Increment: 3. 50 ppb (IQR)

All respiratory admissions <3 yrs:
SO2 alone: OR 1.01 [0.98, 1.05] lag 2
S02 + 03: OR 1.01 [0.97, 1.04] lag 2
SO2 + O3 + CO + COH + NO2: OR 0.98
[0.94, 1.03] lag 2

All respiratory admissions >65 yrs:
SO2 alone: OR 1.02 [1.00, 1.04] lag 0
SO2 + O3: OR 1.02 [1.00, 1.04] lag 0
S02 + 03 + CO + COH + N02: OR 1.01
[0.98, 1.03] lag 0
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               TABLE AX5.2 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

              EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels & Copollutants
Monitoring Stations & Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
CANADA (cont'd)
Yang et al. (2005)
Vancouver, BC,
Canada

Period of Study:
1994-1998
Days: 1826









Hospital admissions
outcomes (ICD 9 codes):
COPD excluding asthma
(490-2, 494, 496)
Age groups analyzed: 65+
Study design: Time series
N: 6,027
Statistical analyses:
Poisson regression with
GAM (with more stringent
criteria)
Covariates: Temperature,
relative humidity, day of
wk, temporal trends,
season
Statistical package:
S-Plus
Lag: 0-6 days, moving
averages
24-havg: 3.79 ppb, SD = PM2.5;r = 0.62
2.12; N02;r=0.61
IQR: 2.75 ppb; CO; r= 0.67
Range: 0.75,22.67 O3;r=-0.34

Winter: 4.10(2.87)
Spring: 3.40(1.58)
Summer: 4.10(1.79)
Fall: 3.56(1.92)
Number of Stations: 3 1







This study produced a
marginally significant
association between
COPD hospitalization
and 6-day SO2
exposure. Most
previous studies have
not QGTGCTGQ 3.
significant effect of
SO2 on respiratory ED
visits or
hospitalizations.







Increment: 2.75 ppb (IQR)

COPD
> 65 yrs, yr round
RR 1.00 [0.97, 1.04] lag 0
RR 1.02 [0.98, 1.06] lag 0-1
RR 1.04 [0.99, 1.08] lag 0-2
RR 1.04 [0.99, 1.09] lag 0-3
RR 1.05 [0.99, 1.11] lag 0-4
RR 1.06 [1.00, 1.13] lag 0-5
RR 1.06 [0.99, 1.1 3] lag 0-6

2-pollutant model
NO2: RR 0.99 [0.91, 1.08] lag 0
CO: RR 0.97 [0.87, 1.07] lag 0-6
03: RR 1.07 [1.00, 1.14] lag 0-6
PM25: 0.97 [0.88, 1.06] lag 0-6

                                                                                           Multipollutant models

                                                                                           SO2, CO, NO2, O3, PM2.5: RR0.94

                                                                                           [0.85, 1.05]

                                                                                           S02, CO, N02, 03: RR 0.96 [0.86,

                                                                                           1.06]
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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

             EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
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Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels &
Monitoring Stations
Copollutants &
Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change &
Confidence Intervals (95%)
AUSTRALIA/NEW ZEALAND
Barnett et al. (2005)
Multicity,
Australia/New
Zealand; (Auckland,
Brisbane, Canberra,
Christchurch,
Melbourne, Perth,
Sydney)
Period of Study:
1998-2001


















Hospital admissions
outcomes (ICD 9/ICD 10):
All respiratory
(460-5 19/JOO-J99 excluding
J95.4-J95.9,RO9.1,RO9.8),
asthma (493/J45, J46, J44.8),
COPD (490-492, 494-
496/J40-J44, J47, J67),
pneumonia with bronchitis
(466, 480-486/J12-17, J18.0
J18.1 J18.8J18.9
J20J21)
Age groups analyzed: 0, 1-4,
5-14
Study design: Case-crossover
Statistical analyses:
Conditional logistic
regression, random effects
meta-analysis
Covariates: Temperature,
current-previous day
temperature, relative
humidity, pressure, extremes
of hot and cold, day of wk,
holiday, day after holiday
Season: Cool, May-Oct;
Warm, Nov-Apr
Statistical package: SAS
Lag: 0-1 days
24-h avg (ppb) (range):
Auckland: 4.3
(0, 24.3)
Brisbane: 1.8
(0, 8.2)
Canberra: NA
Christchurch: 2.8
(0,11.9)
Melbourne: NA
Perth: NA
Sydney: 0.9
fc\ "$ n\
(0, 3.9)

Daily 1-h max (range):
Auckland: NA
Brisbane: 7.6
(0,46.5)
Canberra: NA
Christchurch: 10.1 (0.1,
42.1)
Melbourne: NA
Perth: NA
Sydney: 3.7
(0.1,20.2)
IQR: 5.4 ppb



BS;r= 0.07, 0.29
PM25;r = 0.12,
0.35
PM25;r = 0.17,
0.33
CO; r = 0.25, 0.41
N02;r=0.15,
0.58
O3;r=-0.12,
0.16


















Increased hospital
admissions were
significantly associated
with SO2 for acute
bronchitis, pneumonia,
and respiratory
diseases. In
multipollutant models
the impacts of
particulate matter and
NO2 were isolated.

There were seasonal
impacts on pneumonia
and acute bronchitis
admissions in the
1- to 4-yr-old age
group for SO2.











Increment: 5. 4 ppb
(1-h max IQR)

Pneumonia and acute bronchitis
Oyrs 3.5% [-0.3, 7.3] lag 0-1
1-4 yrs 6.9% [2.3, 11.7] lag 0-1
Respiratory
Oyrs 3.2% [0.3, 6. 3] lag 0-1
1-4 yrs 2.7% [0.6, 4.8] lag 0-1
5-14 yrs 2.0% [-5.5, 10.1] lag 0-1
Asthma
0 yrs No analysis (poor diagnosis)
1-4 yrs 3. 4% [-4. 3, 11.6]
lag 0-1
5-14 yrs 3. 3% [-5.6, 13.0]
lag 0-1












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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

            EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
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Reference, Study
Location, & Period
AUSTRALIA/NEW
Petroeschevsky et al.
(2001)
Brisbane, Australia

Period of Study:
1987-1994
Days: 2922











Outcomes, Design,
& Methods
ZEALAND (cont'd)
Hospital admissions
outcomes (ICD 9): All
respiratory (460-519);
Asthma (493)
Age groups analyzed: 0-4, 5-
14,15-64, 65+, all ages
Study design: Time series
N. 11 71 n
. J J, / 1U
(13,246 = asthma)
Statistical analyses: APHEA
protocol, Poisson regression,
f^T7T7
U\c,ii
Covariates: Temperature,
humidity, season, infectious
disease, day of wk, holiday
Season: Summer, Autumn,
Winter, Spring, All yr
Dose-response investigated?:
Yes
Statistical package: SAS
Lag: Single: 1,2,3 day
Cumulative: 0-2,0-4
Mean Levels &
Monitoring Stations

Mean: 24-h avg:
Overall: 4.1 ppb
Summer: 3. 9 ppb
Autumn: 4.2 ppb
Winter: 4. 8 ppb
Spring' 3 7 ppb

Mean: 1-hmax
Overall: 9.2 ppb
Summer: 7.8 ppb
Autumn: 9.3 ppb
Winter: 11. 3 ppb
Spring: 8.4 ppb
# of stations: 3






Copollutants Method, Findings,
& Correlations Interpretation

Bsp SO2 was highly
O3 correlated with
NO2 maximum daily ER
admissions for
respiratory conditions.
The highest association
was observed in the
winter followed by
autumn, spring, and
surrmiGr For Q.sthrn.3.
the highest association
was observed in the
winter and autumn.
No statistically
significant
contributions for
respiratory admissions
were reported for the
age group 5-14 yr olds
for any pollutant.



Effects: Relative Risk or % Change &
Confidence Intervals (95%)

Increment: 0 ppb

Respiratory:
0-4 yrs 24-h avg 1.224 [1.087, 1.377] lag 0-4
5-14 yrs 1-hmax 1.049 [0.986, 1.116] lag 0-
4
15-64 yrs 24-h avg 1.033 [0.895, 1.118] lag
1
65+ yrs 24-h avg 1.121 [1.019, 1.234] lag 0
All ages 24-h avg 1.080 [1.030, 1.131] lag 1
Asthma:
0-14 yrs 24-h avg 1.080 [0.971, 1.201] lag 0
15-64 yrs 1-h max 0.941 [0.900, 0.984] lag 0
All ages 24-h avg 0.941 [0.876, 1.011] lag 2







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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

            EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
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Reference, Study
Location, & Period
Outcomes, Design, &
Methods
Mean Levels & Copollutants & Method, Findings,
Monitoring Stations Correlations Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
EUROPE
Anderson etal. (1997)
Multicity, Europe
(Amsterdam,
Barcelona, London,
Paris, Rotterdam)

Period of Study:
1977-1989 for
Amsterdam and
Rotterdam
1986-1992 for
Barcelona
1987- 1991 for London
1980-1989 for Milan
1987- 1992 for Paris









Hospital admissions
outcomes (ICD 9):
COPD-unspecified
bronchitis (490),
chronic bronchitis
(491), emphysema
(492), chronic airways
obstruction (496)
Study design: Time
series
Statistical analyses:
APHEA protocol,
Poisson regression,
meta-analysis
Covariates: Trend,
season, day of wk,
holiday, influenza,
temperature, humidity
Season:
Cool, Oct-Mar; Warm,
Apr-Sep
Statistical package:
NR
Lag: 0,1, 2 days and 0-
3 cumulative
24-h all yr avg (ug/m3): NO2
Amsterdam: 21 BS
Barcelona: 40 TSP
London: 31 O3
Milan: 53
Paris: 23
Rotterdam: 32
1-hmax
Amsterdam: 50
Barcelona: 60
London: NR
Milan: NR
Paris: 47
Rotterdam: 82









The effect of SO2 varied
considerably across the cities;
however, the summer estimate
was significantly associated
with COPD for the 1-h
measure and borderline
significant for the daily mean.
Both 24-h and 1-h SO2
concentrations were
significantly associated with
COPD ER admissions in the
warm season. Only
cumulative lags of SO2
showed borderline
significance.









Increment: 50 ug/m

COPDC-Warm season
24 hi. 05 [1.01,1.10]
1 hi. 02 [1.00, 1.04]

COPD-Cool season
24 h 1.02 [0.98, 1.05]
Ih 1.01 [0.99,1.03]

COPD-A11 yr
24-h avg 1.022 [0.981, 1.055] la:
24-h avg 1.021 [0.998, 1.054] la:
cumulative
1-hmax 1.01 [0.994, 1.029] lag
1-hmax 1.015 [1.003, 1.027] lag
cumulative
















gl
gO-3,
1
5 0-3,








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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

             EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design, &
Methods
Mean Levels &
Monitoring Stations
Copollutants
& Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
EUROPE (cont'd)
Atkinson etal. (2001)
Multicity, Europe
(Barcelona,
Birmingham, London,
Milan, Netherlands,
Paris, Rome,
Stockholm)

Period of Study:
1998-1997








Hospital admissions
outcomes (ICD 9):
Asthma (493), COPD
(490-496), All
respiratory (460-519)
Study design: Time
series
Statistical analyses:
APHEA protocol,
Poisson regression,
meta-analysis
Covariates: Season,
temperature, humidity,
holiday, influenza
Statistical package:
NR
Lag: NR


l-hmaxofSO2(ug/m3)

Barcelona: NR
Birmingham: 24.3
London: 23.6
Milan: 29.1
Netherlands: 8.5
Paris: 17.7
Rome: 9.8
Stockholm: 3.8








N02, 03, CO, BS
PM2.5;r =
Barcelona: 0.32
B'gham: 0.77
London: 0.72
Milan: 0.64
Netherlands: 0.67
Paris: 0.63
Rome: 0.15
Stockholm: 0.36








The inclusion of SO2 in
the models only
modified PM2 5
associations in the
0- to 14-yr age group.













Increment: 10 ug/m3 for PM2 s; change in
SO2 not described.

Asthma, 0 to 14 yrs:
ForPM2.5: 1.2 [0.2, 2. 3]
ForPM2.5 + S02: 0.8 [-3.7, 5.6]

Asthma, 1 5 to 64 yrs:
ForPM2.5: 1.1 [0.3,1.8]
ForPM2.5 + SO2: 1.6 [0.6, 2.6]

COPD + Asthma, >65 yrs
ForPM2.5: 1.0 [0.4, 1.5]
ForPM2.5 + SO2: 1.3 [0.7, 1.8]

All respiratory, >65 yrs of age
ForPM2.5: 0.9 [0.6, 1.3]
ForPM2.5 + S02: 1.1 [0.7,1.4]
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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

            EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels & Copollutants Method, Findings,
Monitoring Stations & Correlations Interpretation
Effects: Relative Risk or % Change &
Confidence Intervals (95%)
EUROPE (cont'd)
Schouten et al. (1996)
Multicity, The
Netherlands
(Amsterdam,
Rotterdam)
Period of Study:
04/01/77-09/30/89







Hospital admissions
outcomes (ICD 9): All
respiratory (460-519),
COPD (490-2, 494, 496),
Asthma (493)
Age groups analyzed: 15-
64, 65+, all ages
Study design: Time series
Statistical analyses:
APHEA protocol, Poisson
regression
Covariates: Long-term
trend, season, influenza,
day of wk, holiday,
temperature, humidity
Sficisori'
Cool, Nov-Apr;
Warm: May-Oct
Statistical package: NR
Lag: 0,1,2 days; and
cumulative 0-1 and 0-3
day lags

24-h avg SO2 NO2
Amsterdam BS
Mean/Med: O3
28/21 ug/m3
Rotterdam
Mean: 40/32 ug/m3
Daily 1-hmax
Amsterdam
Mean/Med:
65/50 ug/m3
Rotterdam
Mean/Med:
99/82 ug/m3
# of stations: 1 per city





The relationship between
short-term air pollution
and hospital admissions
was not always
consistent at low levels
of expo sure. One
statistically significant
association between
hospital admissions and
asthma (all ages)
occurred in Amsterdam
after a cumulative lag of
1-3 days in the summer.
Higher SO2 levels were
reported for the winter;
therefore, this
association was not a
concentration response.





Increment: 100 ug/m3 increment.

All respiratory, Amsterdam

24-h avg
15-64 yrs
RR 0.944 [0.864, 1.032] lag 2
RR 0.915 [0.809, 1.035] lag 0-3
>65 yrs
RR 1.046 [0.965, 1.1 34] lag 2
RR 1.008 [0.899, 1.131] lag 0-3
1-hmax
15-64 yrs
RR0.989[0.952, 1028] lag 2
RR 0.977 [0.927, 1.030] lag 0-3

>65 yrs
RR 1.022 [0.985, 1060] lag 2
RR 1.010 [0.955, 1.068] lag 0-3
RR 0.941 [0.863, 1.026] lag 0-3
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                   TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                  EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
            Reference, Study
            Location, & Period
                      Outcomes, Design,
                         & Methods
  Mean Levels &
Monitoring Stations
 Copollutants
& Correlations
Method, Findings,
  Interpretation
Effects: Relative Risk or % Change &
     Confidence Intervals (95%)
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EUROPE (cont'd)
X
oo
          Schouten et al. (1996)
          (cont'd)
                                                                                 In Rotterdam neither
                                                                                 1 day nor cumulative lags
                                                                                 in the summer or winter
                                                                                 increased asthma
                                                                                 admissions to statistical
                                                                                 significance. Rotterdam
                                                                                 had much higher mean
                                                                                 SO2 concentrations. There
                                                                                 were no significant
                                                                                 associations to hospital
                                                                                 admissions when higher
                                                                                 pollution levels were
                                                                                 prevalent.
                                                              COPD, Amsterdam

                                                              24-h avg-all ages
                                                              RR 0.907 [0.814,1.011] lag 0
                                                              RR 0.948 [0.838,1.072] lag 0-1

                                                              1-hmax-all ages
                                                              RR 0.978 [0.933,1.026] lag 0
                                                              RR 0.995 [0.940,1.053] lag 0-1

                                                              Asthma, Amsterdam
                                                              24-h avg-all ages
                                                              RR 0.802 [0.696, 0.924] lag 1
                                                              RR 0.792 [0.654, 0.958] lag 0-3

                                                              1-hmax-all ages
                                                              RR 0.995 [0.942,1.051] lag 0
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                    TABLE AX5.2 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                   EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels &
Monitoring Stations
Copollutants
& Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change &
Confidence Intervals (95%)
EUROPE (cont'd)
           Schouten et al. (1996)
           (cont'd)
The analysis of all
respiratory hospital
admissions for all ages
in the entire country
(Netherlands) produced
a statistically significant
association for both
1-h and 24-h periods
(100 |ig/m3).
All respiratory, Rotterdam

24-h avg
15-64yrs
RR 0.941 [0.855,1.036] lag 1
RR 0.895 [0.787,1.019] lag 0-2
>65yrs 1977-1981
RR 1.027 [0.904,1.165] lag 2
RR1.011 [0.834,1.227] lag 0-3
>65yrs 1982-1984
RR 1.087 [0.890,1.328] lag 0
RR 1.258 [0.926,1.710] lag 0-3
>65yrs 1985-1989
RR 1.045 [0.908,1.204] lag 0
RR 0.968 [0.787,1.190] lag 0-3

1-h max
15-64yrs
RR0.989[0.953, 1025] lag 1
RR 0.965 [0.915,1.018] lag 0-2
>65yrs 1977-1981
RR 0.892 [0.842, 0.945] lag 0
RR 0.987 [0.907,1.074] lag 0-3
>65yrs 1982-1984
RR 1.005 [0.933,1.081] lag 0
RR 1.062 [0.938,1.202] lag 0-3
>65yrs 1985-1989
RR 1.010 [0.955,1.068] lag 0
RR 1.064 [0.992,1.141] lag 0-1
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                    TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                   EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
            Reference, Study
            Location, & Period
                          Outcomes, Design,
                             & Methods
                                 Mean Levels &
                              Monitoring Stations
                         Copollutants
                        & Correlations
 Method, Findings,
   Interpretation
Effects: Relative Risk or % Change &
     Confidence Intervals (95%)
to
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EUROPE (cont'd)
           Schouten et al.
           (1996) (cont'd)
                                                                                                               COPD, Rotterdam
                                                                                                               24-h avg-all ages
                                                                                                               RR 0.963 [0.874,1.059] lag 2
                                                                                                               RR 1.019 [0.887,1.172] lag 0-3
                                                                                                               1-hmax-allages
                                                                                                               RR 0.991 [0.955,1.029] lag 2
                                                                                                               RR 1.013 [0.953,1.076] lag 0-3
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Spixetal. (1998)
Multicity (London,
Amsterdam,
Rotterdam, Paris,
Milan), Europe

Period of Study:
1977 and 1991
Hospital Admissions
Outcomes (ICD 9 codes): All
respiratory (460-519); Asthma
(493)
Age groups analyzed:
15-64, 65+
Study design: Time series
# of Hospitals:
Statistical analyses: Poisson
regression following APHEA
protocol. Pooled meta-analysis
adjusted for heterogeneity
Covariates: trend, seasonality,
day of wk, holiday,
temperature, humidity, unusual
events (strikes, etc.)
Statistical package:
Lag:  1 to 3 days
SO2 daily mean (ug/m3)   NO2, O3, BS, TSP

London: 29
Amsterdam: 21
Rotterdam: 25
Paris:  23
Milan:  66
Daily counts of adult
respiratory
admissions were not
consistently
associated with daily
mean levels of SO2.
Heterogeneity
between cities was
likely due to the
number of stations or
temperature.  Only
hospital admissions
for >65 yr olds were
significantly
associated with SO2
in the warm season.
Increment: 50 ug/m

All cities, yr round
15-64 yrsRR 1.009 [0.992,1.025]
  Warm RR 1.01 [0.98,1.04]
  Cold RR 1.01 [0.97,1.07]
>65 yrsRR 1.02 [1.005, 1.046]
  Warm RR 1.06 [1.01, 1.11]
  Cold RR 1.02 [0.99, 1.04]

APHEA protocol pooled result from >65
yrs old from Europe
All respiratory
RR 1.02 [1.00, 1.05]
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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

            EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
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Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels & Copollutants Method, Findings,
Monitoring Stations & Correlations Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
EUROPE (cont'd)
Sunyeretal. (1997)
Multicity, Europe
(Barcelona, Helsinki,
Paris, London)

Period of Study:
1986-1992










Hospital admissions/ED
visits
outcomes (ICD 9):
Asthma (493)
Age groups analyzed:
<15, 15-64
Study design: Time
series
Statistical analyses:
APHEA protocol,
Poisson regression,
GEE; meta-analysis
Covariates: Humidity,
temperature, influenza,
soybean, Long-term
trend, season, day of wk
Season:
Cool, Oct-Mar; Warm:
Apr-Sep
Statistical package: NR
Lag: 0,1, 2,3 and
cumulative 1-3
24-h median (range)
(ug/m3)
Barcelona: 41
(2, 160)
Helsinki: 16
(3, 95)
London: 31
(9, 100)
Paris: 23
(1,219)
# of stations:
Barcelona: 3
London: 4
Paris: 4
Helsinki: 8





NO2 SO2 alone or as part of a
black smoke mixture was a factor that
O3 exacerbated asthma
admissions.

In 2-pollutant models
with SO2 and BS, the
association of BS with
SO2 was attenuated for
<15 yr olds, compared to
single-pollutant model
associations. In
addition, the association
of NO2 was also
attenuated by the
inclusion of SO2.






Increment: 50 ug/m3 of 24-h avg for all
cities combined.

Asthma
15-64yrs
0.997 [0.961, 1.034] lag
1.003 [0.959, 1.050] lag
<15 yrs
1.075 [1.026, 1.126] lag
1.061 [0.996, 1.1 31]lag
2-pollutant models:
SO2/Black smoke
<15 yrs 1.092 [1.031,1.
SO2/NO2
<15yrs 1.075 [1.019, 1









,2
; 0-3, cum

i
i -i
2-3, cum
156] lag 0-1
.135]





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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

             EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
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Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels &
Monitoring Stations
Copollutants Method, Findings,
& Correlations Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
EUROPE (cont'd)
Sunyer et al. (2003)
Multicity study
(Birmingham (B),
London (L), Milan
(M), Netherlands (N),
Paris (P), Rome (R)
and Stockholm (S),
Europe
Period of Study:
1992 and 1997










Hospital admissions/ED
visits
outcome(s) (ICD 9):
Asthma (493); COPD
and Asthma
(490-496);
All respiratory
(460-519)
Age groups analyzed:
All, 0-14 yrs; 16-64yrs;
>65 yrs
Study design:
Time series
Poisson regression with
GAM following APHEA
2 protocol
Covariates: temperature,
humidity, Long-term
trend, season
Statistical package: NR
Lag: 0, 1
SO2 24-h avg and SD
(ug/m3)

B 24. 3 (12.7)
L 23.6 (23.7)
M 32.5 (37.5)
N 8. 5 (7.7)
P 17.7 (12.5)
R9.8 (9.9)
S 6.8 (6.2)










PM2 5; r = 0.64 The magnitude of
CO; r = 0 . 5 3 association with asthma
across the seven cities was
comparable to earlier
studies of London,
Helsinki and Paris.
Exposure factors may be
important. Children may
spend greater time
outdoors compared with
adults. Pneumonia
requires chronic exposure
to produce inflammatory
response and infection,
whereas asthma is an
acute response.




Increment: 10 ug/m3

Asthma
0-14 yrs 1.3% [0.4, 2.2]
15-64 yrs 0.0% [-0.9, 1.00]

COPD and Asthma
>65 yrs 0.6% [0.0, 1.2]
All Respiratory
>65 yrs 0.5% [0.1, 0.9]

Asthma
0-14 yrs
SO2 + PM2.5: -3.7% (p> 0.1)
SO2 + CO: -0.7%(p>0.1)






















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                     TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                    EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
              Reference, Study
             Location, & Period
                          Outcomes, Design,
                             & Methods
    Mean Levels &
  Monitoring Stations
  Copollutants
& Correlations
    Method, Findings,
      Interpretation
 Effects: Relative Risk or % Change
    & Confidence Intervals (95%)
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           Anderson etal. (1998)
           London, England

           Period of Study:
           Apr 1987-Feb 1992

           Days:  1,782
                       Hospital admissions
                       outcomes (ICD 9):
                       Asthma (493)
                       Age groups analyzed:
                       <15, 15-64,65+
                       Study design:  Time
                       series
                       Statistical analyses:
                       APHEA protocol,
                       Poisson regression
                       Covariates:  Time trends,
                       seasonal cycles, day of
                       wk, public holidays,
                       influenza epidemics,
                       temperature, humidity
                       Season:
                       Cool (Oct- Mar); Warm
                       (Apr-Sep)
                       Statistical package: NR
                       Lag: 0, 1,2 days
24-h avg SO2 (ug/m3)
Mean: 32.0
SD=11.7
Range: 9, 100
5th: 16
10th:  18
25th: 24
50th: 31
75th: 38
90th: 46
95th: 52

# of monitors: 2
03
NO2
BS
The strongest association
between SO2 and asthma
admissions was for those
>65 yrs in the cool season.
A weaker association was
observed for children in the
warm season and all yr.
The adult population
showed no association.
In 2-pollutant models ozone
was overall the strongest
pollutant associated with
hospital admission with
weaker associations with
NO2andBS. The most
consistent yr-round
association for All ages was
found with BS. When
looking at all ages
combined, SO2 association
remained significant in all
2-pollutant models except
with NO2, both for all yr
and the summer (warm)
season.
Increment: 10 ppb in 24-h SO2
0-14 yrs

Whole yr 1.64% [0.29, 3.01] lag 1
          2.04% [0.29, 3.83] lag 0-3
  + 03    1.77% [0.22, 3.36] lag 1
  + N02   1.23% [-0.22, 2.69]  lag 1
  + BS    1.66% [0.23, 3.12] lag 1
Warm season 3.33% [1.09, 5.63] lag 1
          3.40% [0.41, 6.48] lag 0-3
  + O3    3.35% [0.89, 5.87] lag 1
  + N02   2.92% [0.58, 5.32] lag 1
  + BS    3.66% [1.35, 6.02] lag 1
Cool season 0.56% [-1.16, 2.32] lag 1
          1.24% [-0.95, 3.49] lag 0-2

15-64 yrs
Whole yr -0.69% [-2.28, 0.94] lag 2;
         -0.71% [-2.69, 1.30] lag 0-2
Warm     -1.39% [-3.97, 1.27] lag 0;
          -2.2% [-5.46, 11.8] lag 0-2
Cool season -0.24% [-2.28, 1.84] lag 0
          0.20% [-2.28, 2.74] lag 0-2
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                   TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                  EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
             Reference, Study
            Location, & Period
                        Outcomes, Design,
                           & Methods
  Mean Levels &
Monitoring Stations
 Copollutants
& Correlations
Method, Findings,
  Interpretation
Effects: Relative Risk or % Change &
     Confidence Intervals (95%)
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          Anderson etal. (1998)
          (cont'd)
                                                                                                         65+ yrs
                                                                                                         Whole yr 2.82% [-0.82, 5.96] lag 2;
                                                                                                         3.06% [-0.72, 6.98] lag 0-3
                                                                                                         Warm -2.62% [-7.31,2.31] lag 2;
                                                                                                         -4.27% [-9.89, 1.71] lag 0-3
                                                                                                         Cool season 5.85% [1.81, 10.05] lag 2;
                                                                                                         7.28% [2.19, 12.62] lag 0-3
                                                                                                         + O3 7.84% [2.48, 13.48] lag 1
                                                                                                         + NO2 4.19% [-0.53, 9.13] lag 1
                                                                                                         + BS  5.29% [0.42, 10.40] lag 1

                                                                                                         All Ages
                                                                                                         Whole yr 1.64% [0.54, 2.75] lag 1;
                                                                                                         2.75% [1.22, 4.30] lag 0-3
                                                                                                         + O3  1.48% [0.24, 2.73] lag 1
                                                                                                         + SO2 1.14% [-0.04, 2.33] lag 1
                                                                                                         + BS  1.54%[0.36, 2.73] lag 1
                                                                                                         Warm 2.02% [0.22, 3.85] lag 1;
                                                                                                         2.60% [0.02, 5.25] lag 0-3
                                                                                                         + O3  1.91% [0.05, 3.81] lag 1
                                                                                                         + NO2 1.64% [-0.23, 3.56] lag 1
                                                                                                         + BS  2.18% [0.32, 4.07] lag 1
                                                                                                         Cool season 1.41% [0.0, 2.83] lag 1;
                                                                                                         2.83% [0.89, 4.81] lag 0-3
                                                                                                         + 03  -0.09% [-1.61, 1.82] lag 1
                                                                                                         + N02 0.83% [-0.67,2.34] lag 1
                                                                                                         + BS  1.11% [-0.41,2.66] lag 1
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              TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

             EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
to
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Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels & Copollutants
Monitoring Stations & Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
EUROPE (cont'd)
Anderson etal. (2001)
West Midlands
conurbation, United
Kingdom
Period of Study:
10/1994-12/1996















Hospital admissions
outcomes (ICD 9
codes): All respiratory
(460-5 19), Asthma
(493), COPD
(490-496, excluding
493)
Age groups analyzed:
0-14,
15-64, 65+
Study design: Time
series
Statistical analyses:
followed APHEA 2
protocol, GAM
Covariates: Season,
temperature, humidity,
epidemics, day of wk,
holidays
Statistical package: S-
Plus4.5Pro
Lag: 0,1,2,3,0-1,
0-2, 0-3
24-havg: 7.2 ppb, 4.7 PM2.5;r = 0.55
(SD) PM2.5_10;r = 0.31
Min: 1.9 ppb BS;r=0.50
Max: 59.8 ppb SO4;r = 0.19
10th: 3. 3 ppb NO2;r=0.52
90th: 12. 3 ppb O3;r=0.22
#of monitors: 5















When admissions were
analyzed by subgroups,
respiratory and asthma
admissions were positively
correlated with SO2.

SO2 significantly associated
with asthma and respiratory
admissions for the
0 to 14-yr-age group;
however, little evidence of a
seasonal interaction was
observed.










Increment: 9 ppb (90th- 10th)

All respiratory
All ages 1.3% [-0.7, 3.4] lag 0-1
0-14 yrs 4.6% [1.40, 7.8] lag 0-1
15-64 yrs -0.9% [-4.8, 3.3] lag 0-1
>65 yrs -2.0% [-4.9, 1.1] lag 0-1

COPD with asthma
0-14 yrs 10.9% [4.50, 17.8] lag 0-1
15-64 yrs 2.4% [-5. 5, 10.9] lag 0-1
>65 yrs -4.2% [-8.9, 0.8] lag 0-1










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              TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

             EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
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Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels &
Monitoring Stations
Copollutants Method, Findings,
& Correlations Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
EUROPE (cont'd)
Atkinson et al. (1999a)
London, England

Period of Study:
1992-1994

















Hospital admissions
outcomes (ICD 9 codes):
All respiratory (460-5 19);
Asthma (493); Asthma
and COPD (490-496);
LRD (466,480-486)
Age groups analyzed: all
ages, 0-14 yr,
15-64 yr and >65 yr
Study design:
Time series
N: 165,032
Statistical analyses:
Poisson regression
following APHEA
protocol
Covariates: Long-term
seasonal patterns, day of

wk, temperature,
humidity, influenza.
Statistical package: SAS
Investigated
Dose/Response: Yes
Lag: 0,1, 2,3 days
SO2_ 24-h (ug/m3)
Mean: 21.2 (7.8) ug/m3
Min: 7.4
10th: 13
50th: 19.8
90th: 31
Max: 82.2


# of monitors: 5












O3,CO, PM2 5, BS, Asthma was closely linked
N02 with PM, CO, N02, and
traffic pollution.
Correlation
coefficients When SO2 and PM2 5 were
ranged between included in the same
r = 0.5 and 0.6 model, the magnitude of
the individual associations
was reduced, as were their
statistical significance.
This reduction occurred in
children, adults and the
elderly. The other
pollutants all had the
effect of reducing the
magnitude of the
individual SO2 and PM2 s
associations, although
their statistical
significance was
unaffected. This indicates
that both SO2 and PM2 5
were indicators of the
same pollutant mixture.

Increment: 18 ug/m

All respiratory
All ages 2.01% [0.29, 3.76] lag 1
0-14 yrs 5.14% [2.59, 7.76] lag 0
15-64 yrs 1.90% [-0.79, 4.660 lag 3
>65 yrs 2.25 [-0.09, 4.65] lag 3


Asthma
All ages 3.38 [0.42, 6.43] lag 1
0-14 yrs 6.74% [2.92, 10.69] lag 1
15-64 yrs 4. 58% [-0.18, 9.57] lag 3
>65 yrs 6.31% [-1.59, 14.83] lag 2

COPD and Asthma
>65 yrs 1.53% [-1.83, 5.00] lag 3

Lower Respiratory
>65 yrs 5.16% [1.19, 9.28] lag 3



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                     TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                    EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
             Reference, Study
            Location, & Period
                        Outcomes, Design, &
                             Methods
    Mean Levels &
  Monitoring Stations
 Copollutants &
  Correlations
  Method, Findings,
    Interpretation
 Effects:  Relative Risk or % Change &
      Confidence Intervals (95%)
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           Atkinson et al. (1999b)
           London, United
           Kingdom

           Period of Study:
           1/92-1294
                      ED visits
                      outcome(s) (ICD 9):
                      Respiratory ailments (490-
                      496), including asthma,
                      wheezing, inhaler request,
                      chest infection, COPD,
                      difficulty in breathing,
                      cough, croup, pleurisy,
                      noisy breathing
                      Age groups analyzed:  0-
                      14; 15-64; >65;
                      All ages
                      Study design: Time series
                      N: 98,685
                      # of Hospitals: 12
                      Statistical analyses:
                      Poisson regression,
                      APHEA protocol
                      Covariates: Long-term
                      trend, season, day of wk,
                      influenza, temperature,
                      humidity
                      Statistical package: SAS
                      Lag:  0,1,0-2 and
                      0-3 days
24-havg: 21.2ug/m,
SD = 7.8
10th: 13.0
50th: 19.8
90th: 31.0
Range:  7.4,82.2

# of Stations: 5
SO2
03 (8 h)
CO(24h),PM25
(24 h) BS
SO2 was closely related
to PM2 5, but
2-pollutant models
showed that the effect of
SO2 was decreased by
NO2 and PM2 5
inclusion. Inclusion of
other pollutants did not
significantly decrease
the influence of SO2 on
ER admissions in
2-pollutant models.
Increment: 18 ug/m  in 24-h

Single-pollutant model
Asthma only
0-14 yrs 9.92% [4.75, 15.34] lag 1
15-64 yrs 4.19% [-0.53, 9.13] lag 1
All ages 4.95% [1.53, 8.48] lag 1
All respiratory
0-14 yrs 6.01% [2.98, 9.12] lag 2
15-64 yrs 2.72% [-0.18, 5.70] lag 3
65+ yrs -1.82% [-5.72, 2.25] lag 3
All Ages 2.81% [0.72, 4.93] lag 1
Copollutant models for asthma among
children:
SO2 + NO2: 5.42% [0.18, 10.93]
S02 + 03:  8.39% [3.82, 13.17]
SO2 + CO: 8.05% [3.45, 12.86]
S02 + PM25:  5.63 [0.53, 10.98]
S02 + BS: 8.03 [3.32, 12.96]
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                   TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                  EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design, Mean Levels & Copollutants Method, Findings,
& Methods Monitoring Stations & Correlations Interpretation
Effects: Relative Risk or % Change &
Confidence Intervals (95%)
EUROPE (cont'd)
Boutin-Forzano et al.
(2004)
Marseille, France
Period of Study:
4/97-3/98
ED visits Mean: SO2:
outcome(s): Asthma 22.5 ug/m3
ICD9Code(s): NR Range: 0.0,94.0
Age groups analyzed: 3-
49
Study design: Case-
NO2; r = 0.56 No association was
O3;r=-0.25 observed between ER
visits for asthma and SO2
levels.
Only single-pollutant
Increment: 10 ug/m
Increased ER visits
OR 1.0023 [0.9946, 1.0101] lag 0
OR 0.9995 [0.9923, 1.0067] lag 1
crossover
N: 549
Statistical analyses:
Logistic regression
Covariates: Minimal daily
temperature, maximum
daily temperature,
minimum daily relative
humidity, maximum daily
relative humidity, day of
wk
Statistical package: NR
Lag: 0-4 days
                                                                                       models were utilized.
                                                                                                             OR 0.9996 [0.9923, 1.0069] lag 2
                                                                                                             OR 0.9970 [0.9896, 1.0045] lag 3
                                                                                                             OR 0.9964 [0.9889, 1.0040] lag 4
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                    TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                   EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
             Reference, Study
            Location, & Period
                        Outcomes, Design,
                           & Methods
    Mean Levels &
  Monitoring Stations
  Copollutants
 & Correlations
Method, Findings,
  Interpretation
Effects: Relative Risk or % Change &
     Confidence Intervals (95%)
to
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           Buchdahletal. (1996)
           London, United
           Kingdom

           Period of Study:
           3/1/92-2/28/93
                      ED visits
                      outcomes:  Daily acute
                      wheezy episodes
                      ICD9: NR
                      Age groups analyzed:

                      Study design: Case-
                      control
                      N:  1,025 cases, 4,285
                      controls
                      Number of hospitals:  1
                      Statistical analyses:
                      Poisson regression
                      Covariates: Season,
                      temperature, wind
                      speed
                      Season:
                      Spring (Apr-Jun),
                      Summer (Jul-Sep),
                      Autumn (Oct-Dec),
                      Winter (Jan-Mar)
                      Statistical package:
                      Stata
                      Lag: 0-7 days
SO2 24-h yr round Mean:
22 ug/m3,
SD= 14

IQR: ug/m3

Spring: 20(14)
Summer:  18(22)
Fall: 24(14)
Winter: 25(14)
NO2;r=0.62      Variations in SO2 could    Increment:  14 ug/m3 (Std. Dev.)
C>3; r = -0.28      not explain the U-shaped
                 relationship between      No adjustments to model
                 ozone and incidence of    RR U6 [UOj 1.23] lag not specified
                 asthma.
                                        Adjusted for temperature and season.
                                        RR 1.12 [1.06, 1.19] lag not specified

                                        Adjusted for temperature, season and wind
                                        speed.
                                        RR 1.08 [1.00, 1.16] lag not specified
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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

            EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
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Reference, Study
Location, & Period
Outcomes, Design, &
Methods
Mean Levels &
Monitoring Stations
Copollutants Method, Findings, Effects: Relative Risk or % Change
& Correlations Interpretation & Confidence Intervals (95%)
EUROPE (cont'd)
Castellsague et al.
(1995)
Barcelona, Spain

Period of Study:
1986-1989












ED visits
outcome(s): Asthma
ICD9Code(s): NR
Age groups analyzed:
15-64
Study design: Time
series
# of Hospitals: 4
Statistical analyses:
Poisson regression
covariates: Long time
trend, day of wk,
temperature, relative
humidity, dew point
temperature
Seasons :
Winter : Jan-Mar;
Summer : Jul-Sep
Dose-response
investigated: Yes
Statistical package: NR
Lag: 0, 1-5 days and
cumulative.
Summer: lag 2 days
Winter: lag 1 day
Mean SO2 (ug/m )
Summer: 40.8
25th: 25
50th: 36
75th: 54
95th: 82
Winter: 52.0
25th: 36
50th: 49
75th: 67
95th: 94
# of Stations: 15
manual, 3 automatic










NO2 Interaction between Increment: 25 ug/m3
O3 pollutants and asthma
emergency room visits Seasonal differences
was influenced by soy- Summer'
bean dust in the air. RR l Q52 [Q 980> U29] kg 2
Winter:
The daily mean of asthma RR l mo [0.960, 1.084] lag 1
visits and level of SO2
were higher in the winter
than in the summer. A
positive but not
statistically significant
increase in relative risk
was found for SO2 in the
summer. SO2 levels were
higher in the winter, but
the RR was lower
compared to the RR in the
summer. SO2 was not
significantly associated
with asthma related ER
visits.




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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

            EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
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Reference, Study Outcomes, Design, &
Location, & Period Methods
Mean Levels & Copollutants Method, Findings,
Monitoring Stations & Correlations Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
EUROPE (cont'd)
Dab+ et al. (1996) Hospital admissions
Paris, France outcomes (ICD 9): All
respiratory
Period of Study: (460-519), Asthma
1/1/87-9/30/92 (493), COPD
(490-496)
Age groups analyzed:
All ages
Study design: Time
series
Number of hospitals:
27
Statistical analyses:
Poisson regression,
followed APHEA
protocol
Covariates:
Temperature, relative
humidity, influenza,
Long-term trend,
season, holiday,
medical worker strike
Lag: 0,1, 2 days, 0-3
cumulative





All Yr: NO2
24-h avg: 29.7 ug/m3 O3
Median: 23.0 PM13
5th: 7.0 BS
99th: 125.0
1-hmax: 59.9
Median: 46.7
5th: 14.0
99th: 232.7
Warm season
24-h avg: 20.1
Median: 18.3
5th' 6 0

99th: 49.3
1-hmax: 42.7
Median: 37.0
5th: 13.0
99th: 133.7
Cold season
24-h avg: 40.1 ug/m3
ivieciian. 31.3
C4-1-.. Q H
jtn. 5. /
99th: 149.0
1-hmax: 78.3
Median: 60.7
5th: 17.0
99th: 268.3
1-h maximum SO2 levels
yielded lower relative risk
when compared to 24-h avg
levels. COPD effects were
only significantly associated
with SO2 with no lag.

The strongest association was
observed with PM13; 4.5%
increase in respiratory
admission per 100 ug/m3
increment. SO2 was a close
second.

Neither analysis by age or by
season showed a significant
sensitivity for hospital
admissions. The strongest
association for asthma
admission for all pollutants
was with SO2 24-h avg of 7%
[0.14, 14. 10], but one hour
maximum level was not
significant. The strongest
association for admission
with COPD diagnosis was
also for 24-h avg of SO2
(9.9% [2.3, 18]).

Increment: 100 ug/m

All respiratory (1987-1990)
24-h avg RR 1.042 [1.005,
lag 0-2
1-h max RR 1.018 [0.988, 1
lag 0-2

Asthma (1987-1992)
24-h avg RR 1.070 [1.004,1
lag 2
1-h max RR 1.047 [0.998, 1
lag 2


COPD
24-h avg RR 1.099 [1.023,
lagO
1-h max RR 1.051 [1.025,1
lagO











1.080]

.048]



.141]
.098]


1.180]
.077]









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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

            EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels &
Monitoring Stations
Copollutants Method, Findings,
& Correlations Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
EUROPE (cont'd)
de Diego Damia et al.
(1999)
Valencia, Spain
3/1994-3/1995











ED visits
outcome(s) (ICD 9):
Asthma (493)
Age groups analyzed: >12
Study design:
N: 515
# of Hospitals: 1
Statistical analyses:
Stepwise regression and
ANOVA; Linear
regression
Covariates: Season and
temperature
Statistical package: SPSS
Lag:

24-h avg SO2
(Hg/m3)
Winter
Mean: 56
Range: 30,86
Spring
Mean: 47
Range: 34,75
Summer
Mean: 40
Range: 12,62
Autumn
Mean: 50
Range: 42, 59

Number of monitors: 1
BS; r = 0.54 The SO2 concentration
was averaged for each
season and quartiles of
concentration
determined. Asthma
visits that occurred in
each season were
examined. There were
no significant
associations with
asthma ER visits with
any season or with any
quartile of SO2
exposure.



Mean number of asthma-related ED
visits based on quartile of SO2

All yr:
<41 ng/m3: 8.6
41-50 ng/m3: 9.1
51-56 ng/m3: 11.6
>56|ig/m3: 11.9







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                   TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                  EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design, &
Methods
Mean Levels &
Monitoring Stations
Copollutants
& Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
EUROPE (cont'd)
Fuscoetal. (2001)
Rome, Italy
Period of Study:
1/1995-10/1997
Hospital admissions
outcomes
(ICD9codes): All
Respiratory
(460-519, excluding
24-havg: 9.1 (5.8)
ug/m3
25th: 5.1
50th: 7.9
75th: 12.0
03;r=-0.35
CO; r= 0.56
NO2;r=0.33
Particles;
r = 0.25
SO2 did not have an
effect on respiratory
hospitalizations.
Increment: 6.9 ug/m3 (IQR)
Respiratory conditions: All ages:
0.4% [-1.3, 2.2] lag 0
0.8% [-0.9, 2.41 lag 1
470-478); Acute
respiratory infections
including pneumonia
(460-466, 480-486),
COPD
(490-492, 494-496),
asthma (493)
Age groups analyzed:
All ages, 0-14
Study design: Time
series
# of Hospitals:
Statistical analyses:
Poisson regression with
GAM
                                                    # of monitors: 5
0.3% [-1.3, 1.8] lag 2
0-14 yrs:
-0.7% [-4.0, 2.7] lag 0
-2.0 [-5.2, 1.3] lag 1
-0.8 [-3.8, 2.3] lag 2
Acute respiratory infections:  All ages:
0.4% [-2.1, 3.0] lag 0
1.4% [-1.0, 3.9] lag 1
1.2% [-1.0, 3.5] lag 2
0-14 yrs:
-0.1% [-3.9, 3.8] lag 0
-2.7% [-6.3, 1.0] lag 1
-1.2% [-4.5, 2.2] lag 2
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                 TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                 EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels &
Monitoring Stations
Copollutants
& Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change &
Confidence Intervals (95%)
EUROPE (cont'd)
Fuscoetal. (2001)
(cont'd)
Covariates:
Influenza epidemics,



Asthma:
All ages:
                              day of study,
                              temperature,
                              humidity, day of wk,
                              holidays
                              Statistical package:
                              S-Plus 4
                              Lag: 0,1,2,3,4
-1.5% [-6.6, 3.9] lag 0
-1.5% [-6.5, 3.7] lag 1
2.5% [-2.2, 7.4] lag 2

0-14yrs:
-2.6 [-10.4, 6.0] lag 0
4.3% [-3.5, 12.7] lag 1
5.5% [-1.8, 13.2] lag 2

COPD:
All ages:
1.0%[-1.9,4.0]lagO
-1.1% [-3.9,1.8] lag 1
-0.5% [-3.1,2.1] lag 2
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               TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

              EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels & Copollutants
Monitoring Stations & Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
EUROPE (cont'd)
Galan et al. (2003)
Madrid, Spain

Period of Study:
1995-1998










ED visits
outcome(s) (ICD9):
Asthma (493)
Age groups analyzed: All
Study design:
Time series
N: 4,827
Statistical analyses:
Poisson regression, (1)
classic APHEA protocol
and (2) GAM with
stringent criteria
Covariates: Trend, yr,
season, day of wk,
holidays, temperature,
humidity, influenza, acute
respiratory infections,
pollen
Statistical package: NR
Lag: 0-4 days
24-h mean: 23.6 ug/m3 PM2.5; r = 0.581
SD=15.4 NO2;r= 0.717
10th: 9.2 O3;r= -0.188
25th: 12.3
50th: 18.7
75th: 31.3
90th: 43.9
Range: 5,121.2
# of Stations: 15









SO2 registered a
predominately winter
based pattern, and was
positively correlated with
PM2.5,NO2. The lag that
described the strongest
association was 3 days.
Multipollutant models
were fitted for cold season
pollutants. SO2 was the
most affected when PM2 5
was included in the model.

Parametric estimates using
APHEA protocol
produced similar results as
GAM.

The SO2 association may
Increment : 10 ug/m3
Asthma :
RR lag 01.0 18 [0.984,1
RRlagl 1.005 [0.972,1
RR lag 2 1.002 [0.970,1
RR lag 3 1.029 [0.997,1
RR lag 4 1.025 [0.994,1
Multipollutant model:
SO2/PM2.5 0.966 [0.925,











.054]
.039]
.036]
.062]
.058]
1.009]









                                                                         be due to the concealing

                                                                         effects of other pollutants.

                                                                         PM2 5 accounted for most

                                                                         of the observed effects.
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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

            EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study Outcomes, Design, Mean Levels & Copollutants Method, Findings,
Location, & Period & Methods Monitoring Stations & Correlations Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
EUROPE (cont'd)
Garty et al. (1 998) ED visits 24-h mean of SO2 NOX
Tel Aviv, Israel outcome(s): Asthma (estimated from SO2
1993 ICD9Code(s): NR histogram): 27 ug/m3 O3
Age groups analyzed: 1- Range: 11,64
18
Study design: Descriptive
study with correlations
N: 1,076
Statistical analyses:
Pearson correlation and
partial correlation
coefficients
Covariates: Maximum
and minimum ambient
temperatures, relative
humidity and barometric
pressure
Statistical package:
Statistix


Asthma morbidity was
higher in the autumn and
winter than the rest of the
yr. The number of ER
visits is September was
exceptionally high.

The percent of total
variance showed positive
correlation between
asthma ER visits in
children and high levels of
NOX, SO2 and increased
barometric pressure. NOX
enhances the effects of
SO2, whereas O3 had a
reverse relation to SO2.

Air borne pollen was not a
significant contributor to
ER visits.
Correlation between SO2 and ER visits
for asthma:

All Yr:
Daily data r = 0.24
Running mean for 7 days r = 0.53

Excluding September:
Daily data r= 0.31
Running mean for 7 days r = 0.64







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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

            EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels &
Monitoring Stations
Copollutants
& Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change &
Confidence Intervals (95%)
EUROPE (cont'd)
Hagen et al. (2000)
Drammen, Norway

Period of Study:
1994-1997








Hospital admissions
outcomes (ICD 9): All
respiratory admissions
(460-519)
Age groups analyzed:
All ages
Study design:
Time series
Number of hospitals: 1
Statistical analyses:
Poisson regression with
GAM (adhered to HEI
phase l.B report)
Covariates: Time trends,
day of wk, holiday,
influenza, temperature,
humidity
Lag: 0,1, 2,3 days
SO2 24-h avg (ug/m3):
3.64, SD = 2.41
25th: 2.16
50th: 2.92
75th: 4.38
# of Stations: 2







PM2.5; r = 0.42
NO2;r = 0.58
benzene; r = 0.29
NO; r = 0.47
O3;r=-0.24
Formaldehyde;
r=0.54
Toluene; r = 0.48







SO2 was significantly
associated with
respiratory hospital
admissions. This
relationship was robust
to the inclusion of PM2 5,
but attenuated when both
PM2 5 and benzene were
included in the model.







Increment: SO2: 2.22 ug/m3 (IQR)

Single-pollutant model
Respiratory disease only
1.056 [1.013, 1.101]
All disease
0.990 [0.974, 1.007]
2-pollutant model with PM2 5
1.051 [1.005, 1.099]
3-pollutant model with
PM2 5 ~t~ Benzene
1.040 [0.993, 1.089]




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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

            EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
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Reference, Study
Location, & Period
Outcomes, Design, &
Methods
Mean Levels & Copollutants
Monitoring Stations & Correlations
Method, Findings, Effects: Relative Risk or % Change &
Interpretation Confidence Intervals (95%)
EUROPE (cont'd)
Hajatetal. (1999)
London, United
Kingdom

Period of Study:
1992-1994






















GP visits
outcome (ICD9):
Asthma (493); Lower
respiratory disease
(464, 466, 476, 480-3,
490-2, 485-7, 4994-6,
500,503-5,510-5)
Age groups analyzed:
0-14;
15-64; 65+; all ages
Study design: Time-
series analysis
Statistical analysis:
Poisson regression,
APHEA protocol
Covariates: Long-term
trends, seasonality, day
of wk, temperature,
humidity
Seasons:
Warm, Apr-Sep; Cool,
Oct-Mar;
All-yr
Dose-response
investigated? Yes
Statistical package:
SAS

Lag: 0-3 days,
cumulative
Allyr NO2;r = 0.61
24-havg: 21.2 ug/m3, BS;r=0.57
SD = 7.8 CO; r= 0.51
10th: 13.0 PM2.5;r=0.63
90th: 31.0 O3;r=-0.11

Warm:
24-h avg: 20.5 ug/m3,
SD = 6.5
10th: 13.4
90th: 28.4
Cool:

24-h avg: 22.0 ug/m3,
SD = 9.0
10th: 12.8
90th: 33.3












This study showed weak, Increment: 1 8 ug/m3
but consistent (90th-10th percentile)
associations between Asthma
SO2 and consultations All ages 3.6% [0.3, 6.9] lag 2; 4.4% [0.9,
for asthma and other 79] jag Q-2
LRD, especially in 0-14 yrs 4.9% [0.1, 9.8] lag 1; 4.4%
children. Bubble plot [-0 7 9 7] lag 0-2
suggests a concentration- Wam. g Q% [22 162] { l
response relationship. „ . ~ „„, r, c om, ,
F F Cool: 2.0% [4.5, 8.9] lag 1

15-64 yrs 3.6% [-0.6, 8.0] lag 2; 3.5%
[-1.0,8.2] lag 0-3
Warm: 2.5% [-3.3, 8.7] lag 2

Cool: 4. 5% [-1.4, 10.7] lag 2

65 + yrs 4. 5% [-3.5, 13.1] lag 1;4.8%
[-2.9, 13.2] lag 0-1
Warm: 7.5% [-4.0, 20.3] lag 1
Cool: 2.0% [-8.6, 13.9] lag 1

Lower respiratory disease
All ages 1.8% [0.2, 3.4] lag 2; 2.2%
[0.4, 4.1] lag 0-2
0-14 yrs 4.5% [1.4, 7.8] lag 2; 5.7%
[1.7, 9.7] lag 0-3
Warm: 2.4% [-2.6, 7.7] lag 2
Cool: 5.8% [1.6, 10.2] lag 2


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                   TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                  EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
            Reference, Study
           Location, & Period
                     Outcomes, Design, &
                          Methods
  Mean Levels &
Monitoring Stations
 Copollutants
& Correlations
Method, Findings,
  Interpretation
Effects: Relative Risk or % Change
  & Confidence Intervals (95%)
to
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EUROPE (cont'd)
X
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          Hajatetal. (1999)
          (cont'd)
                                                                                                  15-64 yrs 1.5% [-0.7, 3.7] lag 1; 1.6%
                                                                                                  [-0.9, 4.1] lag 0-3
                                                                                                  Warn: -0.5% [-3.8, 2.9] lag 1
                                                                                                  Cool: 2.5% [-0.5, 5.5] lag 1
                                                                                                  65 + -2.2% [-4.9, 0.6] lag 0; -1.4%
                                                                                                  [-4.4, 1.7] lag 0-1
                                                                                                  Warn: -3.1% [-6.9, 0.9] lag 0
                                                                                                  Cool: -1.6% [-5.3, 2.3] lag 0
                                                                                                  2-pollutant model - Asthma
                                                                                                  S02 alone  4.9% [0.1, 9.8]
                                                                                                  SO2/O3 5.9% [1.1,10.9]
                                                                                                  S02/N022.7%[-2.7, 8.4]
                                                                                                  S02/PM2.5 3.4% [-3.0, 10.2]
                                                                                                  2-pollutant model-Lower respiratory disease
                                                                                                  SO2 alone 4.5% [1.4, 7.8]
                                                                                                  S02/034.8%[1.6,8.1]
                                                                                                  SO2/NO23.1%[-0.6, 6.9]
                                                                                                  S02/PM2.5 3.8% [0.4, 7.2]
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                    TABLE AX5.2 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                    EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
             Reference, Study
            Location, & Period
                         Outcomes, Design,
                            & Methods
                             Mean Levels &
                          Monitoring Stations
                          Copollutants
                         & Correlations
 Method, Findings,
   Interpretation
   Effects:  Relative Risk or % Change
     & Confidence Intervals (95%)
to
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EUROPE (cont'd)
                                                                                 NO2;r = 0.61
                                                                                 BS;r=0.57
                                                                                 CO; r= 0.51
                                                                                 PM2.5; r = 0.63
                                                                                 O3;r=-0.11
>
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Hajat*etal. (2001)
London, United
Kingdom

Period of Study:
1992-1994
GP visits
outcome (ICD9): Allergic
Rhinitis (477)
Age groups analyzed: 0-
14; 15-64; 65+;
all ages
Study design:
Time series analysis
N: 4,214
Statistical analysis:
Poisson regression, GAM
Covariates: Long-term
trends, seasonality, day of
wk, temperature,
humidity, variation in
practice population,
counts for lagged allergic
pollen measures, daily
number of consultations
for influenza
Dose-response
investigated?  Yes
Statistical package:
S-Plus
Lag:  0-6 days, cumulative
24-havg: 21.2ug/m,
SD = 7.8
10th: 13.0
90th: 31.0
The number of
allergic rhinitis
admissions peaked in
April and June.  After
2-pollutant model
analysis, SO2 still
remained highly
significant in the
presences of other
pollutants.  For both
children and adults
exposure-response
associations showed
that risk levels off at
higher SO2 levels.
Increment: 18 ug/m
(90th-10thpercentile)

Single-pollutant model
<1 to 14yrs
24.5% [14.6, 35.2] lag 4
24.9% [11.9, 39.4] lag 0-4
15 to 64 yrs
14.3% [6.2, 23.0] lag 3
15.5% [9.1, 22.3] lag 0-5
>64 yrs-too small for analysis

2-pollutant models
<1 to 14 yrs
S02&03: 22.1% [12.0, 33.1]
S02&N02: 28.5% [15.5, 42.9]
SO2&PM2.5: 27.2% [15.3, 40.2]
15 to 64 yrs
S02 & 03: 8.5% [3.4, 13.9]
SO2&NO2: 8.3% [1.7,15.3]
S02&PM2.5: 6.7% [0.7, 13.0]
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                    TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                    EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
             Reference, Study
            Location, & Period
                          Outcomes, Design,
                             & Methods
    Mean Levels &
  Monitoring Stations
  Copollutants
 & Correlations
 Method, Findings,
   Interpretation
  Effects: Relative Risk or % Change
     & Confidence Intervals (95%)
to
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           Hajat*etal. (2002)
           London, United
           Kingdom

           Period of Study:
           1992-1994
                      GP visits
                      outcome (ICD9):  Upper
                      respiratory disease,
                      excluding Rhinitis
                      (460-3, 465, 470-5, 478)
                      Age groups analyzed:
                      0-14; 15-64; 65+; all ages
                      Study design:
                      Time series analysis
                      Statistical analysis: Poisson
                      regression, GAM
                      Covariates: Long-term
                      trends, seasonality, day of
                      wk, holidays, temperature,
                      humidity, variation in
                      practice population, counts
                      for lagged allergic pollen
                      measures, daily number of
                      consultations for influenza
                      Seasons:
                      Warm, Apr-Sep;
                      Cool, Oct-Mar
                      Dose-response investigated?
                      Yes
                      Statistical package:
                      S-Plus
                      Lag:  0,1,2,3 days
Allyr
24-havg: 21.2 ug/m3,
SD = 7.8
10th:  13.0
90th:  31.0

Warm:
24-h avg: 20.5 ug/m3,
SD = 6.5
10th:  13.4
90th:  28.4

Cool:
24-h avg: 22.0 ug/m3,
SD = 9.0
10th:  12.8
90th:  33.3

# of Stations:  3
NO2;r = 0.61
BS;r=0.57
CO; r= 0.51
PM2.5; r = 0.63
O3;r=-0.11
Increased
consultations for
URD were most
strongly associated
with SO2 in children.
For adults and the
elderly the strongest
associations were for
PM2.5andN02. The
most consistent lag in
adults and the elderly
for development of
URD was 2 days (one
day after a pollution
event).
Increment: 18 ug/m
(90th-10thpercentile)

Single-pollutant model
All yr
0-14 yr 3.5% [1.4, 5.8] lag 0
15-64 yrs 3.5% [0.5, 6.5] lag 1
>65 yrs 4.6% [0.4, 9.0] lag 2
Warm
0-14 yrs 3.2% [-0.5, 7.0] lag 0
15-64 yrs 4.6% [1.5, 7.7] lag 1
>65 yrs 1.6% [-4.8, 8.5] lag 2
Cool
0-14 yrs 5.5% [2.4, 8.7] lag 0
15-64 yrs 2.7 [0.0, 5.4] lag 1
>65 yrs 5.7% [0.4, 11.4] lag 2
2-pollutant models
0-14 yrs
SO2&O3: 1.0% [-2.2, 4.2]
SO2 & NO2: 4.7% [2.2, 7.4]
S02&PM2.5: 4.6% [2.1,7.2]
For 15-64 yrs
S02 & 03: 3.7% [0.6, 7.0]
SO2 & NO2: 2.6% [-0.0, 5.2]
SO2&PM2.5: 2.4% [-0.1, 5.0]
For >65 yrs
S02&03: 9.0% [1.7, 16.9]
S02&N02: 4.3% [-1.2, 10.2]
SO2 & PM2.5: 3.2% [-1.9,8.7]
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               TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

              EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design, Mean Levels & Copollutants Method, Findings,
& Methods Monitoring Stations & Correlations Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
EUROPE (cont'd)
Llorca et al. (2005)
Torrelavega, Spain

Period of Study:
1992-1995

Days: 1,461











Hospital admissions 24-h avg SO2:
outcomes (ICD 9): All 13.3 ug/m3,
respiratory admissions SD = 16.7
(460-519)
Age groups analyzed: All # of Stations: 3
ages
Study design:
Time series
Number of hospitals: 1
Statistical analyses:
Poisson regression
Covariates: Short and
Long-term trends
Statistical package: Stata
Lag: NR





NO2; r = 0.588 Associations between
NO; r = 0.544 SO2 and admissions
TSP' r = - 0 40 observed in the
SH2;' r = 0.957 Single-pollutant
model disappear in a
5-pollutant model.
Only NO2 was
significantly
associated with
ciclrrii s s 10 ns


No relation was
described for sulphur
compounds including
H2SorSO2. The
concentration of SO2
changes with
temperature changes,
which may be
responsible for
cardiac stress.
Increment: 100 ug/m3

Single-pollutant model
All cardio-respiratory admissions:
[0.89, 1.07]
Respiratory admissions: 1 .04
[0.90,1.19]
5-pollutant model
All cardio-respiratory admissions:
[0.80, 1.21]



RR0.98




RR0.98

Respiratory admissions: 0.89 [0.64, 1.24]














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                                                                          SO2 was not

                                                                          significantly

                                                                          associated with

                                                                          cardiac respiratory or

                                                                          cardio-respiratory

                                                                          admissions
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                    TABLE AX5.2 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                   EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
             Reference, Study
            Location, & Period
                        Outcomes, Design,
                           & Methods
    Mean Levels &
  Monitoring Stations
  Copollutants
 & Correlations
 Method, Findings,
   Interpretation
   Effects: Relative Risk or % Change
     & Confidence Intervals (95%)
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           Oftedal et al. (2003)
           Drammen, Norway

           Period of Study:
           1994-2000
                     Hospital admissions
                     outcomes (ICD 10): All
                     respiratory admissions
                     (JOO-J99)
                     Age groups analyzed: All
                     ages
                     Study design:
                     Time series
                     Statistical analyses: Semi-
                     parametric Poisson
                     regression, GAM with
                     more stringent criteria
                     Covariates: Temperature,
                     humidity, influenza
                     Lag:  2,3 days
Mean: 2.9 ug/m ,
SD = 2.1

IQR: 2.03 ug/m3
PM2.5
N02
03
Benzene
Formaldehyde
Toluene
The study found
positive associations
between daily
number of hospital
admissions for acute
respiratory diseases
and concentrations of
SO2; associations did
not change
substantially from the
first to the second 3-
yr period.
Increment:  2.03 ug/mj (IQR)

All respiratory disease
1.042 [1.011, 1.073]
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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

            EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
to
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Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels & Copollutants
Monitoring Stations & Correlations
Method, Findings, Effects: Relative Risk or % Change &
Interpretation Confidence Intervals (95%)
EUROPE (cont'd)
Ponce de Leon et al.
(1996)
London, England

Period of Study:
04/1987-1988;
1991-02/1992






















Hospital admissions
outcomes (ICD 9):
All respiratory (460-
519)
Age groups analyzed:
0-14, 15-64, 65+, all
ages
Study design: Time
series
N: 19,901
Statistical analyses:
APHEA protocol,
Poisson regression
GAM
Covariates: Long-
term trend, season,
influenza, day of wk,
holiday, temperature,

iiiumuiiy
Season:
Cool, Oct-Mar;
Warm: Apr-Sep

Dose-response
Investigated?: Yes
Statistical package:
SAS
Lag: 0,1, 2 days, 0-3
cumulative avg



SO2 24-h avg: NO2; r = 0.44
32.2 ug/m3, SD = 12.6 BS; r = 0.44
5th: 15 03;r= -0.067
10th: 18
25th: 24
50th: 31
75th: 39
90th: 47
95th: 54

# of stations: 2


















Though significant effects Increment: 90th- 1 Oth percentile
were observed with SO2 in (24-h avg: 29 ug/m3).
some age groups, they were
not consistent or similar in All yr
magnitude to those of O3. A11 ages j Q092
[0.9926, 1.0261] lag 1
0- 14 yrs 1.0093
[0.9837, 1.0356] lagl
1 5-64 yr 1.0223
[0.9942, 1.05 11] lagl
>65yr 1.0221
[0.9970, 1.0478] lag 2
Warm season
All ages 1.01 11
[0.9864, 1.0364] lagl
0-14 yrs 1.0468
[1.0066, 1.0885] lagl
15-64 yr 0.9996

[0.9596, 1.0411] lagl
>65yr 1.0124
[0.9772, 1.0489] lag 2
Cool season
All ages 1 0079
[0.9857, 1.0306] lagl
0-14 yrs 0.9848
[0.9515, 1.0192] lagl
15-64 yr 1.0389
[1.0010, 1.0783] lagl
>65yr 1.0280
[0.9945, 1.0625] lag 2
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                    TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                   EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
             Reference, Study
            Location, & Period
                       Outcomes, Design,
                          & Methods
    Mean Levels &
  Monitoring Stations
   Copollutants
  & Correlations
    Method, Findings,
      Interpretation
Effects: Relative Risk or % Change &
     Confidence Intervals (95%)
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           Ponka(1991)
           Helsinki, Finland

           Period of Study:
           1987-1989
                      Hospital admissions
                      outcomes (ICD 9
                      codes): Asthma
                      (493)
                      Age groups analyzed:
                      0-14; 15-64; >65yrs
                      Study design: Time
                      series
                      N: 4,209
                      Statistical analyses:
                      Correlations and
                      partial correlations
                      Covariates:
                      Minimum
                      temperature
                      Statistical package:
                      Lag: 0-1
24-havg: 19.2
(12.6) ug/m3
Range: 0.2, 94.6

Number of monitors: 4
NO2;r = 0.4516
NO; r = 0.4773
03;r = 0.1778
TSP;r = 0.1919
CO
The frequency of all
admissions for asthma was
significantly correlated to
SO2.

Child asthma admissions
were not significantly
correlated with SO2, but
were correlated to O3 and
NO.  SO2 was also
significantly correlated with
elderly admissions.
Increased hospitalization
correlated with SO2 was
also observed for adults.

Hospital admissions were
more strongly correlated
with SO2 than other
pollutants.  ER visits were
more strongly correlated
with a mixture of pollutants
(TSP, SO2, O3> and
temperature).

Multipollutant model
co-linear results of SO2,
CO, NO2> and NO suggest a
mixture of pollutants is
responsible for asthma
admissions.
Correlations between hospital admissions
(HA) for asthma and pollutants and
temperature by ages.
0-14yrs
HA:  -0.01391
Emergency HA: 0.0332
15-64yrs
HA:  0.1039 p = 0.0006
Emergency HA: 0.1199 p< 0.0001
>65 yrs
HA:  0.0796 p = 0.0085
Emergency HA: 0.1169 p< 0.0001

Partial correlations between admissions
for asthma and SO2 were standardized for
temperature.
HA:  0.0770 p = 0.0172
Emergency HA: 0.1050
p = 0.0011
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Study design:  Time
series
Statistical analyses:
Poisson regression
Covariates:  Season,
day ofwk, yr,
influenza, humidity,
temperature
Season: Summer
(Jun-Aug), Autumn
(Sep-Nov), Winter
(Dec-Feb), Spring
(Mar-May)
Lag: 0-7 days
In the steps leading to
regression analysis no
association was observed
between SO2 levels and the
>65 population.
Multipollutant models were
only used to examine NO2
and SO2.

SO2 had no significant
association with morbidity
caused by chronic bronchitis
and emphysema in the >65
yr old population.
RR 0.78 [0.59, 1.03] lag 2
RR 1.39 [1.05, 1.86] lag 3
RR 0.89 [0.68, 1.16] lag 4
RR 1.28 [0.97, 1.70] lag 5
RR0.91 [0.69, 1.20] lag 6
RR 1.09 [0.84, 1.40] lag 7
65+ yrs
NR
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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

            EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design, Mean Levels &
& Methods Monitoring Stations
Copollutants Method, Findings,
& Correlations Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
EUROPE (cont'd)
Ponka and Virtanen,
(1996)
Helsinki, Finland

Period of Study:
1987-1989











Hospital admissions 24-h avg (ug/m3):
outcomes (ICD 9 Winter: 26
codes): Asthma Spring: 22
(493) Summer: 13
Age groups analyzed: fa\\- 15
0-14,
15-64, 65+
Study design: Time

series
Statistical analyses:
Covariates: Long-

term trend, season,
epidemics, day of
wk, holidays,
temperature, relative
humidity
Statistical package:
Lag: 0-2
NO2 Significant
O3 associations were
Xgp observed between daily
SO2 concentrations and
daily counts of
hospitalizations among
15-to64-yr-old
patients and among
those over 64 years
old, but not among
children. These effects
were observed when

mean daily SO2 values
were lower than the

maximum value
recommended by
WHO (125 ug/m3).

Parameter estimates (PE) and standard erro (SE)
for a 1-unit increase:

Asthma 15-64yrs :
PE 0.2176 (0.1081) p = 0.44 lag 2
PE 0.3086 (0.1545) p = 0.046 lag 0-3

Asthma 65+ yrs :

PE 0.2412 (0.0956) p = 0.012 lag 2







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                TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels &
Monitoring Stations
Copollutants
& Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
EUROPE (cont'd)
Prescottetal. (1998)
Edinburgh, United
Kingdom
Period of Study:
10/92-6/95
Hospital admissions
outcomes (ICD 9):
Pneumonia
(480-7), COPD + Asthma
(490-496)
Age groups analyzed: <65,
SO2: 14.5(9.0)ppb
Min: 0 ppb
Max: 153 ppb
# of Stations: 1
CO
PM2.5
NO2
03
BS
No effect of SO2 on
hospitalizations
observed in either
age category.
Increment: 10 ppb
Respiratory admissions
>65yrs -2.5 [-11. 0,6.9] lag 0-2
< 65 yrs 0.0 [-8.3, 9.1] lag 0-2
o
oo
                           65+
                           Study design:
                           Time series
                           Statistical analyses:
                           Poisson log linear
                           regression
                           Covariates: Trend, seasonal
                           and weekly variation,
                           temperature, wind speed,
                           day of wk
                           Lag:  0,1, or 3 day rolling
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                   TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                  EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels & Copollutants
Monitoring Stations & Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change &
Confidence Intervals (95%)
EUROPE (cont'd)
Rossi etal. (1993)
Oulu, Finland
Period of Study:
10/1/1985-9/30/1986
ED visits
outcome(s) (ICD 9):
Asthma (493)
Age groups analyzed: 15-
85
Study design:
24-h mean: 10.0 ug/m3 NO2; r = 0.48
Range: 0,56 TSP; r=0.31
H2S
1-hmax:
31.0 ug/m3
Range: 1,24
Same day ER visits
were correlated to
daily SO2 levels, but
the significance was
lost with longer lag
periods.
Pearson correlation coefficients
ED asthma visits and same day
r = 0.13p<0.01
lagO
SO2:
Time series
N: 232
Statistical analyses:
Pearson's and partial
correlation coefficients and
multiple regression with
stepwise discriminate
analysis
Covariates:  Temperature,
humidity
Statistical package: BMDP
software
Lag:  0,1,2,3
                                                        # of monitoring stations:
                                                        4
When asthma visits
were analyzed, SO2
was positively and
significantly
correlated with
asthma visits in the
same wk and the wk
after.

After regression
analyses, SO2
became insignificant.
Weekly ED asthma visits and same wk
SO2:  r = 0.28 p< 0.05
Weekly ED asthma visits and previous wk
SO2:  0.30p<0.05

Multipollutant (NO2; TSP; H2S)
Regression coefficient:
Allyr:  (3 = 0.037, p = 0.535
Winter: p = -0.024, p = 0.710
Summer:  p =-0.003, p = 0.991
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                   TABLE AX5.2 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                  EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels &
Monitoring Stations
Copollutants
& Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change &
Confidence Intervals (95%)
EUROPE (cont'd)
           Sunyeretal. (1991)
           Barcelona, Spain

           Period of Study:
           1985-1986
ED visits
outcome(s) COPD (ICD
9): 490-496
Age groups analyzed: >14
Study design:
Time series
# of Hospitals:  4
Statistical analyses:
multivariate linear
regression
Covariates: Meteorology,
season, day of wk
Statistical package:
Lag: 0 to 2 days
24-havg(SD): 56.5
(22.5) ug/m3
98th: 114.3
Range:  17, 160

l-hmax(SD): 141.9
(98.8) ug/m3
98th: 461.3
Range:  17, 160
                                                       Number of monitors:
                                                       14-720
BS, CO, NO2, O3
An incremental
change of 25 ug/m3
in SO2 was correlated
with an adjusted
increase of 0.5 daily
visits due to COPD.
SO2 and ER visits
were more strongly
correlated in warm
weather.
Even at 24-h avg
levels less than
100 ug/m3, effects of
SO2 were statistically
significant for COPD
admissions.
Change in 24-h SO2 daily ER
ug/m3 admissions P-value
1500.55 < 0.01
100 0.7 < 0.01
72 0.7 0.04
52 0.41 >0.05
39 -1.27 >0.05

0.5 excess daily admissions per 25 ug/m
increment of SO2.
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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

            EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels &
Monitoring Stations
Copollutants Method, Findings,
& Correlations Interpretation
Effects: Relative Risk or % Change &
Confidence Intervals (95%)
EUROPE (cont'd)
Sunyeretal. (1993)
Barcelona, Spain

Period of Study:
1985-1989









ED visits
outcome(s) (ICD 9):
COPD (490-492;
494-496)
Study design:
Time series
Statistical analyses:
Autoregressive linear
regression
Statistical package:
T on- I?
l^ag . 1 ,^





SO2, 24-h

Winter Tertiles (ug/m3)
<40.4
40.4, 61
>61

Winter Tertiles (ug/m3)
<28.1
28.1,46.1
>46.1





BS SO2 concentrations were
associated with the
number of COPD ER
admissions in the winter
and summer. An increase
of 25 ug/m3 in SO2
produced an adjusted
change of ~6% and 9%,
respectively, in the
number of COPD
emergencies in the winter
and summer. Controlling
for particulate matter
resulted in a loss of
significance. Co linearity
ofBSwithSO2was
observed.
Effects were expressed as adjusted
changes in daily COPD ER admissions
based on an increment of 25 ug/m3.

Winter: 6%
Summer: 9%

Mean ER admissions for COPD (winter)
were 15.8 (range 3, 34) and 8.3
(range 1, 24) in the summer.






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                    TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                   EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
             Reference, Study
            Location, & Period
                         Outcomes, Design,
                            & Methods
    Mean Levels &
  Monitoring Stations
  Copollutants
 & Correlations
   Method, Findings,
     Interpretation
 Effects: Relative Risk or % Change
   & Confidence Intervals (95%)
to
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EUROPE (cont'd)
>
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           Teniasetal. (1998)
           Valencia, Spain

           Period of Study:
           1993-1995

           Seasons:
           Cold: Nov-Apr
           Warm:  May-Oct
                      ED visits
                      outcome(s): Asthma
                      ICD 9 Code(s): NR
                      Age groups analyzed:  >14
                      Study design:  Time series
                      N: 734
                      Statistical analyses:
                      Poisson regression,
                      APHEA protocol
                      Covariates: seasonality,
                      temperature, humidity,
                      long-term trend, day of
                      wk, holidays, influenza
                      Seasons:
                      Cold: Nov-Apr;
                      Warm:  May-Oct
                      Dose-Response
                      Investigated: Yes
                      Statistical package: NR
                      Lag:  0-3 days
24 h: 26.6 ug/m3
25th: 17.9
50th: 26.2
75th: 34.3
95th: 42.6
Cold: 31.7
Warm:  21.7
1-hmax:  56.3 ug/m3
25th: 36.3
50th: 52.2
75th: 72.2
95th: 95.2
Cold: 64.6
Warm:  48.2

# of Stations: 2
24 h:
O3;r= -0.431
NO2 (24 h);
r = 0.265
N02 (1 h);
r = 0.199

Ih:
O3;r= -0.304
NO2 (24 h);
r = 0.261
NO2 (1 h);
r = 0.201
SO2 showed the strongest
correlation to asthma
admissions during the
warm months.

Multipollutant models
showed that O3 and black
smoke had a small effect
on the association between
SO2 and asthma ER visits
while NO2 greatly
depressed these effects. It
is likely that NO2 was the
dominant pollutant for
respiratory outcomes.  SO2
was the "most vulnerable
pollutant" to the presence
of other pollutants.
Increment: 10 ug/m

SO2 24-h avg
All yr 1.050
[0.973, 1.133] lag 0
Cold 1.032
[0.937, 1.138] lag 0
Warm 1.070
[0.936, 1.224] lag 0

SO2 1-hmax
Allyr 1.027 [0.998, 1.057] lag 0
Cold 1.018 [0.980, 1.057] lag 0
Warm 1.038 [0.990, 1.090] lag 0
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                    TABLE AX5.2 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                   EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
             Reference, Study
            Location, & Period
                        Outcomes, Design,
                            & Methods
    Mean Levels &
  Monitoring Stations
  Copollutants
 & Correlations
  Method, Findings,
   Interpretation
 Effects:  Relative Risk or % Change &
      Confidence Intervals (95%)
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EUROPE (cont'd)
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           Tenias et al. (2002)
           Valencia, Spain
           Period of Study:
           1994-1995
                      ED visits
                      outcome(s): COPD
                      ICD 9 Code(s): NR
                      Age groups analyzed: >14
                      Study design:
                      Time series
                      N:  1,298
                      # of Hospitals:  1
                      Statistical analyses:
                      Poisson regression,
                      APHEA protocol; basal
                      models and GAM
                      Covariates: Seasonality,
                      annual cycles,
                      temperature, humidity,
                      day of wk, feast days
                      Seasons:
                      Cold, Nov-Apr;
                      Warm, May-Oct
                      Dose-response
                      Investigated:  Yes
                      Statistical package: NR
                      Lag: 0-3 days
24 h: 26.6 ug/m3
25th: 17.9
50th: 26.2
75th: 34.3
95th: 42.6
Cold: 31.7
Warm:  21.7
1-hmax:  56.3 ug/m3
25th: 36.3
50th: 52.2
75th: 72.2
95th: 95.2
Cold: 64.6
Warm:  48.2
BS;r= 0.687
NO2;r=0.194
CO; r= 0.734
O3;r= -0.431
SO2 did not show any
significant association
with COPD ER visits
for all seasons
analyzed.

SO2 did not affect O3
or CO association to
ER admission for
COPD when assessed
together in the
Multipollutant model.

Possibility of a linear
relationship between
pollution and risk of
emergency cases could
not be ruled out.
Increment: 10 ug/m .

24-h avg SO2
All yrRR 0.971
[0.914, 1.031] lag 0
Cold, 24-h avg: RR 0.970
[0.905, 1.038] lag 0
Warm, 24-h avg: RR 0.982
[0.885, 1.090] lag 0

1-hmax SO2
All yrRR 0.981 [0.958, 1.027] lag 3
Cold, 24-h avg: RR 0.972
[0.945,1.000]  lag 3
Warm, 24-h avg: RR 1.003
[0.979, 1.056] lag 3
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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

            EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design, &
Methods
Mean Levels &
Monitoring Stations
Copollutants
& Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
EUROPE (cont'd)
Thompson etal. (2001)
Belfast, Northern
Ireland

Period of Study:
1993-1995














Hospital admissions/ED
visits
Outcome(s): Asthma
ICD9Code(s): NR
Age groups analyzed:
Children
Study design: Time series
N: 1,044
Statistical analyses:
Followed APHEA
protocol, Poisson
regression analysis
Covariates: Season, long-
term trend, temperature,
day of wk, holiday
Season:
Warm (May-Oct); Cold
(Nov-Apr)
Statistical package: Stata
Lag: 0-3
Warm Season
SO2 (ppb):
Mean: 12.60;
SD = 10.60;
IQR: 6.0,16.0

Cold Season
S02 (ppb):
Mean: 20.40;
SD = 17.90;
IQR: 11.0,24.0









PM2.5; r = 0.66
NO2;r=0.82
N0x;r=0.83
NO; r = 0.76
O3;r=-0.58
CO; r= 0.64
Benzene;
r=0.80












This study found weak,
positive associations for
SO2 and adverse
respiratory outcomes in
asthmatic children.















SO2 Increment: Per doubling (ppb)

Lag ORR 1.07 [1.03, 1.11]
Lag 0-1 RR 1.09
[1.04,1.15]
Lag 0-2 RR 1.08
[1.02,1.15]
Lag 0-3 RR 1.08
[1.01,1.15]
Warm only Lag 0-1 RR 1.11
[1.04,1.19]
Cold only Lag 0-1 RR 1.07
[1.00,1.15]
Adjusted for Benzene Lag 0-1 RR 0.99
[0.90, 1.09]





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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

            EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design, & Mean Levels & Copollutants Method, Findings, Effects: Relative Risk or % Change &
Methods Monitoring Stations & Correlations Interpretation Confidence Intervals (95%)
EUROPE (cont'd)
Tobias etal. (1999)
Barcelona, Spain

Period of Study:
1986-1989















ED visits 24-h avg SO2 ug/m3 BS
outcome(s): Asthma NO2
ICD9: NR Non-epidemic days: 85.8 O3
Age groups analyzed: (62.4)
>14 Epidemic days: 116.3
Study design: (79.3)
Time series
Statistical analyses:
Poisson regression,
followed APHEA
protocol
Covariates:
Temperature,
humidity, long-term
trend, season, day of
wk
Statistical package:
NR
Lag: NR

The study failed to find a (3 x 104 (SE x 104 ) using Std Poisson
significant association Without modeling asthma epidemics: 3 ,
between SO2 and asthma (4.14)
ED visits. Modeling epidemics with 1 dummy
variable: 1. 64 (2.76)
Modeling epidemics with 6 dummy
variables: 1.53(2.75)
Modeling each epidemic with dummy
variable: 2.20(2.65)


.99








P x 104 (SE x 104) using Autoregressive
Poisson
Without modeling asthma epidemics: 6,
(14.37)
Modeling epidemics with 1 dummy
variable: 1.68(2.77)
Modeling epidemics with 6 dummy
variables: 1.72(2.75)
Modeling each epidemic with dummy
variable: 2.85(2.89)

.99







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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

            EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
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Reference, Study Outcomes, Design, &
Location, & Period Methods
Mean Levels & Copollutants Method, Findings,
Monitoring Stations & Correlations Interpretation
Effects: Relative Risk or % Change &
Confidence Intervals (95%)
EUROPE (cont'd)
Vigotti et al. (1996) Hospital admissions
Milan, Italy outcomes
(ICD 9 codes):
Period of Study : Respiratory disease
1980-1989 (460-519).
Age groups analyzed:
15-64yrsand
>64 vrs
Study design: Time
series

N: >73,000
# of Hospitals:
Statistical analyses:
APHEA protocol
Covanates'
Season: cold season
(Oct. to March) and
warm season
(Apr to Sept.)
Statistical package:
Lag: 0, cumulative 4
day
(0-3)



24-havg: 117.7 ug/m3 TSP;r=0.63 The effect of single day or
Range: 3.0,827.8
5th: 15.0
25th: 34.0
50th: 65.5
75th: 162.5
95th: 376.3
Winter: 248.6
Range: 30.6,827.8

5th: 78.8
25th: 138.5
50th: 216.0
75th: 327.8
95th: 527.0
Summer: 30.5
Range: 3.0,113.8
5th: 9.1
25th: 18.5
50th: 27.8
75th: 39.2
95th: 62.7
# of monitors: 4;
r = 0.89, 0.91
cumulative day exposure
to SO2 was more
pronounced during the
cool months. Interaction
between seasons was not
significant. SO2 did not
interact with TSP. No
differences were noted
between age groups.


There were increased, but
not significant
(borderline), risks for
increased hospital
admissions based on an
increment change in SO2
of 125 ug/m3 in the
winter.







Increment: 100 ug/m

All respiratory
15-64yrs
All yr round:
RR 1.05 [1.00, 1.10] lag
Warm:
RR 1.04 [0.98, 1.11] lag
Cool:
RR 1.06 [1.00, 1.13] lag

>64 yrs
All yr:
RR 1.04 [1.00, 1.09] lag
Warm:
RR 1.02 [0.96, 1.08] lag
Cool:
RR 1.05 [1.00, 1.11] lag











;0
;0
;0

;0
;0
;0







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           TABLE AX5.2 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY
                             DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
             Reference, Study
            Location, & Period
                       Outcomes, Design, &
                            Methods
    Mean Levels &
  Monitoring Stations
  Copollutants
 & Correlations
  Method, Findings,
    Interpretation
 Effects:  Relative Risk or % Change &
      Confidence Intervals (95%)
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EUROPE (cont'd)
>
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           Walters etal. (1994)
           Birmingham, United
           Kingdom

           Period of Study:
           1988-1990
                     Hospital admissions
                     outcomes
                     (ICD 9 codes):
                     Asthma (493) and acute
                     respiratory conditions
                     (466, 480-486,
                     490-496)
                     Study design:
                     Time series
                     Statistical analyses:
                     Least squares regression
                     Covariates: Temperature,
                     pressure, humidity
                     Lag: 3 day moving avg.
SO2 24-h mean (ug/m )
All yr: 39.06
Max:  126.3
Spring: 42.9
Summer: 37.8
Autumn: 40.9
Winter: 34.2
BS
In 2-pollutant models BS
remained significant but
SO2 was no longer
associated significantly
with admission.

A 100 ug/m3 increment
in SO2 might result in
four (0-7) more asthma
admissions and 15.5
(6-25) move respiratory
admissions/day. Spring
and autumn did not show
associations with
admissions for asthma or
respiratory.
Increment of 100 ug/m

Asthma
Summer:  1.4% [-10, 39] lag 0
Winter: 2.7% [-0.8, 6.1] lag 0

All respiratory
Summer:  5.9% [1.1, 10.6] lag 0
(p < 0.02)
Winter: 18% [8.8,26.8] lag 0
(p < 0.0002)
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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

            EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
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Reference, Study
Location, & Period
LATIN AMERICA
Braga*etal. (1999)
Sao Paulo, Brazil

Period of Study:
10/1992-10/1993



















Outcomes, Design, & Mean Levels & Copollutants
Methods Monitoring Stations & Correlations

Hospital admissions 24-h avg 22.40 (9.90) PM2.5; r = 0.73
outcomes (ICD 9 codes): ug/m3 CO; r = 0.62
All respiratory (466,480- Min: 6.4 NO2; r = 0.53
486,491-492,496) Max: 69.6 O3;r =
Age groups analyzed: <13
Yrs # of monitors: 13
Study design:
Time series
N/~o c\ 1 O
Do y 1 o
# of Hospitals:
1 12 Statistical analyses:
Multiple linear regression
models (least squares).
Also used Poisson
regression techniques.
GLM and GAM using
LOESS for smoothing.
Covariates: Season,
temperature, humidity, day
of wk,
Statistical package: SPSS,
S-Plus
Lag: 1,2,3,4,5,6,7 moving
avgs
Method, Findings, Effects: Relative Risk or % Change
Interpretation & Confidence Intervals (95%)

SO2 did not show a Increment: 22.4 ug/m3
correlation with
respiratory hospital 0. 12 [- 0.04, 0.28] lag 0
admissions with any lag Q lg f_0 OQ; Q 37] lag Q.J
structure. Qlg ^ Q Q^ Q ^ lag Q_2
0.18 [-0.04, 0.40] lag 0-3
0.18 [-0.05, 0.42] lag 0-4
0.12 [-0.13, 0.36] lag 0-5

0.08 [-0.18, 0.35] lag 0-6















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                    TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                   EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
              Reference, Study
             Location, & Period
                        Outcomes, Design,
                           & Methods
    Mean Levels &
  Monitoring Stations
  Copollutants
 & Correlations
   Method, Findings,
     Interpretation
  Effects: Relative Risk or % Change
     & Confidence Intervals (95%)
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LATIN AMERICA (cont'd)
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           Braga*etal. (2001)
           Sao Paulo, Brazil

           Period of Study:
           1/93-11/97
                       Hospital admissions
                       outcomes (ICD 9):
                       All respiratory
                       admissions
                       (460-519)
                       Age groups analyzed:
                       0-19, <2, 3-5,
                       6-13, 14-19
                       Study design:  Time
                       series
                       Statistical analyses:
                       Poisson regression
                       with GAM
                       term trend, season,
                       temperature, relative
                       humidity, day of wk,
                       holiday
                       Statistical package:
                       S-Plus 4.5
                       Lag: 0-6 moving avg
SO2 mean:
21.4 ug/m3;
SD= 11.2
IQR: 14.4 ug/m3
Range:  1.6,76.1

# of stations:  5-6
PM2.5;r = 0.61
N02;r=0.54
CO; r= 0.47
O3;r=0.17
Children <2 yrs were most
susceptible to the effect of
each pollutant.
Pneumonia and
bronchopneumonia were
the main cause of hospital
admissions (71%) in the
<2-yr-old group.
Bronchitis/asthma were
more important for the
intermediate age groups.
However, in all age
groups the largest increase
in admissions was caused
by chronic disease in
tonsils and adenoids.

Multipollutant models
rendered all pollutants
except PM2 5 and SO2
from significance. The
effect of PM2 5 stayed
relatively unchanged
while SO2 was reduced;
however, it remained
significant.
Increment: ug/m (IQR)

All respiratory admissions
<2 yrs 5.9% [4.5, 7.4]
3-5 yrs 1.6% [-1.3, 4.4]
6-13 yrs 0.6% [-2.2, 3.5]
14-19 yrs 1.3% [-3.2, 5.8]
All ages 4.5% [3.3, 5.8]

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                    TABLE AX5.2 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                    EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
             Reference, Study
            Location, & Period
                        Outcomes, Design, &
                             Methods
  Mean Levels &
Monitoring Stations
  Copollutants
 & Correlations
   Method, Findings,
     Interpretation
  Effects: Relative Risk or % Change
     & Confidence Intervals (95%)
to
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LATIN AMERICA (cont'd)
>
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           Farhat* et al. (2005)
           Sao Paulo, Brazil

           Period of Study:
           1996-1997
                      Hospital Admissions/ED
                      Visits
                      Outcome(s) (ICD9):
                      Lower Respiratory
                      Disease (466, 480-5)
                      Age groups analyzed: <13
                      Study design: Time series
                      N: 4,534
                      # of Hospitals: 1
                      Statistical analyses: 1)
                      Poisson regression and 2)
                      GAM - no mention of
                      more stringent criteria
                      Covariates: Long-term
                      trends, seasonality,
                      temperature, humidity
                      Statistical package: S-
                      Plus
                      Lag:  0-7 days, 2,3,4 day
                      moving avg
24-h avg:
Mean: 23.7 ug/m3
SD = 10.0
Range: 3.4,75.2
IQR:  12.5

# of Stations: 6
PM2.5; r = 0.69
N02; r = 0.66
CO; r= 0.49
O3; r = 0.28
This study reports a
significant effect of air
pollution on respiratory
morbidity, though several
pollutants were associated
with increased respiratory
events, making it difficult
to isolate a single agent as
the main atmospheric
contaminant.
Increment: 12.5 ug/m (IQR)

Single-pollutant models (estimated from
graphs):
Pneumonia-21% [4.8, 37]
Asthma-12% [-10, 38]

Pneumonia multipollutant models:
Adjusted for:
PM2.5 13.3 [-5.7, 32.3] 6-day avg
NO2 16.5 [-1.6, 34.6] 6-day avg
CO 18.4 [0.5, 36.2] 6-day avg
O3 18.4 [0.5, 36.2] 6-day  avg
Multipollutant model
13.3 [-5.9, 32.6] 6-day avg

Asthma multipollutant models:
Adjusted for:
PM2.5 3.8 [-23.3, 31.0] 2-day avg
N02 -1.2 [-27.4, 25.0] 2-day avg
CO 6.2 [-18.8, 31.2] 2-day avg
O3 9.4 [-14.6, 33.5] 2-day avg
Multipollutant model
-0.5 [-27.7, 26.6] 2-day avg

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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

            EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
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Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels &
Monitoring Stations
Copollutants Method, Findings,
& Correlations Interpretation
Effects: Relative Risk or % Change &
Confidence Intervals (95%)
LATIN AMERICA (cont'd)
Gouveia and Fletcher,
(2000)
Sao Paulo, Brazil

Period of Study:
11/92-9/94

















Hospital admissions
outcomes (ICD 9): All
respiratory; Pneumonia
(480-486); asthma or
bronchitis (466, 490, 491,
493)
Age groups analyzed:
<1; <5 years
Study design:
Time series
Statistical analyses:

Poisson regression
Covariates: Long-term
trend, season, temperature,
relative humidity, day of
wk, holiday, strikes in
public transport or health
services
Season:
Cool (May-Oct),
Warm (Nov-Apr)
Statistical package: SAS
Lag: 0, 1, 2 days
24-h avg:
Mean: 18.3 ug/m3
SD = 9.0
Range: 3.2,61.1
5th: 7.6
25th: 11.9
50th: 16.6
75th: 22.2
95th: 35.8


$ of stations' 4












PM2 5; r = 0.72 Current ambient air
NO2;r=0.37 pollution
CO' r = 0 65 concentrations have
O • r = 0 08 short-term adverse
effects on children's
respiratory morbidity
assessed through
admissions to
hospitals.















Increment: 27.1 ug/m
(90th -10th)

All Respiratory
<5yrs RR 1.038
[0.983, 1.096] lag 1
<5yrsCool RR1.06
[0.99, 1.11] (estimated from graph)
<5 yrs Warm RR 0.98
[0.89, 1.07] (estimated from graph)


Pneumonia
<5yrs RR 1.024
[0.961, 1.091] lag 1

<1 yr RR 1.071
[0.998, 1.149] lag 0


Asthma
<5yrs RR 1.106
[0.981, 1.247] lag 2



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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

            EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
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Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels & Copollutants
Monitoring Stations & Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change &
Confidence Intervals (95%)
LATIN AMERICA (cont'd)
Ilabacaetal. (1999)
Santiago, Chile

Period of Study:
2/1/95-8/31/96
Days: 578



















ED visits
outcome(s) (ICD9):
Upper respiratory
illness (460-465,
487); Lower
respiratory illness
(466, 480-486, 490-
494,496,519.1,
033.9); Pneumonia
(480-486)
Age groups analyzed:
Studv desisn' Time
series
# of Hospitals: 1
Statistical analyses:
Poisson regression
Covariates: Long-
term trend, season,
day of wk,
temperature,
humidity, influenza
epidemic
Season:
Warm (Sep-Apr),
Cool (May-Aug)
Statistical package:
NR
Lag: 0-3 days



24-h avg SO2 (ug/m3) Warm:
Warm: NO2; r = 0.6556
Mean: 14.9 O3;r= 0.1835
Median: 13.2 PM2.5; r = 0.6687
SD = 8.8 PM2.5; r = 0.5764
Range: 1.9,60.2
5th: 5.6 Cool:
95th: 32.0 NO2;r= 0.7440
O3;r= 0.1252
Cool: PM2 5; r = 0.7337
Mean: 31.8 PM2.5; r = 0.6874
Median: 28.2
SD = 18.4
Range: 5.6,92.1
5th: 9.4
95th: 75.2
# of stations: 4













SO2 was related to the
number of respiratory
ED visits, but because of
the high correlation
between contaminants, it
is difficult to establish
independent health
effects. These results
support the fact that
exposure to air pollution
mixtures may decrease
immune functions and
increase the risk for
respiratory infections
among children.















Increment: IQR
All respiratory
Cool
Lag 2 IQR: RR 1.0289
[1.0151,1.0428]
Lag 3 IQR: RR 1.0374
[1.0236,1.0513]
Lag avg 7 IQR: RR 1.0230
[1.0086,1.0377]
TTT
Warm
Lag 2 IQR: RR 1.0029
[0.9860,1.0200]
Lag 3 IQR: RR 1.0108
[0.9937, 1.0282]
Lag avg 7 IQR: RR 1.0108
[0.9756, 1.0473]
Upper respiratory
Cool

Lag 2 IQR: RR 1.05 84
[1.0394,1.0778]
Lag 3 IQR: RR 1.05 13
[1.0324,1.0706]
Lag avg 7 IQR: RR 1.03 16
[1.0120,1.0515]
Warm
Lag 2 IQR: RR 1.0061
[0.9850,1.0277]
Lag 3 IQR: RR 1.01 30
[0.9916,1.0349]
Lag avg 7 IQR: RR 0.981 5
[0.9390,1.0260]

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                  TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                  EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
            Reference, Study
           Location, & Period
                     Outcomes, Design,
                        & Methods
  Mean Levels &
Monitoring Stations
 Copollutants
& Correlations
Method, Findings,
  Interpretation
Effects: Relative Risk or % Change &
    Confidence Intervals (95%)
to
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LATIN AMERICA (cont'd)
>
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          Ilabacaetal. (1999)
          (cont'd)
                                                                                                 Pneumonia
                                                                                                 Cool
                                                                                                 Lag2IQR: RR 1.0164
                                                                                                 [0.9757,1.0587]
                                                                                                 LagSIQR: RR 1.0342
                                                                                                 [0.9938,1.0762]
                                                                                                 Lagavg7IQR: RR 1.0291
                                                                                                 [0.9850,1.0751]
                                                                                                 Warm
                                                                                                 Lag2IQR: RR 1.1010
                                                                                                 [1.0404,1.1653]
                                                                                                 LagSIQR: RR 1.0248
                                                                                                 [0.9669,1.0862]
                                                                                                 Lagavg7IQR: RR 1.2151
                                                                                                 [1.0771,1.3709]
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                    TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                    EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
 Reference, Study
Location, & Period
                                     Outcomes, Design,
                                        & Methods
   Mean Levels &
 Monitoring Stations
  Copollutants
 & Correlations
  Method, Findings,
   Interpretation
Effects: Relative Risk or % Change &
     Confidence Intervals (95%)
           LATIN AMERICA (cont'd)
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           Lin etal. (1999)
           Sao Paulo, Brazil

           Period of Study:
           May 1991-Apr 1993

           Days: 621
                    ED visits
                    outcome(s): Respiratory
                    disease, Upper respiratory
                    illness, Lower respiratory
                    illness, Wheezing
                    ICD9Code(s): NR
                    Age groups analyzed: <13
                    Study design: Time series
                    # of Hospitals: 1
                    Statistical analyses: Gaussian
                    and Poisson regression
                    Covariates: Long-term trend,
                    seasonality, day of wk,
                    temperature, humidity
                    Statistical package: NR
                    Lag:  5-day lagged moving
                    avgs
SO2 ug/m3:
Mean: 20
SD = 8
Range: 4,60

Number of stations: 3
N02;r=0.38
CO; r= 0.56
PM2.5; r = 0.73
O3;r=0.21
The results of this
study demonstrate a
significant association
between the increase in
emergency visits for all
respiratory illness,
especially URI, and
SO2 levels.
Increment: W ug/m

All respiratory illness
SO2 alone RR 1.079
[1.052, 1.107] 5-day moving avg
S02 + PM2 5 + 03 + N02 + CO RR 0.938
[0.900, 0.977]

Lower respiratory illness
SO2 alone RR 1.052
[0.984, 1.125] 5-day moving avg
S02 + PM2 5 + 03 + N02 + CO RR 0.872
[0.783,0.971]

Upper respiratory illness
SO2 alone RR 1.075
[1.044, 1.107] 5-day moving avg
SO2 + PM2 5 + O3 + NO2 + CO RR 0.951
[0.906, 0.999]

Wheezing
S02 alone RR 1.034 [0.975, 1.096]
5-day moving avg
SO2 + PM2 5 + O3 + NO2 + CO RR 0.908
[0.824,1.002]

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                    TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                   EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
              Reference, Study
             Location, & Period
                           Outcomes, Design,
                              & Methods
  Mean Levels &
Monitoring Stations
                                                    Copollutants
                                                   & Correlations
                                         Method, Findings,
                                           Interpretation
 Effects: Relative Risk or % Change
   & Confidence Intervals (95%)
to
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LATIN AMERICA (cont'd)
64
Study design: Time series
N: 712
# of Hospitals: 1
Catchment area: 13,163 total
ER visits
Statistical analyses:  Poisson
regression and GAM-no
mention of more stringent
criteria
Covariates: Weekdays, time,
minimum temperature,
relative humidity, daily
number of non-respiratory
emergency room visits made
by elderly
Statistical package:
S-Plus
Lag:  2-7 days and 3 day
moving avgs
SO2 24-h avg (ug/m3):
18.7,
SD = 10.6
Range:  2.0,75.2
IQR: 15.1 ug/m3

# of Stations: 13
                                                                        O3;r=0.28
                                                                        N02; r = 0.67
                                                                        PM2.5; r = 0.72
                                                                        CO; r= 0.51
                                       The results of the
                                       study show a
                                       significant
                                       association between
                                       SO2 and CLRD
                                       among the elderly.
Increment: IQR of ug/m

Percent increase:  17.5
[5.0, 23.0] lag 3-day moving avg
(estimated from graph)

Single-pollutant model
P = 0.0140 (0.0056)

Multipollutant model (with ozone)
P = 0.0104 (0.0059)

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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

            EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
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Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels &
Monitoring Stations
Copollutants Method, Findings,
& Correlations Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
ASIA
Wong et al. (2002a)*
London England and
Hong Kong

Period of Study:
London:
1992-1994
Hong Kong:
1995-1997
Days: 1,096










Hospital admissions
outcomes (ICD 9): All
respiratory admissions
(460-519); asthma (493)
Age groups analyzed:
15-64, 65+, all ages
Study design:
Time series
Statistical analyses:
APHEA protocol,
Poisson regression with
GAM
Covanates' Lons-term
trend, season, influenza,
day of wk, holiday,
temperature, humidity,
thunderstorms
Season:
Cool, Oct-Mar; Warm:
Apr-Sep
Dose-Response
Investigated?: Yes
Statistical package:
S-Plus
Lag: 0, 1,2, 3, 4 days,
0-1 cum. avg.
24-h SO2 ug/m3
Hong Kong
Mean: 17.7
Warm: 18.3
Cool: 17.2
SD= 12.3
Range: 1.1,90.0
10th: 6.2
50th: 14.5
90th: 32.8
London
Mean: 23.7
Warm: 22.2
Cool: 25.3
SD=12.3
Range: 6.2,113.6
10th: 13.2
50th: 20.6
90th: 38.1


Hong Kong Similar non-statistically
PM2 5; r = 0.30 significant associations
NCy r = 0 37 between asthma hospital
O • r = -0 18 admissions and SO2 were
found in both cities. The
T , association between
London . ...
respiratory hospital
PM2.5; r - 0.64 admissions and SO2 showed
NO2, r-0.71 significance in the cold
O3; r = -0.25 season in Hong Kong and
on an all yr basis.
Respiratory hospital
admissions were not
significantly associated with
SO2 in Britain.

In the 2-pollutant model the
association between
respiratory hospital
admission and SO2 in
London was insignificant,
and remained insignificant
after adjusted for the second
pollutants.


Increment: 10 ug/m

Asthma, 15-64 years
Hong Kong ER - 0.1
[-2.4, 2.2] lag 0-1
ER- 1.5 [-3.4, 0.5] lag 2
Warm ER 1.5
[-1.5, 4. 6] lag 0-1
Cool ER -2.0
[-5.4, 1.4] lag 0-1
London ER 0.7
[-1.0, 2. 5] lag 0-1
ER2.1 [0.7, 3.6] lag 3
Warm ER-1.4
[-4.7, 1.9] lag 0-1
Cool ER 1.6
[-0.5, 3. 8] lag 0-1
Respiratory 65+ years
Hong Kong ER 1.8
[0.9, 2.6] lag 0-1
ER1.7[1.0,2.4]lagO



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                    TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                   EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
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Reference, Study
Location, & Period
Outcomes, Design, Mean Levels &
& Methods Monitoring Stations
Copollutants Method, Findings,
& Correlations Interpretation
Effects: Relative Risk or % Change &
Confidence Intervals (95%)
ASIA (cont'd)
Wong et al. (2002a)*
(cont'd)










# of stations:
Hong Kong: 7, r
London: 3, r =









In Hong Kong, the
positive association of
SO2 was most affected
by NO2, losing statistical
significance. The
positive association
remained robust when
adjusted for O3, and a
slight decrease in
association after adjusted
forPM2.5.


Warm ER 1.1 [0.0, 2.2] lag 0-1
Cool ER 2.7 [1.4, 4.0] lag 0-1
+O3 ER 1.9 [1.1, 2. 8] lag 0-1
+PM2.5 ER 1.2 [0.3, 2.2] lag 0-1
+NO2 ER 0.3 [-0.7, lag 1.4] lag 0-1
London ER 0.2 [-0.6, 1.1] lag 0-1
ER 1.2 [0.5, 2.0] lag 3
Warm ER 1.3 [-0.5, 3.1] lag 0-1
Cool ER -0.3 [-1.3, 0.8] lag 0-
+O3 ER 0.5 [-0.4, 1.5] lag 0-1
+PM2.5 ER 1.2 [0.3, 2.2] lag 0-1
+N02 ER 0.5 [-0.7, 1.7] lag 0-1
           Chewetal. (1999)
           Singapore

           Period of Study:
           1990-1994
Hospital
Admissions/ED Visits
Outcome(s) (ICD 9):
Asthma (493)
Age groups analyzed:
3-12,
13-21
Study design: Time
series
N: 23,000
# of Hospitals: 2
Statistical analyses:
Linear regression,
GLM
24-havg:  38.1 ug/m3,      NO2;r =
SD = 21.8                Q3;r =
Range:  3.0,141.0         TSP;r =
# of Stations:  15
SO2 was positively
correlated to daily ER
visits and hospitalization
for asthma in children
(3-12 yrs), but not
adolescents. The
association of ER visits
with SO2 persisted after
standardization for
meteorological and
temporal variables. An
adjusted increase in 2.9
ER visits for every 20
ug/m3 increase in
ambient SO2 levels with
a lag of 1 was observed.
Categorical analysis (via ANOVA)
p-value and Pearson correlation coefficient
(r) using continuous data comparing daily
air pollutant levels and daily number of
ER visits

Age Group: 3-12 13-21

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                    TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                   EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design, Mean Levels &
& Methods Monitoring Stations
Copollutants Method, Findings,
& Correlations Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
ASIA (cont'd)
Chewetal. (1999)
(cont'd)
Covariates: variables that
were significantly
associated with ER visits
were retained in the model
Statistical package:
SAS/STAT, SAS/ETS
6.08
Lag: 1,2 days avgs
The increased number
of ER visits/day for
each quartile are listed
below:
Ql: <9
Q2: 10-12
Q3: 13-16
Q4: >16
LagO r = 0.04 r = 0.05
p< 0.001 p = 0.086
Lagl r = 0.10 r = 0.06
p< 0.001 p = 0.016
Lag 2 r = 0.08 r = 0.07
p < 0.001 p = 0.019
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           Hwang and Chan (2002)
           Taiwan

           Period of Study:
           1998
ED Visits
Outcome(s) (ICD 9):
Lower Respiratory
Disease (LRD) (466, 480-
6) including acute
bronchitis, acute
bronchiolits, pneumonia
Age groups analyzed:  0-
14,
15-64, >65, all ages
Study design:  Time series
Catchment area: Clinic
records from 50
communities
Statistical analyses:
Linear regression, GLM
Covariates: temperature,
dew point temperature,
season, day of wk, holiday
Statistical package: NR
Lag:  0,1,2 days and avgs
24-h avg:  5.4 ppb,
SD = 3.0
Range:  1.5, 16.9
N02
PM25
03
CO

No correlations
for individual
pollutants.
Colinearity of
pollutants prevented
use of multipollutant
models
Increment:  10% change in SO2 (natural
avg) which is equivalent to 2.4 ppb.
NOTE: The percent change is for the
rate of clinic use NOT for relative risk for
adverse effect.

Increased clinic visits for lower
respiratory disease (LRD) by age group

0-14yrs
Lag 0 0.5% [0.3, 0.6]
15-64yrs
Lag 0 0.7% [0.5, 0.8]
>65 yrs
Lag 00.8% [0.6, 1.1]
All ages
Lag 0 0.5% [0.4, 0.7]

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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

            EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels &
Monitoring Stations
Copollutants Method, Findings,
& Correlations Interpretation
Effects: Relative Risk or % Change &
Confidence Intervals (95%)
ASIA (cont'd)
Lee et al. (2006)
Hong Kong, China

Period of Study:
1997-2002
Days: 2,191












Hospital admissions
outcomes (ICD 9):
Asthma (493)
Age groups analyzed:
Study design: Time
series
N: 26,663
Statistical analyses:
Semi-parametric
Poisson regression
with GAM (similar to
APHEA 2)
Covariates: Long-
term trend,
temperature, relative
humidity, influenza,
day of wk, holiday
Statistical package:
SAS 8.02
Lag: 0-5 days
SO2 24-h mean:
17.7 ug/m3,
SD= 10.7
IQR: 11.1 ug/m3
25th: 10.6
50th: 15.2
75th: 21.7

# of stations:
9-10










PM2 5; r = 0.37 Absence of an association of
PM2 5; r = 0.47 SO2 with asthma admissions
NOy r = 0 49 was attributed to low ambient
O • r = -0 17 ^®2 levels during the study
period due to restrictions on
sulfur content in fuel.













Increment: 1 1 . 1 ug/m3 (IQR)

Asthma
Single-pollutant model
Lag 0-1. 57% [-2. 87, -0.26]
Lagl -1.77% [-3.06, -0.46]
Lag 2 -1.1 5% [-2.42, 0.14]
Lag 3 0.82% [-0.45, 2.11]
Lag 4 1.40% [0.1 3, 2.69]
Lag5 1.46% [0.1 9, 2.74]

Multipollutant model-including PM,
NO2s and O3
0.81% [-0.75, 2.4] lag 5
Other lags NR





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                    TABLE AX5.2 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                    EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
             Reference, Study
            Location, & Period
                            Outcomes, Design,
                               & Methods
   Mean Levels &
 Monitoring Stations
  Copollutants
 & Correlations
  Method, Findings,
   Interpretation
Effects: Relative Risk or % Change
   & Confidence Intervals (95%)
to
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ASIA (cont'd)
>
X
           Lee* et al. (2002)
           Seoul, Korea

           Period of Study:
           12/1/97-12/31/99

           Days: 822
                      Hospital Admissions
                      Outcomes (ICD 10): Asthma
                      (J45-J46)
                      Age groups analyzed: <15
                      Study design:  Time series
                      N:  6,436
                      Statistical analyses: Poisson
                      regression, log link with GAM
                      Covariates:  Time, day of wk,
                      temperature, humidity
                      Season:  Spring (Mar-May),
                      Summer (Jun-Aug),
                      Fall (Sep-Nov),
                      Winter (Dec-Feb)
                      Statistical package: NR
                      Lag: 0-2 days cumulative
24-h SO2 (ppb)
Mean: 7.7
SD = 3.3
5th: 3.7
25th: 5.1
50th: 7.0
75th: 9.5
95th: 14.3

# of stations: 27
NO2; r = 0.723
O3;r= -0.301
CO; r= 0.812
PM2.5; r = 0.585
This study reinforces
the possible role of
SO2 on asthma attacks,
although it should be
interpreted with
caution because the
effect estimates are
close to the null and
because results in the
multipollutant models
are inconsistent.
Increment: 14.6 ppb (IQR)

Asthma
SO2RR1.11  [1.06, 1.17] lag 0-2
S02 + PM25RR1.08
[1.02, 1.14] lag 0-2
S02 + N02RR 0.95 [0.88, 1.03]
lag 0-2
SO2 + O3RR 1.12 [1.06, 1.17]
lag 0-2
SO2 + CO RR 0.99 [0.92, 1.07]
lag 0-2
S02 + 03 + CO + PM25 + N02 RR
0.949 [0.868, 1.033]
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           Tanakaetal. (1998)
           Kushiro, Japan

           Period of Study:
           1992-1993
                      ED Visits
                      Outcome(s):  Asthma
                      ICD9Code(s): NR
                      Age groups analyzed:
                      15-79
                      Study design: Time series
                      N: 102
                      # of Hospitals: 1
                      Statistical analyses:  Poisson
                      regression
                      Covariates: temperature, vapor
                      pressure, barometric pressure,
                      relative humidity, wind velocity,
                      wind direction at maximal
                      velocity
                      Statistical package: NR
SO2 24-h avg
3.2 (2.4) ppb in fog

3.7 (1.9) ppb in fog
free days

Max SO2 24-h avg
<11 ppb
N02; r = NR
SPM (TSP);
r = O3; r = NR
The results reveal that
ED visits by atopic
subjects increased on
low SO2 days. This
observation is
inconsistent with most
air pollution
epidemiology, as high
levels of air pollutants
have conventionally
been linked with
asthma exacerbation.
Increment: 5 ppb

Nonatopic
OR 1.18 [0.96, 1.46]

Atopic
OR 0.78 [0.66, 0.93]

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                    TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                   EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
             Reference, Study
            Location, & Period
                          Outcomes, Design,
                             & Methods
    Mean Levels &
  Monitoring Stations
 Copollutants &
  Correlations
  Method, Findings,
   Interpretation
Effects:  Relative Risk or % Change
   & Confidence Intervals (95%)
to
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ASIA (cont'd)
X
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o
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O
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H
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           Tsai et al. (2006)
           Kaohsiung, Taiwan

           Period of Study:
           1996-2003

           Days:  2922
                      Hospital admissions
                      outcomes (ICD 9): Asthma
                      (493)
                      Study design:
                      Case-crossover
                      N: 17,682
                      Statistical analyses:
                      Conditional logistic
                      regression
                      Covariates: Temperature,
                      humidity
                      Season:
                      Warm(>25°C);
                      Cool (< 25 °C)
                      Statistical package: SAS
                      Lag: 0-2 days Cumulative
SO2 24-h mean:
9.49 ppb
Range: 0.92,31.33
25th: 6.37
50th: 8.94
75th: 12.16

# of stations:  6
PM2.5
N02
03
CO
Positive associations
were observed between
air pollutants and
hospital admissions for
stroke.  In single-
pollutant models SO2
was not associated
with either PIH or IS.
The season did not
affect these
associations. SO2 was
also not significant in
2-pollutant models.
Increment: 5.79ppb(IQR)

Seasonality
Single-pollutant model
>25°C 1.018 [0.956, 1.083]
lag 0-2
<25°C 1.187 [1.073, 1.314]
lag 0-2
Dual pollutant model
Adjusted for PM2.5
>25°C 0.993 [0.932, 1.058]
lag 0-2
<25°C 1.027 [0.921, 1.146]
lag 0-2
Adjusted for CO
>25 °C] 0.910 [0.847, 0.978]
lag 0-2
<25°C 1.036 [1.027, 1.046]
lag 0-2
Adjusted for NO2
>25°C 0.967 [0.903, 1.035]
lag 0-2
<25 °C 0.735 [0.646, 0.835]
lag 0-2
Adjusted for O3
>25°C 1.055 [0.990, 1.123]
lag 0-2
<25°C 1.195 [1.080, 1.323]
lag 0-2

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             TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

            EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
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Reference, Study
Location, & Period
Outcomes, Design, & Mean Levels & Copollutants &
Methods Monitoring Stations Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
ASIA (cont'd)
Wong etal. (1999)
Hong Kong, China

Period of Study:
1994-1995















Hospital admissions Median 24-h SO2: 17.05 O3
outcomes (ICD 9): All ug/m3 SO2
respiratory admissions Range: 2.74,68.49 PM25
(460-6,471-8,480-7, 25th: 12.45
490-6); Asthma (493), 75m: 25.01
COPD (490-496),
Pneumonia (480-7) #of stations:
Age groups analyzed: 0- 7 r =
4, 5-64, >65, all ages
# of hospitals: 12
Study design:
Time series
Statistical analyses:
Poisson regression
(followed APHEA

protocol)
Covariates: Trend,
season, day of wk,
holiday, temperature,
humidity
Statistical package: SAS
8.02
Lag: days 0-3 cumulative
Adverse respiratory
effects of SO2 were noted
at low concentrations.
Results for respiratory
outcomes were attributed
to the elderly population.
This was also true for the
other pollutants.
Therefore, it is difficult to
be certain that the effects
were due mainly to SO2.

Pair- wise comparisons in
multipollutant models
showed significant
interactions of PM25,

NO2, and O3.






Increment =10 ug/m

Overall increase in admissions:
1. 013 [1.004, 1.021] lag 0

Respiratory relative risks (RR)
0-4 yrs: 1.005 [0.991, 1.018] lag 0
5-64 yrs: 1.008 [0.996, 1.021] lag 0
>65yrs: 1.023 [1.012, 1.036] lag 0

Asthma: 1.017 [0.998, 1.036] lag 0
COPD: 1.023 [1.011, 1.035] lag 0
Pneumonia: 0.990
[0.977, 1.004] lag 4










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               TABLE AX5.2 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH

               EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR RESPIRATORY DISEASES
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Reference, Study
Location, & Period
ASIA (cont'd)
Wongetal. (200 la)
Hong Kong, China

Period of Study:
1993-1994

















Outcomes, Design,
& Methods

Hospital admissions
outcomes (ICD 9):
Asthma (493)
Age groups analyzed:
<15
N: 1,217
# of hospitals: 1
Study design:
Time series
Statistical analyses:
Poisson regression
(followed APHEA
protocol)
Covariates: Season,
temperature, humidity
Season:
Summer (Jun-Aug),
Autumn (Sep-Nov),
Winter (Dec-Feb), Spring
(Mar-May)
Lag: 0,1,2,3,4,5 days; and
cumulative 0-2 and 0-3
days.
Mean Levels &
Monitoring Stations

24-h avg SO2
mean: 12.2 ug/m3
SD= 12.9
Range: 0, 98 ug/m3

Autumn: 10.6(9.6)
Winter: 10.0(7.5)
Spring: 9.6(8.8)
Summer: 18.5(19.5)

# of stations: 9












Copollutants Method, Findings, Effects: Relative Risk or % Change &
& Correlations Interpretation Confidence Intervals (95%)

PM25 SO2 levels were found Increment: 10 ug/m
NO2 to be the highest during
the summer. There Asthma
were consistent and AU yr RR i 06 p = 0 004
statistically significant Autumn: -^
associations between ,,,. , XTr)
. . . . . Winter: NR
asthma admission and .
increased daily levels Sprmg: NK
ofS02. No Summer: NR
associations were
noted in the spring or
winter. No significant
associations were
found between hospital
admissions and day of
the wk, humidity,
temperature or
atmospheric pressure.

Total admissions were
limited to one hospital.



        *Default GAM


        +Did not report correction for over-dispersion


        NR: Not Reported


        APHEA: Air Pollution and Health: a European Approach

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                           TABLE AX5.3.  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                               CARDIOVASCULAR MORBIDITY IN FIELD/PANEL STUDIES
              Reference, Study
            Location, and Period
                               Outcomes and Methods
Mean SO, Levels
 Copollutants
 Considered
 Findings, Interpretation
           Effects
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           Liao et al. (2004)
           Three locations in
           United States:
           Minneapolis, MN;
           Jackson, MS; Forsyth
           County, NC
           1996-1998
           Liao et al. (2005)
           United States,
           1996-1998
                       Cross-sectional study of 6,784 cohort
                       members of the Atherosclerosis Risk in
                       Communities Study.  Participants were 45-
                       64 yrs of age; baseline clinical
                       examinations conducted from 1987-1989.
                       HRV data collected from 1996-1998. Air
                       pollutants obtained form EPA AIRS for
                       this same period.  Resting, supine, 5-min
                       beat-to-beat RR interval data were
                       collected over a 4-h period.  Multivariable
                       linear regression models used to assess
                       associations between pollutants measured
                       1-3 days prior to HRV measurements.
                       Models controlled for age, ethnicity-center,
                       sex, education, current smoking, BMI,
                       heart rate, use of cardiovascular
                       medication, hypertension, prevalent
                       coronary heart disease, and diabetes.

                       Cross-sectional survey 10,208 participants
                       (avg age 54 yrs) from Atherosclerosis Risk
                       in Communities (ARIC) study cohort to
                       assess the association between criteria air
                       pollutants and hemostatic and
                       inflammatory markers.  57% of
                       participants were female and 66% male.
                       Used hemostatis/inflammation variables
                       collected during the baseline examination
                       and air pollution data 1-3 days prior to the
                       event. Used multiple linear regression
                       models that controlled for age, sex,
                       ethnicity-center, education, smoking,
                       drinking status, BMI, history of chronic
                       respiratory disease, humidity, seasons,
                       cloud cover, and temperature.  Also history
                       of CVD and diabetes if not effect modifier
                       in a particular model.
Mean (SD) SO2
measured 1 day
prior to HRV
measurement was
4(4)ppb
PM10
03
CO
N02
SO2 mean (SD)
0.0005 (0.004)
ppm

Ql-3: 0.005
(0.003) ppm

Q4: 0.006
(0.005) ppm
PM10
CO
NO2
03
Significant interaction
between SO2 and
prevalence of coronary
heart disease for low-
frequency power analyses

SO2 inversely associated
with SD of normal R-R
intervals and low-frequency
power and positively
associated with heart rate.
SO2 association with low-
frequency power stronger
among those with history of
coronary heart disease.
Effect size of PM10 larger
than for gaseous pollutants.
Significant curvilinear
association between SO2
with factor VHI-C, WBC,
and serum albumin.
Curvilinear association
indicated threshold effect
Log-transformed low-frequency
power effect estimate and SE per
1 SD increment (4 ppb) SO2 lag
1 day:

Log transformed high-frequency
power  -0.024
(SE 0.016)
Standard deviation of normal R-
R intervals-0.532
(SE 0.270), p< 0.05

Heart rate: 0.295 (SE 0.130),
p<0.05
Prevalent CHD: -0.122
(SE 0.056), p< 0.01
No prevalent CHD -0.012
(SE 0.016)

Results shown in graph.

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                    TABLE AX5.3 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                             CARDIOVASCULAR MORBIDITY IN FIELD/PANEL STUDIES
               Reference, Study
             Location, and Period
                           Outcomes and Methods
 Mean SO, Levels
  Copollutants
   Considered
     Findings, Interpretation
          Effects
to
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UNITED STATES (cont'd)
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           Dockery etal. (2005)
           Boston, MA
           Jull995-Jul2002
                         Cohort study of 203 cardiac
                         patients with implanted
                         cardioverter defibrillators.
                         Patients were followed for
                         an avg of 3.1 yrs from
                         1995-2002 to assess the role
                         of air pollution on the
                         incidence of ventricular
                         arrhythmias. The
                         association of arrhythmic
                         episode-days and air
                         pollutions analyzed with
                         logistic regression using
                         GEE with random effects.
                         Model adjusted for patient,
                         season, minimum
                         temperature, mean
                         humidity, day of the wk,
                         and previous arrhythmia
                         within 3 days.  Only effects
                         of 2-day running mean of
                         air pollution concentration
                         reported.
48-h avg SO2;

Median: 4.9 ppb
25th%: 3.3 ppb
75%:  7.4 ppb
95%:  12.8 ppb
PM2.5
BC
S04
PN
N02
CO
03
No statistically significant
association between any of the air
pollutant and ventricular
arrhythmias when all events were
considered.  However, ventricular
arrhythmias within 3 days of a prior
event were statistically significant
with SO2, PM2.5, BC, NO2, CO, and
marginally with SO4, but not with
O3orPN. CO,NO2,BC,andPM2.5
correlated, thus it was impossible to
differentiate the independent effects.
Since the increased risk of
ventricular tachyarrhythmia was
associated with air pollution
observed among patients with a
recent tachyarrhythmia, it was
suggested that air pollution acts in
combination with cardiac electrical
instability to increase risk of
arrhythmia.
For IQR (4.0 ppb) increase in
48-h mean SO2:
All events: OR = 1.04 (0.94,
1.14),p = 0.28

Prior arrhythmia event
<3days:  1.30
(95% CI: 1.06,1.61),
p = 0.013

Prior arrhythmia event
>3days:  0.98(0.87,1.11)
p = 0.78
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                    TABLE AX5.3 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                             CARDIOVASCULAR MORBIDITY IN FIELD/PANEL STUDIES
             Reference, Study
           Location, and Period
                         Outcomes and Methods
  Mean SO, Levels
 Copollutants
  Considered
 Findings, Interpretation
              Effects
to
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UNITED STATES (cont'd)
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           Gold et al. (2000)
           Boston, MA
           Jun-Sep 1997
                      Panel study on 21 active
                      Boston residents aged 53-87
                      yrs to investigate the
                      association between short-term
                      changes in ambient air
                      pollution and short-term
                      changes in cardiovascular
                      function. Participants observed
                      up to 12 times from  June to Sep
                      1997 (163 observations made
                      in total). Protocol involved
                      25 mins per wk of continuous
                      ECG monitoring, that included
                      5 mins of rest, 5 mins of
                      standing, 5 mins of exercise
                      outdoors, 5 mins of recovery,
                      and 20 cycles of slow
                      breathing. Fixed effects
                      models adjusted for  time-
                      varying covariates and
                      individuals traits.
24-h avg mean
3.2ppb
Range: 0, 12.6 ppb
IQR:  3.0 ppb
PM2.5
coarse matter
03
NO2
CO
In single-pollutant models,
24-h mean SO2 associated
with reduced heart rate in
the first rest period but not
overall. Associations
weaker for shorter
averaging periods.
Association between SO2
and heart rate not
significant with the
multipollutant model (SO2
andPM25).  SO2 not
associated with r-MSSD.
Heart rate, first rest period, mean
66.3 bpm
single-pollutant model
estimated effect (SE) -1.0 (0.5)
%meanl.5,p = 0.03

Heart rate, first rest period, mean
66.3 bpm
Multipollutant model (PM2 5 and SO2):
SO2 estimated effect (SE) -0.8 (0.5)
% mean 1.2, p = 0.09
PM2 5 estimated effect (SE) -1.6 (0.7)
% mean 2.5, p = 0.03

Overall heart rate, mean 74.9 bpm
single-pollutant model
estimated effect (SE) -0.5 (0.5),
p = 0.30

Overall heart rate, mean 74.9 bpm
Multipollutant model
SO2 estimated effect (SE) -0.2 (0.5),
p = 0.6
PM2 5 estimated effect (SE) -1.9 (0.7)
p = 01% mean 2.6

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                    TABLE AX5.3 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                           CARDIOVASCULAR MORBIDITY IN FIELD/PANEL STUDIES
             Reference, Study
            Location, and Period
                                Outcomes and Methods
  Mean SO2
    Levels
  Copollutants
   Considered
  Findings,
Interpretation
                             Effects
to
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UNITED STATES (cont'd)
>
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          Park et al. (2005b)
          Greater Boston area, MA
          Nov2000-0ct2003
                       Cross-sectional study of effect of ambient air
                       pollutants on heart rate variability (HRV) in
                       497 men who were in the Normative Aging
                       Study and who were examined from Nov 2000
                       and Oct 2003. HRV measured between 0600
                       and 1300 h after resting for 5 mins.
                       4-h, 24-h, and 48-h moving avgs of air
                       pollution matched to time of ECG
                       measurement. Linear regression models
                       included: age, BMI, fasting blood glucose,
                       cigarette smoking, use of cardiac medications,
                       room temp, season, and the lagged moving
                       avg of apparent temp corresponding to the
                       moving avg period for the air pollutant. Mean
                       arterial blood pressure (MAP) and apparent
                       temperature also included. Assessed
                       modifying effects of hypertension, IHD,
                       diabetes or use of cardiac/antihypertensive
                       meds.
24-h avg SO2
4.9 ppb
SD = 3.4
Range:  0.95,
24.7 ppb
PM2.5
particle number
concentration
BC
N02
03
CO
                4-h moving avg SO2
                (per 1 SD, 3.4 ppb SO2)
No significant
association
between HRV and
SO2 for any of the  Log 10 SDNN:
averaging periods,  2.3 (-1.7, 6.4)
but positive
relationship.       LoglOHF:
                 5.6 (-4.9, 17.3)

                 LoglOLF:
                 2.2 (-5.9, 11.1)

                 LoglO (LF:HF)
                 -3.2 (-10.1, 4.2)
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                    TABLE AX5.3 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                           CARDIOVASCULAR MORBIDITY IN FIELD/PANEL STUDIES
oo
Reference, Study
Location, and Period
Mean SO2 Copollutants
Outcomes and Methods Levels Considered
Findings,
Interpretation
Effects
UNITED STATES (cont'd)
Peters et al. (2000a)
Eastern Massachusetts,
U.S.
1995-1997













Pilot study to test hypothesis that patients with 24-h avg SO2: PM10
implanted cardio verier defibrillators would 7 ppb PM2 5
experience potentially life-threatening gQ
arrhythmias associated with air pollution Median: 5 ppb QQ
episodes. Records detected arrhythmias and Max: 87 ppb Q
therapeutic interventions downloaded from the „„
implanted defibrillator. Mean age of patients 2
62.2 yrs. 100 patients followed for over 3 yrs
for 63,628 person-days. 33 patients with any
discharges and 6 patients with 10 or more
events. Data analyzed by logistic regression
models using fixed effects models with
individual intercepts for each patient. Model
controlled for trend, season, meteorologic
conditions, and day of week. Evaluated air
pollutants on same day, lags 1, 2, and 3 days,
and 5-day mean.
No association
between increased
defibrillator
discharges and
SO2.












33 patients with at least 1
defibrillator discharge
Lag 00. 76 (0.48, 1.21)
Lag 10.91 (0.60, 1.37)
Lag 2 0.89 (0.59, 1.34)
Lag 3 1.09(0.78,1.52)
5-day mean 0.85 (0.50, 1.43)

6 patients with at least
10 discharges
Lag 00.72 (0.40, 1.31)
Lag 10. 77 (0.44, 1.37)
Lag 2 1.01 (0.63, 1.61)
Lag 3 1.08 (0.72, 1.62)
5-day mean 0.75 (0.38, 1.47)


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          Peters etal. (2001)
          Greater Boston area, MA
          Janl995-May 1996
Case cross over Study design used to          24-h avg SO2:
investigate association between air pollution    7 ppb
and risk of acute myocardial infarctions in 772   SD = 7 ppb
patients (mean age 61.6 yrs) with MI as part of
the Determinants of Myocardial Infarction      1-h avg SO2:
Onset Study. For each subject, one case        7 ppb
period was matched to 3 control periods, 24 h   SD = 10 ppb
apart. Used conditional logistic regression
models that controlled for season, day of wk,
temperature, and relative humidity.
PM2.5
PM10
Coarse mass
BC
O3
CO
NO2
SO2 not
statistically
associated with
risk of onset of
MI. Limitation of
study is only 1 air
pollution
monitoring site
available.
OR for 2-h avg SO2 and 24-h avg
SO2 estimated jointly:

2 h per 2-ppb increase SO2
Unadjusted:  1.00(0.87,1.14)
Adjusted: 0.96(0.83,1.12)

24 h per 2-ppb increase
Unadjusted:  0.92(0.71,1.20)
Adjusted: 0.91(0.67,1.23)

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                     TABLE AX5.3 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                             CARDIOVASCULAR MORBIDITY IN FIELD/PANEL STUDIES
             Reference, Study
            Location, and Period
                              Outcomes and Methods
Mean SO2 Levels
Copollutants
 Considered
  Findings,
Interpretation
Effects
to
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UNITED STATES (cont'd)
>
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Rich et al. (2005)        Case cross-over design used to evaluate
Boston, MA             association between ventricular
Jul 1995-Jul 2002        arrhythmias detected by implantable
                       cardioverter defibrillators and air
                       pollution. Same study population as
                       Dockery et al. (2005): 203 patients with
                       ICD and residential zip codes within
                       40 km of central particle monitoring site.
                       Analyses conducted on 84 subjects with
                       confirmed ventricular arrhythmias during
                       the follow-up.  Case periods defined by
                       time of each confirmed arrhythmic event.
                       Control periods (3-4 per case) selected by
                       matching on weekday and hour of the
                       day within the same calendar mo. Used
                       conditional logistic regression that
                       controlled for temperature, dew point,
                       barometric pressure, and a frailty term for
                       each subject. ORs presented for IQR
                       increase in mean concentration and
                       averaging time.  Moving avg of
                       concentrations considered: lags 0-2, 0-6,
                       0-23, and 0-47 h.
                                                                        l-havgSO2:
                                                                        Median: 4.3 ppb
                                                                        25th %: 2.6
                                                                        75th %: 7.5
                                                                        Max: 71.6

                                                                        24-h avg SO2:
                                                                        Median: 4.8
                                                                        25th %: 3.2
                                                                        75th %: 7.3
                                                                        Max: 31.4
                  PM2.5
                  BC
                  N02
                  CO
                  03
               An IQR increase in the
               24-h moving avg SO2
               (4.1 ppb) marginally
               associated with a 9%
               increased risk of
               ventricular arrhythmia
               and an increased risk
               with 48-h moving avg.
               There was no
               risk associated with
               24-h moving avg after
               controlling for PM2 5
               cases that had a prior
               ventricular arrhythmia
               within 72 h had greater
               risk associated with
               SO2 compared to those
               without a recent event,
               suggesting that risk is
               greater among cases
               with more irritable or
               unstable myocardium.
                   Odds ratios- single-pollutant model
                   0-2-h lag (per 4.7 ppb) 1.07
                   (0.97,1.18)
                   0-6-h lag (per 4.5 ppb) 1.09
                   (0.98, 1.20)
                   0-23-hlag (per 4.1 ppb) 1.09 (0.97,
                   1.22)
                   0-47-hlag(per4.0ppb) 1.17(1.02,
                   1.34)

                   Odds ratios- 2-pollutant model
                   SO2 and PM2 5
                   Per 4.1 ppb SO2: 1.00(0.84,1.20)
                   SO2 and O3
                   Per 4.1 ppb SO2: 1.12(0.99,1.27)

                   Per 4.1-ppb increase SO2
                   Prior arrhythmia event <3 days:
                   1.20(1.01,1.44)
                   Prior arrhythmia event >3 days:
                   0.96(0.83,1.10)
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                    TABLE AX5.3 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                           CARDIOVASCULAR MORBIDITY IN FIELD/PANEL STUDIES
Reference, Study
Location, and Period
Outcomes and Methods
Mean SO2 Levels
Copollutants
Considered
Findings,
Interpretation
Effects
UNITED STATES (cont'd)
Rich et al. (2006)
St. Louis, Missouri,
May 2001 -Dec 2002











Case-crossover design study of
56 patients with implantable cardioverter
defibrillators. Subjects ranged from 20 to
88 years (mean 63). Case period defined
by time of confirmed ventricular
arrhythmia. Control periods matched on
weekday and hour of the day within the
same calendar mo. Used conditional
logistic regression model that included
mean of the previous 24-h temperature,
relative humidity, barometric pressure,
mean pollutant concentration in the 24 h
before the arrhythmia. Model also
included a frailty term for each subject.
599 days

25th percentile:
2ppb
50th percentile:
4 ppb
75th percentile:
7 ppb
Daily IQR: 5 ppb
Case/control IQR:
5 nnb
cc


PM2.5
EC
OC
NO2
CO
o,
v/3







Statistically significant
increase in risk of
ventricular arrhythmias
associated with each 5-
ppm increase in 24-h
moving avg SO2.








OR for ventricular arrhythmia
associated with IQR increase

6-h moving avg SO2 per 4 ppb: 1 .04
(95% CI: 0.96,1.12)

12-h moving avg SO2 per 5 ppb: 1.17
(95% CI: 1.04,1.30)

24-h moving avg SO2 per 5 ppb:
1.24
(95% CI: 1.07,1.44)

48-h moving avg SO2 per 4 ppb:
          Schwartz et al. (2005)
          Boston, MA
          12 wks during the
          summer of 1999
Panel study of 28 subjects (aged
61-89 yrs) to examine association
between summertime air pollution and
HRV.  Subjects examined once a wk up
to 12 wks and HRV measured for
approximately 30 mins. Analyses used
hierarchical models that controlled for
baseline medical condition, smoking
history, day of wk and hour of day,
indicator variable for whether subjects
had taken their medication before they
came, temperature and time trend.
24-h avg SO2:

25th %:
0.017 ppm
50th %:
0.020 ppm
75th %: 0.54 ppm
03
NO2
CO
PM2.5
black carbon
No significant
association with SO2
1.15 (95% CI: 1.00,1.34)

Percentage change in HRV associated
with IQR (0.523 ppm) increase in SO2
SDNN(ms)0.4(-1.3to2.1)
RMSSD (ms) 1.4 (-2.6 to 5.5)
PNN50 (ms) 3.8 (-12.1 to 22.5) for
1-h avg SO2
SDNN (ms) 0.4 (-4.2 to 5.1) for 24-h
avg SO2
RMSSD (ms) -0.3 (-1.3 to 0.8)
PNN50 (%) -0.2 (20.9 to 17.6)
LFHFR2.9(-4.9toll.4)

-------
                     TABLE AX5.3 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                              CARDIOVASCULAR MORBIDITY IN FIELD/PANEL STUDIES
              Reference, Study
            Location, and Period
                            Outcomes and Methods
  Mean SO2 Levels
 Copollutants
 Considered
        Findings, Interpretation
      Effects
to
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CANADA
>
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           Rich et al. (2004)
           Vancouver, British
           Columbia, Canada
           Feb-Dec 2000
Vedal et al. (2004)
Vancouver, British
Columbia, Canada
1997-2000
Case-crossover analysis used to
investigate association between air
pollution and cardiac arrhythmia in
34 patients (aged 15-85 yrs, mean
62) with implantable cardioverter
defibrillators.  Study included only
patients who experienced at least 1
ICD discharge during the study
period. Control days were 7 days
before and 7 days after day of ICD
discharge.  Conditional logistic
regression analyses were stratified
by individual.

Retrospective, longitudinal panel
study  of 50 patients, aged 12-77 yrs
with implantable cardioverter
defibrillators.  Total of
40,328 person-days over 4-yr
period. GEE used to assess
associations between short term
increases in air pollutants and
implantable cardioverter
defibrillator discharges. Models
controlled for  temporal trends,
meteorology, and serial
autocorrelation.
                                                         24-havg: 2.6 ppb
                                                         SD= 1.3 ppb
                                                         IQR:  1.6 ppb
24-h mean (SD) SO2:
2.4 (1.2) ppb

Range: 0.3, 8.1 ppb
Median: 2.2 ppb
25th percentile: 1.5
75th percentile: 3.1
                     PM2.5
                     EC
                     OC

                     PM10
                     CO
                     N02
                     03
PM10
03
N02
CO
                No statistically significant association
                between SO2 and implantable cardioverter
                defibrillator discharges. However, when
                an analysis was stratified by season, OR
                for SO2 were higher in the summer
                compared to winter.
Concluded that in general no consistent
effect of air pollution on cardiac
arrhythmias in this population.

There were no statistically significant
associations between SO2 and cardiac
arrhythmias at any lag day, but positive
associations at lag 2. When analysis was
restricted to only patients who had at least
2 arrhythmias per yr over their period of
observation
(n = 16), a positive and significant
association was seen with SO2 at 2 days
lag. When analysis was restricted to
patients averaging 3 or more arrhythmias
per yr (n = 13), there was no significant
association, but a positive association was
seen at 2 day slag.
                                        No quantitative
                                        results provided.
                                        Results shown in
                                        graph.
No quantitative
results, but %
change in
arrhythmia event-
day rate for each
SD increase in
pollution
concentration on
log scale provided
in figures.

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                    TABLE AX5.3 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                            CARDIOVASCULAR MORBIDITY IN FIELD/PANEL STUDIES
             Reference, Study
           Location, and Period
                          Outcomes and Methods
Mean SO2 Levels
Copollutants
 Considered
Findings, Interpretation
Effects
to
o
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CANADA (cont'd)
           Vedal et al. (2004)
           (cont'd)
                                                                                         When stratified by season, SO2 effects
                                                                                         were in the in the positive direction in
                                                                                         the winter, but in the negative
                                                                                         direction in the summer. Authors
                                                                                         noted results may be due to chance
                                                                                         because of multiple comparisons or
                                                                                         SO2 may be surrogate for some other
                                                                                         factor.
>
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                                                                                         Summer analysis: significant
                                                                                         negative association with SO2 at lag
                                                                                         days 2 and 3 (data not shown). When
                                                                                         stratified to patients with 2 or more
                                                                                         arrhythmia event-days per yr,
                                                                                         significant negative associations
                                                                                         observed with SO2 at lag of 3 days.
to
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                                                                                         Winter analysis:  significant positive
                                                                                         effect of SO2 at 3 days lag (data not
                                                                                         shown). If restricted to patients with
                                                                                         at least 2 arrhythmias per yr, a
                                                                                         significant positive association was
                                                                                         seen at lags 2 and 3 days. When
                                                                                         restricted to patients with 3 or more
                                                                                         arrhythmia event days per yr, positive
                                                                                         associations observed for SO2 at lags
                                                                                         of 2 and 3 days.

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                     TABLE AX5.3 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                             CARDIOVASCULAR MORBIDITY IN FIELD/PANEL STUDIES
to
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Reference, Study
Location, and Period Outcomes and Methods
Copollutants
Mean SO2 Levels Considered
Findings, Interpretation
Effects
EUROPE
           Ibald-Mullietal. (2001)
           Augsburg, Germany
           1984-85, 1987-88
Retrospective analysis of 2607
subjects (25-64 yrs, subset of the
participants of first and second
MONICA survey who had valid
electrocardiograms recordings in
both surveys and blood pressure
measurements).  Used regression
models for repeated measures
that controlled for age, current
smoking, and cardiovascular
medication, BMI, total and high
density lipoprotein cholesterol,
temp, RH, and barometric
pressure.
24-h avg SO2 (|ig/mj)    TSP, CO

1984-1985:
Mean: 60.2
SD = 47.4
Range: 13.0,238.2

follow up 1987-1988
Mean: 23.8
SD=12.3
Range: 5.6,71.1
SO2 and TSP associated
with increases in systolic
blood pressure.  In the
multipollutant model with
TSP, the effect of IPS
remained significant, but
the SO2 effect was
substantially reduced. No
clear association between
SO2 and CO and diastolic
blood pressure was
observed.
Same day concentrations:
mean change in systolic blood pressure
per 5th to 95th percentile increase in
SO2 (per 80 |ig/m3)

Same day concentrations
(per 80 ng/m ):
Men(n=1339):  0.96(0.07,1.85)
Women (n= 1268): 0.96
(-0.46, 1.49)
Men and women: 0.74 (0.08, 1.40)

5-day avgs:
Mean change in systolic blood
pressure per 5th to 95th percentile
increase in SO2 (per 75 |ig/m3)
Men: 0.97(0.09,1.85)
Women:   1.23(0.23,2.22)
Men and women: 1.07
(0.41,1.73)
2-pollutant model
Men and women: 0.23
(-0.50,0.96)

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                    TABLE AX5.3 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                           CARDIOVASCULAR MORBIDITY IN FIELD/PANEL STUDIES
             Reference, Study
            Location, and Period
                           Outcomes and Methods
   Mean SO2 Levels
 Copollutants
  Considered
    Findings,
  Interpretation
Effects
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EUROPE (cont'd)
          Peters etal. (1999)
          Augsburg, Germany
          winter 1984-1985
          winter 1987-1988
                       Retrospective analysis on
                       subsample of 2,681 subjects (25-64
                       yrs) of the MONICA cohort who
                       had valid electrocardiogram
                       readings from both surveys and no
                       acute infections.  GEE for clusters
                       used to assess association between
                       heart rate and air pollution.
                       Analyses adjusted for temperature,
                       relative humidity, and air pressure.
24-h avg SO2 (ng/m3)

Winter 1984-1985
Outside episode:
Mean: 48.1
SD = 23.1
Range: 13,103

Winter 1984-1985
During episode:
Mean: 200.3
SD = 26.6
Range: 160,238

Winter: 1987-1988
Mean: 23.6
SD= 12.2
Range: 6, 71
CO
TSP
Increases in SO2    Mean change in heart rate per 5th to 95th
concentrations      percentile SO2
associated with     Same day concentrations
increases in heart   (per 80 |ig/m3 SO2)
rate              Men:  1.02(0.41,1.63)
                 Women:  1.07(0.41,1.73)
                 Men and women: 1.04 (0.60, 1.49)

                 5-day avg (per 75 |ig/m3 SO2)
                 Men:  1.29(0.68,1.90)
                 Women:  1.26(0.57,1.95)
                 Men and women: 1.28 (0.82, 1.74)
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                    TABLE AX5.3 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                            CARDIOVASCULAR MORBIDITY IN FIELD/PANEL STUDIES
              Reference, Study
            Location, and Period
                              Outcomes and Methods
 Mean SO2 Levels
  Copollutants
   Considered
     Findings,
   Interpretation
           Effects
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EUROPE (cont'd)
>
X
          Ruidavets et al. (2005)
          Toulouse, France
          1995-1997
                       Cross-sectional survey of 863 randomly
                       chosen adults (35-65 yrs) living in
                       Toulouse (MONICA center) to examine
                       the relationship between resting heart rate
                       and air pollution. Resting heart rate was
                       measured twice in a sitting position after
                       a five minute rest. Used polytomous
                       logistic regression models with quintiles
                       ofRHR.  Final model controlled for sex,
                       physical  activity, systolic blood pressure,
                       cardiovascular drug use, CRP, relative
                       humidity, and season mos.
MeanSO2: 13.3
(7.5) ug/m3
Range:  1.3,
47.7 ug/m3
NO2
03
Marginally significant
association between
SO2 and RHR in Q5
compared with Ql.
No association with
SO2at 1,2, or 3 days
OR based on daily levels of SO2

OR for resting heart rate =1.19
(95% CI:  1.02, 1.39) in 5th
quintile (>75 bpm) compared to
first quintile (<60 bpm) for
5 ug/m3 increase in SO2 same day
0 am-12 pm

OR for resting heart rate 1.14
(95% CI:  1.01 to 1.30) in 5th
quintile (>75 bpm) compared to
first quintile (<60 bpm) for
5 ug/m3 increase in SO2 same day
12 am-12 pm
Not-significant associations not
listed
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LATIN AMERICA
Holguinetal. (2003)
Mexico City, Mexico
Feb 8 to April 30, 2000





Panel study of 34 nursing home residents
(60-96 yrs) to assess association between
heart rate variability and air pollution.
Heart rate variability measured every
alternate day for 3 mos. Thirteen of the
subjects had hypertension. Used GEE
models that controlled for age and avg
heart rate during HRV measurement.
24-h mean SO2
(Ppb)
Mean: 24
SD= 12
Range: 6, 85



Indoor PM2 5
Outdoor PM2 5
03
NO2
CO



SO2 not related to
heart rate variability
on the same day or
lag 1 day




Change in HRV per

HRV-HF -0.003
(-0.035,0.035)
HRV-LF -0.004
(-0.004,0.003)
HRV-LF/HF 0.012
(-0.060,0.082)
lOppb








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               TABLE AX5.4. ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY
                         DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
             Reference, Study
            Location, & Period
  Outcomes, Design, & Methods
 Mean Levels & Monitoring
         Stations
  Copollutants     Effects:  Relative Risk or % Change & Confidence
  (Correlations)            Intervals ([95% Lower, Upper])
to
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          UNITED STATES
>
X
           Morris etal. (1995)
           U.S. (Chicago, Detroit,
           LA, Milwaukee, NYC,
           Philadelphia)

           Study period:
           1986-1989, 4 yrs
Outcome(s) (ICD9): CHF 428.
Daily Medicare hospital admission
records.
Study design: Time series
Statistical analyses: GLM, negative
binomial distribution
Age groups analyzed:  >65 yrs
Covariates: Temperature, indicator
variables for mo to adjust for weather
effects and seasonal trends, day of
wk, yr
Statistical software: S-PLUS
Lag(s):  0-7 days
SO2 1-h max (ppm)
Mean (SD)
LA: 0.010(0.005)
Chicago: 0.025(0.011)
Philadelphia:  0.029(0.015)
New York: 0.032(0.015)
Detroit: 0.025(0.013)
Houston: 0.018(0.009)
Milwaukee: 0.017(0.013)
NO2 1 -h max       Results reported for RR of admission for CHF
O3 1-h max         associated with an incremental increase in SO2 of
CO 1-h max        0.05 ppm.

Correlations of      CHF:
S02 with other      LA: 1.60(1.41,1.82)
pollutants strong.    Chicago: 1.05(1.00,1.10)
                  Philadelphia:  1.01(0.96,1.06)
Multipollutant      New York: 1.04(1.01,1.08)
models run.         Detroit:  1.00 (0.95, 1.06)
                  Houston: 1.07(0.97,1.17)
                  Milwaukee:  1.07(0.99,1.15)

                  RR diminished in multipollutant (4 copollutants)
                  models for all cities.
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        TABLE AX5.4 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY

                    DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
to
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Reference, Study
Location, & Period
Outcomes, Design, & Methods
Mean Levels &
Monitoring Stations
Copollutants
(Correlations)
Effects: Relative Risk or % Change &
Confidence Intervals ([95% Lower, Upper])
UNITED STATES (cont'd)
Moolgavkar (2000)*
Cook County IL, Los
Angeles County, CA,
Maricopa County, AZ

1987-1995













Outcome(s) (ICD9): CVD
390-429; Cerebrovascular disease
430-448. Hospital admissions from
CA department of health database.
Age groups analyzed: 20-64, 65+
yrs
Study design: Time series
N: 118 CVD admissions/days
# Hospitals: NR
Statistical analysis: Poisson
regression, GAM
Covariates: Adjustment for day of
wk, long-term temporal trends,
relative humidity, temperature
Statistical package: SPLUS
Lag: 0-5 days







SO2 24-h avg (ppb)

Cook County:
Min: 0.5
Ql: 4
Median: 6
Q3: 8
Max: 36

LA County:
Min: 0
Ql: 1
Median: 2
Q3: 4
Max: 16

Maricopa County:
Min: 0
Ql: 0.5
Median: 2
Q3: 4
Max: 14

PMio (0.1 1,0.42)
PM2.5 (0.42) (LA only)
CO (0.35, 0.78)
NO2 (0.02, 0.74)
03 (-0.37, 0.01)

2-pollutant models
(see results)












Results reported for percent change in hospital
admissions per 10 ppb increase in SO2. T statistic
in parentheses.

CVD, 65+:
Cook County
4.0(6.1), lag 0
3. 1 (4.5), lag 0, 2-pollutant model (CO)
1.0(1 .4), lag 0, 2-pollutant model (NO2)
LA County
14.4 (15.2), lag 0
-2.5 (- 1 .6), lag 0, 2-pollutant model (CO)
7.7 (5.7), lag 0, 2-pollutant model (NO2)
Maricopa County
7.4 (4.5), lag 0
3.0 (1 .8), lag 0, 2-pollutant model (CO)
3.9(1 .5), lag 0, 2-pollutant model (SO2)

Cerebrovascular Disease, 65+:
Cook County
3.1(3.3)
LA County
6.5 (4.9)
                                                                                             Lags 1-5 also presented. Effect size generally

                                                                                             diminished with increasing lag time. Increase in

                                                                                             hospital admissions (10.3 for CVD and 9.0 for

                                                                                             Cerebrovascular) also observed for the

                                                                                             20-64 age group.

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          TABLE AX5.4 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY
                        DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
Reference, Study
Location, & Period
Outcomes, Design, & Methods
Mean Levels &
Monitoring Stations
Copollutants
(Correlations)
Effects: Relative Risk or Percent Change &
Confidence Intervals ([95% Lower, Upper])
UNITED STATES (cont'd)
Moolgavkar (2003)
Cook County IL, Los
Angeles County, CA,
Maricopa County, AZ
Outcome(s) (ICD9): CVD
390-429; Cerebrovascular disease
430-448 was not considered in the
reanalysis. Hospital admissions from
See original analysis
(Moolgavkar, 2000)
above.
See original
analysis
(Moolgavkar,
2000) above.
Use of stringent criteria in GAM did not alter results
substantially. However, increased smoothing of
temporal trends attenuated results for all gases and effect
size diminished with increasing lag.
          1987-1995
CA department of health database.
Age groups analyzed: 20-64,
65+ yrs
Study design:  Time series
N: 118 CVD admissions/day
# Hospitals: NR
Statistical analysis:  Poisson
regression, GAM with strict
convergence criteria (10-8), GLM
using natural splines
Covariates: Adjustment for day of
wk, long-term temporal trends,
relative humidity, temperature
Statistical package:  SPLUS
Lag: 0-5 days
Results reported for incremental increase of 10 ppb SO2.
Estimated coefficient and T statistic in parentheses.

GLM with 100 df (LA County)
13.67 (11.82), lag 0
6.44 (5.23), lag 1
0.23(0.18), lag 2
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           TABLE AX5.4 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY
                          DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
              Reference, Study
             Location, & Period
                              Outcomes, Design, & Methods
    Mean Levels &
  Monitoring Stations
  Copollutants       Effects: Relative Risk or % Change &
  (Correlations)     Confidence Intervals ([95% Lower, Upper])
to
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UNITED STATES (cont'd)
>
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           Wellenius et al. (2005a)
           Birmingham, Chicago,
           Cleveland, Detroit,
           Minneapolis, New
           Haven, Pittsburgh,
           Seattle

           Study period:
           Jan 1986-Nov 1999
           (varies slightly
           depending on city)
                        Outcome(s) IS, primary diagnosis of acute but
                        ill-defined cerebrovascular disease or
                        occlusion of the cerebral arteries; HS,
                        primary diagnosis of intracerebral
                        hemorrhage.  ICD codes not provided.
                        Hospital admissions ascertained from the
                        Centers for Medicare and Medicaid Services.
                        Cases determined from discharge data were
                        admitted from the ER to the hospital.
                        NIS:  155,503
                        NHS:  19,314
                        Study design:  Time-stratified Case-crossover.
                        Control days chosen such that they fell in
                        same mo and same day of wk. Design
                        controls for seasonality, time trends, chronic
                        and other slowly varying potential
                        confounders.
                        Statistical analysis: 2-stage hierarchical
                        model (random effects), conditional logistic
                        regression for city effects in the first stage
                        Software package: SAS
                        Covariates:
                        Lag(s): 0-2, unconstrained distributed lags
SO2 24 h (ppb)
10th: 2.17
25th: 3.57
Median:  6.22
75th: 10.26
90th: 16.17

SO2 data not available
for Birmingham, AL
PM10 (0.39)

CO,N02

Correlation only
provided for PM
because study
hypothesis
involves PM
Results reported for percent increase in stroke
admissions for an incremental increase in SO2
equivalent to one IQR (6.69).

Ischemic Stroke: 1.35 (0.43, 2.29), lag 0
Hemorrhagic Stroke: 0.68 (-1.77, 3.19)

Multipollutant models not run.

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           TABLE AX5.4 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY
                          DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
             Reference, Study
            Location, & Period
                             Outcomes, Design, & Methods
    Mean Levels &
  Monitoring Stations
  Copollutants         Effects: Relative Risk or % Change &
  (Correlations)     Confidence Intervals ([95% Lower, Upper])
to
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UNITED STATES (cont'd)
>
X
          Kokenetal. (2003)
          Denver, United States

          Study period:
          Jul and Aug,
          1993-1997,
          n= 310 days
                      Outcome(s) (ICD9):
                      Acute MI 410.00-410.92;
                      Atherosclerosis 14.00-414.05;
                      Pulmonary Heart Failure 416.0-416.9;
                      Dysrhythmia 427.0-427.9; CHF 428.0.
                      Discharge data from Agency for Healthcare
                      Research and Quality (AHRQ) database.
                      Age group analyzed: 65+ yrs
                      Study population: 60,000
                      Covariates : Seasonal adjustment not needed.
                      Adjustment for temperature, dew point
                      temperature made.
                      Study design: Time series
                      Statistical analysis: GLMs to analyze frequency
                      of admissions as a function of exposure. GEEs
                      to estimate parameters in Poisson regression
                      models, adjusting for overdispersion.
                      Lag(s): 0-4 day
SO2 24-h avg (ppb)

Mean(SD): 5.7(2.94)
Min: 0.4
25th: 3.8
50th: 5.3
75th: 7.2
Max: 18.9
O3 (- 0.10)         Effects were reported as percent change in
CO (0.21)          hospitalizations based on an increment of
PM10(0.36)        3.4 ppb.
NO2(0.46)         Single-pollutant model
                  Dysrhythmia
                  8.9% (-0.34, 18.93) lag 0, adjusted for gender
                  but not temperature

                  SO2 was found to be associated with cardiac
                  dysrhythmia but not other outcomes. No
                  association was observed for PM or NO2 with the
                  outcomes.
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          Low et al. (2006)
          New York City, NY

          Study period:
          1995-2003, 3287 days
                      Outcome(s) (ICD): Ischemic stroke 433-434;
                      Undetermined stroke 436; monitored intake in
                      11 hospitals (ER or clinic visits). Excluded
                      stroke patients admitted for rehabilitation.
                      Study design:  Time series
                      Statistical Analysis: Autoregressive integrated
                      moving avg (ARIMA) models
                      Software package:  SAS
SO2 24-h avg (ppm)

Mean(SD): 0.009124
Min: 0
25th: 0.005
Median: 0.009
75th: 0.014
Max: 0.096
PM10 (0.042)       At the highest concentration of SO2 (96 ppb) in
NO2 (0.33)        New York city over the study period the expected
CO (0.303)        increase in strokes would be 0.857 visits on the
Pollen (0.085)      day of the event.

                  Each 1000 ppb (1 ppm) SO2 would produce an
                  additional 8.878 visits (SE 4.471)
                  (p = 0.0471) for stroke.

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           TABLE AX5.4 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY
                          DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
              Reference, Study
             Location, & Period
                              Outcomes, Design, & Methods
     Mean Levels &
  Monitoring Stations
                                                                                                       Copollutants        Effects: Relative Risk or % Change &
                                                                                                       (Correlations)     Confidence Intervals ([95% Lower, Upper])
to
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UNITED STATES (cont'd)
X
           Metzger et al. (2004)
           Atlanta, GA

           Period of Study:
           Janl993-Aug312000,
           4yrs
                         Outcome(s):  IHD 410-414; AMI 410;
                         Dysrhythmias 427; cardiac arrest 427.5;
                         congestive heart failure 428; peripheral and
                         cerebrovascular disease 433-437, 440, 443-
                         444, 451-453; atherosclerosis 440; stroke
                         436. ED visits from billing records.
                         N: 4,407,535 visits, 37 CVD visits/days
                         # Hospitals:  31
                         Age groups analyzed:  adults > 19, elderly
                         56+
                         Statistical Analysis: Poisson regression,
                         GLM. Sensitivity analyses using GEE and
                         GAM (strict convergence criteria)
                         Covariates:  long-term trends, mean and
                         dew point temp, relative humidity (cubic
                         splines)
                         Statistical Software: SAS
                         Season: Warm, Apr 15-Oct 14,
                         Cool, Oct 15-Apr 14.
                         Lag(s): 0-3 days
SO2l-hmax(ppb)

Median: 11.0
10th-90th range: 2.0 to 39
ppb
                                                                                                    PM10 (0.20)
                                                                                                    03(0.19)
                                                                                                    NO2 (0.34)
                                                                                                    CO (0.26)
                                                                                                    PM2.5(0.17)
                                                                                                    Course PM (0.21)
                                                                                                    Ultrafme (0.24)

                                                                                                    Multipollutant
                                                                                                    models used. All
                                                                                                    models specified a
                                                                                                    priori.
Results presented for RR of an incremental
increase in SO2 of 20 ppb (a priori lag 3 day
moving avg).

All CVD:  1.007(0.993,1.022)
Dysrhythmia:  1.001 (0.975, 1.028)
CHF:  0.992(0.961,1.025)
IHD:  1.007(0.981,1.033)
PERI: 1.028(0.999,1.059)
Finger wounds 1.007 (0.998, 1.026)

Single day lag models presented graphically.

No multipollutant models run for SO2 since
association was not observed in single-
pollutant models.
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           Michaud et al. (2004)
           Hilo, Hawaii

           Study period:
           1997-2001,
           N= 1385 days
                         Outcome(s) (ICD9):
                         Cardiac 410-414, 425-429,
                         Emergency visits, primary diagnosis.
                         Study design:  Time series
                         Statistical Analysis: Exponential
                         regression, autocorrelation assessed by
                         regressing square root of number of ED
                         visits on covariates (Durbin-Watson
                         statistic). Newey-West procedure also
                         conducted for assessment of
                         autocorrelation.
                         Covariates:  Temperature, humidity,
                         interaction between SO2 and PM
                         Lag(s):  1-3 days
SO2 (all hourly
measurements) (ppb)

Mean(SD): 1.92(12.2)
Min: 0
Max: 447

Daily SO2
(12am-6am) (ppb)
Mean(SD): 1.97(7.12)
Min: 0
Max: 108.5
                                                                                                    PM
Effects were presented as relative risk based
on an increment of 10 ppb and the 24-h avg
SO2 concentration.

Cardiac
0.92(0.85, 1.00) lag 3

No associations of cardiac ER visits with
VOG (SO2-acidic aerosols) observed.

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           TABLE AX5.4 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY
                         DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
             Reference, Study
            Location, & Period
                           Outcomes, Design, & Methods
Mean Levels & Monitoring
        Stations
  Copollutants        Effects: Relative Risk or % Change &
  (Correlations)     Confidence Intervals ([95% Lower, Upper])
to
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UNITED STATES (cont'd)
>
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           Peel et al. (2007)
           Atlanta, GA

           Study period:
           Jan 1993-Aug 2000
                      Outcome(s) (ICD9):  IHD 410-414;
                      dysrhythmia 427; CHF 428; peripheral
                      vascular and cerebrovascular disease 433-
                      437= 440, 443, 444, 451-453.
                      Computerized billing records for ED
                      visits.
                      Comorbid conditions: Hypertension 401-
                      405; diabetes 250; dysrhythmia 427, CHF
                      428; atherosclerosis 440; COPD 491, 492,
                      496; pneumonia 480-486; upper
                      respiratory infection 460-465, 466.0;
                      asthma 493, 786.09.
                      # Hospitals: 31
                      N: 4,407,535 visits
                      Study design: Case-crossover. CVD
                      outcomes among susceptible groups with
                      comorbid conditions.
                      Statistical analyses:  Conditional logistic
                      regression.
                      Covariates: Cubic splines for temperature
                      and humidity included in models. Time
                      independent variables controlled through
                      design.
                      Statistical Software:  SAS
                      Lag(s): 3 day avg, lagged 0-2 day
SO2 1-h max (ppb)

Mean(SD):  16.5 (17.1)
10th: 2
90th: 39
PM10 24-h avg
O3 8 h-max
NO2l-hmax
CO 1-h max

Correlations not
reported
Results expressed as OR for association of CVD
admissions with a 20 ppb incremental increase in
S02.

All CVD
1.009 (0.995,1.024), 3 day moving avg
IHD
1.013 (0.988, 1.039), 3 day moving avg
Dysrhythmia
1.003 (0.975, 1.031), 3 day moving avg
Peripheral and Cerebrovascular
1.024 (0.993, 1.055), 3 day moving avg
CHF
0.993 (0.961, 1.026), 3 day moving avg

Effect modification by comorbid conditions was
not observed.

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           TABLE AX5.4 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY
                          DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
             Reference, Study
            Location, & Period
                          Outcomes, Design, & Methods
                                         Mean Levels &
                                       Monitoring Stations
                         Copollutants      Effects: Relative Risk or % Change & Confidence
                         (Correlations)             Intervals ([95% Lower, Upper])
to
o
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UNITED STATES (cont'd)
           Schwartz and Morris
           (1995)*
           Detroit, MI
           Study period:
           1986-1989
                      Outcome(s) (ICD9):  IHD 410-414; CHF
                      428; Dysrhythmia 427.  Medicare data,
                      diagnosis at discharge.
                      Study design: Time series
                      Statistical analysis: Poisson regression,
                      GAM
                      Age groups analyzed: 65+ yrs
                      Covariates: Adjustments for long-term
                      patterns, temperature, humidity, days of
                      the wk, holidays, viral infections, etc.
                      Lag(s): 0-3, cumulative up to 3 days
                                     SO2 24-h avg (ppb):
                                     Mean: 25.4
                                     IQR: 18 ppb
                                     Q2: 15
                                     Q3: 33

                                     # Stations:  6
                       PM10 (0.42)
                       CO (0.23)
                       03(0.15)
                  Effects were expressed as relative risk based on an
                  increment of 18 ppb.
                  IHD
                  1.014 (1.003, 1.026) lag 0, single pollutant
                  1.009 (0.994, 1.023), 2-pollutant model with PM10
                  CHF
                  1.002 (0.978, 1.017), single-pollutant model
                  Risks for dysrhythmia were not reported for SO2.
>
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Schwartz (1997)*
Tuscon, AZ

Study period:
Jan 1988-Dec 1990
Outcome(s) (ICD9):  CVD 390-429.
Ascertained from hospital discharge
records.
Study design: Time series
Statistical analysis:  Poisson regression,
GAM
Age groups analyzed: 65+
Covariates: Long-term and seasonal
trends, day of the wk, temperature, dew
point,
Statistical software: S-PLUS
SO2 24-h avg (ppb)
Mean: 4.6 ppb
IQR: 3.9 ppb
10th: 0.7
Q2: 2.0
Median:  3.4
Q3: 5.9
90th: 10.1
PM10 (0.095)       Results were expressed as percent change based on an
NO2 (0.482)        increment of 3.9 ppb.
CO(0.395)         0.14% (-1.3%, 1.6)
O3 (- 0.271)        No other statistically significant associations for
                  cardiovascular outcomes were observed.

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           TABLE AX5.4 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY
                         DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
             Reference, Study
            Location, & Period
                          Outcomes, Design, & Methods
Mean Levels & Monitoring
        Stations
   Copollutants          Effects: Relative Risk or % Change &
  (Correlations)       Confidence Intervals ([95% Lower, Upper])
to
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UNITED STATES (cont'd)
>
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           Wellenius et al. (2005b)
           Allegheny County, PA
           (near Pittsburgh)

           Study period:
           Jan 1987-Nov 1999
                       Outcome(s): CHF 428. Cases are
                       Medicare patients admitted from ER
                       with discharge of CHF
                       Study design: Case-crossover, control
                       exposures same mo and day of wk,
                       controlling for season by design.
                       Statistical analysis: Conditional
                       logistic regression
                       N:  55,019 admissions, including
                       repeat admissions, 86% admitted < 5
                       times
                       Age groups analyzed: 65+ yrs
                       (Medicare recipients)
                       Covariates:  Temperature and pressure.
                       Effect modification by age, gender,
                       secondary diagnosis arrhythmias, atrial
                       fibrillation,  COPD, hypertension, type
                       2 diabetes, AMI within 30 days, angina
                       pectoris, IHD, acute respiratory
                       infection.
                       Statistical software:  SAS
                       Lag(s): 0-3
SO2 24-h avg (ppb):

Mean(SD): 14.78(9.8
5th: 3.98
25th: 7.70
Median: 12.24
75th: 18.98
95th: 33.93

# Stations: 10
PM10 (0.51)
CO (0.54)
NO2 (0.52)
Os (-0.19)
Effects were reported as percent change based on
an increment of 11 ppb.

CHF, single-pollutant models:
2.36(1.05, 3.69) lag 0, or
2.14 (0.95, 3.35) lag 0 after adjusted to an
increment of 10 ppb.

CHF, 2-pollutant models:
1.35 (-0.27, 2.99), S02/PMio
0.10 (-1.35, 1.57), SO2/CO
0.68 (-0.82, 2.21), SO2/NO2
2.02 (0.68, 3.37), SO2/O3
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            TABLE AX5.4 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY
                          DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
              Reference, Study
             Location, & Period
                         Outcomes, Design, & Methods
  Mean Levels & Monitoring
          Stations
 Copollutants         Effects: Relative Risk or % Change &
(Correlations)       Confidence Intervals ([95% Lower, Upper])
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CANADA
>
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           Burnett etal. (1997)*
           Metropolitan Toronto
           (Toronto, North York,
           East York, Etobicoke,
           Scarborough, York),
           Canada

           Study period:
           1992-1994, 388 days,
           summers only
                       Outcome(s) (ICD9):
                       IHD 410-414;
                       Cardiac Dysrhythmias 427;
                       Heart failure 428. All Cardiac 410-
                       414, 427, 428.  Obtained from
                       hospital discharge data.
                       Population: 2.6 Million residents
                       Study design: Time series
                       Age groups analyzed:  All
                       # Hospitals:  NR
                       Statistical analysis: Relative risk
                       regression models, GAMs.
                       Covariates: Adjusted for long- term
                       trends, seasonal and subseasonal
                       variation, day of the wk,
                       temperature, dew point
                       Seasons: Summer only
                       Dose response: Figures presented
                       Statistical package: NR
                       Lag:  1-4 days
SO2 daily 1-h max (ppb):         H+ (0.45)
Mean: 7.9                     SO4(0.42)
CV:  64                        TP(0.55)
Min: 0                        FP (0.49)
25th percentile: 4               CP(0.44)
50th percentile: 7               COH(O.SO)
75th percentile: 11              O3(0.18)
Max: 26                       NO2 (0.46)
                              CO (0.37)
# of Stations: 4-6

(Results are reported for
additional metrics including 24-h
avg and daytime avg (day)
                Effects were expressed as relative risk based on an
                increment of 7.00 ppb (IQR).  T ratio in parentheses.

                All cardiac disease
                Single-pollutant model
                1.041 (2.66), daily max over 4 days, lag 0

                Multipollutant model w/ SO2, O3, NO2
                Of 7.72 excess hospital admissions, 2.8% attributed
                to SO2.

                Objective of study was to evaluate the role of particle
                size and chemistry on cardiac and respiratory
                diseases.
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           TABLE AX5.4 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY
                          DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
              Reference, Study
             Location, & Period
                         Outcomes, Design, & Methods
  Mean Levels & Monitoring
          Stations
   Copollutants       Effects: Relative Risk or Percent Change &
  (Correlations)       Confidence Intervals ([95% Lower, Upper])
to
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CANADA (cont'd)
>
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           Burnett etal. (1999)*
           Metropolitan Toronto
           (Toronto, North York,
           East York, Etobicoke,
           Scarborough, York),
           Canada

           Study period:
           1980-1995, 15 yrs
                       Outcome(s) (ICD9): IHD 410-414;
                       Cardiac Dysrhythmias 427; Heart
                       failure 428; All cardiac 410-414,
                       427, 428; Cerebrovascular Disease
                       obtained from hospital discharge
                       data 430-438; Peripheral Circulation
                       Disease 440-459.
                       Population: 2.13-2.42 million
                       residents
                       Study design: Time series
                       Statistical analysis: GAMs to
                       estimate log RR per unit changes,
                       stepwise regression used to select
                       minimum number of air pollutants in
                       multipollutant models.
                       Covariates: Long-term trends,
                       seasonal variation, day of wk,
                       temperature, and humidity.
                       Statistical package: S-PLUS
                       Lag(s): 0-2 days
SO2 daily avg (ppb)
Mean: 5.35
5th percentile:  0
25th percentile: 1
50th percentile: 4
75th percentile: 8
95th percentile: 17
Max:  57
                                                                  Multiple day avgs used in
                                                                  models
PM2.5 (0.50)
PM10-2.5 (0.38)
PM10 (0.52)
CO (0.55)
SO2 (0.55)
O3 (-0.04)
Effects were reported as % change based on an
increment of 5.35 ppb.

Single-pollutant model
Dysrhythmias 0.8% (-0.3, 1.9)
Cerebrovascular 0.04% (-0.7, 0.8)
CHF 1.93% (0.9, 2.9)
IHD 2.32% (1.6, 3.1)

Attributed percent increase in admissions for SO2
were determined from multipollutant models.
IHD
Attributed percent increase: 0.95%

Authors note SO2 effects could be largely
explained by other variables in the pollution mix as
demonstrated by the multipollutant model.
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                    TABLE AX5.4 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
              Reference, Study
             Location, & Period
                         Outcomes, Design, & Methods
     Mean Levels &
   Monitoring Stations
                       Copollutants     Effects:  Relative Risk or % Change & Confidence
                      (Correlations)             Intervals ([95% Lower, Upper])
to
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CANADA (cont'd)
>
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           Fung etal. (2005)
           Windsor, Ontario,
           Canada

           Study period:
           Apr 1995-Jan 2000
           Stieb et al. (2000) *
           Saint John, New
           Brunswick Canada

           Study period:
           Jull992-Marl996
                       Outcome(s) (ICD9):  CHF 428; IHD
                       410-414; dysrhythmias 427 and all
                       cardiac. Hospital admissions from
                       Ontario Health Insurance Plan
                       records.
                       Study design: Time series
                       Statistical analysis:  GLM
                       N:  11,632 cardiac admission,
                       4.4/day for 65+ age group
                       Age groups analyzed: 65+, <65 yrs
                       Statistical Software:  SPLUS
                       Lag(s):  lag 0, 2, 3 day avg
                       Outcome(s): Angina pectoris; MI;
                       dysrhythmia/conduction disturbance;
                       CHF; All Cardiac. ED Visits
                       collected prospectively.
                       Study design: Time series
                       Statistical analyses: Poisson
                       regression, GAM
                       N:  19,821ER visits
                       # Hospitals:  2
                       Lag(s):  1-8 days
SO2 1-hmax (ppb)
Mean(SD): 27.5(16.5)
Min:
Max:
0
 129
IQR: 19.3 ppb
SO2 24-h avg (ppb)
Mean(SD): 6.7(5.6)
95th:  18
Max:  60

SO2 max (ppb)
Mean(SD): 23.8(21.0)
95th:  62
Max:  161
CO (0.16)
O3(-0.02)
PM10 (0.22)
N02 (0.22)
                     CO, (0.31)
                     H2S(-0.01)
                     O3(-0.02)
                     NO2(0.41)
                     PM10 (0.36)
                     PM2.5(0.31)
                     H+(-0.24)
                     SO4 (0.26)
                     COH(0.31)
Effects were expressed as percent change of cardiac
disease hospital admissions based on an increment of
19.3 ppb.
Single-pollutant model:
<65 yrs
2.3% (-1.8, 6.6) lag 0
3.9% (-1.5, 9.6) lag 0-1
3.4% (-3.0, 10.1) lag 0-2
>65 yrs
2.6% (0.0, 5.3) lag 0
4.0% (0.6, 1.6) lag 0-1
5.6% (1.5, 9.9) lag 0-2
Inclusion of particulate matter and adjustment for
meteorological variables did not change the association
between SO2 and cardiac hospitalization.

Results reported for percent change in admissions based
on a single-pollutant model for incremental increase in
NO2 equivalent to one IQR (8.9 ppb)
Cardiac visits (p-value in parentheses):
4.9 (0.002), 1 day avg, lag  8, all yr
2.8 (0.067), 5 day avg, lag  6, May-Sept
Multi-pollutant models:
4.9, (1.7, 8.2), 1 day avg, lag 8, all yr (O3)
Lags 0-10 presented graphically. All but lag 8 in single-
pollutant model approximately null.

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                    TABLE AX5.4 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
             Reference, Study
             Location, & Period
                        Outcomes, Design, & Methods
     Mean Levels &
   Monitoring Stations
  Copollutants      Effects: Relative Risk or % Change & Confidence
  (Correlations)             Intervals ([95% Lower, Upper])
to
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CANADA (cont'd)
>
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           Villeneuve et al.
           (2006a)
           Edmonton, Canada

           Study period: Apr
           1992-Mar2002
                      Outcome(s) (ICD9): Acute
                      ischemic stroke 434, 436;
                      hemorrhagic stroke 430, 432;
                      transient ischemic attach (TIA)
                      435; Other 433, 437, 438.  ED
                      visits supplied by Capital Health.
                      N:  12,422
                      Stroke Visits Catchment area: 1.5
                      million people
                      Study design:  Case-crossover,
                      exposure index time compared to
                      referent time.  Time independent
                      variables controlled in the design.
                      Index and referent day matched by
                      day of wk.
                      Statistical Analysis: Conditional
                      logistic regression, stratified by
                      season and gender.
                      Covariates:  Temperature and
                      humidity
                      Statistical software:  SAS
                      Season:
                      Warm: Apr-Sept;
                      Cool: Oct-Mar.
                      Lag(s):  0, 1, 3 day avg
SO2 24 h ppb:
Allyr
Mean(SD): 2.6(1.9)
Median:  2.0
25th:  1.0
75th:  4.0
IQR:  3.0
Summer
Mean(SD): 2.1(1.6)
Median:  2.0
25th:  1.0
75th:  3.0
IQR:  2
Winter
Mean(SD): 3.1(2.0)
Median:  3.0
25th:  2.0
75th:  4.0
IQR:  2.0
Correlation
between SO2 and
other pollutants
(all yr):

NO2 (0.42)
CO (0.41)
03(-0.25)
PM25(0.22)
PM10(0.19)
Effects were reported as odds ratios based on an
increment of 3 ppb.

Acute Ischemic stroke, >65 yrs
Allyr OR 1.05 (0.99,1.11) lag 0
Warm OR 1.11 (1.01, 1.22) lag 0
Cold OR 1.00 (0.93, 1.09) lag 0
Effect stronger among males

Hemorrhagic stroke, >65 yrs
Allyr: 0.98 (0.90, 1.06), lag 0
Cold: 0.94(0.84, 1.05), lag 0
Warm: 1.03(0.90,1.17)
Effect stronger among males

Transient Cerebral Ischemic Attack, >65 yrs
Allyr: 1.06 (1.00, 1.12), lag 0
Cold: 1.03(0.95, 1.11), lag 0
Warm OR 1.11 (1.02, 1.22) lag 0

2-pollutant models presented graphically. Association
of SO2 with Acute Ischemic stroke diminished with
inclusion of CO and NO?.

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           TABLE AX5.4 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY
                          DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
             Reference, Study
             Location, & Period
    Outcomes, Design, & Methods
      Mean Levels &
    Monitoring Stations
    Copollutants          Effects: Relative Risk or % Change &
   (Correlations)      Confidence Intervals ([95% Lower, Upper])
to
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           EUROPE
>
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           Ballester et al. (2006)
           Multi-city, Spain:
           Barcelona, Bilbao,
           Castellon, Gijon,
           Huelva, Madrid,
           Granada, Oviedo,
           Seville, Valencia,
           Zaragoza

           Period of Study:
           1995/1996-1999,
           N= 1,096 days
Outcome(s) (ICD9):
All CVD 390-459;
Heart diseases 410-414,427,428.
Emergency admission from hospital
records. Discharge data used.
Study design:  Time series, meta-
analysis to pool cities
N: Daily mean admissions reported by
city
Statistical analyses:  Poisson regression
and GAM, with stringent convergence
criteria, meta-analysis with random
effect model. Tested linearity by
modeling pollutant in linear and non-
linear way (spline smoothing). Linear
model provided best results 55% of time
but used in all cases to facilitate
comparability.
Covariates: Temperature, humidity and
influenza, day of wk unusual events,
seasonal variation and trend of the series
Seasons:
Hot: MaytoOct;
Cold: NovtoApr
Statistical package: S-PLUS
Lag: 0-3
SO224-havg (ug/m2)

Mean, 10th, 90th
Barcelona:  15.5,6.6,27.9
Bilbao: 18.6,10.2,29.3
Cartagena: 27.1,14.6,40.8
Castellon:  7.7, 3.8, 12.7
Gijon: 29.4, 10.3, 52.4
Granada:  19.1,8.8,31.5
Huelva:  11.9,4.5,22.6
Madrid:  21.8,8.7,41.8
Oviedo:  40.9,16.3,75.5
Pamplona: 7.6, 1.8, 17.0
Seville: 9.6,5.6,14.6
Valencia:  16.6,9.4,24.4
Vigo: 9.3,2.6,18.2
Zaragoza:  9.3,2.0, 19.9

# of Stations: Depends on the
city

Correlation among stations:
Correlations between SO2
stations within cities poor.
CO 8-h max (0.58)
O38-h max (-0.03)
NO2 24 h (0.46)
BS 24 h (0.24)
TSP24h(0.31)
PM10 24 h (0.46)

Correlations reported
are the median for all
cities.

2-pollutant models
used to adjust for
copollutants
Results reported for % change in admissions,
increment 10 (ug/m3).

All cardiovascular
1.33% (0.21,2.46) lag 0-1

Heart diseases
1.72% (0.50,2.95) lag 0-1

Single day lags presented graphically. Effect
size decreased with increasing lag.

Multi-pollutant results presented graphically.
Control for CO and particulates diminished SO2
effects.

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          TABLE AX5.4 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY
                         DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
             Reference, Study
            Location, & Period
                           Outcomes, Design, & Methods
    Mean Levels &
  Monitoring Stations
  Copollutants         Effects: Relative Risk or % Change &
  (Correlations)      Confidence Intervals ([95% Lower, Upper])
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EUROPE (cont'd)
>
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          Anderson et al. (2001)*
          West Midlands
          conurbation, UK
          Study period:
          1994-1996,
          n = 832 days
                      Outcome(s) (ICD9): All CVD 390-459;
                      cardiac disease 390-429; IHD 410-414;
                      stroke 430-438. Emergency admissions
                      counted.
                      Catchment area: 2.3 million
                      Age groups analyzed: 0-14, 15-64, >65.
                      Study design: Time series, APHEA 2
                      methods
                      Statistical analyses: GAMs for modeling
                      non-liner dependence of some variables.
                      Covariates: Adjusted for effects of seasonal
                      patterns, temperature and humidity,
                      influenza episodes, day of wk and holidays.
                      Software package:  S-PLUS
                      Seasons:  Interaction by warm and cool
                      season investigated.
                      Lag(s): 0-3 days
SO2 24-h avg (ppb)

Mean(SD):  7.2(4.7)
Min: 1.9
10th: 3.3
Median:  5.8
90th: 12.3
Max: 59.8

# of Stations: 5 sites
PM10 (0.55)
PM2.5 (0.52)
PM2.5.10(0.31)
BS(0.50)
SO4(0.19)
NO2 (0.52)
03 (-0.22)
Results reported for % change in admissions,
increment = 9 ppb (10th-90th).

All CVD all ages
-0.4 (-2.2, 1.5), mean lags 0 + 1
Cardiac all ages:
0.7 (-1.3, 2.8), mean lags 0 + 1
IHD >65 yrs
1.5 (-2.5, 5.6), mean lags 0 + 1
Stroke >65 yrs
-5.1 (-9.6, -0.4), mean lags 0+ 1
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           TABLE AX5.4 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY
                          DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
              Reference, Study
             Location, & Period
                           Outcomes, Design, & Methods
   Mean Levels &
 Monitoring Stations
     Copollutants           Effects: Relative Risk or % Change &
     (Correlations)        Confidence Intervals ([95% Lower, Upper])
to
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           Atkinson etal. (1999a)
           London, England

           Period of Study:
           1992-1994,
           N= 1,096 days
                       Outcome(s) (ICD9):
                       All CVD 390-459; IHD 410-414.
                       Emergency admissions obtained from
                       the Hospital Episode Statistics (HES)
                       database (complaints).
                       Ages groups analyzed: 0-14 yrs, 15-64
                       yrs, 0-64 yrs, 65+ yrs, 65-74 yrs, 75+
                       yrs
                       Study design:  Time series, hospital
                       admission counts
                       N: 189,109 CVD admissions
                       Catchment area:  7 million residing in
                       1,600 Km  area of Thames basin.
                       Statistical analyses: APHEA protocol,
                       Poisson regression
                       Covariates: adjusted long-term seasonal
                       patterns, day of wk, influenza,
                       temperature, humidity (compared
                       alternative methods for modeling
                       meteorological including linear,
                       quadradic, piece-wise, spline)
                       Seasons: Warm season Apr-Sept, cool
                       season remaining mos, interactions
                       between season investigated
                       Dose response investigated: Yes,
                       bubble charts presented
                       Statistical package: SAS
                       Lag: 0-3
                       Dose response: Bubble plots presented
SO2 24 h avg (ppb):
Mean: 21.2
SD: 7.8
Min: 7.4
10th:  13
Median: 19.8
90th:  31
Max:  82.2
10th-90thpercentile:
11.2

# of Stations: 3, results
averaged across stations
PM10 24 h
C024h
S02 24 h
O38h
BS24h

Correlations of SO2 with
CO, NO2, O3, BS ranged
from 0.5-0.6
Correlation of SO2 with
O3 negative

2-pollutant models to
used adjust for
copollutants
Results reported for % change in admissions,
increment 10th-90th percentile (11.2 ppb).

All CVD, all ages
1.57(0.22,2.93), lag 0
All CVD, 0-64 yrs
2.44(0.3,4.63), lag 0
All CVD, 65+
1.72(0.15, 3.32), lag 0
IHD, 0-64 yrs
-2.03 (-5.35, 0.91), lag 2
IHD, 65+
3.10(0.61,5.65), lag 0

Effect size  and significance diminished in models
containing  SO2 and BS.

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           TABLE AX5.4 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY
                          DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
              Reference, Study
              Location, & Period
                              Outcomes, Design, & Methods
  Mean Levels &
Monitoring Stations
 Copollutants      Effects: Relative Risk or Percent Change &
(Correlations)      Confidence Intervals ([95% Lower, Upper])
to
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EUROPE (cont'd)
>
X
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           Ballesteretal. (2001)*
           Valencia, Spain

           Period of Study:
           1992-1996
Outcome(s) (ICD9):
All CVD 390-459;
heart diseases 410-414, 427,428;
cerebrovascular diseases 430-438.
Admissions from city registry - discharge
codes used.
Study design: Time series
N: 1080 CVD admissions
# of Hospitals: 2
Catchment area: 376,681 inhabitants of
Urban Valencia
Statistical analyses: Poisson regression,
GAM, APHEA/ Spanish EMECAM
protocol. Both Linear and nonparametric
model, including a loess term was fitted,
departure from linearity assess by
comparing deviance of both models.
Covariates: Long-term trend and
seasonality, temperature and humidity,
weekdays, flu, special events, air pollution.
Seasons:
Hot season May to Oct;
Cold season Nov to Apr

Statistical package: SAS
Lag:  0-4
                                                               24 h (ug/mj):
                                                               Mean: 25.6
                                                               SD: NR
                                                               Min:  4.4
                                                               Max: 68.4
                                                               median: 25

                                                               # of Stations: 14
                                                               manual, 5 automatic

                                                               Correlation among
                                                               stations:  0.3-0.62 for
                                                               BS, 0.46-0.78 for
                                                               gaseous pollutants
                     CO 24 h, (0.74)
                     N02 24 h, (0.22)
                     O38h, (-0.35)
                     BS, (0.63)
                                                                                               2-pollutant models
                                                                                               used to adjust for
                                                                                               copollutants
                 Results expressed as relative risk, increment of
                 10 ug/m3.

                 All CVD
                 1.0302(1.0042, 1.0568), lag 2
                 Heart disease
                 1.0357(1.0012, 1.0714), lag 2
                 Cerebrovascular disease
                 1.0378 (0.9844 to 1.0940), lag 5
                 Digestive diseases
                 1.0234(0.9958, 1.0518), lag 1
                 All CVD, hottest semester
                 1.050(1.010,1.092), lag 2

                 Effect size for all CVD and cerebrovascular
                 disease diminished in 2-pollutant models.

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           TABLE AX5.4 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY
                          DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
              Reference, Study
             Location, & Period
                             Outcomes, Design, & Methods
    Mean Levels &
  Monitoring Stations
   Copollutants         Effects:  Relative Risk or % Change &
  (Correlations)      Confidence Intervals ([95% Lower, Upper])
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           D'lppolitietal. (2003)
           Rome, Italy

           Study period:
           Jan 1995-June 1997
                       Outcome(s) (ICD):  AMI 410 (first episode).
                       Computerized hospital admission data.
                       Study design: Case-crossover, time stratified,
                       control days within same mo falling on the
                       same day.
                       Statistical analyses: Conditional logistic
                       regression, examined homogeneity across co-
                       morbidity categories
                       N: 6531 cases
                       Age groups analyzed:  18-64yrs,
                       65-74 yrd, >75
                       Season:  Cool: Oct-Mar;
                       Warm:  Apr-Sept.
                       Lag(s): 0-4 day, 0-2 day cum avg
                       Dose Response: OR for increasing quartiles
                       presented and p-value for trend.
SO2 24 h (ug/mj)
All yr:
Mean(SD): 9.5(6.0)
25th: 5.4
50th: 8.2
75th: 12.6
IQR: 7.2
Cold season:
Mean(SD): 12.7(6.5)
Warm season:
Mean(SD): 88.3(15.4)

# Stations: 5
TSP 24 h (0.29)
N02 24 h (0.37)
CO 24 h (0.56)

No multipollutant
models
Results reported as odds ratios for increment
equal to one IQR (7.2 ug/m3).

AMI
Quartile I (referent)
Quartile II
0.987(0.894, 1.089), lag 0-2
Quartile III
1.008(0.892, 1.140), lag 0-2
Quartile IV
1.144 (0.991, 1.321), lag 0-2

Results at various lags not reported for SO2.
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           Llorca et al. (2005)
           Torrelavega, Spain

           Study period:
           1992-1995
                       Outcome(s) (ICD):  CVD (called cardiac in
                       paper) 390-459. Emergency admissions,
                       excluding nonresidents.  Obtained admissions
                       records from hospital admin office.
                       Study design: Time series
                       Statistical analyses: Poisson regression,
                       APHEA protocol
                       Covariates: Rainfall, temperature, wind speed
                       direction
                       N: 1 8, 1 37 admissions
                       Statistical software:  STATA
                       Lag(s):  not reported
SO2 24 h ug/m3:
Mean(SD): 13.3(16.7)
TSP (-0.40)
NO2 (0.588)
SH2 (0.957)
NO (0.544)

Multipollutant
models
Results expressed as rate ratios.  Increment =
100 ug/m3.

Cardiac admissions, single-pollutant model
0.94(0.84,1.05)
Five-pollutant model
1.09(0.83,1.42)

All cardiorespiratory admissions, single-
pollutant model
RR 0.98 (0.89, 1.07)
Five-pollutant model
0.98(0.80,1.21)

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           TABLE AX5.4 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY
                         DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
              Reference, Study
             Location, & Period
                            Outcomes, Design, & Methods
     Mean Levels &
   Monitoring Stations
  Copollutants        Effects: Relative Risk or % Change &
  (Correlations)     Confidence Intervals ([95% Lower, Upper])
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           Poloniecki et al. (1997)*
           London, UK

           Study period:  Apr, 1987-
           Mar 1994, 7yrs
                        Outcome(s): All CVD 390-459; MI 410;
                        Angina pectoris 413; other IHD 414;
                        ARR 427; congestive heart failure 428;
                        cerebrovascular disease 430-438.
                        Hospital Episode Statistics (HES) data
                        on emergency hospital admissions.
                        Study design: Time series
                        N: 373, 556 CVD admissions
                        Statistical analyses:  Poisson regression
                        with GAM, APHEA protocol
                        Covariates: Long-term trends, seasonal
                        variation, day of wk, influenza,
                        temperature and humidity.
                        Season: Warm, Apr-Sept;
                        Cool, Oct-Mar.
                        Lag:  0-1
SO2 24 h ppb:
Min: 0
10%: 2
Median:  6
90%: 21
Max:  114
Black Smoke
CO24h
N02 24 h
O38h

Correlations
between
pollutants high
but not specified.
Effects were expressed as relative risk based on
an increment of 19 ppb
(10th-90thpercentile).

Single-pollutant models (lag 0-1)
MI: 1.0326(1.0133,1.0511)
Angina:  1.0133(0.9907,1.0383)
IHD: 0.9944(0.9651,1.0239)
ARR:  1.0181(1.0000,1.0448)
CHF:  1.0057(0.9846,1.0258)
Cerebrovascular:  1.0019 (0.9837,1.0189)
All circulatory: 1.0248 (1.0062, 1.0444)

MI, 2-pollutant models, cool season
1.0399 (1.0171, 1.0628), SO2 only
1.0285 (1.0019, 1.0571), SO2/NO2
1.0380 (1.0057, 1.0704), SO2/CO
1.0285 (1.0019, 1.0552), SO2/BS
1.0476 (1.0209, 1.0742), SO2/O3

In the warm season no significant associations
were observed in 2-pollutant models.
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           TABLE AX5.4 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY
                          DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
             Reference, Study
            Location, & Period
                          Outcomes, Design, & Methods
                                         Mean Levels &
                                       Monitoring Stations
   Copollutants     Effects:  Relative Risk or % Change & Confidence
  (Correlations)             Intervals ([95% Lower, Upper])
to
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           Prescott et al. (1998)*
           Edinburgh, UK

           Study period:
           Oct 1992-Jun 1995
                      Outcome(s) (ICD9):  Cardiac and
                      cerebral ischemia 410-414,426-429, 434-
                      440. Extracted from Scottish record
                      linkage system.
                      Study design: Time series
                      Statistical analysis:  Poisson, log linear
                      regression models
                      Age groups analyzed: <65, 65+ yrs
                      Covariates: Seasonal and weekday
                      variation, temperature, and wind speed.
                      Lag(s):  0, 1, 3 day moving avg
                                     NO2 24 h ppb
                                     Mean(SD): 8.3(5.6)
                                     Range: 1-50
                                     90th-10th
                                     Percentile = 12 ppb
O3,24 h
PM, 24 h
N02,24 h
CO, 24 h

Correlations not
reported.
Results reported as % increase in admissions,
increment 10 ppb.

A11CVD, < 65 yrs
4.9 (-1.0, 11.1), 3 day moving avg
A11CVD, > 65 yrs
-3.7 (-12.4, 5.9), 3 day moving avg
>
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Yallop et al. (2007)

London, England
Study period:
Jan. 1998-Oct. 2001,
>1400 days
Outcome(s): Acute pain in Sickle Cell
Disease (HbSS, HbSC, HbS/pO,
thalassaemia, HbS/(3+). Admitted to
hospital for at least one night.
Study design: Time series
Statistical analyses: Cross-correlation
function
N: 1047 admissions
Covariates: No adjustment made in
analysis, discussion includes statement
that the effects of weather variables and
copollutants are inter-related.
Statistical package: SPSS
Lag(s): 0-2 days
Dose response: quartile analysis, graphs
presented, ANOVA comparing means
across quartiles.
                                                                      NR
03,CO,NO,N02,
PM10:
daily avg used for
all copollutants
No association for SO2

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           TABLE AX5.4 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY
                          DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
             Reference, Study
             Location, & Period
  Outcomes, Design, & Methods
 Mean Levels & Monitoring
         Stations
  Copollutants         Effects:  Relative Risk or % Change &
  (Correlations)       Confidence Intervals ([95% Lower, Upper])
to
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           AUSTRALIA
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           Jalaludin et al. (2006)
           Sydney, Australia

           Period of Study:
           Jan. 1997-Dec. 2001
Outcome(s) (ICD9): All CVD 390-
459; cardiac disease
390-429; IHD 410-413; and
cerebrovascular disease or stroke
430-438; Emergency room
attendances obtained from health
department data.
Age groups included: 65+
Study design: Time series, multi-city
APHEA2 Protocol.
Statistical analysis: GAM (with
appropriate convergence criteria) and
GLM Models. Only GLM presented.
Lag: 0-3
Covariates: Daily avg temperature
and daily relative, humidity, long-
term trends, seasonality, weather, day
of wk, public school holidays,
outliers and influenza epidemics.
Dose response: quartile analysis

Season: Separate analyses for warm
(Nov-Apr) and cool periods (May-
Oct).
SO2 24 h avg (ppb)
Mean(SD): 1.07(0.58)
Min: 0.09
25th: 0.64
Median:  1.01
75th: 1.39
Max: 3.94
IQR: 0.75

# of Stations: 14
BS(0.21)
PM10 (0.37)
O3 (0.454)
NO2(lh)(0.52)
CO (8 h) (0.46)

2-pollutant models
to adjust for
copollutants
Effects were presented as percent change based on
an increment of 0.75 ppb.

Single-pollutant model:
All CVD, all yr
1.33% (0.24,2.43) lag 0
Cardiac: 1.62% (0.33, 2.93) lag 0
IHD: 1.12% (-0.84, 3.12) lag 0
Stroke: -1.41% (-3.67, 0.90) lag 0

Cool Season
All cardiovascular:  2.15% (0.84, 3.46) lag 0
Cardiac: 2.48% (0.94, 4.04) lag 0
IHD: 2.49% (0.13,4.91) lag 0
Stroke: -0.19% (-2.90,2.60) lag 0

Warm Season
All cardiovascular:  0.06% (-1.48, 1.62) lag 0
Cardiac: 0.38% (-1.37, 2.16) lag 0
IHD: -0.47% (-3.08, 2.22) lag 0
Stroke: -2.74% (-5.92, 0.55) lag 0

Results for lags 0-3 presented. In general, effect
size diminished with increasing lag.

Effects of SO2 on all CVD were diminished with
inclusion of PM and CO (graphically presented.)

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           TABLE AX5.4 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY
                         DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
              Reference, Study
             Location, & Period
                          Outcomes, Design, & Methods
 Mean Levels & Monitoring
         Stations
  Copollutants         Effects: Relative Risk or % Change &
  (Correlations)      Confidence Intervals ([95% Lower, Upper])
to
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>
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           Petroeschevsky et al.
           (2001)
           Brisbane, Australia

           Study period:
           Jan 1987-Dec 1994,
           2,922 days
                        Outcome(s) (ICD9):  CVD 390-459.
                        Hospital admissions, non-residents
                        excluded.
                        Study design: Time series
                        Statistical analyses: Poisson
                        regression, APHEA protocol, linear
                        regression and GEEs
                        Age groups analyzed: 15-64,65+
                        Covariates: Temperature, humidity,
                        rainfall. Long-term trends, season,
                        flu, day of wk, holidays.
                        Dose response: Quintile analysis.
                        Statistical software: SAS
                        Lag(s): lag 0-4, 3 day avg,
                        5 day avg
SO2 24-h avg (pphm)
Summer: Mean, min, max
0.39,0.0,1.63
Fall: Mean, min, max
0.42,0.01,3.55
Winter: Mean, min, max
0.48,0.0,2.08
Spring: Mean, min, max
0.37,0.0,6.02
Overall: Mean, min, max
0.41,0.0,3.55

SO2 1-h max (pphm)
Summer: Mean, min, max
0.78,0.0,5.5
Fall: Mean, min, max
0.93,0.05,5.95
Winter: Mean, min, max
1.13,0.0,6.68
Spring: Mean, min, max
0.84,0.0,6.01
Overall: Mean, min, max
0.92,0.0,6.68
BSP
03
NO2

Correlation
between
pollutants not
reported.
Effects were expressed as relative risk based on an
increment of 10 ppb and the 24-h avg SO2
concentrations.

All CVD
15 to >65 yrs
1.028(0.987, 1.070) lag 0
15 to 64 yrs
1.081(1.010, 1.158) lag 0
>65 yrs
1.038(0.988, 1.091) lag 1

Non-significant increasing risk for CVD in those
15-64 by quintile of SO2 concentration observed.

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           TABLE AX5.4 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY
                         DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
            Reference, Study
           Location, & Period
                        Outcomes, Design, & Methods
   Mean Levels &
 Monitoring Stations
   Copollutants         Effects: Relative Risk or % Change &
   (Correlations)     Confidence Intervals ([95% Lower, Upper])
to
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          Chan et al. (2006) *
          Taipai, Taiwan

          Period of Study:
          Apr 1997-Dec 2002,
          2090 days
                      Outcome(s) (ICD9):  Cerebrovascular
                      disease 430-437; stroke 430-434;
                      hemorrhagic stroke 430-432; ischemic
                      stroke 433-434. Emergency admission
                      data collected from National Taiwan
                      University Hospital.
                      Ages groups analyzed:  age >50
                      included in study
                      Study design:  Time series
                      N:  7341 Cerebrovascular admissions
                      among those >50 yrs old
                      # of Hospitals:
                      Catchment area:
                      Statistical analyses: Poisson
                      regression, GAMs used to adjust for
                      non-linear relation between
                      confounders and ER admissions.
                      Covariates: Time trend variables:  yr,
                      mo, and day of wk, daily temperature
                      difference, and dew point temperature.
                      Linearity: Investigated graphically by
                      using the LOESS smoother.
                      Statistical package: NR
                      Lag: 0-3, cumulative lag up to 3 days
SO224-havg (ppb):
Mean: 4.3
SD: 2.4
Min: 0.4
Max: 17.1
IQR: 3.1 ppb

# of Stations: 16

Correlation among
stations: NR
PM10 24 h (0.59)
PM2.524h(0.51)
CO 8-h avg (0.63)
N02 24 h (0.64)
O3l-h max (0.51)

2-pollutant models to
adjust for copollutants
but not for SO2, which
was not associated
with health outcomes.
Results reported for OR for association of emergency
department admissions with an IQR increase in SO2
(3.1 ppb)

Cerebrovascular:
1.008(0.969,1.047), lag 0
Stroke:
0.991(0.916,1.066), lag 0
Ischemic stroke:
1.044(0.966,1.125), lag 0
Hemorrhagic stroke:
0.918(0.815,1.021), lag 0

No significant associations for SO2 reported. Lag 0
shown but similar null results were obtained for lags
0-3.

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          TABLE AX5.4 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY
                          DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
             Reference, Study
            Location, & Period
                            Outcomes, Design, & Methods
    Mean Levels &
  Monitoring Stations
  Copollutants         Effects:  Relative Risk or % Change &
  (Correlations)       Confidence Intervals ([95% Lower, Upper])
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          Chang et al. (2005)
          Taipei, Taiwan

          Study period:
          1997-2001, 5 yrs
                      Outcome(s) (ICD9): CVD 410-429.
                      Daily clinic visits or hospital admission from
                      computerized records of National Health
                      Insurance. Discharge data.
                      Source population: 2.64 Million
                      N: 40.8 admissions/day, 74,509/5 yrs
                      # Hospitals:  41
                      Study design: Case-crossover, referent day 1
                      wk before or after index day
                      Statistical analyses:  Conditional logistic
                      regression.
                      Covariates:  Same day temperature and
                      humidity.
                      Season: warm/cool (stratified by temperature
                      cutpointof20°C)
                      Lag(s):  0-2 days
SO2 24-h avg (ppb)
Mean: 4.32
Min: 0.15
25th: 2.74
Median: 3.95
75th: 5.49
Max: 14.57
IQR: 2.75
                                                                         # of Stations: 6
CO 24-h avg
O3 24-h avg
NO2 24-h avg
PM10 24-h avg

Correlations not
reported.

2-pollutant models
to adjust for
copollutants
Effects were expressed as odds ratios based on an
increment of 2.75 ppb.

Warm (>20 °C) 0.967 (0.940, 0.995)
Cool(<20 °C) 1.015 (0.965, 1.069)

In 2-pollutant models with (PM10, NO2, CO, or O3)
the effect of SO2 was attenuated for both
temperature ranges such that it was negatively
associated with CVD.
>20°C:  0.874 (0.77, 0.880), w/PM10
<20 °C:  0.986 (0.928, 1.048), w/ PM10
>20°C:  0.826 (0.798, 0.854), w/N02
<20°C:  0.922(0.865, 0.984), w/NO2
>20°C:  0.903(0.876, 0.931), w/CO
<20°C:  0.960(0.901, 1.022), w/ CO
>20°C:  0.953(0.926, 0.981), w/O3
<20°C:  1.014(0.963, 1.067), w/O3
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           Lee et al. (2003)
           Seoul, Korea

           Study period:
           Dec 1997-Dec 1999,
           822-day s, 184 day sin
           summer
                       Outcome(s)(ICD10):  IHD: Angina pectoris
                       120; Acute or subsequent MI 121-123; other
                       acute IHD 124. Electronic medical
                       insurance data used.
                       Study design: Time series
                       Statistical methods: Poisson regression,
                       GAM with strict convergence criteria.
                       Age groups analyzed:  all ages, 64+
                       Covariates: Long-term trends LOESS
                       smooth, temperature, humidity, day of wk.
                       Season: Presented results for summer (Jun,
                       Jul, Aug) and entire period.
                       Lag(s):  0-6
SO2 24 h (ppb):
5th:  3.7
10th:  5.1
Median: 7.0
75th:  9.5
95th:  14.3
Mean(SD): 7.7(3.3)
IQR:  4.4
Allyr
NO2 (0.72)
03(-0.30)
CO (0.81)
PM10 (0.59)

Warm season
N02 (0.79)
O3(-0.56)
CO (0.41)
PM10 (0.61)

2-pollutant
models
Results reported for RR of IHD hospital admission
for an incremental increase in SO2 equivalent to
one IQR (4.4 ppb).

Single-pollutant model:
Entire season- IHD
All ages 0.96 (0.92, 0.99) lag 3
>64 yrs 0.95 (0.90, 1.01) lag 3

Summer- IHD
All ages 1.09 (0.96, 1.24) lag 3
>64 yrs 1.32 (1.08, 1.62) lag 3

2-pollutant model:
Entire season; SO2 and PM10
>64 yrs 0.98 (0.94, 1.03) lag 3

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                    TABLE AX5.4 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                EMERGENCY DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
            Reference, Study
           Location, & Period
                           Outcomes, Design, & Methods
                                                                            Mean Levels &
                                                                          Monitoring Stations
 Copollutants     Effects:  Relative Risk or % Change & Confidence
 (Correlations)             Intervals ([95% Lower, Upper])
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           Tsai et al. (2003a)
           Kaohsiung, Taiwan

           Study period:
           1997-2000
          Wong etal. (1999)
          Hong Kong, China

          Study period:
          1994-1995
                     Outcome(s) (ICD9):  All cerebrovascular 430-
                     438; SHS 430;
                     PIH 431-432; IS 433-435; Other
                     436-438. Ascertained from National Health
                     Insurance Program computerized admissions
                     records.
                     Study design: Case-crossover
                     Statistical analysis: Conditional logistic
                     regression.
                     N: 23,179 stroke admissions
                     # Hospitals: 63
                     Statistical software:  SAS
                     Seasons: Warm(>20°C);  Cool (<20 °C).
                     Lag(s):  0-2, cumulative lag up to 2 previous
                     days
                     Outcome(s) (ICD9):  CVD:
                     410-417, 420-438, 440-444; CHF 428; IHD
                     410-414; Cerebrovascular Disease 430-438.
                     Hospital admissions through ER departments
                     via Hospital Authority (discharge data).
                     Study design: Time series
                     Statistical analyses:  Poisson regression,
                     APHEA protocol
                     # Hospitals:  12
                     Covariates: Daily temperature, relative
                     humidity day of wk, holidays, influenza, long-
                     term trends (yr and seasonality variables).
                     Interaction of pollutants with cold season
                     examined.
                     Season: Cold (Dec-March)
                     Lag(s):  0-3 days
                                                                         S02 (ppb)
                                                                         Min:  1.25
                                                                         25th:  6.83
                                                                         Median:  9.76
                                                                         75th:  13.00
                                                                         Max:  26.80
                                                                         Mean: 10.08

                                                                         # Station: 6
PM10
S02
CO
03
                                                                         SO2 24-h avg (ug/m3)   PM10
                                                                         Mean: 20.2           SO2
                                                                         IQR: 10              03
Results reported as OR for the association of admissions
with an incremental increase of SO2 equivalent to the
IQRof6.2ppb

PIH admissions
Warm: 1.06 (0.95, 1.18), lag 0-2
Cool: 0.85(0.58, 1.26), lag 0-2
IS admissions:
Warm: 1.06 (1.00, 1.13), lag 0-2
Cool: 1.11(0.83, 1.48), lag 0-2
2-pollutant models:
PIH 0.91 (0.80, 1.03) w/N02
180.93(0.87, 1.00) w/NO2
PIH 0.94 (0.83, 1.06), w/CO
180.94(0.88, 1.02), w/ CO
PIH 1.08 (0.96, 1.20) w/O3
IS 1.08 (1.01,1.15) w/03
PIH0.99 (0.88, 1.11) w/PM
IS 1.01 (0.95-1.08) w/PM

Results reported for RR associated with incremental
increase inNO2 equal to 10 ug/m .

All CVD, All ages
1.016(1.006, 1.026) lag 0-1
All CVD, 5-65 yrs
1.004(0.989, 1.020) lag 0-1
All CVD, >65 yrs
1.021(1.010, 1.032) lag 0-1
CHF
1.036(1.013, 1.059) lag 0
IHD
1.010(0.995, 1.025) lag 0-1
Cerebrovascular
0.990(0.978, 1.002) lag 3
2-pollutant model results not presented for SO2

-------
           TABLE AX5.4 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY
                         DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
to
o
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 Reference, Study
Location, & Period
Outcomes, Design, & Methods
                                                                     Mean Levels & Monitoring
                                                                             Stations
  Copollutants        Effects: Relative Risk or % Change &
  (Correlations)     Confidence Intervals ([95% Lower, Upper])
          ASIA (cont'd)
X
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          Wong et al. 2002a*
          Hong Kong, London

          Study period:  1995-1997
          (Hong Kong),
          1992-1994 (London)
                     Outcome(s) (ICD9):  Cardiac disease
                     390-429; IHD 410-414. Patients
                     admitted to hospitals from emergency
                     departments, out patient departments
                     or directly to inpatient wards.
                     Statistical analysis: Poisson
                     regression, GAMs
                     Covariates: Smooth functions of time,
                     temperature, humidity (up to 3 days
                     before admission) day of wk, holidays
                     and unusual events.
                     Statistical software:
                     S-PLUS
                     Seasons: Warm/cold
                     Lag(s): 0-3, cumulative 0-1
                               SO224-havg (ug/mj)

                               Hong Kong
                               Mean, all yr:  17.7(12.3)
                               Mean, warm:  18.3
                               Mean, cold:  17.2
                               Min:  1.1
                               10th:  6.2
                               50th:  14.5
                               90th:  32.8
                               Max:  90

                               London
                               Mean, all yr: 23.7(12.3)
                               Mean, warm:  22.2
                               Mean, cold: 25.3
                               Min 6.2
                               10th:  13.2
                               50th:  20.6
                               90th:  38.1
                               Max:  113.6
Hong Kong         Effects expressed as % change, increment was
NO2 (0.37)         10 ug/m3 Cardiac (all ages)
PM10 (0.30)         Hong Kong
O3(-0.18)         Allyr: 2.1% (1.3, 2.8) lag 0-1
                  Warm: 1.0% (0.0, 2.0) lag 0-1
London            Cold: 1.9% (1.2, 2.7) lag 0-1
NO2 (0.71)         London
PM10(0.64)         Allyr: 1.6% (1.0, 2.2) lag 0-1
O3 (-0.25)         Warm: 0.6% (-0.6, 1.7) lag 0-1
                  Cold: 1.9% (1.2, 2.7) lag 0-1
                  IHD (all ages)
                  Hong Kong
                  Allyr: 0.1% (-1.1, 1.2) lag 0-1
                  Warm: -0.6% (-2.0, 0.8) lag 0-1
                  Cold: 1.0% (-0.8, 2.8) lag 0-1

                  London
                  Allyr: 1.7% (0.8, 2.6) lag 0-1
                  Warm: 1.0% (-0.6, 2.6) lag 0-1
                  Cold: 2.0% (0.9, 3.1) lag 0-1

                  Multipollutant model
                  Cardiac (all ages)
                  Hong Kong
                  SO2 alone 2.1% (1.3, 2.8)
                  SO2/NO21.4%(0.4,2.3)
                  S02/032.1%(1.4,2.9)
                  SO2/PMi02.0%(l.l,2.8)

                  London
                  SO2 1.6% (1.0, 2.2)
                  SO2/NO21.4%(0.6,2.3)
                  SO2/O31.6%(0.9,2.2)
                  S02/PM102.2%(1.2, 3.2)

-------
           TABLE AX5.4 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY
                         DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
              Reference, Study
             Location, & Period
                          Outcomes, Design, & Methods
    Mean Levels &
  Monitoring Stations
    Copollutants     Effects: Relative Risk or % Change & Confidence
   (Correlations)             Intervals ([95% Lower, Upper])
to
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ASIA (cont'd)
>
X
to
          Yang et al. (2004a)
          Kaohsiung, Taiwan

          Period of Study:
          1997-2000
                       Outcome(s) (ICD9): All CVD: 410-
                       429 * (All CVD typically defined to
                       include ICD9 codes 390-459)
                       N: 29,661
                       Study design: Case-crossover
                       Statistical analysis: Poisson Time
                       series regression models, APHEA
                       protocol
                       # of Hospitals:  63
                       Seasons:  Authors indicate not
                       considered because the Taiwanese
                       climate is tropical with no apparent
                       seasonal cycle
                       Covariates: Stratified by warm (>25°)
                       and cold (<25°) days, temperature, and
                       humidity measurements included in
                       the model
                       Statistical package: SAS
                       Lag: 0-2 days
SO2 24-h avg (ppb)
Min: 1.25
25%: 6.83
50%: 9.76
75%: 13.00
Max: 26.80
Mean: 10.08

# of Stations: 6
Correlation among
stations: NR
PM10
CO
SO2
038

2-pollutant models
used to adjust for
copollutants

Correlations NR
OR's for the association of one IQR (17.08 ppb)
increase in SO2 with daily counts of CVD hospital
admissions are reported

All CVD (ICD9:  410-429), one-pollutant model
>25°:  0.999(0.954,1.047)
<25°:  1.187(1.092,1.291)

All CVD (ICD9:  410-429), 2-pollutant models
Adjusted for PM10:
>25°:  0.961(0.917,1.008)
<25°:  1.048(0.960,1.145)
Adjusted for NO2:
>25°:  0.921(0.875,0.969)
<25°:  0.711(0.641,0.789)
Adjusted for CO:
>25°:  0.831(0.785,0.879)
<25°:  0.996(0.910,1.089)
Adjusted for: O3
>25°:  1.034(0.987,1.084)
<25°:  1.194(1.098,1.299)
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            TABLE AX5.4 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE WITH EMERGENCY
                           DEPARTMENT VISITS AND HOSPITAL ADMISSIONS FOR CARDIOVASCULAR DISEASES
              Reference, Study
             Location, & Period
                           Outcomes, Design, & Methods
                                           Mean Levels &
                                         Monitoring Stations
                             Copollutants           Effects:  Relative Risk or % Change &
                            (Correlations)       Confidence Intervals ([95% Lower, Upper])
to
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           MIDDLE EAST
           Hosseinpoor et al.
           (2005)
           Tehran, Iran

           Study period:
           Mar 1996-Mar 2001,
           5yrs
                       Outcome(s) (ICD9): Angina pectoris
                       413.  Primary discharge diagnosis from
                       registry databases or records.
                       Study design:  Time series
                       Statistical methods:  Poisson regression
                       # Hospitals: 25
                       Covariates: Long-term trends,
                       seasonality, temperature, humidity,
                       holiday, post-holiday, day of wk.
                       Lag(s): 0-3
                                       SO2 24-h avg (ug/m3)
                                       Mean(SD):  73.74(33.30)
                                       Min:  0.30
                                       25th:  48.23
                                       Median:  74.05
                                       75th:  98.64
                                       Max:  499.26
                          NO2 CO O3 PM1(

                          Correlations not
                          reported
                    Results reported for relative risk in hospital
                    admissions per increment of 10 ug/m3 SO2.

                    Angina
                    0.99995 (0.99397, 1.00507), lag 1

                    In a multipollutant model only CO (lag 1) was
                    significantly associated with angina pectoris related
                    hospital admissions.
>
X
* Default GAM

AMI Acute Myocardial
Infarction
ARR Arrhythmia
BC Black Carbon
COH coefficient of haze
CP Course Particulate
CVD Cardiovascular Disease
EC Elemental Carbon
FP Fine Particulate
HS Hemorrhagic Stroke
ICD9 International Classification of Disease,
9th Revision
IHD Ischemic Heart Disease
IS ischemic stroke
MI Myocardial Infarction
OC Organic Carbon
OHC Oxygenated
Hydrocarbons
PERI Peripheral Vascular and
Cerebrovascular Disease
PM Particulate Matter
PIH primary intracerebral hemorrhage
PNC Particle Number Concentration
SHS Subarachnoid hemorrhagic stroke
TP Total Particulate
UBRE Unbiased Risk Estimator
H
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O
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            TABLE AX5.5. ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE ON MORTALITY
to
o
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>
X
H

6
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o
H

O


o
H
W

O


O
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W
Reference, Study Outcome
Location, and Period Measure
META ANALYSIS
Stieb et al. All cause
(2002; reanalysis 2003)
meta-analysis of estimates
from various countries.




UNITED STATES
Dockery et al. (1992) All cause
St. Louis, MO and Eastern
Tennessee
1985-1986


Moolgavkar (2000; Cardiovascular;
reanalysis 2003a). cerebrovascular;
Cook County, IL; Los COPD
Angeles County, CA; and
Maricopa County, AZ
1987-1995





Copollutants Lag Structure
Mean SO2 Levels Considered Reported

24-h avg ranged from PM10, O3, NO2, The lags and
0.7 ppb CO multiday
(San Bernardino) to averaging used
75 ppb (Shenyang) varied

"Representative"
concentration:
9.4 ppb

24-h avg: PM10, PM2.5, 1
St. Louis: 9 ppb SO42", 1^,03,
Eastern Tennessee: NO2,
5 ppb


24-h avg median: PM2 5, PM10, O3, 0, 1, 2, 3, 4, 5
Cook County: 6 ppb NO2, CO; 2- and
Los Angeles: 2 ppb 3-pollutant
Maricopa County: models
2 ppb







Method/Design

Meta-analysis of time-
series study results.







Poisson with GEE.
Time-series study.




Poisson GAM with
default convergence
criteria in the original
Moolgavkar (2000);
GAM with stringent
convergence criteria
and GLM with natural
splines in the 2003 re-
analysis. The 2000
analysis presented total
death risk estimates
only in figures.
Effect Estimates* % Increase
in Risk (95% CI)

Single-pollutant model
(29 estimates):
1.0% (0.6, 1.3)

Multipollutant model estimates
(10 estimates):
0.9% (0.3, 1.4)


All cause:
St. Louis, MO:
0.8% (-1.7, 3.2)

Eastern Tennessee:
0.4% (-0.4, 1.1)
GLM (re-analysis):
Cook County:
All-cause:
Lag 1: 2. 6% (1.4, 3.8)
Cardiovascular:
Lag 1: 2. 9% (1.0, 4. 8)

Los Angeles: Cardiovascular:
Lag 1: 5. 9% (3. 0,9.0)



-------
        TABLE AX5.5 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE ON MORTALITY
to
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>
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H

6
o


o
H

O


o
H
W

O


O
HH
H
W
Reference, Study Outcome
Location, and Period Measure
Mean SO2 Levels
Copollutants Lag Structure
Considered Reported
Method/Design
Effect Estimates* % increase
in risk (95% CI)
UNITED STATES (cont'd)
Moolgavkar (2003b) All cause;
Cook County, IL and cardiovascular
Los Angeles County, CA
1987-1995







Samet et al. (2000a,b; All cause;
reanalysis Dominici cardiopulmonary
et al., 2003)
90 U.S. cities
(58U.S.citieswithSO2
data) 1987-1994

Schwartz (2004) All cause
14 U.S. cities that had
daily PM10 data

24-h avg median:
Cook County: 6 ppb
Los Angeles: 2 ppb







24-h avg ranged from
0.4 ppb (Riverside) to
14.2 ppb (Pittsburgh)

24-h avg median ranged
from 2.2 ppb (Spokane,
WA) to 39.4 ppb
(Pittsburgh, PA)

PM25,PM10, 03, 0,1,2,3,4,5
N02, CO; 2-
pollutant models







PM10,03,N02, 0,1,2
CO;
multipollutant
models

PM10 risk 1
estimates
computed,
matched by the
levels of SO2,
CO, NO2, and
03
Poisson GAM with
default convergence
criteria. Time-series
study.







Poisson GAM,
reanalyzed with
stringent convergence
criteria; Poisson GLM.
Time-series study.

Case-crossover design,
estimating PM10 risks
by matching by the
levels of gaseous
pollutants.

All cause:
Cook County:
Single pollutant:
Lagl: 2.6% (1.5, 3.7)
WithPM10:
Lagl: 1.9% (0.6, 3.2)
Los Angeles:
Single pollutant:
Lagl: 6. 9% (5 .4, 8.4)
With PM2.5:
Lagl: 7.6% (3 .4, 12.0)
Posterior means:
All cause:
Single pollutant:
Lagl: 0.6% (0.3, 1.0)
With PM10 and N02:
Lagl: 0.4% (-0.6, 1.4)
SO2 risk estimates not
computed. PM10 risk estimates
showed the largest risk estimate
when matched for SO2.


-------
TABLE AX5.5 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE ON MORTALITY

t^) '
CD
^
to
O
C2









>
X
^yi
i
i~i
ON


O
£>
Tj
H
1
o
o

0
H
O
O
H
W
O
O
H
W
Reference, Study
Location, and Period

Outcome Measure Mean SO2 Levels
Copollutants Lag Structure
Considered Reported Method/Design
Effect Estimates* %
increase in risk (95% CI)
UNITED STATES (cont'd)
Chock et al. (2000)
Pittsburgh, PA
1989-1991


De Leon etal. (2003)
New York City
1985-1994




Gamble (1998)
Dallas, TX
1990-1994




Gwynn et al. (2000)
Buffalo, NY













All cause; age <74 Not reported.
yrs; age 75+ yrs



Circulatory and 24-h avg: 15 ppb
cancer with and
without
contributing
respiratory causes


All cause; 24-h avg: 3 ppb
respiratory;
cardiovascular




All cause; 24-h avg: 12 ppb
respiratory;
circulatory












PMio, O3,NO2, 0,1,2,3 Poisson GLM. Time-
CO; 2-, 5-, and 6- series study. Numerous
pollutant models results


PMio, O3, NO2, 0 or 1 Poisson GAM with
CO; 2-pollutant stringent convergence
models criteria;
Poisson GLM.
Time-series study.


PM10, 03,NO2, 0 Poisson GLM.
CO; 2-pollutant Time-series study.
models




PMio, CoH, 0, 1, 2, 3 Poisson GAM with
SO4 , O3, NO2, Default convergence
CO, ET" criteria. Time-series
study.











All cause:
Age 0-74 yrs:
Lagl: 0.7% (-0.7, 2.2)
Age 75+ yrs:
Lag 1: -0.2% (-1.6, 1.3)
Gaseous pollutants results
were given only in figures.

Circulatory:
Age <75 yrs: -2%
Age 75+ yrs: -2%

All cause:
-0.8% (-3.8, 2.4)
Respiratory:
-1.0% (-5. 8, 4.1)
Cardiovascular:
-0.5% (-11.4, 11.8)

All cause:
LagO: -0.1% (-1.8, 1.7)
Circulatory:
Lag 3: 1.3% (-2.9, 5.6)
Respiratory:
Lag 0: 6.4% (-2.5, 16.2)










-------
             TABLE AX5.5 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE ON MORTALITY
to
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Reference, Study
Location, and Period
Outcome Copollutants
Measure Mean SO2 Levels Considered
Lag Structure
Reported Method/Design
Effect Estimates* %
increase in risk (95% CI)
UNITED STATES (cont'd)
Kelsalletal. (1997)
Philadelphia, PA
1974-1988
All cause; 24-havg: 17ppb TSP, CO, NO2, O3
respiratory;
cardiovascular
0 Poisson GAM.
(AIC presented
for 0 through 5)
All cause:
Single-pollutant:
0.8% (0.3, 1.4)
                                                                                                                             With all other pollutants:
                                                                                                                             0.8% (0.1, 1.6)
          Kinney and Ozkaynak    All cause;
          (1991)                 respiratory;
          Los Angeles County, CA  circulatory
          1970-1979
24-havg:  15ppb
KM (particle optical
reflectance), Ox, NO2,
CO; multipollutant
models
OLS (ordinary least
squares) on high-pass
filtered variables.
Time-series study.
All cause:
Exhaustive multipollutant
model:
0.0% (-1.1, 1.2)
>
X
H
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o
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O
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O
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Klemm and Mason
(2000); Klemm et al.
(2004)
Atlanta, GA
Aug 1998-M2000



Lipfert et al. (2000a)
Seven counties in
Philadelphia, PA area
1991-1995




All cause; 1-hmax: 19ppb
respiratory;
cardiovascular;
cancer; other;
age <65 yrs; age
65+ yrs


All cause; 24-h avg: 8 ppb
respiratory; 1-hmax: 18 ppb
cardiovascular;
all ages; age 65+
yrs; age
<65 yrs; various
subregional
boundaries
PM25,PM10.25,EC,OC, 0-1
S042\ N03", 03, N02,
CO





PM10, PM2.5, PM10.2.5, 0-1
SO42 , other PM indices,
O3, NO2, CO; 2-
pollutant models




Poisson GLM using
quarterly, monthly, or
biweekly knots for
temporal smoothing.
Time-series study.



Linear with 1 9-day
weighted avg
Shumway filters.
Time-series study.
Numerous results.



All cause
Age 65+ yrs:
Quarterly knots:
4.7% (-2.6, 12.5)
Monthly knots:
3.4% (-4.1, 11. 5)
Bi-weekly knots:
1.0% (-6.7, 9.3)
All-cause:
Philadelphia:
0.7% (p > 0.05)






-------
        TABLE AX5.5 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE ON MORTALITY
to
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>
X
oo
H
6
o
Reference, Study Outcome
Location, and Period Measure Mean SO2 Levels
Copollutants Lag Structure
Considered Reported
Method/Design
Effect Estimates* % increase
in risk (95% CI)
UNITED STATES (cont'd)
Lippmann et al. (2000; All cause; 24-h avg:
reanaly sis Ito, 2003, respiratory; 1985-1990: lOppb
2004) circulatory; 1992-1994: 7ppb
Detroit, MI cause-specific
1985-1990
1992-1994


Mar et al. (2000; All cause, 24-h avg: 3.1 ppb
re-analysis in 2003) cardiovascular
Phoenix, AZ.
1995-1997.





Moolgavkar et al. (1995) All cause 24-h avg:
Philadelphia, PA Spring: 17 ppb
1973-1988. Summer: 16 ppb
Fall: 18 ppb
Winter: 25 ppb
PM10,PM25, 0,1,2,3,0-1,
PM10.25,S042-, 0-2,0-3
FI+,03,N02,CO;
2-pollutant
models



PM2 5, PMi o, 0 for all cause;
PM10.2.5,CO, 0,1,2, 3, 4 for
NO2, O3, and cardiovascular
selected trace
elements, ions,
EC, OC, TOC,
and factor
analysis
components
TSP, O3; 1
2-pollutant
models


Poisson GAM,
reanalyzed with
stringent convergence
criteria; Poisson GLM.
Numerical SO2 risk
estimates were not
presented in the re-
analysis. Time-series
study.
Poisson GAM with
default convergence
criteria (only
cardiovascular deaths
were reanalyzed in
2003). Time-series
study.


Poisson GLM. Time-
series study.



Poisson GAM:
All cause:
1985-1990:
Lagl: 0.5% (-1.5, 2.4)

1992-1994:
Lagl: 1.1% (-1.4, 3.6)

Poisson GAM:
All cause:
LagO: 11. 2% (-1.5, 25.6)

Poisson GLM:
Cardiovascular:

Lagl: 7.4% (-13. 1,32.6)

Allyr: 1.3% (0.8, 1.8)
Spring: 1.7% (0.6, 2.9)
Summer: 0.9% (-0.7, 2.5)
Fall: 1.3% (0.0, 2.6)
Winter: 2.0% (0.9, 3.0)
o
H

O
c
o
H
W

O
V
O
HH
H
W

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        TABLE AX5.5 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE ON MORTALITY
to
o
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>
X
Reference, Study Outcome
Location, and Period Measure
Mean SO2 Levels
Copollutants Lag Structure
Considered Reported
Method/Design
Effect Estimates* % increase in
risk (95% CI)
UNITED STATES (cont'd)
Schwartz (1991) All cause
Detroit, MI
1973-1982






Schwartz (2000) All cause
Philadelphia, PA
1974-1988





24-h avg: 12 ppb








24-h avg summer
mean declined from
20 ppb in 1974 to 9
ppb in 1988; winter
mean declined from
35 ppb in 1974 to 17
in 1988


TSP (predicted 0,1,0-1
from
extinction
coefficient); 2-
pollutant
models



TSP, 0
extinction
coefficient





Poisson GEE. Time-
series study.







Poisson GAM model
in 1 5 winter and 1 5
summer periods. The
second stage
regressed the TSP
and SO2 risk
estimates on
SO2/TSP
relationships.
Poisson regression coefficient
Single pollutant:
Lagl: 0.863 (SE = 0.323)

With TSP:
Lagl: 0.230 (SE = 0.489)
(Though SO2 levels were reported in
ppb, these coefficients must have been
for SO2 inppm.)
Single pollutant:
2. 3% (1.6, 3.0)

With TSP:
0.4% (-2.2, 3.1)



H
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O
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O
HH
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W

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         TABLE AX5.5 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE ON MORTALITY
to
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>
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oo
o
H

6
o


o
H

O


o
H
W

O


O
HH
H
W
Reference, Study
Location, and Period
Outcome Measure
Mean SO2 Levels
Copollutants
Considered
Lag Structure
Reported Method/Design
Effect Estimates* %
increase in risk (95% CI)
CANADA
Burnett et al. (2004)
12 Canadian cities
1981-1999


Burnett etal. (1998a)
1 1 Canadian cities
1980-1991
Burnett etal. (1998b)
Toronto
1980-1994

Goldberg et al. (2003)
Montreal, Quebec
1984-1993


All cause


All cause
All cause

Congestive heart
failure (CHF) as
underlying cause of
death versus those
classified as having
CHF 1 yr prior to death

24-h avg ranged from
1 ppb (Winnipeg) to
10 ppb (Halifax)


24-h avg ranged from
1 ppb (Winnipeg) to
1 1 ppb (Hamilton)
24-h avg: 5 ppb

24-h avg: 6 ppb


PM25,PM10.25,
03, N02, CO


O3, NO2, CO
03, N02, CO,
TSP, COH,
estimated PM10,
estimated PM2 5

PM2.5,
coefficient of
haze, SO42~, O3,
NO2, CO


1 Poisson GLM. Time-
series study.


0,1,2,0-1,0-2 Poisson GAM with
examined but the default convergence
best lag/averaging criteria. Time-series
for each city study.
chosen
0,1,0-1 Poisson GAM with
default convergence
criteria. Time-series
study.

0,1,0-2 Poisson GLM with
natural splines. Time-
series study.


Single pollutant:
0.7% (0.3, 1.2)
WithNO2:
0.4% (0.0, 0.8)
Single pollutant:
3.4% (2.0, 4.7)
With all gaseous pollutants:
2.6% (1.3, 3.9)
Single pollutant:
LagO: 1.0% (0.3, 1.8)
With CO:
LagO: 0.6% (-0.4, 1.5)
CHF as underlying cause of
death:
Lag 1: -0.1% (-8. 9, 9.6)
Having CHF 1 yr prior to
death:
Lag 1: 5.4% (1.3, 9.5)

-------
TABLE AX5.5 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE ON MORTALITY
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Reference, Study
Location, and Period
CANADA (cont'd)
Vedal et al. (2003)
Vancouver, British
Columbia
1994-1996




Villeneuve et al. (2003)
Vancouver, British
Columbia
1986-1999




EUROPE
Ballester et al. (2002)
13 Spanish cities
1990-1996




Biggeri et al. (2005)
8 Italian cities
Period variable between
1990-1999







Outcome
Measure

All cause;
respiratory;
cardiovascular





All cause;
respiratory;
cardiovascular;
cancer;
socioeconomic
status



All cause,
cardiovascular,
respiratory




All cause;
respiratory;
cardiovascular








Copollutants Lag Structure
Mean SO2 Levels Considered Reported Method/Design

24-havg: 3 ppb PM10, 03,NO2, 0,1,2 Poisson GAM with
CO stringent convergence
criteria. Time-series
study. By season.




24-havg: 5 ppb PM25, PM10, 0,1,0-2 Poisson GLM with
PM10.2.5, TSP, natural splines. Time-
coefficient of series study.
haze, SO42~, O3,
N02, CO




24-h avg SO2 ranged TSP, BS, PM10 0- 1 for 24-h avg Poisson GAM with
from 2.8 ppb (Sevilla) SO2;Oforl-h default convergence
to 15.6ppb(Oviedo) max SO2 criteria. Time-series
study.



24-h avg ranged from O3,NO2,CO, 0-1 Poisson GLM. Time-
2 ppb (Verona) to 14 PM10 series study.
ppb (Milan)








Effect Estimates* %
increase in risk (95% CI)

Results presented in figures
only.

All cause:
Summer:
LagO: -3%
Winter:
Lagl: -1%
All yr:
All cause:
Lagl: 1.7% (-1.1, 4. 5)
Cardiovascular:
Lagl: 1.1% (-3. 1,5.4)
Respiratory:
Lagl: 8. 3% (0.6, 16.6)


All cause:
Lag 0-1: 1.4% (0.2, 2.7)
Cardiovascular:
Lag 0-1: 1.4% (-0.4, 3.3)
Respiratory:
Lag 0-1: 3. 5% (1.0, 6.0)

All cause:
4.1% (1.1, 7.3)
Respiratory:
7.4% (-3.6, 19.6)
Cardiovascular:
4.9% (0.4, 9.7)






-------
             TABLE AX5.5 (cont'd).  ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE ON MORTALITY
            Reference, Study Location,       Outcome                            Copollutants      Lag Structure                         Effect Estimates* % increase
                   and Period
                                 Measure
                  Mean SO2 Levels
                       Considered
                     Reported
  Method/Design
      in risk (95% CI)
           EUROPE (cont'd)
to
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o
Hoek et al.
(2000; reanalysis Hoek, 2003)
The Netherlands:  Entire
country, four urban areas
1986-1994
All cause;
COPD;
pneumonia;
cardiovascular
24-h avg median:
3.5 ppb in the
Netherlands;
5.6 ppb in the four
major cities
PMio, BS, SO/
NO3~, O3,NO2,
CO;
2-pollutant
models
                                                                                               1,0-6
Poisson GAM,
reanalyzed with
stringent
convergence criteria;
Poisson GLM. Time-
series study.
Poisson GLM:

All cause:
Lagl:  1.3% (0.7, 1.9)
Lag 0-6: 1.8% (0.9, 2.7) With
BS:  1.1% (-0.3, 2.4)
                                                                                                                                     Cardiovascular:
                                                                                                                                     Lag 0-6: 2.7% (1.3, 4.1)

                                                                                                                                     COPD:
                                                                                                                                     Lag 0-6: 3.6% (-0.3, 7.7)
>
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to
Katsouyanni et al. (1997)
12 European cities Study
periods vary by city, ranging
from 1977 to 1992
                                        All cause
                 24-h avg median of
                 the median across
                 the cities was
                 14 ppb, ranging
                 from 5 ppb
                 (Bratislava) to
                 26 ppb (Cracow)
                    BS,PM1(
                  "Best" lag
                  variable across
                  cities from
                  Oto3
Poisson
autoregressive.
Time-series study.
Pneumonia:
Lag 0-6: 6.6% (1.2, 12.2)

All cities:
1.1% (0.9, 1.4)
Western cities:
2.0% (1.2, 2.8)
Central eastern cities:
0.5% (-0.4, 1.4)
H
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O
O
HH
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           Le Tertre et al. (2002)
           Bordeaux , Le Havre, Lille,
           Lyon, Marseille, Paris, Rouen,
           Strasbourg, France
           Study periods vary by city,
           ranging from 1990-1995
                             All cause;
                             respiratory;
                             cardiovascular
                 24-h avg ranged
                 from 3 ppb
                 (Bordeaux) to 9 ppb
                 (Rouen)
                    BS, 03, N02
                  0-1
Poisson GAM with
default convergence
criteria. Time-series
study.
8-city pooled estimates:
All cause:
2.0% (1.2, 2.9)
Respiratory:
3.2% (0.1, 6.3)
Cardiovascular:
3.0% (1.5, 4.5)	

-------
           TABLE AX5.5 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE ON MORTALITY
to
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H

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o
H

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o
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W

O


O
HH
H
W
Reference, Study
Location, and Period
Outcome
Measure
Mean SO2 Levels
Copollutants
Considered
Lag Structure
Reported
Method/Design
Effect Estimates* % increase in
risk (95% CI)
EUROPE (cont'd)
Peters et al. (2000b)
NE Bavaria, Germany
1982-1994
Coal basin in Czech
Republic
1993-1994

Saez et al. (2002)
Seven Spanish cities
Variable study periods
between 199 land 1996
Zmirouetal. (1998)
10 European cities
Study periods vary by city,
ranging from 1985-1 992

All cause;
respiratory;
cardiovascular;
cancer



All cause;
respiratory;
cardiovascular

Respiratory;
cardiovascular



24-h avg:

Czech Republic:
35ppb

Bavaria, Germany:
14 ppb
Values for SO2 not
reported.


24-h avg:
Cold season:
Ranged from 12 ppb
(London) to 87 ppb
(Milan) ppb
TSP, PMio, 03,
NO2, CO





03, PM, N02,
CO


BS, TSP, NO2,
03



0,1,2,3






0-3



0,1,2,3,0-1,0-
2, 0-3 (best lag
selected for each
city)

Poisson GLM.
Time-series study.





Poisson GAM with
default convergence
criteria. Time-series
study.
Poisson GLM.
Time-series study.



Czech Republic:
All cause:
Lagl: 0.8% (-0.2, 1.8)

Bavaria, Germany:
All cause:
Lagl: 0.3% (-0.3, 0.9)
Risk estimates for SO2 was not
reported. Including SO2 in
regression model did not appear to
reduce NO2 risk estimates.
Western cities:
Respiratory:
2.8% (1.7, 4.0)
Cardiovascular:
2. 3% (0.9, 3.7)
                                             Warm season:

                                             Ranged from 5 ppb

                                             (Bratislava) to 21 ppb

                                             (Cracow) in warm

                                             season
Central eastern cities:

Respiratory:

0.6%(-1.1,2.3)

Cardiovascular:

0.6% (0.0, 1.1)
Zeghnoun et al. (2001)
Rouen and Le Havre,
France 1990-1995


All cause;
respiratory;
cardiovascular


24-h avg: NO2, BS, PM13, 0, 1, 2, 3, 0-3,
Rouen: 10 ppb O3
Le Havre: 12 ppb


Poisson GAM with
default convergence
criteria. Time-series
study.


All cause:
Rouen:
Lagl: 2.3% (-1.
Le Havre:
Lagl: 1.1% (-0.
.1,5.9)

.3,2.5)

-------
        TABLE AX5.5 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE ON MORTALITY
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o
H

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W

O


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HH
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Reference, Study
Location, and Period
Outcome Measure Mean SO2 Levels
Copollutants
Considered
Lag Structure
Reported Method/Design
Effect Estimates* % increase
in risk (95% CI)
EUROPE (cont'd)
Anderson et al. (1996)
London, England
1987-1992


Anderson etal. (2001)
West Midlands region,
England
1994-1996

Bremner etal. (1999)
London, England
1992-1994
Clancy et al. (2002)
Dublin, Ireland
1984-1996

All cause; 24-h avg: 11 ppb
respiratory;
cardiovascular


All cause; 24-h avg: 7 ppb
respiratory;
cardiovascular

All cause; 24-h avg: 7 ppb
respiratory;
cardiovascular; all
cancer; all others; all
ages; age specific (0-
64, 65+, 65-74,
75+ yrs)
All cause, 24-h avg:
cardiovascular, and
respiratory 1984-1990:
11. 7 ppb
1990-1996:
7.7 ppb
BS, 03, N02;
2-pollutant
models


PM10, PM2.5,
PM10.2 5, BS,
S042\ 03, N02,
CO

BS, PMio, O3,
NO2, CO;
2-pollutant
models
BS

1 Poisson GLM.
Time-series
study.


0-1 Poisson GAM
with default
convergence
criteria. Time-
series study.

Selected best from Poisson GLM.
0, 1, 2, 3, (all Time-series
cause); study.
0,1,2,3,0-1,0-2,
0-3 (respiratory,
cardiovascular)
NA Comparing
standardized
mortality rates
for 72 mos
before and after
the ban on coal
sales in Sept
1990.
All cause:
1.0% (0.0, 2.0)
Respiratory:
Cardiovascular:
0.2% (-1.4, 1.8)
All cause:
-0.2% (-2.5, 2.1)
Respiratory:
-2.2% (-7.4, 3.2)
Cardiovascular:
-0.2% (-3. 5, 3.1)
All cause:
Lagl: 1.6% (-0.5, 3.7)
Respiratory:
Lag 2: 4.8% (-0.2, 10.0)
Cardiovascular
Lagl: 1.3% (-1.7, 4.3)
BS mean declined by a larger
percentage (70%) than SO2
(34%) between the two
periods.
All cause death rates reduced
by 5.7% (4, 7); respiratory
deaths by 15.5% (12, 19);
cardiovascular deaths by
10. 3% (8, 13).

-------
t/3

T3
r+





to
         TABLE AX5.5 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE ON MORTALITY
X

-------
            TABLE AX5.5 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE ON MORTALITY
             Reference, Study
           Location, and Period
                       Outcome Measure    Mean SO2 Levels
                                         Copollutants
                                         Considered
                                        Lag Structure
                                          Reported
 Method/Design
                                         Effect Estimates* %
                                       increase in risk (95% CI)
          EUROPE (cont'd)
to
o
o
Garcia-Ay merich et al.
(2000)
Barcelona, Spain
1985-1989
All cause;
respiratory;
cardiovascular;
general population;
patients with COPD
Levels not reported.    BS, O3, NO2
Selected best
averaged lag
Poisson GLM.
Time-series study.
All cause:
General population:
Lag 0-3:  4.4% (2.3, 6.5)
COPD patients:
Lag 0-2:  2.6% (-5.0, 10.7)

Respiratory:
General population:
Lag 0-1:  3.5% (-0.6, 7.8)
COPD patients:
Lag 0-2:  2.3% (-8.9, 15.0)
>
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(Si
1
oo
Hoek et al. (2002) All cause 24-h avg median: TSP, BS, Fe, O3, 1
Rotterdam, the 7.7 ppb CO
2 Netherlands
^ 1983-1991
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O
O
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W
O
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HH
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W
Cardiovascular:
General population:
Lag 0-3: 5.1% (2.3, 8.0)
COPD patients:
Lag 0-2: 2.0%
(-11.5,17.5)
Poisson GAM Single pollutant:
with default \1 .5% (0.0, 3.0)
convergence
criteria. Time- With TSP and O3:
senes study. 0.5% (-1.2, 2.3)


-------
September
to
o
o
^i








>
X
(.yi
TABLE AX5.5 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE ON MORTALITY
Reference, Study Copollutants Lag Structure
Location, and Period Outcome Measure Mean SO2 Levels Considered Reported
EUROPE (cont'd)
Hoeketal. (2001; Total 24-havg median: 3.5 PM10, 03,NO2, 0-6
reanalysis Hoek, 2003) cardiovascular; ppb in the CO
The Netherlands myocardial Netherlands; 5.6 ppb
1986-1994 infarction; in the four major
arrhythmia; heart cities
failure;
cerebrovascular;
thrombosis-related






Method/Design

Poisson GAM,
reanalyzed with
stringent
convergence
criteria; Poisson
GLM. Time-
series study.







Effect Estimates* %
increase in risk (95% CI)

Poisson GLM:

Total cardiovascular:
2. 7% (1.3, 4.1)

Myocardial infarction:
0.8% (-1.2, 2. 8)
Arrhythmia:
2. 3% (-3. 9, 8.8)
Heart failure:
7.1% (2.6, 11.7)
Cerebrovascular:
4.4% (1.4, 7.5)














oo
                                                                                                                                           Thrombo sis-related:
                                                                                                                                           9.6% (3.1,16.6)


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2|
0
H
O

H
W
O
O
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W
Kotesovec et al. (2000) All cause, 24-havg: 34. 9 ppb TSP
Northern Bohemia, cardiovascular
Czech Republic (only age = <65
1982-1994 presented), cancer


Michelozzi et al. (1998) All-cause 24-havg: 5.7 ppb PM13,NO2, 03,
Rome, Italy 1992-1995 CO










0,1,2,3,4,5,6,0-6 Poisson GLM,
time-series study




0,1,2,3,4 Poisson GAM
with default
convergence
criteria. Time-
series study.







All cause:
Lag 1:0.1% (-0.1, 0.4)










Lagl: -2.0% (-4.4, 0.5);
(negative estimates at all
examined)









lags











-------
TABLE AX5.5 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE ON MORTALITY
ft>

a"
to
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~-J










X
i

-------
             TABLE AX5.5 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE ON MORTALITY
                                                                             Copollutants      Lag Structure                     Effect Estimates* % increase
    Reference, Study
   Location, and Period
                                    Outcome Measure    Mean SO2 Levels
                       Considered
                     Reported
 Method/Design
      in risk (95% CI)
           EUROPE (cont'd)
to
o
o
Spix and Wichman (1996)
Koln, Germany
1977-1985
                                    All-cause
24-h avg:  15 ppb

1-hmax: 32 ppb
TSP,PM7,NO2       0,1,0-3          PoissonGLM.      Lag 1: 0.8% (0.2, 1.4)
                                   Time-series study.
>
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oo
VO
           Sunyer et al. (2002)
           Barcelona, Spain
           1986-1995
                         All cause,
                         respiratory, and
                         cardiovascular
                         mortality in a
                         cohort of patients
                         with severe asthma
24-h avg median:
6.6 ppb
PM10, BS, NO2, O3,   0-2
CO, pollen
Conditional
logistic (case-
crossover)
Odds ratio:
Patients with 1 asthma
admission:
All cause:
14.8% (-19.8, 64.4)

Patients with more than 1
asthma adm:
All cause:
50.4% (-48.6, 340.4)

Patients with more than 1
asthma or COPDadm:
All cause:
20.2% (-17.5, 75.0)
H
6
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H
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W
O
O
HH
H
W
                                                                                                                               NO2 and O3 were more
                                                                                                                               strongly associated with
                                                                                                                               outcomes than SO7.

-------
TABLE AX5.5 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE ON MORTALITY
T3
3
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to
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^


Reference, Study
Location, and Period
EUROPE (cont'd)
Sunyeretal. (1996)
Barcelona, Spain
1985-1991



Outcome Measure

All cause;
respiratory;
cardiovascular; all
ages; age
70+ yrs
Copollutants
Mean SO2 Levels Considered

24-h avg median: BS, NO2, O3

Summer: 1 3 ppb

Winter: 16 ppb
Lag Structure
Reported

Selected best
single-day lag



Effect Estimates* % increase
Method/Design

Autoregressive
Poisson. Time-
series study.


in risk (95% CI)

All

All
Lag


yr, all ages:

cause:
;1: 3.5% (1





.9,5.1)

                                                                                         Respiratory:
                                                                                         LagO: 3.5% (-0.2, 5.0)

                                                                                         Cardiovascular:
                                                                                         Lagl: 2.2% (0.5, 3.9)

Verhoeffetal. (1996) All cause; all ages; 24-h avg: 4.5 ppb BS, PM10, 03, CO; 0,1,2 Poisson GLM. Single pollutant:

Amsterdam, the age 65+ yrs multipollutant models Time-series study. Lagl: 1.4% (-1.4, 4.2)

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0
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O
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W
O
O
H
W
Netherlands
1986-1992 WithBS:
-3.7% (-8.1, 0.9)

Zmirouetal. (1996) All cause; 24-h avg: 16 ppb PMi3,NO2, 03 Selected best Poisson GLM. All cause:
Lyon, France respiratory; from 0, 1,2, 3 Time-series study. LagO: 3.4% (1.4,
1985-1990 cardiovascular; Respiratory:
digestive Lag 3: 2.8% (0.9,
Cardiovascular:
Lag 0-3: 4. 5% (2.



















5.4)

4.8)

0, 7.0)















-------
  TABLE AX5.5 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE ON MORTALITY
                                                                                   Lag Structure                             Effect Estimates* %
              Reference, Study
            Location, and Period
                        Outcome Measure     Mean SO2 Levels
                                           Copollutants
                                           Considered
                                         Reported
                                      Method/Design
                       increase in risk (95% CI)
           LATIN AMERICA
to
o
o
Borja-Aburto et al.
(1998)
SW Mexico City
1993-1995
All cause;
respiratory;
cardiovascular; other;
all ages; age >65 yrs
24-havg: 5.6ppb
PM2.5, O3, NO2; 2-    0,1,2,3,4,5,
pollutant models     and multiday
Poisson GAM with
default convergence
criteria (only one
smoother). Time-
series study.
SO2 risk estimates not
reported. PM2 5 and O3 were
associated with mortality.
X
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VO
H
6
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o
H
O
o
H
W
O
O
HH
H
W
           Borja-Aburto et al.
           (1997)
           Mexico City
           1990-1992
                       All cause;
                       respiratory;
                       cardiovascular; all
                       ages; age <5 yrs; age
                       >65 yrs
                     24-h avg median:
                     5.3 ppb
                    TSP, O3 CO;
                    2-pollutant models
                   0,1,2
Poisson iteratively
weighted and filtered
least-squares method.
Time-series study.
All-cause:
LagO: 0.2% (-1.1, 1.5)
Cardiovascular:
LagO: 0.7% (-1.6, 3.0)
Respiratory:
LagO: -1.0%(-5.0, 3.2)

-------
             TABLE AX5.5 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE ON MORTALITY
                                                                                              Lag Structure                            Effect Estimates* %
              Reference, Study
            Location, and Period
                                   Outcome Measure
                       Mean SO2 Levels
                       Copollutants
                        Considered
Reported
                                     Method/Design
                                                        increase in risk (95% CI)
          LATIN AMERICA (cont'd)
to
o
o
>
X
           Cakmak et al. (2007)
           7 Chilean urban centers
           1997-2003
All cause;
respiratory;
cardiovascular; all
ages; age
<65 yrs; age
65-74 yrs; age 75-84
yrs; age 85+ yrs
24-h avg ranged from
9.12ppb(LasCondes)
to 64.06 ppb
(Independencia)

Population-weighted
avg concentration:
14.08 ppb
PM10,03,CO
                                                                                             0,1,2,3,4,5,0-5
              Poisson GLM with
              random effects
              between cities.
              Time-series study.
                                                       All cause:
                                                       All ages:
                                                       Single pollutant:
                                                       Lagl: 4.0% (2.4, 5.6)
                                                       Lag 0-5: 6.5% (4.5, 8.5)
                                                       Multipollutant:
                                                       Lagl: 3.2% (1.3, 5.1)

                                                       <65 yrs:
                                                       Lag 0-5: 3.0% (0.6, 5.5)
                                                       65-74 yrs:
                                                       Lag 0-5: 5.1% (1.2, 9.1)
                                                       75-84 yrs:
                                                       Lag 0-5: 7.8% (4.1, 11.6)
                                                       85+ yrs:
                                                       7.8% (4.2, 11.5)
vo
to
                                                                                                                                    Warm season:
                                                                                                                                    Lag 0-5: 7.2% (4.1,10.3)
                                                                                                                                    Cool season:
                                                                                                                                    Lag 0-5: 3.0% (-0.4, 6.5)
H
6
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o
H
O
o
H
W
O
O
HH
H
W
          Cifuentes et al. (2000)
          Santiago, Chile
          1988-1966
                                  All cause
                     24-h avg: 18.1 ppb
PM25,PM10.25,
CO, NO2, O3
                                       1-2
                                  Poisson GAM with
                                  default convergence
                                  criteria;
                                  Poisson GLM. Time-
                                  series study.
                                   Poisson GLM:

                                   Single pollutant:
                                   Lag ^ 0.2% (-0.9, 1.3)

                                   With other pollutants:
                                   Lag 1-2: -0.6%
                                   (-1.7,0.5)

-------
        TABLE AX5.5 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE ON MORTALITY
to
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H

O


o
H
W

O


O
HH
H
W
Reference, Study
Location, and Period
Outcome Measure Mean SO2 Levels
Copollutants Lag Structure
Considered Reported
Method/Design
Effect Estimates* %
increase in risk (95% CI)
LATIN AMERICA (cont'd)
Concei9aoetal. (2001)
Sao Paulo, Brazil
1994-1997


Loomisetal. (1999)
Mexico City
1993-1995
Ostroetal. (1996)
Santiago, Chile
1989-1991
Pereiraetal. (1998)
Sao Paulo, Brazil
1991-1992


Saldivaetal. (1994)
Sao Paulo, Brazil
1990-1991
Saldivaetal. (1995)
Sao Paulo, Brazil
1990-1991


Child mortality (age 24-h avg: 7.4 ppb
under 5 yrs)



Infant mortality 24-h avg: 5. 6 ppb
All cause 1-hmax: 60 ppb

Intrauterine mortality 24-h avg: 6.6 ppb



Respiratory; age 24-h avg: 6.0 ppb
<5yrs
All cause; 24-h avg: 6. 5 ppb
age 65+ yrs


PMio, CO, O3 2



PM2.5,03 0,1,2,3,4,5,3-5
PMio, O3, NO2; 2- 0
pollutant models

PMio, 03, N02, CO 0



PMio, 03, N02, 0-2
CO; multipollutant
models
PMm, O3, NO2, 0-1
CO; 2-pollutant
models


Poisson GAM with
default convergence
criteria. Time-series
study.

Poisson GAM with
default convergence
criteria. Time-series
study.
OLS, Poisson. Time-
series study.

Poisson GLM. Time-
series study.



OLS of raw or
transformed data.
Time-series study.
OLS; Poisson with
GEE. Time-series
study.


Single pollutant:
Lag 2: 17.0% (7.0, 28.0);

With all other pollutants:
Lag2: 13.7%(-1.1, 30.8)
SO2 risk estimates not
reported. PM2 5 and O3 were
associated with mortality.
LagO: 0.7% (-0.3, 1.7)

Single-pollutant model:
11. 5% (-0.3, 24.7)

With other pollutants:
8.6% (-8.7, 29.3)
-1.0% (-47.1, 45.1)
Single pollutant: 8. 5% (1.3,
15.6)
With other pollutants:
-3.1% (-13.0, 6.9)

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         TABLE AX5.5 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE ON MORTALITY
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o
H

O


o
H
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O


O
HH
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W
Reference, Study
Location, and Period
Outcome Measure Mean SO2 Levels
Copollutants Lag Structure
Considered Reported Method/Design
Effect Estimates* %
increase in risk (95% CI)
ASIA
Lee et al. (2000)
7 Korean cities
1991-1997


Leeetal. (1999)
Seoul and Ulsan, Korea
1991-1995


Ha et al. (2003)
Seoul, Korea
1995-1999


Hong et al. (2002)
Seoul, Korea
1995-1998

Kwonetal. (2001)
Seoul, Korea
1994-1998




All cause 24-h avg SO2 ranged
from
12.1 ppb (Kwangju) to
3 1 .4 ppb (Taegu)

All cause 1-h max:

Seoul: 26 ppb

Ulsan: 31 ppb
All cause; 24-h avg: 11.1 ppb
respiratory;
postneonatal(l mo
to 1 yr); age 2-
64 yrs; age 65+
Acute stroke 24-h avg: 12.1 ppb
mortality


Mortality in a 24-h avg: 13. 4 ppb
cohort of patients
with congestive
heart failure



TSP, NO2, O3, CO 0- 1 Poisson GAM with
default convergence
criteria. Time-series
study.

TSP, O3 0-2 Poisson with GEE.
Time-series study.



PM10, O3, NO2, CO 0 Poisson GAM with
default convergence
criteria. Time-series
study.

PMio, O3, NO2, CO 2 Poisson GAM with
default convergence
criteria. Time-series
study.
PMm, O3, NO2, CO 0 Poisson GAM with
default convergence
criteria; case-crossover
analysis using
conditional logistic
regression.

Single pollutant:
Lag 0-1: 0.6% (0.3, 0.8)

Multipollutant:
Lag 0-1: 0.6% (0.2, 0.9)
Seoul:
1.5% (1.1, 1.9)

Ulsan:
1.0% (-0.2, 2.2)
All cause:
Postneonates:
11.3% (4.0, 19.1)
Age 65+ yrs:
3.2% (3. 1,3. 3)
5.2% (1.4, 9.0)



Odds ratio in general
population:
1.0% (-0.1, 2.1)

Congestive heart failure
cohort:
6.9% (-3.4, 18.3)

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        TABLE AX5.5 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE ON MORTALITY
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O


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Reference, Study
Location, and Period
Copollutants
Outcome Measure Mean SO2 Levels Considered
Lag Structure
Reported Method/Design
Effect Estimates* %
increase in risk (95% CI)
ASIA (cont'd)
Lee and Schwartz (1999)
Seoul, Korea
1991-1995


Tsai et al. (2003b)
Kaohsiung, Taiwan
1994-2000




Verniers etal. (2003)
Chonqing, China
1995



Wong et al. (2002b)
Hong Kong
1995-1998



All cause 1-hmax: 26 ppb TSP, O3




All cause; 24-havg: 11. 2 ppb PM10, NO2, O3, CO
respiratory;
cardiovascular;
tropical area



All cause, 24-havg: 74.5 ppb PM2.5
cardiovascular,
respiratory, cancer,
and other


Respiratory; 24-havg: 29 ppb PM10, 03, NO2; 2-
cardiovascular; pollutant models
COPD; pneumonia
and influenza;
ischemic heart dis.;
cerebrovascular
0-2 Conditional logistic
regression. Case-
crossover with
bidirectional control
sampling.
0-2 Conditional logistic
regression. Case-
crossover analysis.




0, 1 , 2, 3, 4, 5 Poisson GLM, time-
series study




0, 1 , 2, 0- 1 , Poisson GLM. Time-
0-2 series study.




Two controls, ± 1 wk:
0.3% (-0.5, 1.0)

Four controls, ± 2 wks:
1.0% (0.3, 1.6)
Odds ratios:
All cause:
1.1% (-4.4, 6.8)
Respiratory:
3. 5% (-17.6, 29. 9)
Cardiovascular:
2.4% (-9. 1,1 5.4)
All cause:
Lag 2: 1.1% (-0.1, 2.4)
Cardiovascular:
Lag 2: 2.8% (0.4, 5.2)
Respiratory:
Lag 2: 3.0% (0.4, 5.7)
Respiratory:
Lag 0-1: 2.6% (0.2, 5.1)
Cardiovascular:
Lag 0-1: 1.2% (-1.0, 3.5)



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TABLE AX5.5 (cont'd). ASSOCIATIONS OF SHORT-TERM EXPOSURE TO SULFUR DIOXIDE ON MORTALITY
<*J
i
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X

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ON


O
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0
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O
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Reference, Study Copollutants Lag Structure
Location, and Period Outcome Measure Mean SO2 Levels Considered Reported Method/Design
ASIA (cont'd)
Wong et al. (2001 b) All cause; 24-h avg: PM10, 03,NO2; 0,1,2 Poisson GAM with
Hong Kong respiratory; Warm season: 2-pollutant models default convergence
1995-1997 cardiovascular 6. 4 ppb criteria. Time-series
Cool season: 6.0 ppb smdy.


Yang et al. (2004b) All cause; 24-h avg: 5.5 ppb PM10, NO2, 03, CO 0-2 Conditional logistic
Taipei, Taiwan respiratory; regression. Case-
1994-1998 cardiovascular; crossover analysis.
subtropical area




AUSTRALIA
Simpson etal. (1997) All cause; 24-h avg: 4.2 ppb PM10, bsp, O3, NO2, 0 Autoregressive
Brisbane, Australia respiratory; CO Poisson with GEE.
1987-1993 cardiovascular 1-hmax: 9.6 ppb Time-series study.







* Effect estimates standardized to 10 ppb incremental change in 24-h avg SO2 or 40 ppb incremental change in 1-h max SO2.










Effect Estimates* %
increase in risk (95% CI)

All cause:
Lagl: 3.2% (1.1, 5. 3)
Respiratory:
LagO: 5. 3% (2.2, 8.6)
Cardiovascular:
Lagl: 4. 3% (1.1, 7.5)
Odds ratios:
All cause:
-0.5% (-7.0, 6.6);
Respiratory:
-1.8% (-23.1, 25. 3);
Cardiovascular:
-3.4% (-15.2, 10.0)


All cause:
All yr:
LagO: -2.8% (-2.7, 8.6)
Summer:
LagO: 2. 8% (-8. 3, 15.2)
Winter:
LagO: 2. 8% (-3. 9, 9.8)















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                          TABLE AX5.6. ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                                                 RESPIRATORY MORBIDITY
              Reference, Study
             Location, and Period
                             Mean SO2 Levels
             Study Description
               Results and Comments
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UNITED STATES and CANADA
>
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           Dockeryetal. (1996)
           18 sites in U.S.
           6 sites in Canada
                         Sulfur Dioxide mean
                         4.8 ppm
                         SD3.5
                         Range 0.2, 12.9
Study of the respiratory health effects of acid
aerosols in 13,369 white children aged 8 to 12 yrs
old from 24 communities in the United States and
Canada between 1988 and 1991.  Information was
gathered by questionnaire and a pulmonary
function.
With the exception of the gaseous acids (nitrous and nitric
acid), none of the particulate or gaseous pollutants,
including SO2, were associated with increased asthma or
any asthmatic symptoms. Stronger associations with
particulate pollutants were observed for bronchitis and
bronchitic symptoms.

Odds Ratio (95% CI) for 12.7 ppb range of SO2 pollution
Asthma 1.05 (057, 1.93)
Attacks of Wheeze 1.07 (0.75, 1.55)
Persistent Wheeze 1.19 (0.80, 1.79)
Any asthmatic symptoms 1.16 (0.80,1.68)
Bronchitis 1.56 (0.95,2.56)
Chronic cough 1.02 (0.66, 1.58)
Chronic phlegm 1.55 (1.01, 2.37)
Any Bronchitic symptoms 1.29 (0.98, 1.71)
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                      TABLE AX5.6 (cont'd). ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                                                    RESPIRATORY MORBIDITY
  Reference, Study
Location, and Period
Mean SO2 Levels
Study Description
                                                                                                                               Results and Comments
           UNITED STATES and CANADA (cont'd)
>
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           Dockeryetal. (1989)
           Watertown, MA;
           St. Louis, MO;
           Portage, WI;
           Kingston-Harriman, TN;
           Steubenville, OH; Topeka,
           KS
           1980-1981 school yr
                         Daily mean concentrations,
                         averaging hourly
                         concentrations for each day
                         with at least 18 hourly
                         values

                         Portage:  4.2 ppb
                         Topeka:  3.5
                         Watertown: 10.5
                         Kingston: 6.5
                         St. Louis: 13.5
                         Steubenville: 27.8
                       Cross-sectional assessment of the association
                       between air pollution and chronic respiratory
                       health of 5,422 (10-12 yrs) white children
                       examined in the 1980-1981 school yr. Children
                       were part of the cohort of children in the Six Cities
                       Study  of Air pollution and Health. Symptoms
                       were analyzed using logistic regression that
                       included sex, age, indicators of parental education,
                       maternal smoking, indicator for gas stove, and an
                       indicator for city.  Respiratory symptoms
                       investigated were bronchitis, chronic cough, chest
                       illness, persistent wheeze, asthma. The logarithm
                       of pulmonary function was fitted to a multiple
                       linear regression model that included sex, sex-
                       specific log of height, age, indicators of parental
                       education, maternal smoking, a gas stove indicator,
                       and city indicator. Annual means of the 24 h avg
                       air pollutant concentration for the 12 mos
                       preceding the examination of each child was
                       calculated for each city.
                                 No significant associations between SO2 and any
                                 pulmonary function measurements. No significant
                                 association between SO2 and symptoms.

                                 Relative odds and 95% CI between most/least polluted
                                 cities:
                                 Bronchitis:  1.5(0.4,5.8)
                                 Chronic cough: 1.8 (0.3, 12.5)
                                 Chest illness:  1.5(0.4,5.9)
                                 Persistent wheeze:  0.9(0.4,1.9)
                                 Asthma: 0.6(0.3,1.2)

                                 Reference symptoms:
                                 Hay fever: 0.6(0.2,1.7)
                                 Earache: 1.2(0.3,5.3)
                                 Nonrespiratory illness:  1.0 (0.6, 1.5)

                                 Analysis stratified by asthma or persistent wheeze
                                 bronchitis
                                 No wheeze or asthma 1.5 (0.5, 4.3)
                                 Yes wheeze or asthma 2.0 (0.3,  14.3)

                                 Chronic cough
                                 No wheeze or asthma 2.4 (0.5, 11.7)
                                 Yes wheeze or asthma 1.9 (0.1, 44.1)

                                 Chest illness
                                 No wheeze or asthma 1.5 (0.4, 5.6)
                                 Yes wheeze or asthma 1.9 (0.3,  13.0)

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                     TABLE AX5.6 (cont'd).  ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                                                  RESPIRATORY MORBIDITY
              Reference, Study
            Location, and Period
                                         Mean SO2 Levels
              Study Description
               Results and Comments
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           UNITED STATES and CANADA (cont'd)
>
X
          Euleretal. (1987)
          California, USA
                                    None provided
Cross-sectional study of 7,445 (25 yrs or older)
Seventh-Day Adventists who lived in their 1977
residential areas (Los Angeles and it border
counties, San Francisco, and San Diego) for at
least 10 yrs to determine the effect of long-term
cumulative exposure to ambient levels of TSP and
SO2 on COPD symptoms. Study population is
subgroup of NCI-funded ASHMOG study that
enrolled 36,805 Seventh-Day Adventists in 1974.
Each participant's cumulative exposure to the
pollutant exceeding 4 different threshold levels
were estimated using  moly residence ZIP code
histories and interpolated dosages from state
monitoring stations.  Participants completed a
questionnaire on respiratory symptoms, smoking
history, occupational history, and residence
history.
Study reported that SO2 exposure was not associated with
symptoms of COPD until concentrations exceeded 4 ppm.
The correlation coefficient of SO2 (above 4 ppm) with TSP
(above 200 ug/m3) the highest exposure levels for these two
pollutants was 0.30; thus, the authors believed that it was
possible to separate the effects of SO2 from TSP. Multiple
regressions used in the analysis.  No significant effect at
exposures levels below 4 ppm or above 8 ppm.

Relative risk estimate (based on  1,003 cases)
SO2 exposure above 2 ppm during 11 yrs of study
 2000 h/yr:  1.09
 lOOOh/yr: 1.04
 500 h/yr:  1.03

SO2 exposure above 4 ppm
 500 h/yr:  1.18
 250 h/yr:  1.09
 100 h/yr:  1.03
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                                                                                                            SO2 above 8 ppm
                                                                                                             60 h/yr: 1.07
                                                                                                             30 h/yr: 1.03
                                                                                                             15 h/yr: 1.02

                                                                                                            SO2 above 14 ppm
                                                                                                             10 h/yr: 1.03
                                                                                                             5 h/yr: 1.01
                                                                                                             Ih/yr: 1.00

-------
                      TABLE AX5.6 (cont'd).  ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                                                   RESPIRATORY MORBIDITY
               Reference, Study
             Location, and Period
                              Mean SO, Levels
                                         Study Description
                                                              Results and Comments
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UNITED STATES and CANADA (cont'd)
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           Goss et al. (2004)
           U.S. nationwide
           1999-2000
                          Mean(SD): 4.91
                          (2.6) ppb
                          Median: 4.3 ppb
                          IQR: 2.7-5.9 ppb
McDonnell etal. (1999)
California, U.S.
1973-1992
Mean:  SO2 6.8 ug/m3
Range: 0.0-10.2 ug/m3

Correlation coefficient
r = 0.25 with O3
Cohort study of 18,491 cystic fibrosis patients over
6 yrs of age who were enrolled in the Cystic
Fibrosis Foundation National Patient Registry in
1999 and 2000. Mean age of patients was 18.4 yrs;
92% had pancreatic insufficiency. Air pollution
from the Aerometric Information Retrieval System
linked with patient's home ZIP code. Air
pollutants studied included O3, NO2, SO2, CO,
PM10, and PM2 5.  Health endpoints of interest were
pulmonary exacerbations, lung function, and
mortality. However, study did not have enough
power to assess the outcome of mortality.  Logistic
regression and polytomous regression models that
adjusted for sex, age, weight, race, airway
colonization, pancreatic function, and insurance
status were used.

Prospective study (over 15 yrs) of 3,091
nonsmokers aged 27-87 yrs that evaluated the
association between long-term ambient O3
exposure and the development of adult-onset
asthma. Cohort consisted of nonsmoking, non-
Hispanic white, California Seventh Day Adventists
who were enrolled in 1977 in the AHSMOG study.
Logistic regression used to assess the association
between the 1973-1992 mean 8-h avg ambient O3
concentration and the 1977-1992 incidence of
doctor-told asthma.  Levels of PM10, NO2, and SO4
were measured but no effect estimates were given.
                                                                          With the single-pollutant model, no significant association
                                                                          between SO2 and pulmonary exacerbations.

                                                                          Odds ratio per 10 ppb increase in SO2:
                                                                          0.83 (95% CI:  0.71, 1.01), p = 0.068

                                                                          No clear association between pulmonary function and SO2.
                                                                          No effect estimates provided.
No significant positive association between SO2 and asthma
for males or females. Addition of a second pollutant to the
O3 model for the male subjects, did not result in a decrease
of more than 10% in the magnitude of the regression
coefficient for O3, and for the females addition did not
cause the coefficient for O3 to become significantly positive

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                      TABLE AX5.6 (cont'd).  ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                                                   RESPIRATORY MORBIDITY
               Reference, Study
             Location, and Period
                              Mean SO2 Levels
                                         Study Description
                                                              Results and Comments
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EUROPE
           Ackermann-Liebrich et al.
           (1997)
           8 communities in
           Switzerland
           Aarau, Basel, Davos,
           Geneva, Lugano,
           Montana, Payerne, and
           Wald
           1991-1993
                          Mean SO2 in 1991 (ug/m3)
                          Mean:  11.7
                          SD = 7.1
                          Range: 2.5,25.5
                           Cross-sectional population based study of 9,651
                           adults (18-60 yrs) in 8 areas in Switzerland
                           (SAPALDIA), to evaluate the effect of long-term
                           exposure of air pollutants on lung function.
                           Examined the effects of SO2, NO2, O3, TSP, and
                           PM10. Participants were given a medical exam that
                           included questionnaire data, lung function tests,
                           skin prick testing, and end-expiratory CO
                           concentration. Subjects had to reside in the area
                           for at least 3 yrs to be in the study.
                                               Mean values of SO2, PM10, andNO2 were significantly
                                               associated with reduction in pulmonary function.  SO2 was
                                               correlated with PM30 (r = 0.78), PM10 (r = 0.93) and NO2 (r
                                               = 0.86). Authors stated that the association with SO2
                                               disappeared after controlling for PM10 but no data was
                                               shown.

                                               Regression coefficients and 95% CI in healthy never
                                               smokers (perlO ug/m3 increase in annual  avg SO2)

                                               FVC:  -0.0325 (-0.0390,-0.0260)
                                               FEVj: -0.0125 (-0.0192,-0.0058)
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Braun-Fahrlander et al.
(1997)
10 communities in
Switzerland
Anieres, Bern, Biel,
Geneva, Langnau, Lugano,
Montana, Pay erne,
Rheintal, Zurich
1992-1993
Annual mean SO2 (ug/m3)

Lugano: 23
Geneva: 13
Zurich:  16
Bern: 11
Anieres:  4
Biel:  15
Rheintal: 8
Langnau: NA
Payerne:  3
Montan: 2
Cross-sectional study of 4,470 children
(6-15 yrs) living in 10 different communities in
Switzerland to determine the effects of long term
exposure to PM10, NO2, SO2, and O3 on respiratory
and allergic symptoms and illnesses. Part of the
Swiss Study on Childhood Allergy and Respiratory
Symptoms with Respect to Air Pollution
(SCARPOL).
This study reported that the annual mean SO2, PM10, and
NO2 were positively and significantly associated with
prevalence rates of chronic cough, nocturnal dry cough, and
bronchitis and conjunctivitis symptoms.  Strongest
association found with PM10. However, there was no
significant association between SO2 and asthma or allergic
rhinitis.

Adjusted relative odds between the most/least polluted
community 2-23 ug/m2 (0.8, 8.8 ppb)
Chronic cough: 1.57(1.02,2.42)
Nocturnal dry cough: 1.66 (1.16,2.38)
Bronchitis:  1.48(0.98,2.24)
Wheeze: 0.88(0.54,1.44)
Asthma (ever): 0.74(0.45,1.21)
Sneezing during pollen season: 1.07 (0.67, 1.70)
Hay fever: 0.84(0.55,1.29)
Conjunctivitis symptoms: 1.74 (1.22, 2.46)
Diarrhea: 1.02(0.75,1.39)

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                      TABLE AX5.6 (cont'd).  ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                                                    RESPIRATORY MORBIDITY
               Reference, Study
             Location, and Period
                              Mean SO2 Levels
                                         Study Description
                                                              Results and Comments
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EUROPE (cont'd)
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           Charpinetal. (1999)
           Etang de Berre area of
           France:  Aries, Istres, Port
           de Bouc, Rognac-Velaux,
           Salon de Provence,
           Sausset, Vitrolles
           Jan-Feb 1993
Frischer et al. (2001)
Nine communities in
Austria
Sep-0ctl997
                          24-h mean (SD) SO2
                          (ug/m3)

                          Aries: 29.7(15.5)
                          Istres: 23.8(12.7)
                          Port de Bouc: 32.3(24.5)
                          Rognanc-Velaux:
                          39.5(21.8)
                          Salon de Provence:
                          17.3(11.6)
                          Sausset: 29.0(28.7)
                          Vitrolles:  57.4(32.0)
'/2-hour avg SO2:

30-day mean 2.70 ppb
IQR2.1ppb
Cross-sectional cohort study of 2,073 children (10-
11 yrs) from 7 communities in France (some with
the highest photochemical exposures in France) to
test the hypothesis that atopy is greater in towns
with higher photochemical pollution levels. Mean
levels of SO2, NO2, and O3 were measured for 2
mos in 1993. Children tested for atopy based on
skin prick test (house dust mite, cat dander, grass
pollen, cypress pollen, and Altemaria). To be
eligible for the study, subjects must have resided in
current town for at least 3 yrs.  Questionnaire filled
out by parents that included questions on
socioeconomic status and passive smoking at
home.  Two-mo mean level of air pollutants used
in logistic regression analysis.

Cross-sectional cohort study of 877 children (mean
age 11.2 yrs) living in 9 sites with different O3
exposures. Urinary eosinophil protein U-EPX)
measured as a marker of eosinophil activation. U-
EPX determined from a single spot urine sample
analyzed with linear regression models.
                                                                          Study did not demonstrate any association between air
                                                                          pollution and atopic status of the children living in the
                                                                          seven communities, some with high photochemical
                                                                          exposures. A limitation of study is that authors did not
                                                                          consider short-term variation in air pollution and did not
                                                                          have any indoor air pollution measurements.
No significant association between SO2 and U-EPX

Regression coefficient and SE -10.57 (0.25) per ppb SO2
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                      TABLE AX5.6 (cont'd).  ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH
            	RESPIRATORY MORBIDITY	
              Reference, Study
             Location, and Period
                            Mean SO2 Levels
                Study Description
              Results and Comments
to
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EUROPE (cont'd)
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           Frischeretal. (1999)
           Nine communities in
           Austria
           1994-1996
           Frye et al. (2003)
           Zerbst, Hettstedt,
           Bitterfeld,East Germany,
           1992-93, 1995-1996,
           1998-1999
                        Annual mean SO2 (ppb) in
                        1994

                        Amstetten:  3.75
                        St. Valentin: 3.00
                        Krems: 3.75
                        Heidenreichstein: 4.13
                        Gansemdorf: 5.63
                        Mistelbach: 5.25
                        Wiesmath:  6.00
                        Bruck: 4.88
                        Pollau: 2.25
                        Used avg of annual means
                        of pollutants 2 yrs
                        preceding health
                        measurement

                        High of 113 ug/m3 (in
                        Bitterfeld) to a low of
                        6 ug/m .  (Pollution values
                        only described in figure)
Longitudinal cohort study of 1150 children (mean age
7.8 yrs) to investigate the long-term effects of O3 on
lung growth. Children were followed for 3 yrs and lung
function was recorded biannually, before and after
summertime. The dependant variables were change in
FVC, FEVi, and MEF50. The 9 sites were selected to
represent a broad range of O3 exposures. GEE models
adjusted for baseline function, atopy, gender, site,
environmental tobacco smoke exposure, season, and
change in height. Other pollutants studied included
PM10, SO2, andNO2.
Three consecutive cross-sectional surveys of children
(11-14 yrs) from three communities in East Germany.
Parents of 3,155 children completed a questionnaire on
symptoms. Lung function tests performed on
2,493 children. Study excluded children if they lived
for less than 2 yrs in current home and if their previous
home was more than 2 km away. The log-transformed
lung function parameters were used as the response
variables in a linear regression analysis that controlled
for sex, height, season of examination, lung function
equipment, parental education, parental atopy, and
environmental tobacco smoke. Used avg of annual
means of pollutants 2 yrs preceding each survey.
No consistent association observed between lung
function and SO2, NO2 and PM10.  A negative effect
estimate was observed during the summer and a positive
estimate during the winter.

Change in lung function (per ppb SO2):
FEVj (mL/day):
Summer: -0.018 (0.004), p< 0.001
Winter :  0.003 (0.001), p < 0.001

FVC (mL/day):
Summer: -0.009 (0.004), p = 0.02
Winter:  0.002 (0.001), p = 0.03

MEF50 (mL/s/day):
Summer: -0.059 (0.010), p< 0.001
Winter:  0.003 (0.003), p = 0.26

The annual mean TSP declined from 79 to 25 ug/m3 and
SO2 from 113 to 6 ug/m3 and the mean FVC and FEVj
increased from 1992-1993 to 1998-1999.  Study
concluded that reduction of air pollution in a short time
period may improve children's lung function.

Percent change of lung function for a 100-ug/m3
decrease in SO2 2 yrs before the investigation
(n=  1,911)
FVC: 4.9(0.7,9.3)
FEVi: 3.0 (-1.1, 7.2)
FEVj/FVC:  -1.5 (-3.0, 0.1)

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                      TABLE AX5.6 (cont'd). ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                                                    RESPIRATORY MORBIDITY
               Reference, Study
             Location, and Period
                                  Mean SO2 Levels
                                              Study Description
                                                                           Results and Comments
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           Heinrich et al. (2002)
           Reunified Germany
           Bitterfeld, Hettstedt,
           Zerbst
           1992-1993, 1995-1996,
           1998-1999
                          SO2 concentration in ug/m

                          Yr    Zerbst   Bitterf.   Hettst.
                          1991   78      113       84
                          1992   58       75       46
                                 42
1993
1994
1995
1996
1997
1998
                                             29
                                             21
                                             25
                                             13
60
35
30
24
13
 9
49
38
26
25
13
 6
Three cross-sectional surveys of children (5-
14 yrs) from 3 areas that were formerly part of
East Germany to investigate the impact of
declines in TSP and SO2 on prevalence of
nonallergic respiratory disorders in children.
Study excluded children if they lived for less
than 2 yrs in current home and if their
previous home was more than 2 km away.
GEE used for analysis.
Study found that SO2 exposure was significantly
associated with prevalence of bronchitis, frequent colds,
and febrile infections. While results are reported as risk
for an increase in air pollutant, the respiratory health of
children improved with declines in TSP and SO2.
Authors concluded that exposure to combustion-derived
air pollution is causally related to nonallergic respiratory
health in children.

Odds ratio and 95% CI: (per 100 ug/m3 in 2 yr mean
S02)
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                                                                                                       All children:
                                                                                                       Bronchitis:  2.72(1.74,4.23)
                                                                                                       Otitis media: 1.42(0.94,2.15)
                                                                                                       Sinusitis: 2.26 (0.85, 6.04)
                                                                                                       Frequent colds: 1.81(1.23,2.68)
                                                                                                       Febrile infections:  1.76 (1.02, 3.03)
                                                                                                       Cough in morning: 1.10(0.73,1.64)
                                                                                                       Shortness of breath: 1.31(0.84,2.03)

                                                                                                       Children without indoor exposures (living in damp
                                                                                                       houses with visible molds, ETS in the home, gas
                                                                                                       cooking emissions, and contact with cats)
                                                                                                       Bronchitis:  4.26(2.15,8.46)
                                                                                                       Otitis media: 1.43 (0.73, 2.81)
                                                                                                       Sinusitis: 2.95 (0.52,16.6)
                                                                                                       Frequent colds: 2.29(1.15,4.54)
                                                                                                       Febrile infections:  1.75 (0.78, 3.91)
                                                                                                       Cough in morning: 1.00(0.38,2.64)
                                                                                                       Shortness of breath: 2.07(0.90,4.75)

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                     TABLE AX5.6 (cont'd).  ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                                                   RESPIRATORY MORBIDITY
               Reference, Study
             Location, and Period
                              Mean SO2 Levels
              Study Description
               Results and Comments
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           Herbarthetal. (2001)
           East Germany
           1993-1997
                          Avg lifetime exposure
                          burden of SO2(ug/m3)

                          KIGA: 142
                          LISS:  48
                          LESS: R47
                          KIGA-IND: 59
Meta-analysis of three cross-sectional studies: (1)
Study on Airway Diseases and Allergies among
Kindergarten Children (KIGA), (2) the Leipzig
Infection, Airway Disease and Allergy Study on
School starters (LISS), and (3) KIGA-IND, which
was based on the KIGA design but conducted in 3
differentially polluted industrial areas.  A total of
3,816 children participated in the three studies.
Analysis of data from parent-completed
questionnaires to determine the effect of life time
exposure to SO2 and TSP on the occurrence of
acute bronchitis. Total lifetime exposure burden
corresponds to the exposure duration from birth to
time of the study. The LISS study was divided in
to LISS-U for the urban area and  LISS-R for the
rural area.  Logistic regression analysis used that
adjusted for predisposition in the  family (mother or
father with bronchitis), ETS, smoking during
pregnancy or in the presence of the pregnant
This study found the highest bronchitis prevalence in the
KIGA cohort and the lowest in the LISS cohort, which is
consistent with the SO2 concentrations in these cohorts.
Study found a correlative link between SO2 and bronchitis
(R = 0.96, p < 0.001) but not TSP (R = 0.59).  Results of
study suggest that SO2 may be a more important factor than
TSP in the occurrence of bronchitis in these study areas.

Odds ratio for bronchitis adjusted for parental
predisposition, smoking, and lifetime exposure to SO2 and
TSP (2-pollutant model).

SO2: 3.51(2.56,4.82)
TSP: 0.72(0.49,1.04)
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                     TABLE AX5.6 (cont'd).  ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                                                  RESPIRATORY MORBIDITY
               Reference, Study
             Location, and Period
                              Mean SO2 Levels
              Study Description
              Results and Comments
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           Horak et al. (2002)
           Eight communities in
           Austria
           1994-1997
                         Seasonal mean SO2 ug/m
                         Winter:
                         Mean:  16.8
                         Range: 7.5,37.4

                         Summer:
                         Mean: 6.9 ug/m3
                         Range: 3.1,11.7
Longitudinal cohort study that continued the work
of Frischer et al. (1999) by adding one more yr of
data and analyzing the effects of PM10 in addition
to SO2, NO2, and O3.  At the beginning of the study
975 children (mean age 8.11 yrs) were recruited for
the study, but only 80.6% of the children
performed all 6 lung function tests (twice a yr).
The difference for each lung function parameter
between two subsequent measures was divided by
the days between measurements and presents as
difference per day (dpd) for that parameter.
860 children were included in the GEE analysis
that controlled for sex, atopy, passive smoking,
initial height, height difference, site, and initial
lung function.
Moderate correlation between PM10 and SO2 in the winter
(r = 0.52).  In a one-pollutant model for SO2, long term
seasonal mean concentration of SO2 was had a positive
association with FVC dpd and FEV! dpd in the winter, but
no effect on MEF25_75 dpd. In a two-pollutant model with
PMio, wintertime SO2 had a positive association with
FEVj dpd.

Single-pollutant model
FVC dpd:
Summer: 0.009, p = .336
Winter:  0.006, p = .009

FEVj dpd:
Summer:  0.005, p = 0.576
Winter:  0.005, p = 0.013

MEF25.75:
Summer: 0.015, p = 0.483
Winter:  0.003, p = 0.637

Two-pollutant model:
SO2+ PM10
FVC dpd:
Summer: 0.008, p = 0.395
Winter:  0.004, p = 0.225

FEVj dpd:
Summer:  0.010(0.271)
Winter:  0.007(0.025)

MEF25.75 dpd:
Summer:  0.037, p = 0.086
Winter:  0.007, p = 0.429

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                     TABLE AX5.6 (cont'd).  ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                                                  RESPIRATORY MORBIDITY
               Reference, Study
             Location, and Period
                                  Mean SO2 Levels
                Study Description
        Results and Comments
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           Kopp et al. (2000)
           Ten communities in
           Austria and
           SW Germany
                         Mean SO2 (95% CI) ppb
                         Apr-Sep 1994
                         Amstetten:  3.7(0.7,3.9)
                         St Valentin: 2.6(1.5,5.2)
                         Krems: 3.7(0.7,7.5)
                         Villingen:  0.7(0,3.0)
                         Heindenreichstein: 3.7, (0.7, 7.5)
                         Gansemdorf: 3.7(0.7,11.2)
                         Mistelbach: 3.7(0.7,7.5)
                         Wiesmath:  6.3(3.4,9.4)
                         Bruck: 1.5(0.7,4.1)
                         Freudenstadt: 0.7(0,3.0)

                         Octl994-Marl995
                         Amstetten:  3.7(0.7,7.5)
                         St Valentin: 3.0(1.1,9.4)
                         Krems: 3.7(0.7,11.0)
                         Villingen: 1.9(0,3.0)
                         Heindenreichstein: 3.7(0.7,15.0)
                         Gansemdorf: 3.7(0.7,22.5)
                         Mistelbach: 3.7(0.7,22.5)
                         Wiesmath:  2.23(0.7,10.1)
                         Bruck: 15(1.1,7.9)
                         Freudenstadt:  1.57 (0.4, 5.3)

                         Apr-Sep 1995
                         Amstetten:  3.7(0.7,3.8)
                         St Valentin: 2.6(1.1,6.8)
                         Krems: 3.7(0.5,3.8)
                         Villingen: 0.7(0,2.6)
                         Heindenreichstein: 0.7 (0.5, 0.9)
                         Gansemdorf: 3.7(0.7,7.5)
                         Mistelbach: 3.7(0.7,7.5)
                         Wiesmath:  7.5 (0.7, 14.9)
                         Bruck: 3.7(0.4,4.9)
                         Freudenstadt: 0.7(0,3.4)
Longitudinal cohort study of 797 children (mean age
8.2 yrs) from 2nd and 3rd grades of 10 schools in
Austria and SW Germany to assess the effects of
ambient O3 on lung function in children over a
2-summer period. Study also examined the association
between avg daily lung growth and SO2, NO2, and
PM10. Each child performed 4 lung function tests
during spring 1994 and summer  1995. ISAAC
questionnaire used for respiratory history. Linear
regression models used to assess effect of air pollutants
on FVC and FEVi, which were surrogates of lung
growth.
Lower FVC and FEV! increases observed
in children exposed to high ambient O3
levels vs. those exposed to lower levels in
the summer. This study found no effect of
SO2 and PM10 on FVC increase during the
summer of 1995 and winter 1994/1995,
however, SO2 was negatively associated
with FVC during the summer of 1994.

Change in FVC (per ppb SO2)
Summer 1994:  -0.044,  p = 0.006
Winter 1994/95: 0.007, p = 0.243
Summer 1995:  0.045, p = 0.028

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                      TABLE AX5.6 (cont'd). ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                                                    RESPIRATORY MORBIDITY
               Reference, Study
             Location, and Period
                              Mean SO2 Levels
              Study Description
               Results and Comments
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           Kramer etal. (1999)
           East and West Germany,
           1991 to 1995
                          East Germany 2-yr avg
                          concentration ranged from
                          45 to 240 ng/m3

                          West Germany 2-yr avg
                          concentration ranged from
                          18-33
Repeated cross-sectional studies between 1991 and
1995 on 7-yr-old children in East Germany and
between 1991 and 1994 in West Germany.
Comparison of prevalence of airway diseases and
allergies in East and West Germany during the first
five yrs after reunification. A total of 19,090
children participated in the study.  Logistic
regression used to assess the effect of SO2 and TSP
on airway diseases and allergies. Analysis
performed on 14,144 children with information on
all covariates of interest.
All infectious airway diseases and irritation of the airways
was associated with either SO2 or TSP in East Germany in
1991. The decrease of pollution between 1991 and 1995
had a favorable effect on the prevalence of these illnesses.
SO2 was significantly associated with more than 5 colds in
the last 12 mos, tonsillitis, dry cough in the last 12 mos, and
frequent cough in 1991-1995.

Odds ratio and 95% CI: (per 200 |ig/m3 SO2) in East
Germany areas, 1991-1995 for children living at least 2 yrs
in the areas, adjusted for time trend:

Infectious airway diseases
Pneumonia ever diagnosed:  1.17 (0.85, 1.62)
Bronchitis ever diagnosed: 0.85(0.68, 1.05)
>5 colds in last 12 mos:  1.55 (1.18, 2.04)
Tonsillitis in the last 12 mos: 1.89 (1.49, 2.39)
Dry cough in the last 12 mos: 1.46(1.12, 1.91)
Frequent cough ever: 2.51 (1.79. 3.53)

Allergic diseases and symptoms:
Irritated eyes in the last 12 mos:  1.06 (0.66, 1.70)
Irritated nose in the last 12 mos:  1.26 (0.96, 1.66)
Wheezing ever diagnosed: 0.68 (0.46,1.01)
Bronchial asthma ever diagnosed: 2.73 (1.24, 6.04)
Hay fever ever diagnosed: 0.60 (0.24, 1.52)
Eczema ever diagnosed: 0.87 (0.65,1.18)
Allergy ever diagnosed:  0.93 (0.67, 1.29)

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                      TABLE AX5.6 (cont'd).  ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH
           	RESPIRATORY MORBIDITY	
              Reference, Study
            Location, and Period
                                Mean SO2 Levels
              Study Description
               Results and Comments
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           Penard-Morand et al.
           (2005)
           Six communities in
           France: Bordeaux,
           Clermont-Ferrand,
           Creteil, Marseille,
           Strasbourg and Reims
           Mar 1999-Oct 2000
                         Estimated 3-yr avg
                         concentrations at 108 schools

                         Low cone: 4.6 ug/m3
                         (range: 1.3,7.4),
                         High cone:  9.6 ug/m3
                         (range 7.7, 13.7)
Cross-sectional study of 4,901 children
(9-11 yrs) form 108 randomly selected schools in
6 cities to assess the association between long-
term exposure to background air pollution (NO2,
SO2, PMio, O3) and atopy and respiratory
outcomes. Analysis restricted to children who
had lived at least the last 3 yrs in their house at
the time of the examination.  Analysis used three
yr avgd air pollutant concentrations at the
children's schools. Parents completed
questionnaire on respiratory and allergic
disorders (asthma, allergic rhinitis [AR], and
atopic dermatitis) and children underwent
examination that included a skin prick test to
assess allergic sensitization, evidence of visible
flexural dermatitis and measure of exercise-
induced bronchial reactivity (EIB).
Increased concentrations of SO2 were significantly
associated with an increased risk of EIB, lifetime asthma
and lifetime AR.  Past yr wheeze and asthma were also
associated with SO2. In a two-pollutant model with PM10,
significant associations were observed between SO2 and
EIB and past yr wheeze.

Odds ratio and 95% CI (per 5 ug/m3  SO2)
EIB: 1.39(1.15,  1.66), p< 0.001
Flexural dermatitis: 0.86 (0.73, 1.02), p < 0.10
Past yr wheeze:  1.23(1.0, 1.51), p< 0.05
Past yr asthma: 1.28(1-00, 1.65), p< 0.01
Past yr rhinoconjunctivitis: 1.05 (0.89, 1.24)
Past yr atopic dermatitis: 1.01 (0.86, 1.18)
Lifetime asthma:  1.19 (1.00, 1.41), p< 0.10
Lifetime allergic rhinitis:  1.16 (1.01, 1.32), p < 0.05
Lifetime atopic dermatitis: 0.93 (0.82,1.05)
Two-pollutant model with PM10
EIB: 1.46(1.12,1.90)
Past yr wheeze:  1.45 (1.09, 1.93)
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           Ramadour et al. (2000)
           Seven towns in SE
           France
           Jan-Feb 1993
                         Mean (SD) ug/m3 of SO2 during
                         2-mo period

                         PortdeBouc: 32.3(24.5)
                         Istres: 23.8(12.7)
                         Sausset: 29.0(28.7)
                         Rognanc-Velaux: 39.5 (21.8)
                         Vitrolles:  57.4(32.0)
                         Aries: 29.7(15.5)
                         Salon:  17.3(11.6)
Cross-sectional cohort study of 2,445 children
(age 13-14 yrs) who had lived for at least 3 yrs in
their current residence to compare the levels of
O3, SO2, and NO2 to the prevalence rates of
rhinitis, asthma, and asthmatic symptoms.  Some
of the communities had the heaviest
photochemical exposure in France. Subjects
completed ISAAC survey of asthma and
respiratory symptoms. Analysis conducted with
logistic regression models  that controlled for
family history of asthma, personal history of early
-life respiratory diseases, and SES. Also
performed simple univariate linear regressions.
Study found no relationship between mean levels of SO2,
NO3, or O3 and rhinitis ever, 12-mo rhinitis,
rhinoconjunctivitis, and hay fever or asthmatic symptoms.
Simple regression analyses of respiratory outcomes vs.
mean SO2 levels in the 7 towns indicated that nocturnal
dry cough was associated with mean SO2 levels (r =
0.891). Potential confounding across towns.

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                      TABLE AX5.6 (cont'd). ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                                                    RESPIRATORY MORBIDITY
               Reference, Study
             Location, and Period
                              Mean SO2 Levels
              Study Description
               Results and Comments
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           Soysethetal. (1995)Ardal
           and Laerdal, Norway
           winter seasons 1989-92
                          Median SO2

                          37.1 ug/m3 at ages
                          0-12 mos

                          37.9 ug/m3 at
                          ages 13-36 mos
           Garcia-Marcos et al.
           (1999)
           Cartagena, Spain
           winter 1992
                          Annual mean SO2 (ug/m3)
                          Polluted areas 75 ug/m3
                          Nonpolluted areas:
                          20 ug/m
Cross-sectional study of 529 children
(aged 7-13 yrs) to determine whether exposure to
SO2 during infancy is related to the prevalence of
bronchial hyperresponsiveness (BHR). A sulfur
dioxide emitting aluminum smelter is present in
Ardal, but there is no air polluting industry in
Laerdal. Parents filled out questionnaire regarding
family history of asthma, type of housing,
respiratory symptoms and parent's smoking habits.
Spirometry was performed on each child and
bronchial hyperactivity was determined by
methacholine challenge or reversibility test.  Skin
prick test done to assess atopy.  Also examined, the
effects of fluoride.

A total of 340 children (10-11 yrs) living in and
attending schools within a polluted and a relatively
nonpolluted area were included in this study which
aimed to establish the relative contribution
socioeconomic status, parental smoking,  and air
pollution on asthma symptoms, spirometry, and
bronchodilator response. Parents completed
questionnaire on respiratory symptoms and risk
factors including, living in polluted area, maternal
smoking, paternal smoking, number of people
living in the house, proximity to heavy traffic
roads. Spirometry was performed before and after
an inhaled 0.2 mg fenoterol was delivered to
determine bronchodilator response.
Bronchodilator response was considered positive if
the FVC after fenoterol was increased by at least
10% or PEF by 12%. Logistic regression included
as independent variables all the risk factors.
This study found that the risk of BHR was associated with
SO2 exposure at 0-12 mos

Odds ratio for BHR (per 10 ug/m3 SO2) for various ages at
exposure
0-12 mos:  1.62(1.11,2.35)
13-36 mos: 1.40(0.90,2.21)
37-72 mos: 1.19(0.77,1.82)
73-108 mos: 1.19(0.63,2.22)
This study found that living in the polluted areas reduced
the risk of a positive bronchodilator response (RR = 0.61,
p = 004).

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                     TABLE AX5.6 (cont'd). ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                                                   RESPIRATORY MORBIDITY
               Reference, Study
             Location, and Period
                            Mean SO2 Levels
             Study Description
                 Results and Comments
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           Gokirmak et al. (2003)
           Malatya, Turkey
                          SO2 cone ranged from
                          106.6 to 639.2 ppm in
                          9 apricot farms.

                          Mean cone around
                          sulfurization chamber:
                          324.1(35.1) ppm
Study on occupational exposure to SO2 in apricot
sulfurization workers that investigated the role of
oxidative stress resulting exposure to high
concentrations of SO2 on bronchoconstriction.
Forty workers (mean age: 28 yrs, range
16-60 yrs) who have been working in apricot
sulfurization for 20-25 days each yr and
20 controls (mean age: 29 yrs, range 17-42) who
had no SO2 exposure participated in the study.
Activities of antioxidant enzymes (glutathione
peroxidase [GSH-Px], superoxide dismutase
[SOD] and catalase) malondialdehyde (MDA)
concentrations (marker of lipid peroxidation), and
pulmonary function test measured in subjects.
SOD, GSH-Px, and catalase activities were lower and
malondialdehyde concentrations were higher in the apricot
sulfurization workers compared to controls.  Pulmonary function
decreased after SO2 exposure among the apricot sulfurization
workers. Authors concluded that occupational exposure to high
concentrations of SO2 enhances oxidative stress and that lipid
peroxidation may be a mechanism of SO2 induced
bronchoconstriction.

Apricot sulfurization workers vs. controls
Mean (SD)
SOD (U/mL):  2.2 (0.6) vs. 3.2 (0.7) U/m , p < 0.0001
Glutathione peroxidase (U/mL): 0.6 (0.3) vs. 1.1 (0.3),
p< 0.0001
Catalase (L/L): 107.6 (27.4) vs. 152.6 (14.3), p < 0.0001
MDA(nmol/L): 4.1(0.9) vs. 1.9 (5.3), p<  0.0001

Before vs. after SO2 exposure among apricot sulfurization
workers
Mean (SD)
FVC (% predicted) 88 (17) vs.  84 (16), p <  0.001
FEVj (% predicted) 98 (14) vs. 87 (14), p <  0.001
FEVV1/FVC:  92 (7) vs. 86 (9), p < 0.001
FEF25-75% (% predicted) 108 (19) vs. 87 (23), p < 0.001

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                      TABLE AX5.6 (cont'd). ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH
            	RESPIRATORY MORBIDITY	
              Reference, Study
            Location, and Period
                               Mean SO, Levels
              Study Description
              Results and Comments
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EUROPE (cont'd)
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           Hirschetal. (1999)
           Dresden, Germany
                         Mean(ug/m3): 48.3
                         Range:  29.0-69.3
                         25-75 percentile 42.7-54.3
Cross sectional study to relate the prevalence of
respiratory and allergic diseases in childhood to
measurements of outdoor air pollutants.
5,421 children ages 5-7 yrs and 9-11 yrs were
evaluated by questionnaires, skin-prick testing,
venipuncture for (Ig)E, lung function, and
bronchial challenge test.
Sox was positively associated with current morning
cough but not with bronchitis.

Prevalence odds ratio (95% CI) for symptoms within
past 12 mos, +10 ug/m3:
Wheeze:
Atopic 103 (0.79, 1.35) ug/m3
Nonatopic 1.36 (1.01, 1.84)
Morning Cough:
Atopic 1.22 (0.92, 1.61)
Nonatopic 1.32 (1.07, 1.63)

Prevalence odds ratio (95% CI) for doctor's diagnosis,
+10 ug/m3:
Asthma
Atopic 1.07 (0.79, 1.45)
Nonatopic 1.35 (1.00, 1.82)
Bronchitis
Atopic 1.04 (0.87, 1.25)
Nonatopic 0.99 (0.88, 1.12)
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           Koksal et al. (2003)
           Malatya, Turkey
                         SO2 cone ranged from 106.6 to
                         721.0ppm
Study on occupational exposure to high
concentrations of SO2 on respiratory symptoms and
pulmonary function on apricot sulfurization
workers. Apricot sulfurization workers (n = 69)
from 15 apricot farms who have been working in
sulfurization of apricots for 20-25 days a yr during
each summer were recruited for the study.
Subjects rated symptoms (itchy eyes, runny nose,
stuffy nose, itchy or scratchy throat, cough,
shortness of breath, phlegm, chest pain, and fever)
before during and 1 h after each exposure.
SO2 exposure at high concentrations increased
symptoms of itchy eyes, shortness of breath, cough,
running and/or stuffy nose, and itchy or scratchy throat
during exposure
(p < 0.05). Inhalation of high concentrations of SO2 for
1 h caused significant decreases in pulmonary function.
Difference in pulmonary function measured before and
after exposure:
FVC (L) 0.16 (0.42), p< 0.05
FEVi(L) 0.39 (0.36), p< 0.001
FEVj/FVC: 5.22 (6.75), p < 0.001
PEF (L/s) 1.39 (1.06), p < 0.001
FEF25.75% (L/s) 0.82 (0.70), p < 0.001

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                      TABLE AX5.6 (cont'd).  ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH
            	RESPIRATORY MORBIDITY	
              Reference, Study
             Location, and Period
                           Mean SO2 Levels
                Study Description
                 Results and Comments
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Pikhart et al. (200 1 )
Czech Republic, Poland,
1993-1994
                                    Mean SO2 (ug/m3)

                                    Prague: 83.9,
                                    Range: 65.8-96.6

                                    Poznan: 79.7,
                                    Range: 44.2-140.2
Part of the small-area variation in air pollution and
health (SAVIAH) study to assess long-term effects of
air pollution on respiratory outcomes.  Analysis on
data from two centers of the multicenter study:
Prague, Czech Republic, and Poznan, Poland. Both
cities had wide variation in air pollution levels.
Parents/guardians of 6,959 children
(7-10 yrs) completed a questionnaire about the
socioeconomic situation of the family, type of
housing, family history of atopy, parental smoking,
family composition, and health of the child. SO2 was
measured at 80 sites in Poznan and 50 sites in Prague
during 2-wk campaigns. From these data GIS was
used to estimate pollutant concentrations at a small
area level. Logistic regression used to assess effect of
air pollution on the prevalence of respiratory
outcomes.
SO2 levels (mean of home and school) were associated with
the prevalence of wheezing/whistling in the past 12 mos.
There was a marginal association between SO2 and lifetime
prevalence of wheezing and physician diagnosed asthma.
Fully adjusted model controlled for age, gender, maternal
education, number of siblings, dampness at home, heating and
cooking on gas, maternal smoking, and family history of atopy
and center. Authors noted SO2 is strongly spatially correlated
with particles in the Czech Republic and probably Poland, so
SO2 may be proxy for exposure to other pollutants. Not other
pollutants measured in study.

Odds ratio (per 50 ug/m3) SO2
Wheezing/whistling in past 12 mos: 1.32 (1.10, 1.57)
Wheezing/whistling ever: 1.13 (0.99,  1.30)
Asthma ever diagnosed by doctor:  1.39 (1.01, 1.92)
Dry cough at night: 1.06 (0.89, 1.27)
           von Mutius et al. (1995)
           Leipzig, East Germany,
           Octl991-Jull992
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                         During winter mos,
                         SO2 daily max
                         concentrations ranged
                         from 40-1283 ug/m3.

                         During high pollution
                         period, mean
                         concentration of SO2
                         was 188 ug/m3 and
                         during low pollution
                         mean was 57 ug/m3.
The effects of high to moderate levels of air pollution
(SO2, NOX, and PM) on the incidence of upper
respiratory were investigated in 1,500 schoolchildren

(9-11 yrs) in Leipzig, East Germany.
Logistic regression models controlled for paternal
education, passive smoke exposure, number of
siblings, temperature, and humidity.
The daily mean values of SO2 and NOX were significantly
associated with increased risk of developing upper respiratory
illnesses during the high concentration period. In the low
concentration period, only NOX daily mean values were
associated with increased risks. In a two-pollutant model with
PM, similar estimates to the single-pollutant model were
obtained, thus collinearity of data may not account for the
effects of high mean concentrations of SO2.

Odds ratio and 95% CI:  (did not indicate per what level of
SO2 increase)
Daily mean SO2
High period: 1.72(1.19,2.49)
Low period:  1 .40 (0.95, 2.07)
Daily maximum SO2
High period: 1.26 (0.80, 1.96)
Low period:  0.99(0.66,1.47)

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                          TABLE AX5.7. ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                                                    INCIDENCE OF CANCER
              Reference, Study
             Location, & Period
                                 Design & Methods
     Mean SO2 Levels
   Copollutants
   Considered
              Conclusions
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X
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J^.
           Nafstad et al. (2003)
           Oslo, Norway
           1972-1998
                        Retrospective study associating
                        cardiovascular risk factors to a national
                        cancer register among 16,209 men ages
                        10-49yrs. Survival analyses and Cox
                        proportional hazards regression were
                        used to estimate associations.
Estimated for each person each
year from 1974 to 1998

Five-year median average
levels SO2 participants home
address, 1974-1978: 9.4 ug/m3
(range 0.2 to 55.8)

Median levels within the
quartiles:
2.5  ug/m3
6.2  ug/m
14.7 ug/m3
31.3 ug/m3
NOX
Adjusted risk ratios (95% CI) of developing
lung cancer:
Model 1:
0-9.99 ug/m3:  Ref
10-19.99 ug/m3:  1.05(0.81,1.35)
20-29.99 ug/m3:  0.95(0.72,1.27)
30+ ug/m3: 1.06(0.79,1.43)
Model 2:
Per 10 ug/m3:  1.01(0.94,1.08)

Adjusted risk ratios (95% CI) of developing
non-lung cancer
Model 1:
0-9.99 ug/m3:  Ref.
10-19.99 ug/m3:  1.07(0.96,1.19)
20-29.99 ug/m3:  0.90 (0.80, 1.02)
30+ ug/m3: 0.98(0.86,1.10)
Model 2:
Per 10 ug/m3:  0.99(0.96,1.02)
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                    TABLE AX5.7 (cont'd). ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH
                                                                  INCIDENCE OF CANCER
Reference, Study
Location, & Period
Design & Methods
Mean SO2 Levels
Copollutants
Considered
Conclusions
EUROPE (cont'd)
          Nyberg et al. (2000)
          Stockholm County,
          Sweden
          Janl,1985-Dec31,
          1990
Case-control study of men 40-70 yrs,
with 1,042 cases of lung cancer and
1,274 controls, to evaluate the suitability
of an indicator of air pollution from
heating.
Annual levels computed for
each year between 1950 and
1990, but not provided herein
NOX/N02
Little effect of SOX in any time window, but
highest correlations in early years.

SOX RR (CI 95%) from heating (per 10 |ig/m3)
for 30-yr avg
<41.30ng/m3: 1
>41.30to<52.75:  1.06(0.83,1.35)
>52.75 to <67.14:  0.98 (0.77, 1.24)
>67.14to<78.20:  0.90(0.68,1.19)
>78.20:  1.00(0.73,1.37)

SOX RR (CI 95%) from heating (per 10 |ig/m3)
for 10-yravg
<66.20 ng/m3: 1
>66.20 to <87.60:  1.16(0.91,1.47)
>87.60to<110.30:  1.00(0.79,1.27)
>110.30to<129.10: 0.92(0.70,1.21)
>129.10: 1.21(0.89,1.66)
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                   TABLE AX5.8.  ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH PRENATAL
                                                                   AND NEONATAL OUTCOMES
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Reference, Study Outcomes, Design, Mean Levels & Copollutants & Method, Findings,
Location, & Period & Methods Monitoring Stations Correlations Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
UNITED STATES
Bell et al. (2007)
Connecticut and
Massachusetts

Period of Study:
1999-2002






Outcome: LEW Gestational exposure NO2
Study design: Case-control (ppb) CO
N: 358,504 live singleton PM10
births Mean: 4.7 PM2.5
Statistical analysis: Linear SD-1.2
models and logistic IQR. 1.6
regression
Covariates: Gestational
length, prenatal care, type
of delivery, child's sex,
birth order, weather, yr,
and mother's race,
education, marital status,
age, and tobacco use.
No relationship between
gestational exposure to
SO2 and birth weight.
First trimester exposure
to SO2 was associated
with low birth weight.
No statistical difference
n the effect estimates of
SO2 for infants of black
and white mothers.




Increment: 1.6 ppb (IQR)

Change in birth weight:
Entire pregnancy: -0.9 g (-4.4, 2.6)
Black mother: 1.2 (-6.5, 8.8)
White mother: -1.4 (-5.1, 2.3)
1 st trimester: - 3 .7 to -3.3 grams
LEW: OR 1.003 (0.961, 1.046)




Gilboa et al. (2005)
Seven Texas Counties

Period of Study:
1997-2000
Outcome:  Selected birth
defects
Study design:  Case-control
N: 4,570 cases and
3,667 controls
Statistical analysis:
Logistic regression
Covariates: Maternal
education, maternal
race/ethnicity, season of
conception, plurality,
maternal age, maternal
illness
Statistical package:
SAS vs. 8.2
NR
PM10
03
N02
CO
When the fourth quartile
of exposure was
compared with the first,
SO2 was associated with
increased risk of isolated
ventricular septal
defects.  Inverse
associations were noted
for SO2 and risk of
isolated atrial septal
defects and multiple
endocardial cushion
defects.
Aortic artery and valve defects
<1.3ppb:  1.00
1.3to<1.9: NA
1.9to<2.7: 1.06 [0.34, 3.29]
>2.7:  0.83 [0.26, 2.68]
Atrial septal defects
<1.3ppb:  1.00
1.3to<1.9: 1.22 [0.79, 1.88]
1.9to<2.7: 0.76 [0.47, 1.23]
>2.7:  0.42 [0.22, 0.78]
Pulmonary artery and valve defects
<1.3ppb:  1.00
1.3to<1.9: 0.63 [0.23, 1.74]
1.9to<2.7: 0.93 [0.36, 2.38]
>2.7:  1.07 [0.43, 2.69]

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             TABLE AX5.8 (cont'd).  ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH PRENATAL
                                                                 AND NEONATAL OUTCOMES
              Reference, Study
             Location, & Period
                         Outcomes, Design,
                            & Methods
  Mean Levels &
Monitoring Stations
Copollutants &
 Correlations
Method, Findings,
  Interpretation
Effects:  Relative Risk or % Change
   & Confidence Intervals (95%)
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           Gilboa et al. (2005)
           (cont'd)
                                                                                                           Ventricular septal defects
                                                                                                           <1.3ppb:  1.00
                                                                                                           1.3to<1.9: 1.02 [0.68, 1.53]
                                                                                                           1.9to<2.7: 1.13 [0.76,1.68]
                                                                                                           >2.7: 2.16 [1.51, 3.09]
                                                                                                           Conotruncal defects
                                                                                                           <1.3ppb:  1.00
                                                                                                           1.3to<1.9: 0.71 [0.46,1.09]
                                                                                                           1.9to<2.7: 0.71 [0.46,1.09]
                                                                                                           >2.7: 0.58 [0.37, 0.91]
                                                                                                           Endocardial cushion and mitral valve defects
                                                                                                           <1.3ppb:  1.00
                                                                                                           1.3to<1.9: 0.89 [0.50, 1.61]
                                                                                                           1.9to<2.7: 0.89 [0.49, 1.62]
                                                                                                           >2.7: 1.18 [0.68, 2.06]
                                                                                                           Cleft lip with or without cleft palate
                                                                                                           <1.3ppb:  1.00
                                                                                                           1.3to<1.9: 0.79 [0.52, 1.20]
                                                                                                           1.9to<2.7: 0.95 [0.64, 1.43]
                                                                                                           >2.7: 0.75 [0.49, 1.15]
                                                                                                           Cleft palate
                                                                                                           <1.3ppb:  1.00
                                                                                                           1.3to<1.9: 0.89 [0.40, 1.97]
                                                                                                           1.9to<2.7: 1.49 [0.72, 3.06]
                                                                                                           >2.7: 1.22 [0.56, 2.66]

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        TABLE AX5.8 (cont'd). ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH PRENATAL

                                         AND NEONATAL OUTCOMES
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Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels & Copollutants &
Monitoring Stations Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
UNITED STATES (cont'd)
Maisonet et al. (2001)
6 Northeastern cities of
U.S.

Period of Study:
1994-1996













Outcome: Term LEW
Study design: Case-
control
N: 89,557 live singleton
births
Statistical analysis:
Logistic regression
models linear regression
models
Covariates: Maternal
age, race, season of the
yr, smoking and alcohol
use during pregnancy,
firstborn, gender, marital
status, and previous
terminations, prenatal
care (ordinal variable),
weight gain, and
gestational age
Stratified by
race/ethnicity
Statistical package:
STATA
Exposure distribution CO
(<25th, 25th to <50th, PM10
50th to <75th, 75th to
<95th, >95th)

First trimester: <7.09,
7.090 to 8. 906, 8.907 to
11.969, 11. 970 to
18.447, > 18.448
Second trimester:
<6.596, 6.596 to 8.896,
8. 897 to 11. 959, 11.960
to 18.275, >18.276

Third trimester: <5.810,
5. 810 to 8.453,
8.454 to 11. 777, 11.778
to 18.134, >18.135




This study provides
evidence of an
increased risk for term
LEW in relation to
increased ambient air
levels of SO2 at
concentrations well
below the established
standards.
Higher risk estimates
among whites when
stratified by
race/ethnicity










First trimester:
<25th: Referent
25th-50th: 1.04 [0.88, 1.23]
50th-75th: 1.04 [0.94, 1.15]
75th-95th: 0.98 [0.81, 1.17]
>95th: 0.88 [0.73, 1.07]
Increment (10 ppm) : 0.98
[0.93, 1.03]
Second trimester:
25th-50th: 1.18 [1.12, 1.25]
50th-75th: 1.12 [1.07, 1.17]
75th-95th: 1.13 [1.05, 1.22]
>95th: 0.87 [0.80, 0.95]
Increment (10 ppm) : 1.01
[0.93,1.10]
Third trimester:
25th-50th: 1.04 [0.92, 1.18]
50th-75th: 1.02 [0.87, 1.18]
75th-95th: 1.04 [0.84, 1.28]
>95th: 1.06 [0.76, 1.47]
Increment (10 ppm) : 1.01
[0.86, 1.20]

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        TABLE AX5.8 (cont'd). ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH PRENATAL

                                         AND NEONATAL OUTCOMES
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Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels & Copollutants &
Monitoring Stations Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
UNITED STATES (cont'd)
Sagivetal. (2005)
4 Pennsylvania counties

Period of Study:
1997-2001







Outcome: Pre-term birth
Study design:
Time-series
N: 187,997 births
Study design: Poisson-
regression models
Covariates: Long-term
trends, copollutants,
temperature, dew point
temperature, and day of
wk.
Lag: Daily lags ranging
from 1-7 days
6-wk mean: PM10; r = 0.46
7.9 ± 3.5 ppb CO
(Range: 0.8,17), NO2
Median: 8.1

Daily mean: 7.9 ± 6.2
(Range: 0,54.1),
Median: 6.4





This study found an
increased risk for
preterm delivery
during the last 6 wks
of pregnancy with
exposure to SO2.






Increment: 1 5 ppb

Mean: 6-wk SO2:
RR= 1.15 [1.00, 1.32]
<4.9ppb: Referent
4. 9 to 8.1 ppb: 1.02 [0.97, 1.
8.1 to 10. 6 ppb: 1.04 [0.98, :
10.6 to 17.0 ppb: 1.06 [0.99,

Mean: Daily SO2:
RR= 1.07 [0.99, 1.15] lag 3







06]
1. 10]
1.14]





CANADA
Dales et al. (2004)
12 Canadian cities

Period of Study:
1984-1999







Outcome: SIDS 24-havg:
Study design: Time
series 5.51 ppb
N: 1556 SIDS deaths IQR: 4.92
Statistical analysis:
Random effects
regression model
Covariates:
Temperature, humidity,
barometric pressure,
season
Lag: 0-5 days
CO
NO2
03
PM10
PM25
PM,n-2 5
J. J-VJ-IQ Z..-J





SIDS was associated Increment: 4.92ppb(IQR)
with air pollution,
with the effects of Increase in SIDS incidence: 8.49%;
SO2 seeming to be p = Q.0079 lag 1
independent of
sociodemographic
factors, temporal
trends, and weather.





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        TABLE AX5.8 (cont'd). ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH PRENATAL

                                         AND NEONATAL OUTCOMES
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Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels &
Monitoring Stations
Copollutants &
Correlations
Method, Findings,
Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
CANADA (cont'd)
Dales et al. (2006)
1 1 Canadian cities

Period of Study:
1986-2000









Liu et al. (2006)
Calgary, Edmonton and
Montreal, Canada

Period of Study:
1986-2000




Outcome: Hospitalization for
respiratory disease in the
neonatal period
Study design: Time series
N: 9,542
Statistical analysis: Random
effects regression model;
Poisson using fixed- or
random-effects model
Covariates: Fay of wk,
temperature, humidity, pressure
Lag: 0-5 days
Statistical package:
S-PLUS vs. 6.2
Outcome: IUGR
Study design: Case-control
N: 386,202 singleton live
births
Statistical analysis: Multiple
logistic regression
Covariates: Maternal age,
parity, infant sex, season of
birth, city of residence

24-h avg:
4.3 ppb
IQR: 3.8











24-h avg: 3. 9 ppb,
25% 2.0 ppb
50% 3.0 ppb
75% 5.0 ppb
95% 10.0 ppb
1-hmax: 10. 8 ppb,
25% 5.0 ppb
50% 8.6 ppb
75% 14.0 ppb
95% 28.0 ppb
NO2; r = 0.20,
0.67
CO; r= 0.19, 0.66
03;r= -0.41, 0.13
PM10;r=-0.09,
0.61
SO4







N02; r = 0.34
CO; r= 0.21
O3;r=-0.30
PM2.5; r = 0.44






This study detected a
significant
association for
respiratory disease
among neonates and
gaseous air
pollutants.







IUGR did not
increase with
maternal exposure to
SO2. Risk decreased
during first 3 mos.





Increment: 3. 8 ppb (IQR)

Increase in neonatal respiratory
hospital admissions:
S02 alone: 2.06% [1.04, 3.08]
Multipollutant model: 1 . 66%
[0.63,2.69]
Multipollutant model restricted to days
with PM10 measures: 1.41%
[0.35,2.47]




Increment: 3.0 ppb

ORs estimated from graph:
Istmo: OR~0. 966 (0.94, 0.99)
2nd mo: OR-0.97 (0.95, 0.995)
3rd mo: OR~0. 97 (0.95, 0.995)

1st trimester: OR~0 .96 (0.93, 0.99)



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             TABLE AX5.8 (cont'd).  ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH PRENATAL
                                                                   AND NEONATAL OUTCOMES
              Reference, Study
             Location, & Period
                              Outcomes, Design,
                                 & Methods
  Mean Levels &
Monitoring Stations
Copollutants &
  Correlations
   Method, Findings,
    Interpretation
 Effects:  Relative Risk or % Change
   & Confidence Intervals (95%)
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CANADA (cont'd)
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           Dugandzic et al. (2006)
           Nova Scotia, Canada

           Period of Study:
           1988-2000
                         Outcome: Term LEW
                         Study design: Retrospective
                         cohort study
                         N:  74,284 term, singleton
                         births
                         Statistical analysis: Logistic
                         regression models
                         Covariates: Maternal age,
                         parity, prior fetal death, prior
                         neonatal death, and prior low
                         birth weight infant, smoking
                         during pregnancy,
                         neighborhood family income,
                         infant gender, gestational age,
                         weight change, and yr of birth.
                         Statistical package: SAS vs.
                         8.0
Mean:  SO2 10 ppb
Median: 10
25th%: 7
75th%: 14
Max:  38
03
PM10
In the analyses
unadjusted for birth yr,
first trimester exposures
in the highest quartile
for SO2 associated with
increased risk of LEW.
After adjusting for birth
yr, RR attenuated and
not statistically
significant.  There was a
linear concentration-
response effect with
increasing levels of SO2
during the first trimester.
First Trimester
25th-50th: 0.96 [0.73, 1.28]
51st-75th: 1.18 [0.88, 1.58]
>75th:  1.36 [1.04, 1.78]
Increment (7 ppb): 1.20 [1.05, 1.38]
Second Trimester
25th-50th: 1.12 [0.86, 1.46]
51st-75th: 1.13 [0.85, 1.50]
>75th:  1.04 [0.79, 1.37]
Increment (7 ppb): 0.99 [0.87, 1.13]
Third Trimester
25th-50th: 1.04 [0.80, 1.34]
51st-75th: 0.85 [0.63, 1.15]
>75th:  0.88 [0.67, 1.15]
Increment (7 ppb): 0.93 [0.81, 1.06]
Liu et al. (2003) Outcomes: Preterm birth,
Vancouver, Canada LEW, IUGR
Study design: Case-control
Period of Study: N: 229,085 singleton live
1986-1998 births
Statistical analysis: Multiple
logistic regressions Covariates:
Maternal age, parity, infant
sex, gestational age or birth
weight and season of birth






24-havg: 4.9ppb, NO2; r
5th: 1.5 CO;r =
25th: 2.8 Q3;r =
50th: 4.3
75th: 6.3
95th: 10.5
100th: 30.5
1-hmax: 13.4ppb,
5th: 4.3
25th: 7.8
50th: 11.7
75th: 16.8
95th: 28.3
100th: 128.5


= 0.61 LEW and IUGR were
: 0.64 associated with maternal
_0 35 exposure to SO2 during
the first mo of
pregnancy and preterm
birth was associated
with SO2 during the last
mo. These results were
robust to adjustment for
copollutants.






Increment: 5 ppb
Low birth weight
Firstmo: OR 1.11 [1.01,1.22]
Last mo: OR 0.98 [0.89, 1.08]

Preterm birth
Firstmo: OR 0.95 [0.88, 1.03]
Lastmo: OR 1.09 [1.01, 1.19]
IUGR
Firstmo: OR 1.07 [1.01, 1.13]
Lastmo: OR 1.00 [0.94, 1.06]
First trimester: OR 1.07 (1.00, 1.14)
Second trimester: 0.98 [0.91, 1.04]
Third trimester: 1.03 [0.96, 1.10]

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        TABLE AX5.8 (cont'd). ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH PRENATAL

                                         AND NEONATAL OUTCOMES
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Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels & Copollutants & Method, Findings,
Monitoring Stations Correlations Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
EUROPE
Mohorovic (2004)
Labin, Istra, Croatia

Period of Study:
1987-1989













Outcomes: LEW and
preterm delivery
Study design: Cross-
sectional
N: 704 births
Statistical analysis:
Multiple correlation
analyses, factor analyses,
chi-square
Statistical package:
DBASE IV, SPSS










Monthly ground The results show an
levels of SO2: association between
Range: 34.1, SO2 exposure at the
252.9ug/m3 end of the first and
second mo of
pregnancy and a
negative correlation
between length of
gestations and lower
birth weight of
newborns.










Correlation coefficients:

1st mo:
Gestation length: -0.09, p = 0.008
Birthweight: -0.08, p = 0.016
^nH inn'
Z.11U. 111U .
Gestation length: -0.08, p = 0.016
Birthweight: -0.07, p = 0.026
3rd mo:
Gestation length: - 0.04, p = 0. 147
Birthweight: -0.04, p = 0.135
6th mo:
Gestation length: -0.02, p = 0.266
Birthweight: -0.04, p = 0.151
Whole pregnancy:
Gestation length: -0.09, p = 0.007
Birthweight: -0.04, p = 0.153
Weekly avg during whole pregnancy:
Gestation length: -0.05, p = 0.086
Birthweight: -0.06, p = 0.069

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             TABLE AX5.8 (cont'd).  ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH PRENATAL
                                                                 AND NEONATAL OUTCOMES
             Reference, Study
             Location, & Period
                          Outcomes, Design,
                             & Methods
  Mean Levels &
Monitoring Stations
Copollutants &
  Correlations
Method, Findings,
  Interpretation
                           Effects: Relative Risk or % Change
                              & Confidence Intervals (95%)
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EUROPE (cont'd)
X
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           Bobak et al. (2000)
           Czech Republic

           Period of Study:
           1990-1991
                       Outcomes:  LEW, preterm
                       birth
                       Study design: Case-control
                       N:  108,173 live singleton
                       births
                       Statistical analysis:
                       Logistic regression
                       Covariates: Temperature,
                       humidity, day of wk,
                       season, residential area,
                       maternal age, gender
                       Statistical package:
                       STATA
Mean trimester
exposures

25th: 17.5 ug/m3
50th: 32.0 ug/m3
75th: 55.5 ug/m3
TSP;r = 0.68,
0.73
NOx;r=0.53,
0.63
LEW and preterm birth
were associated with
maternal exposure to SO2,
though the association
between SO2 and LEW
was explained to a large
extent by low gestational
age.
                      Increment: 50 ug/m

                      LEW (adjusted for sex, parity, maternal
                      age group, education, marital status, and
                      nationality, and mo of birth)
                      Isttrimester: 1.20(1.11,1.30)
                      2nd trimester:  1.14 (1.06, 1.22)
                      3rd trimester:  1.14(1.06,1.23)

                      LEW (also adjusted for gestational age)
                      Isttrimester: 1.01(0.88,1.17)
                      2nd trimester:  0.95(0.82,1.10)
                      3rd trimester: 0.97(0.85,1.10)

                      Preterm birth (AOR)
                      Isttrimester: 1.27(1.16,1.39)
                      2nd trimester:  1.25(1.14,1.38)
                      3rd trimester:  1.24(1.13,1.36)

                      Reduction in mean birth weight:
                      Isttrimester: 1.4 g (5.9, 16.9)
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            TABLE AX5.8 (cont'd). ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH PRENATAL
                                                             AND NEONATAL OUTCOMES
Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels & Copollutants & Method, Findings,
Monitoring Stations Correlations Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
LATIN AMERICA
Gouveia et al. (2004)
Sao Paulo, Brazil

Period of Study:
1997













Outcome: LEW
Study design: Case-control
N: 179,460 live singleton
births
Statistical analysis: Logistic
regression with GAM
Covariates: Gender,
gestational age, maternal age,
maternal education, antenatal
care, parity, delivery method
Statistical package: S-Plus
2000







Annual mean: SO2 PM10
(ug/m3) CO
Mean: 19.6 NO2
SD=10.3 o
Range: 3.4,56.9 3
Jan-Mar: 22.3(7.7)
Apr- June: 28.1
(10.1)
Jul-Aug: 17.9(8.7)
Oct-Dec: 10.3(3.9)








First and second
trimester exposures to
SO2 had a significant
association with birth
weight, though in
different directions.
When air pollutants
were divided into
quartiles and the lowest
quartile was used as the
referent exposure
category, SO2 during the
second trimester was
marginally associated
with low birth weight.




Increment: 10 ug/m3

Reduction in birth weight
First trimester: -24.2g(-55.5,7
Second trimester: 33.7 g (1 .6, 65.
Third trimester: 9.7 g (-25.6, 44.

First trimester:
2nd: 0.902 (0.843, 0.966)
3rd: 0.911(0.819,1.013)
4th: 0.906(0.793,1.036)
Second trimester:
2nd: 0.986(0.922,1.053)
3rd: 1.005(0.904,1.117)
4th: 1.017(0.883,1.173)
Third trimester:
2nd: 1.203(0.861,1.68)
3rd: 1.225(0.872,1.722)
4th: 1.145(0.749,1.752)



•1)
.8)
9)












          Pereiraetal. (1998)
          Sao Paulo, Brazil

          Period of Study:
          1991-1992
Outcome: Intrauterine
mortality
Study design: Time series
N:
Statistical analysis: Poisson
regression models
Covariates: Mo, day of wk,
minimum daily temperature,
relative humidity
Lag:  2 to 14 days
                                                            24-h avg SO2:
                                                            18.90(8.53)mg/m3
                                                            Range:  3.80,59.70
PM10; r = 0.45
NO2;r=0.41
03;r=0.17
CO; r = 0.24
SO2 exhibited a
marginal association
with intrauterine
mortality, but only when
Poisson regression was
employed. A
concentration-response
relationship was found.
Estimated regression coefficients and
standard errors:

SO2 alone:  0.0038 (0.0020)
SO2 + NO2 + CO + PM10 + O3: 0.0029
(0.0031)

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              TABLE AX5.8 (cont'd).  ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH PRENATAL
                                                                  AND NEONATAL OUTCOMES
              Reference, Study
             Location, & Period
                             Outcomes, Design,
                                & Methods
                               Mean Levels &
                             Monitoring Stations
                      Copollutants &
                       Correlations
                    Method, Findings,
                      Interpretation
                          Effects: Relative Risk or % Change
                             & Confidence Intervals (95%)
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Lin et al. (2004c)
Kaohsiung and Taipei,
Taiwan

Period of Study:
1995-1997
Kaohsiung and Taipei,
Taiwan

Period of Study:
1995-1997

Lin et al. (2004d)
Kaohsiung and Taipei,
Taiwan

Period of Study:
1995-1997
                                    Outcome: LEW
                                    Study design: Case-control
                                    N:  92,288 live births
                                    Statistical analysis: Multiple
                                    logisistic regression
                                    Covariates: Gestational
                                    period, gender, birth order,
                                    maternal age, maternal
                                    education, season of birth
Outcome:  Term LEW
Study design:  Cohort
N: 92,288 live births
Statistical analysis: Multiple
logisistic regression
Covariates: Gestational
period, gender, birth order,
maternal age, maternal
education, season of birth
                            24-h avg:
                            Kaohsiung
                            Range:  10.07,
                            25.36ppb
                            Taipei:
                            Range:  5.65,9.33
                            ppb
                     CO
                     NO2
                     03
                     PM10
24-h avg:
Kaohsiung
Range: 10.07,
25.36 ppb
Taipei:
Range: 5.65,9.33
ppb
CO
NO2
03
PM10
Few women living in
Taipei were exposed to
high levels of SO2. In
Kaohsiung, almost all
women were exposed to
high levels of SO2.
Women living in
Kaohsiung had
significantly higher risk of
term LEW compared with
women living in Taipei.

This study found a 26%
higher risk of term LEW
delivery for mothers
exposed to mean SO2
concentrations exceeding
11.4 ppb during the entire
pregnancy, as compared
with mothers exposed to
mean concentrations less
than 7.1 ppb. Trimester
specific analysis showed a
significant association
only for the third
trimester.
                                           OR for Kaoshiung births (compared to
                                           Taipei births)
                                           All births:
                                           OR:  1.13 [1.03, 1.24]
                                           Female births only:
                                           OR:  1.14 [1.01, 1.28]
Lowest quartile of exposure = referent
Entire pregnancy:
25th-75th: 1.16 [1.02, 1.33]
>75th:  1.26 [1.04, 1.53]
1 st trimester:
25th-75th: 1.02 [0.90, 1.16]
>75th:  1.11 [0.94,1.33]
2nd trimester:
25th-75th: 1.09 [0.96, 1.24]
>75th:  1.17 [0.99, 1.37]
3rd trimester:
25th-75th: 1.13 [0.99, 1.28]
>75th:  1.20 [1.01, 1.41]	

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              TABLE AX5.8 (cont'd).  ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH PRENATAL
                                                                  AND NEONATAL OUTCOMES
              Reference, Study
             Location, & Period
                             Outcomes, Design,
                                & Methods
                               Mean Levels &
                             Monitoring Stations
                      Copollutants &
                        Correlations
                     Method, Findings,
                       Interpretation
 Effects:  Relative Risk or % Change
   & Confidence Intervals (95%)
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ASIA (cont'd)
           Wang etal. (1997)
           Four residential areas:
           Dongcheng, Xicheng,
           Congwen, Xuanwu
           Beijing, China

           Period of Study:
           1988-1991
                        Outcome:  Term LEW
                        Study design:  Cohort study
                        N: 74,671 first parity live
                        births
                        Statistical analysis: Multiple
                        linear regression and logistic
                        regression with GAM
                        Covariates: Gestational age,
                        residence, yr of birth,
                        maternal age, and infant
                        gender.
                            Mean pollution
                            concentrations
                            provided in graph
TSP; r = 0.92       Exposure-response
                  relationship between
                  SO2 during the third
                  trimester of pregnancy
                  and low birth weight.
                                                                3rd trimester:
                                                                9 to 18 ug/m3 (reference)
                                                                18 to 55:  1.09(0.94,1.26)
                                                                55 to 146:  1.12(0.97,1.29)
                                                                146 to 239:  1.16(1.01,1.34)
                                                                239 to 308:  1.39(1.22,1.60)

                                                                SO2 as continuous variable:
                                                                Odds ratio per 100 ug/m3
                                                                1.11(1.06,1.16)
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Xuetal. (1995)
Four residential areas:
Dongchen, Xichen,
Congwen, Xuanwu
Beijing, China

Period of Study:  1988
Outcome:  Preterm delivery
Study design:  Prospective
cohort study
N: 25,370 singleton first live
births
Statistical analysis: Multiple
linear and logistic regression
Covariates: Temperature,
humidity, day  of wk, season,
residential area, maternal age,
and gender of child.
2 monitors for SO2:
Dongcheng and
Xicheng
Dongcheng Annual
mean:
108 ug/m3
SD = 141 ug/m3)
Xicheng annual
mean:
93 ug/m
(SD = 122 ug/m3)
                                                                                     TSP
                  Exposure response
                  relationship between
                  quartiles of SO2 and
                  crude incidence rates of
                  preterm birth. Dose
                  dependent relationship
                  between SO2 and
                  gestational age.  The
                  estimated reduced length
                  of gestation was
                  0.075 wks or 12.6 h per
                  100/m increase in SO2.
                  When TSP and SO2
                  included in a
                  multipollutant model,
                  the effect of SO2 was
                  reduced by 32%.
Effect on gestational age (wk) per
100 ug/m3
regression coef and SE for lagged
moving avg of SO2.
lagO: -0.016(0.021)
lagl: -0.022(0.021)
lag 6: -0.067 (0.024), p< 0.01
lag 7: -0.075 (0.024), p< 0.01
lag 8: -0.075 (0.025), p< 0.01

OR for each quartile of SO2
1st:  1.00
2nd:  1.70(1.15,2.52)
3rd:  1.74(1.03,2.92)
4th:  1.58(0.87,2.86)

Adjusted OR for preterm delivery:
1.21  (1.01, 1.46) per Ln ug/m3 increase
in SO,

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        TABLE AX5.8 (cont'd). ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH PRENATAL

                                        AND NEONATAL OUTCOMES
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Reference, Study Outcomes, Design,
Location, & Period & Methods
Mean Levels &
Monitoring Stations
Copollutants & Method, Findings,
Correlations Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
ASIA (cont'd)
Haetal. (2001)
Seoul, Korea

Period of Study:
1996-1997





Lee et al. (2003)
Seoul, Korea
Period of Study:
1996-1998












Outcome: LEW
Study design: Case-control
N: 276,763
Statistical analysis: Logistic
regression, GAM
Covariates: Gestational age,
maternal age, parental
education level, infant's birth
order gender

Outcome: Term LEW
Study design:
N: 388,105 full-term
singleton births
Statistical analysis: GAM
Covariates: Infant sex, birth
order, maternal age, parental
education level, time trend,
and gestational age.







24-h avg:
1 st trimester:
25th: 10.0 ppb
50th: 13.2 ppb
75th: 16.2 ppb
3rd trimester:
25th: 8.4 ppb
50th: 12.2 ppb

75th: 16.3 ppb
Avg concentration
(Ppb)

Mean: 12.1
SD = 7.4
Range: 3, 46
25th: 6.8
50th: 9.8
75th: 15.6







CO; r = 0. 83 Ambient SO2
NO2; r = 0.70 concentrations during
TSP' r = 0 67 me fi1"8^ trimester of
O3; r = - 0.29 pregnancy were
associated with LEW





PM10; r = 0.78, Second trimester
0.85 exposures to SO2 as
CO; r= 0.79, 0.86 well as during the
NO2' r = 0 75 entire pregnancy were
0.76 associated with LEW.
Reduction in birth
weight was 14.6 g for
IQR increase in SO2 in
the second trimester.
When the exposure for
each mo of pregnancy
was evaluated
separately, SO2
exposure during 3 to 5
mos of pregnancy
associated with LEW.
Increment: 1st trimester: 6. 2 ppb;
3rd trimester: 7.9 ppb
1st trimester: RR 1.06 [1.02, 1.10]
3rd trimester: RR 0.93 [0.88, 0.98]

Reduction in birth weight: 8.06 g
[5.59, 10.53]



Increment: 8. 8 ppb (IQR)

First trimester: 1 .02 (0.99, 1 .06)
Second trimester: 1.06 (1.02, 1.11)
Third trimester: 0.96 (0.91, 1.00)
All trimesters: 1.14 (1.04, 1.24)











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        TABLE AX5.8 (cont'd). ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH PRENATAL

                                         AND NEONATAL OUTCOMES
to
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Reference, Study
Location, & Period
Outcomes, Design,
& Methods
Mean Levels &
Monitoring Stations
Copollutants & Method, Findings,
Correlations Interpretation
Effects: Relative Risk or % Change
& Confidence Intervals (95%)
ASIA (cont'd)
Leem et al. (2006)
Incheon, Korea

Period of Study:
2001-2002









Yang et al. (2003b)
Kaohsiung, Taiwan

Period of Study:
1995-1997









Outcome: Preterm
delivery
Study design:
N: 52,113 singleton
births
Statistical analysis:
Log-binomial regression
Covariates: Maternal
age, parity, sex, season,
maternal education,
paternal education




Outcome: Term LEW
Study design: Case-
control
N: 13, 3 96 first parity
singleton live births
Statistical Analysis:
Multiple linear
regression
Covariates: Maternal
age, season, marital

status, maternal
education, gender
Statistical package: SAS

Mean: SO2
Concentrations by
trimester:
1 st trimester:
Min: 7.86 ug/m3
25th: 17.61
50th: 22.74
75th: 45.85
Max: 103.96
3rd trimester:
Min: 6.55 ug/m3
25th: 17.03
50th: 25.62
75th: 46.53
Max: 103.15
Mean: trimester exposure
(ug/m3)
1 st trimester
33rd: 26.02
67th: 36.07
2nd trimester
33rd: 25.76
67th: 35.63
3rd trimester
"5 "1 A O £ "5 n
33rd: 25.39

67th: 36.96


NO2; r = 0.54 This study found the
CO; r= 0.31 highest SO2
PM10' r = 0 13 concentrations during
the first trimester to
be significantly
associated with
elevated risks of
preterm delivery.






PM10; r = 0.45, 0.46 A significant
expo sure-response
relationship between
maternal exposures
to SO2 and birth
weight was found
during the first
trimester of
pregnancy.






1 st trimester:
7.86 to 17.61 ug/m3: referent
17.62 to 22.74: 1.13 [0.99, 1.28]
22.75 to 45. 85: 1.13 [0.98, 1.30]
45.86 to 103. 96: 1.21 [1.04,1.42]

3rd trimester:
6.55 to 17.03 ug/m3: referent
17.04 to 25. 62: 0.87 [0.76, 1.01]
25.63 to 46.53: 0.97 [0.83, 1.13]
46. 54 to 103. 15: 1.11 [0.94,1.31]




Reduction in birth weight:
1 st trimester:
33rd-67th: 3.68 g [-12.45, 19.21]
>67th: 18.1 Ig [1.88, 34.34]
Continuous: 0.52 g [0.09, 2.63]
2nd trimester:
33rd-67th: 1.78 g [-17.91, 14.35]
>67th: 13. 53 g [-2.62, 29. 68]
Continuous: 0.19 g [-0.78, 1.8]


J1U. UllllCSlCl.
33rd-67th: 0.43 g [-16.56, 15.70]
>67th: 1. 97 g [- 18.24, 14.30]
Continuous: 0.03 g [-1.21, 1.37]

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                  TABLE AX5.9.  ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH MORTALITY
             Reference, Location,
                 Study Period
                             Mean SO,, Levels
                                          Study Description
                                                                 Results and Comments
           UNITED STATES
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Abbey etal. (1999)
Three California air
basins: San Francisco,
South Coast (Los Angeles
and eastward), San Diego
1977-1992
24-h avg SO2: 5.6 ppb
Prospective cohort study of 6,338 nonsmoking non-
Hispanic white adult members of the Adventist Health
Study followed for all cause, cardiopulmonary,
nonmalignant respiratory, and lung cancer mortality.
Participants were aged
27-95 yrs at enrollment in 1977.  1,628
(989 females, 639 males) mortality events followed
through 1992. All results were stratified by gender.
Used Cox proportional hazards analysis, adjusting for
age at enrollment, past smoking, environmental tobacco
smoke exposure, alcohol use, education, occupation,
and body mass index. Analyzed mortality from all
natural causes, cardiopulmonary, nonmalignant
respiratory, and lung cancer.
SO2 was not associated with total (RR = 1.07
[95% CI: 0.92, 1.24] for male and 1.00
[95% CI: 0.88, 1.14] for female per 5-ppb increase in
multiyear average SO2), cardiopulmonary, or respiratory
mortality for either sex. Lung cancer mortality showed
large risk estimates for most of the pollutants in either
or both sexes, but the number of lung cancer deaths in
this cohort was very small (12 for female and 18 for
male) Generally wide confidence intervals (relative to
other U.S. cohort studies).
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Beesonetal. (1998)
Three California air
basins: San Francisco,
South Coast (Los Angeles
and eastward), San Diego
1977-1992
                                     24-h avg SO2:  5.6 ppb
                          Prospective cohort study of 6,338 nonsmoking non-
                          Hispanic white adult members of the Adventist Health
                          Study aged 27-95 yrs at time of enrollment.
                          36 (20 females, 16 males) histologically confirmed lung
                          cancers were diagnosed through 1992.  Extensive
                          exposure assessment, with assignment of individual
                          long-term exposures to O3, PM10, SO42~, and SO2, was a
                          unique strength of this study.  All results were stratified
                          by gender. Used Cox proportional hazards analysis,
                          adjusting for age at enrollment, past smoking,
                          education, and alcohol use.
                                                   Lung cancer incidence relative risk:
                                                   Male:  RR = 3.72 (95%CI:  1.91,7.28);
                                                   Female: RR = 2.78 (95%CI:  1.51,5.12)
                                                   per 5-ppb increase in SO2.

                                                   Case number very small (16 for male, 20 for female).

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             TABLE AX5.9 (cont'd).  ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH MORTALITY

                                                                                Study Description
  Reference, Location,
      Study Period
    Mean SO,, Levels
                                                                  Results and Comments
            UNITED STATES (cont'd)
 to
 o
 o
Dockeiy etal. (1993)
Portage, WI; Topeka, KS;
Watertown, MA;
Harriman, TN;
St. Louis, MO;
Steubenville, OH
1974-1991.
24-h avg NO2 ranged
from 1.6 (Topeka) to 24.0
(Steubenville) ppb.
A prospective cohort study to study the effects of air
pollution with main focus on PM components in six
U.S. cities, which were chosen based on the levels of air
pollution (Portage, WI, the least polluted to
Steubenville, OH, the most polluted).  Cox proportional
hazards regression was conducted with data from a
14-to-16-yr follow-up of 8,111 adults in the six cities,
adjusting for smoking, sex, BMI, occupational
exposures, etc. PM2 5 and sulfate were associated with
these causes of deaths.
SO2 result presented only graphically. Fine particles
and sulfate showed better fit than SO7.
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            Krewski et al. (2000)
            Re-analysis and
            sensitivity analysis of
            Dockery etal. (1993)
            study.
            Krewski et al. (2000);
            Jerrett et al. (2003)
            Re-analy sis/sensitivity
            analysis of Pope et al.
            (1995) study.
                          24-h avg NO2 ranged
                          from 1.6 (Topeka) to 24.0
                          (Steubenville) ppb
                          Gaseous pollutants risk estimates were presented.
                          Multiyear avg of 24-h
                          avg 9.3 ppb.
                          Re-analysis of Pope et al. (1995) study. Extensive
                          sensitivity analysis with ecological covariates and
                          spatial models to account of spatial pattern in the ACS
                          data.
                                                    SO2 showed positive associations with total
                                                    (RR = 1.05 [95% CI:  1.02, 1.09] per 5-ppb increase in
                                                    the average SO2 over the study period),
                                                    cardiopulmonary (1.05 [95% CI:  1.00, 1.10]), and lung
                                                    cancer deaths (1.03 [95% CI:  0.91, 1.16]), but in this
                                                    dataset, SO2 was highly correlated with PM2 5 (r = 0.85),
                                                    sulfate (r = 0.85), and NO2 (r = 0.84)

                                                    The relative risk estimates for total mortality was 1.06
                                                    (95% CI:  1.05, 1.07) per 5-ppb increase in the annual
                                                    average SO2. In the spatial filtering model (this was the
                                                    model that resulted in the largest reduction of SO2 risk
                                                    estimate when  sulfate was included), the SO2 total
                                                    mortality risk estimate was 1.07 (95% CI:  1.03, 1.11) in
                                                    the single-pollutant model and 1.04 (95% CI:  1.02,
                                                    1.06) with sulfate in the model. The risk estimates for
                                                    PM2 5 and sulfate were diminished when SO2 was
                                                    included in the models.

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             TABLE AX5.9 (cont'd). ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH MORTALITY
             Reference, Location,
                 Study Period
                             Mean SOV Levels
                                         Study Description
                                                                      Results and Comments
           UNITED STATES (cont'd)
to
o
o
Lipfert et al.
(2000b; 2003)
32 Veterans
Administration hospitals
nationwide in the U.S.
1976-1996
SO2 mean levels not
reported.
Cohort study of approximately 50,000 U.S. veterans
(all males) diagnosed with hypertension. Mean age at
recruitment was 51 yrs.  Exposure to O3 during four
periods (1960-1974, 1975-1981, 1982-1988, 1989-1996)
associated with mortality over three periods (1976-1981,
1982-1988, 1989-1996).  Long-term exposures to TSP,
PMis, PMio, PM2.5, PMi5.2.5, S042~, N02, and CO also
analyzed. Used Cox proportional hazards regression,
adjusting for race, smoking, age, systolic and diastolic
blood pressure, body mass index, and socioeconomic
factors.
                                                                                                                    "SO2 and Pb were considered less thoroughly".  The
                                                                                                                    authors presented only qualitative results for SO2 from the
                                                                                                                    "Screening regressions" which indicated negatively
                                                                                                                    significant risk estimate in the univariate model and non-
                                                                                                                    significant positive estimate in the multivariate model.
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(Si
to
Lipfert et al. (2006a)
32 Veterans
Administration hospitals
nationwide in the U.S.
1976-2001
Mean of the 95th        Update of the Lipfert et al. (2000) study, with follow-up
percentile of the         period extended to 2001.  Study focused on the traffic
24-h avg SO2  for        density data.  The county-level traffic density was derived
1997-2001 period:       by dividing vehicle-km traveled by the county land area.
15.8 ppb.               Because of the wide range of the traffic density variable,
                       log-transformed traffic density was used in their analysis.
                       They reported that traffic density was a better predictor of
                       mortality than ambient air pollution variables, with the
                       possible exception of O3. The log-transformed traffic
                       density variable was weakly correlated with SO2
                       (r = 0.32) in this data set.
                                                      P%T< using the 1997-2001 air quality data period:
                                                      0.99 (95% CI: 0.97, 1.01) per 5-ppb increase; in a single-
                                                      pollutant model.

                                                      The 2-pollutant model with the traffic density variable:
                                                      0.99 [95% CI: 0.96, 1.01] per 5 ppb.
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           Lipfert et al. (2006b)
           32 Veterans
           Administration hospitals
           nationwide in the U.S.
           1997-2001
                          Mean of the 95th
                          percentile of the
                          24-h avg SO2 for
                          1999-2001 period:
                          16.3 ppb.
                       Update of the Lipfert et al. (2000) study, examined PM2.5
                       chemical constituents data. The analysis used county-
                       level air pollution data for the period 1999-2001 and
                       cohort mortality data for 1997-2001.
                                                      Traffic density was the most important predictor of
                                                      mortality, but associations were also seen for elemental
                                                      carbon, V, nitrate, and Ni. NO2, ozone, and PM10 also
                                                      showed positive but weaker associations.  The risk estimate
                                                      for SO2 was essentially the same as that reported in the
                                                      2006a Lipfert et al. analysis (0.99  [95% CI:  0.96,1.01] per
                                                      5 ppb) in a single-pollutant model. Multipollutant model
                                                      results were not presented for SO2.

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             TABLE AX5.9 (cont'd).  ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH MORTALITY
              Reference, Location,
                 Study Period
                             Mean SO,, Levels
                                          Study Description
                                                                    Results and Comments
            UNITED STATES (cont'd)
 to
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O
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Miller et al. (2007).
36 U.S. metropolitan
areas from 1994 to 1998
Not reported.
Pope etal. (1995)
U.S. nationwide
1982-1989
Not analyzed/ reported.
Cohort study of 65,893 postmenopausal women between
the ages of 50 and 79 yrs without previous cardiovascular
disease in 36 U.S. metropolitan areas from 1994 to 1998.
They examined the association between one or more fatal
or nonfatal cardiovascular events and the women's
exposure to air pollutants.  Subject's exposures to air
pollution were estimated by assigning the annual mean
levels of air pollutants measured at the nearest monitor to
the location of residence on the basis of its five-digit ZIP
Code centroid. A total of 1,816 women had one or more
fatal or nonfatal cardiovascular events, including 261
deaths from cardiovascular causes.  Hazard ratios were
estimated for the first cardiovascular event using Cox
proportional hazards model, adjusting for age, race or
ethnic group, smoking status, educational level,
household income, BMI, and presence or absence of
diabetes, hypertension, or hypercholesterolemia

Investigated associations between long-term exposure to
PM and the mortality outcomes in the American Cancer
Society cohort. Ambient air pollution data from 151 U.S.
metropolitan areas in 1981 were linked with individual
risk factors in 552,138 adults who resided in these areas
when enrolled in the prospective study in 1982. Death
outcomes were ascertained through 1989. Cox
proportional hazards model adjusted for smoking,
education, BMI, and occupational exposures. PM2 5 and
sulfate were associated with total, cardiopulmonary, and
lung cancer mortality, but not with mortality for all other
causes.
In the single-pollutant model results, PM2 5 showed the
strongest associations with the CVD events by far
among the pollutants, followed by SO2 (HR of 1.07
[95% CI: 0.95, 1.20] per 5 ppb increase in the annual
avg). In the multipollutant model (apparently, all the
pollutants were included in the model), the PM2 5's
association with the overall CVD events was even
stronger and the estimate larger, and the  association
with SO2 also became stronger and the estimate larger
(1.13 [95% CI: 0.98,1.30]).  Correlations among these
pollutants were not described, and therefore it is not
possible to estimate the extent of confounding among
these pollutants in these associations, but it is clear that
PM2 5 was the best predictor of the CVD events.
Gaseous pollutants not analyzed.

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             TABLE AX5.9 (cont'd). ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH MORTALITY
              Reference, Location,
                 Study Period
                             Mean SO,, Levels
                                          Study Description
                                                                 Results and Comments
            UNITED STATES (cont'd)
 to
 o
 o
Pope et al. (2002)
U.S. nationwide
1982-1998
24-h avg mean of
118 MSA's in!980:
9.7 ppb; mean of
126 MSA's during
1982-1998: 6.7 ppb.
Prospective cohort study of approximately 500,000
members of American Cancer Society cohort enrolled in
1982 and followed through 1998 for all cause,
cardiopulmonary, lung cancer, and all other cause
mortality. Age at enrollment was 30+yrs.  Air
pollution concentrations in urban area of residence at
time of enrollment assessed from 1982 through 1998.
Other pollutants considered include TSP, PM15, PM10,
PM2.5, PMi5_2.5, SO42~, SO2, NO2, and CO.
PM2 5 was associated with total, cardiopulmonary, lung
cancer mortality, but not with deaths for all other
causes. SO2 was associated with all the mortality
outcomes, including all other causes of deaths. SO2's
risk estimate for total mortality was 1.03 (95% CI:
1.02, 1.05) per 5 ppb increase (1982-1998 average).
Residential location was known only at enrollment to
study in 1982. Thus, exposure misclassification
possible.
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 to
            Willis etal. (2003)
            Re-analy sis/sensitivity
            analysis of Pope et al.
            (1995) study.
                          Multiyear average of 24-
                          h avg using MSA scales:
                          9.3 ppb; using county
                          scales:  10.7 ppb.
                          Investigation of the effects of geographic scale over
                          which the air pollution exposures are averaged.
                          Exposure estimates were averaged over the county
                          scale, and compared the original ACS results in which
                          MSA scale average exposures were used. Less than half
                          of the cohort used in the MSA-based study were used in
                          the county scale based analysis because of the limited
                          availability of sulfate monitors and because of the loss
                          of subjects from the use of five-digit zip codes
                                                    In the analysis comparing the 2-pollutant model with
                                                    sulfate and SO2, they found that, in the MSA-scale
                                                    model, the inclusion of SO2 reduced sulfate risk
                                                    estimates substantially (>25%), but not substantially
                                                    (<25%) in the county-scale model. In the MSA-level
                                                    anlaysis (with 113 MSA's), SO2 relative risk estimate
                                                    was 1.04 (95% CI:  1.02, 1.06) per 5 ppb increase, with
                                                    sulfate in the model. In the county-level anaysis
                                                    (91 counties) with sulfate in the model, the
                                                    corresponding estimate was smaller (RR = 1.02
                                                    [95% CI:  1.00,1.05]). The correlation between
                                                    covariates are different between the MSA-level data and
                                                    county-level data.
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             TABLE AX5.9 (cont'd).  ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH MORTALITY
              Reference, Location,
                 Study Period
                              Mean SO,, Levels
                                        Study Description
                                                                Results and Comments
            EUROPE
 to
 o
 o
Elliott et al. (2007)
Great Britain; 1966-1994
air pollution; 1982-1998
mortality in four periods.
24-h avg SO2 levels
declined from 41.4 ppb in
1966-1970 to 12.2 ppb in
1990-1994
A small area analysis of mortality rates in
electoral ward, with the mean area of 7.4 km2 and
the mean population of 5,301 per electoral ward.
Deaths rates were computed for four successive
4-yr periods from 1982 to 1994. The number of
wards in these four periods ranged from 118 in
the 1994-1998 period to 393 in the 1982-1986
period.  Poisson model was fit to model observed
deaths for each ward with a linear function for
pollutant and random intercept, with and without
adjustment for social deprivation.
They observed associations for both BS and SO2 and mortality
outcomes. The estimated effects were stronger for respiratory
illness than other causes of mortality for the most recent
exposure periods and most recent mortality period (pollution
levels were lower). The adjustment for social deprivation
reduced the risk estimates  for both pollutants. The adjusted
risk estimates for SO2 for the pooled mortality periods using
the most recent exposure windows were: 1.021  (95% CI:
1.018, 1.024) for all-cause; 1.015 (95% CI: 1.011, 1.019) for
cardiovascular; and 1.064% (95% CI: 1.056,1.072) for
respiratory causes per 5 ppb increase in SO2.  The risk
estimates for the most recent mortality period using the most
recent exposure windows were larger.
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O
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Filleul et al. (2005)
Seven French cities
1975-2001
24-h avg SO2 ranged from
5.9 ppb ("Area 3" in Lille)
to 29.7 ppb ("Area 3" in
Marseille) in the 24 areas
in seven cities during
1974-1976. Median
levels during 1990-1997
ranged from 3.0 ppb
(Bordeaux) to 8.2 ppb
(Rouen) in the five cities
where data were available.
Cohort study of 14,284 adults who resided in
24 areas from seven French cities when enrolled
in the PAARC survey (air pollution and chronic
respiratory diseases) in 1974. Daily
measurements of SO2, TSP, black smoke, NO2,
and NO were made in 24 areas for three yrs
(1974-76).  Cox proportional hazards models
adjusted for smoking, educational level, BMI,
and occupational exposure. Models were run
before and after exclusion of six area monitors
influenced by local traffic as determined by the
NO/NO2 ratio >3.
Before exclusion of the six areas, none of the air pollutants
were associated with mortality outcomes. After exclusion of
these areas, analyses showed associations between total
mortality and TSP, BS, NO2, and NO, but not SO2 (1.01 [95%
CI: 0.97,1.06] per 5 ppb multi-yr average).  From these
results, the authors noted that inclusion of air monitoring data
from stations directly influenced by local traffic could
overestimate the mean population exposure and bias the
results. It should be noted that the table describing air
pollution levels in Filleul et al.'s report indicates that the
SO2 levels in these French cities declined markedly between
1974-76 and 1990-1997 period,  by a factor of 2 to 3,
depending on the city, whereas NO2 levels between the two
periods were variable, increased in some cities, and decreased
in others.  These changes in air pollution levels over the study
period complicates interpretation of reported risk estimates.

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             TABLE AX5.9 (cont'd). ASSOCIATIONS OF LONG-TERM EXPOSURE TO SULFUR DIOXIDE WITH MORTALITY
              Reference, Location,
                 Study Period
                             Mean SO,, Levels
                                          Study Description
                                                                 Results and Comments
            EUROPE (cont'd)
 to
 o
 o
 X
 (Si
 to
Nafstad et al. (2004)
Oslo, Norway
1972-1998.
           Nafstad et al. (2003)
           Oslo, Norway
           1972-1998
The yearly averages of
24-h avg SO2 were
reduced with a factor of
7 during the study period
from 5.6 ppb in 1974 to
O.Sppbin 1995.
                          The yrly averages of 24-h
                          avg. SO2 were reduced
                          with a factor of 7 during
                          the study period from
                          5.6 ppb in 1974 to 0.8  ppb
                          in 1995.
Cohort study of 16,209 Norwegian men 40-49 yrs of
age living in Oslo, Norway, in 1972-1973.  Data from
the Norwegian Death Register were linked with
estimates of average yrly air pollution levels at the
participants' home addresses from 1974 to 1998. NOX,
rather than NO2 was used.  Exposure estimates for NOX
and SO2 were constructed using models based on the
subject's address, emission data for industry, heating,
and traffic, and measured concentrations. Addresses
linked to 50 of the busiest streets were given an
additional exposure based on estimates of annual
average daily traffic. Cox proportional-hazards
regression was used to estimate associations between
exposure and total and cause-specific mortality,
adjusting for age strata, education, occupation, smoking,
physical activity level, and risk groups for
cardiovascular diseases.

Lang cancer incidence was examined in the above
cohort. During the follow-up period, 418 men
developed lung cancer.
NOX was associated with total, respiratory, lung cancer,
and ischemic heart disease deaths.  SO2 did not show
any associations with mortality (e.g., 0.97 [95% CI:
0.94, 1.01] per 5 ppb multi-yr average). The risk
estimates presented for categorical levels of these
pollutants showed mostly monotonic exposure-response
relationships for NOX, but not for SO2. Note the very
low levels of SO2.
                                                                             NOX was associated with lung cancer incidence.  SO2
                                                                             showed no association (1.01; [95% CI: 0.92, 1.12] per
                                                                             5 ppb multi-yr average).
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