EPA 450/05 86-013

   REVIEW OF THE NATIONAL AMBIENT AIR

  QUALITY STANDARDS FOR SULFUR OXIDES:

   UPDATED ASSESSMENT OF SCIENTIFIC
        AND TECHNICAL INFORMATION


ADDENDUM TO THE  1982  OAQPS STAFF PAPER
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            Stratigits ind Air Standirds Division
         Office of Air duality Planning and Standards
            U.S. Environmental Pratsetion Aginey
             flescarcn Triangle Park,  N.C, 2T711
                    December 1986

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Cover Illustration.  Individual  dose-response curves of percentage
(normalized)  changes  in airway  resistance  (SRaw), adjusted for
response to clean air exposure,  as a  function of S02 exposure for
asthmatic subjects,  (A)  6 subjects  with response at < 0,5 ppm,
(3)  9 subjects with response between 0.5 and 1.0 ppm, (C)  8
subjects with response between 1.0 and 2.0 ppm,  and (D)  4 subjects
with response at > 2.0 ppm S0£.   Data are not included for 0.0 ppm
since they were used to adjust for exercise-induced bronchocon-
striction.  The interrupted horizontal line represents 100% increase
in SRaw and the S02 concentration corresponding  to its point of inter-
cept with each subject's curve was defined as PC(S02)  (Horstman et
al.  1986).  The substantial variability in sensitivity to peak SO;?
exposures among asthmatics is an important consideration in the
review of the sulfur oxides standards.

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REVIEW OF THE NATIONAL  AMBIENT AIR  QUALITY STANDARDS FOR SULFUR OXIDES

       UPDATED ASSESSMENT OF SCIENTIFIC AND TECHNICAL INFORMATION



                 ADDENDUM TO THE  1982 QAQPS STAFF PAPER
                 Strategies  and  Air  Standards  Division
              Office of Air  Quality  Planning and Standards
                  U.S.  Environmental  Protection Agency
                  Research Triangle  Park,  N.C.  27711
                             December  1986

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                              Ac k n ow1ed geme nts

     This staff paper is the product of the Office  of  Air Quality
Planning and Standards (OAQPS).  The principal  authors include  Jeff  Cohen,
John Bachmann, and Henry Thomas.  The report  incorporates comments from
OAQPS, the Office of Research and  Development,  the  Office of  Policy,
Planning, and Evaluation, and the  Office of  General  Counsel within EPA
and was formally reviewed by the Clean Air Scientific  Advisory  Committee.
     Helpful comments and suggestions were also submitted by  independent
scientists, by officials from the California  Air Resources Board, and by
environmental and industry groups  including  the Natural  Resources Defense
Council, the Environmental Defense Fund, the  American  Mining  Congress,  and
several member companies, the Utility Air Regulatory Group, the Air  Pollution
Institute, Standard Oil Company, Phelps Dodge Corporation, and  Kennecott
Company.
     The authors wish to thank Teresa demons and Tricia Holland for
word processing, and Dick Atherton for graphics assistance.

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                                TABLE OF CONTENTS
                                                                       Page
 List of Figures	.,.,,...	   iv
 List of Tables	   iv
 Executive Summary  .......  	 „....    v
   I.   Introduction   ........  	  ........    1
       A. Purpose  »...,.,..  	  .  	    1
       B. Background	    1
       C. Approach	    3
 II.  Air Quality Considerations   ......  	  .  	     $
     A. Peak  to  Mean Ratios	  ......     5
     B. Factors  Affecting  Assessment of .Peak  Air Quality  Levels   .  .     7
III,  Critical  Elements  in  the Review of the Primary  Standards   ...     9
     A.  Mechanisms	•...,.....     9
     B.  Concentration/Response  Information   	  .  	    12
 IV.  Factors  to  be Considered in Selecting Primary Standards for
     Sulfur Oxides 	  ...........  	    33
     A.  Levels  and  Averaging Times  of the Standards .  .  ,  	    33
        *
     B.  Analysis  of Relative Protection  Afforded  by Alternative
         Standards 	  ....................    SO
     C.  Summary of  Staff  Conclusions and Recommendations  .....    58
 Appendix A.  Analysis of Oose Response Relationships
              from  Controlled  S0£ Exposure Studies  on
              Asthmatics  ..... 	  .    A-l
 Appendix B.  CAS AC Closure Memorandum	,	    8-1
 References

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                               LIST OF TABLES
Number                               Title                            Page

1              Updated Staff Assessment of Key Controlled Human
               Studies                                                vii

2              Updated Staff Assessment of Short-Term
               Epidemiological  Studies                                x

3-1            Summary of Recent (1982-86) Epidemiological  Studies
               Providing Most Useful  Concentration Response
               Information for Short-Term SO2 Exposures               24

3-2            Summary of Recent (1982-86) Epidemiological  Studies
               Providing Most Useful  Concentration Response
               Information on Long-Term Exposures to SO3              30

4-1            Updated Staff Assessment of Key Controlled Human
               Studies       .                                         3b

4-2            Updated Staff Assessment of Short-Term
               Epidemiological  Studies                                4b

A-l            Summary of Data from SOg Controlled Asthmatic
               Studies Used in Dose-Response Analysis                 A-2
                              LIST  OF FIGURES


3-1            Combined S0£ Dose Response Relationships               19

3-2            Distribution of Individual Airway Sensitivity to S02   20

4-1            Gradiation of Physiological  Responses to SOg           38

4-2            Expected Percentage  of Asthmatics with One Exposure
               of Concern Per Year.  1) Current Emissions
               2)  Current NAAQS                                      55

4-3            Expected Percentage  of Asthmatics with One Exposure
               of Concern Per Year.  Alternative One Hour Standards   57

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                            EXECUTIVE SUMMARY


     This paper evaluates and interprets the updated scientific and

technical information that the EPA staff believes is most relevant  to

the review of primary (health) national  ambient air quality standards

(NAAQS) for sulfur oxides* and represents an update of the 1982 sulfur

oxides staff paper.  This paper assesses what the staff believes should be

considered in selecting appropriate averaging times and levels for  the

primary sulfur oxides standards, updating and supplementing previous

staff conclusions and recommendations in these areas to incorporate more

recent information.  The assessment in this staff paper addendum is

intended to help bridge the gap between the scientific review contained

in the EPA criteria document addendum "Second Addendum Air Quality  Criteria

for Particulate Matter and Sulfur Oxides (1982):  Assessment of Newly

Available Health Effects Information" and the judgments required of the

Administrator in setting ambient standards for sulfur oxides.  The  staff

paper and this addendum are, therefore, an important element in the

standards review process and provide an opportunity for public comment on

proposed staff recommendations before they are presented to the Administrator,

The focus of this paper is an sulfur dioxide  (502), alone and in combination

with other pollutants.

     SOg is a rapidly diffusing reactive gas that is quite soluble  in

water.   It is emitted principally from combustion or processing of

sulfur-containing fossil fuels and ores.  S02 occurs In the atmosphere
 *The  current  standards for sulfur dioxide (S02) are;  primary, 0.03 ppm
 (80 ug/m3)  annual arithmetic mean and 0.14 ppm (365 Mg/m3) 24-hour
 average  not to be exceeded more than once per year; and, secondary,"0.5
 ppm  (1300  ug/m3) 3-hour average not to be exceeded more than once per
 year.

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                                    VI
with a variety of particles and other gases, and undergoes chemical  and
physical  interactions with them forming sulfates and other transformation
products.
     Because much of the recently available health effects information  on
S02 is related to short-term exposures, the staff paid particular attention
to updating information on short-term peak concentrations.  The staff
found that:
     1)  Maximum 5 minute to hourly S02 concentrations are found" near
major point sources.  The newer information tends to support earlier
conclusions that near such sources, the 5 to 10 minute peak SUg concen-
tration is likely to be within a factor of 1.4 to 2.4 times the hourly
average.   Maximum peak to mean ratios can be higher.
     2)  Short duration peaks (less than 30 seconds to 2  minutes)  in excess
of 0.5 ppm appear likely to occur near numerous smaller sources of SOg.
None of the recently published assessments of the health  effects of  S02
has addressed exposures of such limited duration.  Due to limitations of
the monitoring instruments, it is not presently possible  to assess the
extent to which such peaks may be occurring in particular urban locations.
UpdatedAssessment of the Primary Standards
     Conclusions and recommendations based on the updated staff assessment
of the information in the criteria document addendum are  summarized  below.
     1)  The present staff assessment of the more recent  studies reinforce
the earlier conclusion reached in the 1982 staff assessment that the most
striking  acute response to S02 is reflex bronchoconstriction,  or airway
narrowing, in exercising asthmatics and others with hyperreactive  airways,
     2) a) The updated staff assessment of key controlled human studies
of peak (minutes to an hour) S02 exposures is summarized  in Table  1. Both

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     SO 2
Concentration
(5-60 minutes)
Observed Effects1
Comments /1 rnpli cat i ons
1-2 ppm
Substantial changes in 8 of 12
subjects ( A SRaw 100-600%)
exposed to 2 ppm.  At 1 ppm,
functional changes ( & SRaw 170-
200%), symptoms in free
breathing asthmatics at
moderate exercise^
Effects range from moderate to incapacitatin
for some individuals.  At 2 ppm, 80% of mild
asthmatics could experience at least a
doubling of SRaw.  Some might not tolerate
exposure at moderate exercise.  Approx. 60%
at 1 ppm could experience at least a doublin
of SRaw.^  Some asthmatic mouth breathers
have significant bronchoconstriction at 2 pp
even at light activity.	
0.6-0.75 ppm
Functional changes ( A SRaw 120-
260%), symptoms in free breath-
ing asthmatics at light-moderate
exercise*
Effects indicative of clinical significance;
on average, changes were mild to moderate
although severe for some individuals; 25-50%
of mild, free-breathing asthmatics at
moderate exercise could experience at least
a doubling of airway resistance.3        	
0.5 ppm
Significant functional changes
( 4 SRaw 50-100%), symptoms
in free breathing asthmatics at
moderate, but not at light
exercise.^  At heavy exercise,
A SRaw 220-240%.6
On average, mild responses at moderate or
higher exercise, symptoms possibly of
clinical significance; severe responses for
some individuals.  About 20-25% could ex-
perience at least a doubling in airway
resistance.
    ppm         Functional changes ( A SRaw 70%),  Lowest level  of clinically significant
                symptoms in free breathing         response for some free breathers.  Approx. 1C
                asthmatics at moderate-   -        . of mild, free breathing asthmatics, could ex-
                heavy exercise?	perience a doubling in airway resistance.^
0.1-0.3 ppm     No effects in free breathing
                asthmatics at light exercise.
                Slight but not significant
                functional changes in free-
                breathing subjects at moderate-
                heavy exercise (0.25 ppm)^» but
 	            not at lower levels.?
                                   Significant effects unlikely at moderate
                                   exercise.  Effects of SOg indistinguishable
                                   at heavy exercise.  Possibility of more
                                   significant responses in small percentage
                                   of sensitive asthmatl ~, at 0.28
Specific Airway Resistance (SRaw) is the lung function measure most often reported in S02
 studies.  Unless otherwise noted, ( A SRaw	%) reflects group mean increase over clean afr
 control at rest.  Light, moderate, heavy exercise refers to ventilation rates approximating
 £35 L/rnin, 40-45 L/min, and >_ 50 L/min, respectively.  Effects reflect results from range of
 moderate temperature/humidity conditions (i.e., 7-26aC, 36-90% RH).  Studies at 0.5-0.6 ppm
 indicate that exercise-induced bronchoconstriction associated with cold and/or dry air
 exacerbates response to S02 while warm, humid air mitigates asthmatic responses relative to
 moderate conditions.
2schacter et al. (1984); Roger et al. (1985); Horstman it al. (1986).
JHorstman et al., (1986).
^Hackney et il. (1984); Schacter et al. (1984); Linn et al. (1983a,b, 1984a,b,c, 1985a).
=Kirkpatrick et al. (1982); Linn et al. (1984b); Roger tt al. (1985); Schacter et al.  1984).
"Bethel et al. (1983a,b; 1985),
7Linn et al. (1983b, 1984a).

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recently published studies and those assessed in the 1982 staff paper are
included.  The table focuses on those studies involving free breathing
                                   *
(chamber) or facemask exposures, which provide the closest approximation
of natural breathing.  After account is made for differences in ventilation
rates and oral/nasal breathing patterns, consistent results are derived
from the various studies including even those that used mouthpiece exposures.
The major effects observed in these studies are increases in airway
resistance and decreases in other functional measures indicative of
significant bronchoconstriction in sensitive asthmatic or atopic subjects.
At 0.4 ppm SOg, changes in functional  measures are accompanied by mild
increases in perceptible symptoms such as wheezing, chest tightness, and
coughing.  At higher concentrations, effects are more pronounced and the
fraction of asthmatic subjects who respond increase, with clearer
indications of clinically or physiologically significant effects at
0.6-0.75 ppm and above.
     b)  Significant bronchconstriction has been observed in asthmatics
after 5-10 minutes of exposure and usually diminishes within one hour once
either exposure or exercise alone is discontinued.  Responses are mitigated
with repeated exposures within one hour but not with continuous exposure,
nor with subsequent exposures 5-24 hours later.  Recent work indicates
that the combined effect of S02 and cold, dry air further exacerbates the
asthmatic response while warm, humid conditions mitigate S02 effects.
     c)  Given practical considerations related to monitoring, modeling,
data manipulation and storage, and implementation, the staff previously
recommended consideration of a 1-hour averaging time to protect against
the responses to short-term peak (5-10 minute) S02 exposures observed in
the controlled human studies.  Based on this updated staff assessment,   •-

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                                    IX
the range of potential  1-hour levels of interest is  revised from 0.25 to
0.75 ppm to 0.2 to 0.5  ppm (525 to 1300 ug/m3).   The lower bound represents
a 1-hour level for which the maximum § to 10 minute  peak exposures are
unlikely to exceed 0.4  ppm, which is the lowest  level  where potentially
significant responses in free (oronasal) breathing asthmatics have been
reported in the criteria document addendum.  The upper bound of the range
represents a 1-hour level for which 5 to 10 minute peak concentrations
are unlikely to exceed  1 ppm, a concentration at which the risk of significant
functional and symptomatic responses in exposed  sensitive asthmatics and
atopies appears high.  In evaluating these laboratory data in the context
of decision making on possible 1-hour standards, the following considerations
are important:  (a) the significance of the observed or anticipated
responses to health, (b) the relative effect of S02 compared to normal
day to day variations in asthmatics from exercise and other stimuli,
(c) the low.probability of exposures of exercising asthmatics to peak
levels, and (d) five to ten minute peak exposures may be a factor of two
greater than  hourly averages.
     d)   Independent of  frequency of exposure considerations, the upper
bound of  the  range contains little or no margin of safety for exposed
sensitive  individuals.  The limited geographical areas likely to be
affected  and  low  frequency of peak exposures to active asthmatics if the
standard  is met add to the margin of safety.  The widespread use of medica-
tion among  asthmatics that prevents or  rapidly  relieves bronchoconstrictive
effects due to natural and commonly encountered stimuli (e.g., exercise,
cold air)  further adds to the margin of safety.  The data do not suggest
other groups  that are more sensitive than  asthmatics to single peak
exposures,  but qualitative data  suggest repeated peaks might produce

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effects of concern in other sensitive individuals.  Potential  interactions
of S02 and 03 have not been investigated in asthmatics.   The qualitative
data, potential  pollution interactions, and other considerations listed
above should be considered in determining the need for and evaluating the
margin of safety provided by alternative 1-hour standards.
     3)  Based on a staff assessment of the recent short-term  epidemiological
data summarized in Table 2, the original staff range of  24-hour S0£ levels of
interest - 0.14 to 0.19 ppm (365 to 500 uy/m3) - still  appears appropriate,
although some consideration could be given to the findings of  physiological
changes of uncertain significance at levels as low as 0.1 ppm.  Earlier
staff conclusions and recommendations concerning retaining the present
24-hour standard remain appropriate.

 Table 2. UPDATED STAFF ASSESSMENT OF SHORT-TERM EP10EMIOLOGICAL STUDIES

Effects/
Study


Effects
Likely
Effects
Possible

No Effects
Observed
Measured SO? - ug/m3 (ppm) - 24 hour mean
Daily Mortality
in London1


500-1000
(0.19-0.38)

-

_

Aggravation of
Bronchitis*


500-600
(0.19-0.23)

<500 (0.19)

—

Small , Reversible
Declines in
Children's Lung
Function^
._


250-450
(0.10-0.18)
100-200
(0.04-0.08)
Combined
Effects
Levels

500 (0.19)


260 (0.10)

<200 (.08)

^Deviations in daily mortality during London  winters  (1958-1972).   Early
 winters dominated by high smoke and SQg,  principally from  coal  combustion
 emissions, and with frequent fogs (Martin and  Bradley,  1960;  Ware  et  al.,
 1981; Mazumdar et al., 1981, 1982;  Schwartz  and  Marcus,  1986).
^Examination of symptoms reported by bronchi tics  in  London.  Studies
 conducted from the mid-1950's to the early 1970's  (Lawther et al., 1970).
3Studies of children in Steubenville (1978-80)  and  in the Netherlands
 (1985-86) before, during, and after pollution  episodes  characterized
 by high particle and S02 levels (Oockery  et  al., 1982;. Dassen et al.,  1986).

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                                    XI

     4)  The previous staff assessment  concluded that although the possibility
of effects from continuous lower level  exposures to S0£ cannot be ruled out,
no quantitative rationale could be offered to support a specific range of
interest for an annual standard.  The more recent epidemiological data,
indicating associations between respiratory illnesses and symptoms and
persistent exposures to $02 in areas with long-term averages exceeding
.04 ppm (100 pg/m3), provide additional support for the original recommen-
dation for retaining an annual standard at or near the current level  of
0.03 ppm (80 ug/m3).  This recommendation was based in part on a finding
that alternative short-term standards  (1, 3, and 24-hour) would not
prevent annual levels in excess of the "current standard in a limited
number of heavily populated urban areas.  In addition, recent evidence
suggests smaller sources in urban areas may produce short duration (< 1
minute) peaks of potential concern.  The long-term standard often serves
to limit the emissions of numerous smaller sources in such areas.  Given
the additional information and the possibility of both chronic and acute
effects from a large increase in population exposure, the staff recommends
maintaining the primary annual standard at its current level.
     5)  Analyses of alternative averaging times -and population exposures
suggest that:
     a)  The current standards provide substantial protection against
         the effects identified as being associated with 24 hour and
         annual exposures.                       ';
     b)  The current standards - as reflected by current emissions or
         emissions when the standards  are just met with somewhat less
         restrictive implementation assumptions — also provide.some limit
         on peak SOg exposures of concern for asthmatics.  In some cases,

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                                  • XI 1

         however, up to 1 to 14% of the sensitive  population  in  the
         vicinity of major sources  could be exposed  once  a year  to levels  at
         or above 0.5 ppm for 5 minutes, while  at  elevated ventilation,
     c)  The range of 1-hour standards analyzed (0.25  to  0.5  ppm) provides
         increased protection against  such  exposures,  limiting the fraction
         of asthmatics exposed living  near  certain major  point sources
         to less than 4%, although  very short-term (<2 minutes)  exposures
         greater than 0.5 ppm around smaller facilities would not be
         eliminated.
     The relative protection afforded  by current vs. alternative standards
as indicated by current and ongoing exposure analyses  is  an important
consideration in determining what,  if  any,  standard  revisions may be necessary,

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 REVIEW OF THE NATIONAL  AMBIENT  AIR  QUALITY STANDARDS  FOR SULFUR OXIDES
        UPDATED ASSESSMENT  OF  SCIENTIFIC  AND TECHNICAL INFORMATION

                  ADDENDUM  TO  THE  1982 OAQPS STAFF  PAPER
I.  INTRODUCTION

    A.  Purpose

        This paper evaluates and Interprets  the most  relevant  scientific

and technical information reviewed in the draft EPA document,  Second

Addendum to Air Quality Criteria for Partieulate Matter and  Sulfur

Oxides (1982):  Assessment of Newly Available Health  Effects Information

(EPA, 1986a) and represents an update of the 1982 sulfur oxides  staff

paper (EPA, 1982a).  This staff paper addendum is intended to  help  bridge

the gap between the scientific review of recent health effects information

contained in the criteria document (CD)  addendum and  the judgments  required

of the Administrator in setting primary  national ambient air quality

standards (NAAQS) for sulfur oxides.  As such, particular emphasis  in

this paper is placed on conclusions, recommendations, and uncertainties

regarding the averaging times and levels for the primary standards.

While the paper should be of use to all  parties, interested in  the standards

review, it is written for those decision makers, scientists, and staff

wHo have some familiarity with the technical discussions contained  in the

criteria document addendum.

B.  Background

1.  Legi siati ve Requirements

     Since 1970 the Clean Air Act as amended has provided authority and

guidance for the listing of certain ambient  air pollutants which may  endanger

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                                    2
public health or welfare and the setting and revising of NAAQS for those
pollutants.  Primary standards must be based on health effects criteria and
provide an adequate margin of safety to ensure protection of public health.
As several recent judicial decisions have made clear, the economic and
technological feasibility of attaining primary standards are not to be
considered in setting them, although such factors may be considered to a
degree in the development of State plans to implement the standards (D.C.
Cir., 1980, 1981).  Further guidance provided in the legislative history
of the Act indicates that the standards should be set at "the maximum
permissible ambient air level . . . which will  protect the health of any
(sensitive) group of the population." Also, margins of safety are to be
provided such that the standards will afford "a reasonable degree of
protection . . . against hazards which research has not yet identified."
(Committee on Public Works, 1974).  In the final analysis, the EPA
Administrator must make a policy decision in setting the primary standards,
based on his judgment regarding the implications of all the health effects
evidence and the requirement that an adequate margin of safety be provided.
     2.  OriginalSulfurOxides Standardsand Review to Date
     The current primary standards for sulfur oxides (to protect
public health) are 0.03 parts per million (ppm) or 80 micrograms per
cubic meter (ug/m^), annual arithmetic mean, and U.14 ppm (366 M9/m^).
maximum 24-hour concentration not to be exceeded more than once per year.
The current secondary standard for sulfur oxides (to protect public welfare)
is 0.5 ppm (1300 Mg/^), maximum 3-hour concentration, not to be exceeded
more than once per year.  For both primary and secondary standards,
sulfur oxides are measured as sulfur dioxide (SOg).  Thus, $02 is the
current indicator for the sulfur oxides standards.

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     The formal  review of the original  S02 criteria and  standards  was
initiated in 1978.   The Clean Air Scientific Advisory Committee (CASAC)
closed on the criteria document (which  also addressed participate  matter)
in January 1982,  The first addendum to the criteria document (CD),  which
summarized the recent controlled human  studies on the health effects of
S02» was issued the same year,  A staff paper, which identified critical
issues and summarized the staff's interpretation of key  studies, received
verbal closure at a CASAC meeting in August 1982 and formal  written
closure in August 1983 (See Appendix A for Executive Summary of staff
paper).  The decision to produce a second addendum to the combined PM/S02
criteria document and this sulfur oxides staff paper addendum was  taken
in context of the recommendations to review certain new studies on the
effects of particulate matter and announced on April 1,  1986 [51 FR  11058].
     A preliminary draft of this paper was reviewed by the CASAC in
October 1986.  This final product incorporates the suggestions and
recommendations of the CASAC as well as other comments received on the
initial draft.  The CASAC closure memorandum  (Lippmann,  1987) is reprinted
in Appendix B.
C.  Approach
    The approach in this paper is to address the newly available health
effects information in the second criteria document addendum (CD addendum
or CDA; EPA, 1986a) in the context of those critical elements which  the
staff believes have implications for previous conclusions reached  on the
primary sulfur oxides standards.  Particular  attention is drawn to judgments
related to the ranges of interest for the primary standards.  Previous
staff conclusions related to the secondary standard, and the form  of the
standards will not be addressed here.

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                                    4

     Because sulfur oxides are often studied in combination with particulate
matter, much of the more important literature has already been assessed
in the companion staff paper and staff paper addendum on particulate
matter (EPAt 1982c; 1986b).  Where possible, pertinent references are
made to those papers, with only summaries presented in this paper,
     The principal  focus of this paper is on the effects of S02> alone
and in combination  with other pollutants.  Other sulfur oxide vapors
(e.g., 503) are not commonly found in the atmosphere.  The effects of the
principal atmospheric transformation products of SQ2 (i.e., sulfuric acid
and sulfates) are discussed in the companion staff paper on particulate
matter (EPA, 1982c) and will be further examined in a forthcoming document
on acid aerosols.
    Section II provides an update of air quality information on sulfur oxides
to support discussions of the primary standards.  Section III addresses those
essential elements  that require re-examination in light of the new information
reviewed in the CD  addendum; these elements include identification of
possible mechanisms of taxi city and discussion of controlled human and
community studies, relating level(s) and duration(s) of exposure to indicators
of health effects.
    Drawing from the discussion in Sections II and III, Section IV
identifies and assesses the factors the staff believes should be considered
in selecting the averaging times and levels of primary standards.  Updated
staff findings and  recommendations on the alternative policy options in
these areas are also presented.

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II.  AIR QUALITY CONSIDERATIONS
       The major chemical  and physical  properties  of SOg  in  the atmosphere
and characterization of ambient  concentrations at  U.S.  sites are presented
in the 1982 staff paper ("SP"; EPA 1982a)  and discussed in more detail
in Chapters 2 and 5 of the CD (EPA, 1982b).   Because most of the recently
available health effects information on SQg  is related  to short-term (5 to
10 minute) exposures, this section will update information on short-term
peak-to-mean ratios and related issues. This information is relevant in
estimating human exposures and examining relationships  among different
standard averaging times.
       A.  Peak-to-Mean Ratios
       The shortest averaging period retained in many monitoring data banks
and produced by atmospheric models is one  hour.  The 1982 staff paper
summarized the available information on the  variance of 5 to 10 minute peak
concentration within particular hourly periods.  That assessment concluded
that, based on typical distributons, the 5 to 10 minute peak is likely to be
within  a factor of 1.4 to 2.4 times the hourly average (Larsen, 1968; Burton
and Thrall, 1982).
     Recent work  (Thrall-et al.; 1982, Rote  and Lee, 1983;  Armstrong,
1985, 1986) on peak-to-mean ratio appears  consistent with the earlier
assessment.  Thrall et al. (1982) analyzed monitoring data  taken from a
-dense  (18  site) network around the Kincaid (Illinois) power  plant.  The
network was established, as a  part of an Electric Power Research Institute
(EPRI)  model validation study.  Kincaid is an isolated 1300  MWe, base load,
coal-fired plant  with a single  187 meter stack.  A 23-week  sample (March-
August  1980) was  examined.  The maximum hourly value in this sample was
approximately 0.34 ppm and the  maximum 5-minute value was 0.56 ppm.  Thrall

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et al. found that the peak-to-mean ratios tend to fall as the hourly average
increases.  Thus, although the overall ratio of 5-mlnute peak to hourly
mean was 2.3 _+ 1,3* for all hours, the ratio for hours over u.l ppm was only
1.8.  The overall ID-minute peak to hourly mean ratio was 2,0 +_ 0.96*,
dropping to 1.6 for hours over 0.1 ppm.
     Thrall and coworkers considered the situation of an isolated fuel combustion
source.  Rote and Lee (1983) provides a similar analysis for urban areas.
In this case, the Regional Air Pollution Study (RAPS) data base was used.
RAPS was a two year (1975-1976) study of air pollution in St. Louis which
included 13 S0£ monitoring sites.  Unfortunately, the instruments were
spanned to 1.0 ppm and for 10 sites, as many as 6% of the 1-minute values
exceeded 1.0 ppm.  Analyzing a large random sample of station hours (40,000),
Rote and Lee found that the overall ratio of 5 minute peak to hourly mean
concentration was 1.5 +_ 0.48* while the 10-minute peak-to-mean ratio was
1.4 _+ 0.39*.  These ratios for all hours combined were found to be unaffected
by hours containing out-of-range 1-minute "values.  At higher mean concentrations,
the ratios also tended to be lower.  However, in this case Rote and Lee found
evidence that, for hours > 0.5 ppm, the apparent decline in ratio with
increasing mean concentration was in part due to the spanning of the instruments.
     Recent air quality analyses of sites near two primary copper smelters
in Arizona estimated six minute peak-to-one-hour mean ratios (Armstrong,
1985, 1986).  Although the ratios found at the Magma - San Manuel  smelter
were in the range of those found at Kincaid and other sites, the ratios
at a second smelter (Phelps-Dodge, Douglas) were higher, with a 6 minute
peak to hourly mean ratio of 3.3.
*Standard deviation

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     B.  Factors Affecting Assessment of Peak Air Quality Levels
     The 1982 staff paper concluded that short-term peak levels in excess
of 0.5 ppm were most likely in the vicinity of major SC>2 point sources.
Recent theoretical work on low persistance meteorological events (Huber and
Pooler, 1985) as well as analyses of ambient data (Kilkelly and Roberson,
1985) have raised questions regarding both the impact of smaller sources of
SOg and the adequacy of monitoring data to assess such impacts.  A staff
assessment of these issues found that small sources with less than Good
Engineering Practice (GEP) stack height may also produce SO^ peaks in
excess of 0.5 ppm (EPA, 1986c).  Most of these peaks are due to buildiny
downwash, are of limited area and extent (usually within U.5 km of the
stack), and are of very short duration (usually 30 seconds to 2 minutes).
Based on the analyses noted above, it appears that very short duration
peaks in excess of 0.5 ppm may occur on the order of 1000 per year at a
fixed location.  No accurate determination of how many sources may be
subject to downwash appears feasible.  Preliminary, but very rough, calculations
indicate that the numbers may be quite significant.  In addition, small sources
regardless of stack height, may also produce comparable short duration peaks
due to looping plumes.  These exceedances would likely be found within 3 km
of the stack and occur on the order of 10 times per year (EPA, 1986c).
     A review of Kilkelly and Roberson (1985) and related strip charts
permits several insights regarding the monitoring of very short-term (2-3
minute) peak S02 concentrations.  The data in question were recorded near
facilities with short stacks and are reported to show evidence of building
downwash  (Docket No. A-83-49, Item  IV.H.39).  Staff examination showed
that the  instruments were spanned to 1 ppm and frequently hit this limit
for short-time periods.  This means that the true peaks can not be readily

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estimated but were presumably in excess of 1 ppm.  This "peak lopping" does
not appear to affect significantly the hourly averages at the sites in ques-
tion because the area under the curve at the peak is quite small.  Clearly,
for peaks of longer duration (>_ 5-10 minutes), peak lopping would lead to a
significant underestimate of the hourly average.  Peaks in excess of the
spanned value for 5-10 minutes were seen at some of the facilities in the
Kilkelly set and around some TVA facilities (Lott, 1985).  In such cases,
it is possible that hourly averages may be underestimated due to spanning.
Peak lopping, if it occurs, would also bias any analysis of peak to mean
ratios.  EPA monitoring guidance calls for S02 instruments to be spanned to
0,5 ppm with a requirement that they be respanned if the limit is reached.
     A related concern examined by the recent staff assessment (EPA, 1986c)
is instrument response time.  Many S0£ instruments now in wide use require
4-5 minutes to reach 95% of scale.  Thus, if the actual peak lasts only 30
seconds to 1 minute, most instruments would not respond fast enough to
register the true peak.
       In summary, the recent staff assessment of short-term peaks and smaller
sources prompts the following conclusions:
       1) Peaks well in excess of 0.5 ppm appear likely to occur around
numerous small sources of S0£.  Although of very limited duration and areal
extent, they can occur with relatively high frequency.  None of the recently
published assessments of the health effects of SOg has addressed exposures
of such limited duration (< 30 seconds to 2 minutes); and
     2) It appears that, due to spanning and instrument response time, most
monitored data are not accurately measuring very short-term peaks.  It is
therefore not presently possible to assess the extent to which such peaks
may be occurring.

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III.   CRITICAL ELEMENTS  IN THE REVIEW  OF THE  PRIMARY  STANDARDS
     This section summarizes relevant  aspects of recent  information  in
the CD addendum on the mechanisms by which S02 may  cause airway  reactions
and concentration/response relationships  derived from controlled human
and community studies of SUg effects.   A  comprehensive discussion of
these and other critical elements including mechanicms of toxicity,
effects of concern, and sensitive populations is contained in Section V
of the 1982 staff paper (EPA, 1982a).   The present  summary provides  a
basis for later discussions of the implications of  the more recent studies
for the standards review.
A.   Mechanisms
     The previous staff assessment found  that the most striking  acute
response to SOg for asthmatics and others with hyper-reactive airways is
rapid bronchoconstriction  (airway narrowing), usually evidenced  in increased
airway resistance, decreased expiratory flow rates, and the occurrence of
symptoms such as wheezing, chest tightness, and shortness of breath.  Several
of the more recent studies discussed in the CD addendum contribute further
to understanding mechanisms and factors that affect these responses  (CDA,
Section 4.4).  The discussion below highlights insights from the CD
addendum with respect to the impact of breathing mode, temperature/humidity
conditions, and the time course of exposure and recovery.
1.    Inhalation Patterns and Airway Cooling/Drying
     The penetration of S02 to sensitive portions of the respiratory
tract is largely determined by the efficiency of the oral or nasal mucosa
in absorbing S02, which in turn depends on the mode of breathing (nasal,
oral, or oronasal) and  the rate of airflow.  Newly  published controlled
S02 exposure  studies on asthmatics confirm previous findings that at

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                                    10


comparable S0£ concentrations, bronchoconstriction effects increase with


both increased ventilation rates and as the relative contribution of oral
                                                                          <*

ventilation to total ventilation increases, as seen by comparing oral-only


(i.e., mouthpiece) breathing with oronasal breathing (Bethel  et a!.,


1983b, 1985; Roger et a!., 1985; Koenig et al.» 1985).


     The CO addendum notes that increased oral ventilation not only


allows more direct penetration of SQg but may also result in  airway


drying and alterations in airway surface liquid that further  affects


SOg absorption and penetration (CDA, pp. 4-41 to 4-42).  Evaporation of


airway surface liquid and perhaps convective cooling of the airways


caused by cold, dry air can act as direct bronchoconstrictive stimuli in


asthmatics (Deal et al., 1979; Strauss et al., 1977; Anderson, 1985).


Recent studies indicate that the combined effect of S02 and cold, dry air


further exacerbates the asthmatic response (Bethel et al., 1984; Sheppard


et al., 1984; Linn et al., 1984a,b, 198Sa),  It has been suggested that


reduced water content and not cold per se could be responsible for much

                                                                       *
of this effect.  This is consistent with other recent findings that the


bronchoconstrictive effects of SOg are reduced under warm, humid conditions


(Linn et al., 1985a).  It appears that the interactive effects of breathing


$02 and dry (or cold) air range from less than additive to synergistic


depending on whether oral airway geometry is altered by use of mouthpieces,


preventing any initial conditioning of inspired air in the mouth (e.g.,


warming, humidifying) (CDA, p. 4-42).


2.   Time Course of Response, Recovery andAdaption


     The time required for S02 exposure to elicit significant bronchoconstriction


in exercising asthmatics is brief.  Exposure durations as short as 3 minutes


have produced significant responses in a mouthpiece study (Sheppard et al., 1984)

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                                    11

with the majority of studies using 5-10 minute exposure durations.  Little
enhancement of response is apparent with prolonged exposure beyond 6 minutes,
although some suggestion of an increase is seen with continuous exercise
between 10 and 30 minutes (Kehrl et al,, 1986).  On mechanistic grounds,
it would appear possible for some response to occur with exposures of
less than 5 minutes with high enough concentrations.  The relationship
between concentration, time and response for such periods has not, however,
been systematically examined.
     Following a single SQ2 exposure during exercise, airway resistance
in asthmatics appears to almost fully recover within one hour, even if
low-level SOg exposure is continued without exercise (Hackney et al.,
1984).  A reduced response is observed if S0£ exposure is repeated within
15-60 minutes, but not with subsequent exposures 5-24 hours later (Sheppard
et al., 1983; Roger et al., 1985; Kehrl et al., 1986; Linn et al., 1984c;
Snashall and Baldwin, 1982).  Similar attenuation of airway constriction,
induced by exercise or hyperventilation of cold, dry air, is observed
when the exercise exposure is repeated at short-time intervals, with a
refractory period that persists for 2-4 hours  (Stearns et al., 1981;
Bar-Yishay et al.» 1983).  Significantly, while repeated short exercise
periods over a 1-hour period result in reduced response, 30 minutes of
continued exercise results in responses that equal or exceed those observed
after a single 10 minute period (Kehrl et al., 1986).
     The CO addendum discusses-several possible mechanisms that might
account for the mitigated responses to $02 over time (e.g., decreased
responsiveness of airway smooth muscle or vagal reflex pathways due to
mediator depletion or inhibition of SQ2~receptors) (COA, p. 4-43).
Since continuous exercise apparently  prevents a recovery period,  Kehrl

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                                    12
at al. (19^6) suggest that the mechanism for "adaptation" to rapidly
repeated SOg exposures may be increased production and/or secretion of
airway surface liquid during recovery following an SOg challenge.  This
would act to decrease relative SQ£ penetration in subsequent exposures.
B.   Concentration/Response Information
     The following review summarizes key results from those recent studies
cited by the CD addendum as providing the most reliable quantitative
information as well as some that provide reasonable evidence of concentra-
tion-response relationships without allowing derivation of specific
levels.  Responses to S02» alone or in combination with other pollutants,
are examined in three time scales:  1) peak exposures (minutes-hours),
2) short-term exposures (hours-days) and 3) long-term exposures (months-years).
A further assessment of these studies as applied to selecting alternative
levels for air quality standards is presented in Section IV.
1.   Peak Exposures
     Information on the effects of relatively brief (minutes-hours) peak
exposures to SOg is derived from studies of humans under controlled
laboratory conditions.  The importance and limitations of controlled
human exposure studies are discussed in the CD and CD addendum
as well as the 1982 staff paper (EPA, 1982a,b; I986a).  Recent controlled
exposure studies confirm that "normal", healthy subjects, even at moderately
heavy exercise, do not experience significant effects on pulmonary function
due to peak SOg exposures in the range of 0,25 to 2 ppm (CDA, p.  4-10).
A single recent chamber study of chronic obstructive pulmonary disease
patients was conducted under conditions that the CD addendum states are
unlikely to produce effects even in sensitive individuals.  Thus, the
preponderance of newly available exposure-response information on peak
S02 exposures is for exercising asthmatic subjects.

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                                    13

     The results of the recent studies of asthmatic subjects are summarized

in Table 7 of the CD addendum, which organizes the data according to

concentration.  Most of the data reflect 6 to 1U minute exposures to young,

relatively healthy, mild non-smoking volunteers with no symptoms and fairly

stable pulmonary function at the time of exposure.  The following discussion

of anticipated responses associated with particular concentrations is

drawn from that tabular summary.

     a)  1.0 to 2.0 ppm

     Recent studies by two separate research laboratories of the effects of

1 ppm S02 on freely breathing, mild asthmatics at moderate exercise are

qualitatively consistent with each other as well as with previous studies

that administered exposures through mouthpieces.  All found statistically

and potentially clinically significant* changes in respiratory mechanics,

most pronounced within minutes after exercise had ceased, followed by gradual

recovery  (within 1 hour).  When reported, associated symptoms (e.g., shortness

of breath, chest discomfort) also increased significantly (Schacter et al.,

1984; Roger et al,, 1985).  Group mean functional changes were increases in

specific  airway resistance (SRaw) (170 to 230%) and declines in FEV^

(CDA, Table 7).  A third laboratory found consistent reductions in FEV]_

(-23%) using mouthpiece exposures (Koenig et al., 1983b).   Individual

variability is illustrated by the Roger et al.  results.  One subject

could not be tested at 1.0 ppm because he required medication following

exposure  to a lower concentration.  Another was removed after the second

exercise  period due to pronounced wheezing and  chest tightness and a

10-fold increase period in SRaw.  Two other subjects had a  greater than

500% increase.  The responses in asthmatics observed by Kehrl et al,
*Unless otherwise modified  (as in this case), the use of "significant" with
respect to measured changes could be understood as "statistically" significant
and  not necessarily clinically or medically significant.

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                                    14
(1986) appear to be greatest after 30 minutes of continuous exercise
although the increase in airway resistance was statistically no greater
than the changes observed after 10 minute exposure (233% vs. 172% increase
over baseline).  Successive exercise periods separated by 15 minute
intervals resulted in attenuated responses even to 1 ppm SOg (Roger et
al., 1985; Kehrl et al . , 1986).
     Horstman et al . (1986) report that 12 (of 27) subjects in the Roger
et al . (1985) study, whose SRaw values did not increase by 100% at 1 ppm
or lower levels, were also exposed to 2 ppm using the same protocol.  At
this level, 7 of these less sensitive asthmatics had SRaw increases of
100 to over 600%.
     b)  0.75 ppm
     Recently published studies of moderately exercising asthmatics exposed
to 0.75 ppm S02 for 10 minutes (Linn et al., 1983a;  Hackney et al., 1984;
Schacter et al,» 1984) replicate earlier results, finding significant
increases in airway resistance (group mean SRaw increase was 1B6 to
263%), substantial decreases in FEVj^Q, and significantly increased reports
of lower airway symptoms.  In contrast to functional  measurements, the
increase in symptom scores were not significantly greater when SO 3 was
administered through mouthpieces compared to freebreathing in a chamber.
     c)  Q._6
     Highly consistent and significant bronchoconstrictive responses
have been observed in freely breathing mild asthmatics  exposed  to  0.6 ppm
for 5 minutes while exercising at fairly high levels (minute ventilation,
Ve, ~ 50 L/min) under a wide range of temperature and humidity  conditions
(Linn et al . , 1983b; 1984a,b; 1985a).  Increases in airway resistance
and symptom scores were most pronounced ( - 207% over control )
in either cold or dry air (-6°C, 20% RH) compared with  more humid,  wanner

-------
                                    15


conditions (e.g., 39% increase in SRaw in 38°C,  8.0% RH).   Even under

moderate conditions ( ~ 22°C, 85% RH), Linn et al.  (1984a)  found that

typical respiratory symptoms were sufficient to  impair subjective well-being

and "normal performance capabilities".  Three of the 23 subjects in this

study required medications to relieve symptoms following exposures and four

had SRaw increases in excess of 250%.  In this and  a subsequent study

(Linn et al., 1984c)t these investigators examined  symptoms during the

week after S02 exposures.  In the latter study,  they reported a tendency

toward less favorable clinical states (i.e., increased symptoms) in the

week following exposures on two successive days  to  0.6 ppm and that three

(of 14) subjects reported experiencing an asthma attack during the week

after SQ2 exposure, whereas no subject reported  such an attack after clean

air exposure.  In contrast, two subjects reported a need for extra broncho-

dilator medication after the S02 exposures while four reported such a need

after clean air exposures.  The authors concluded that these post-exposure

effects "were small and inconsistent enough that they might be attributable

to chance, or to preferential recall of symptoms after the clinically

stressful SQg exposure experience." Comparable findings have not been

noted in other studies.

     d)  0.5 ppm
                                        a
     Recent studies of airway responses in free breathing mild asthmatics

exposed at exercise to 0.5 ppm S02 for durations of 5, 10, and 20 minutes

indicate that significant bronchoconstriction occurs at moderate to heavy

exercise rates (Ve - 40-60 L/min) (Bethel et al., 1983a, b; Koenig et

al., 1983; Roger et al., 1985) but not at lower exercise rates  (Ve - 27-40

L/min)  (Schacter et al., 1984; Bethel et al., 1983b).

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                                    16





     Roger et al. (1985) examined both repeated exposures and subject



variability.  Responses to SOg were mitigated after repeated, free-breathing



exposures separated by IS-minute intervals,  although they remained significant.



Elevations in airway resistance over baseline averaged 93% after the first



exercise period and 52% after the third exercise period.   Cumulative



frequency distributions of the subjects'  SRaw values at rest and at exercise



in clean air and after IQ-minute exercise in 0.5 ppm S0£  indicate that



exercise and SOg each contributed about equally to the overall  increase



in SRaw,  As in other studies, there was  a wide range in  the magnitude  of



the induced bronchoconstriction in various subjects.  For example, after



exercise in 0.5 ppm S02> 25% of the subjects had a SRaw increase of ~ 17U%



over baseline compared to the mean of 93%, while 25% had  negligible



changes.  In addition, while significant  increases in symptoms  were not



reported for the group as a whole, three  subjects had SRaw increases



of over 320% and one, who was removed before completion of the  full  protocol,



had an eight-fold SRaw increase after ID-minutes of 0.5 ppm and an 11-fold



increase after the 2nd exposure, with audible wheezing and chest tightness.



     e)'  0,4 ppm



     Mild asthmatics performing moderately heavy exercise (Ve = 48 L/min)



while freely breathing 0.4 ppm S02 for 5  minutes had statistically
                              *


significant increases in SRaw (group mean 69% increase vs. 35%  in clean



air) and mild increases in several symptoms  (e.g., cough, wheeze, chest



tightness) after 5 minute exposure (Linn  et  al., 1983b).   One subject (of



23) was reported to have experienced "clinically significant bronchoconstriction'



after this exposure and required medication  to relieve asthma symptoms. As



part of another study discussed previously,  a group of mild asthmatics  exer-



cising at a similar level ( ~ 50 L/min) at a much colder  temperature (S^C),

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responded with apparent Increases in airway resistance and respiratory symptoms
at 0.4 ppm S02 under both high and low humidity (Linn et al., 1984a).
     f)  0.1 - 0.3 ppm
     Most recent chamber exposures found no clearly significant increases
in airway resistance among freely breathing mild asthmatics exercising at
moderate to high levels (35-50 L/min) below 0,4 ppm (Linn et al., 1984a,b;
1983b; Roger et al., 1985; Schacter et al., 1984).  At 0.25 ppm with heavy
exercise (60 L/min), Bethel et al. (1985), found apparently significant
responses although the application of a more appropriate statistical
test did not confirm this  (CDA, p. 4-27).  Even here, a significant increase
over exercise control was not observed with 0.25 ppm in the same study at
an even higher ventilation rate (80-90 L/min), suggesting that the broncho-
constriction induced by exercise alone overshadowed any effects of SOg
(Bethel et al., 1985).  Although some minimal increases in symptom scores
were reported even as low  as 0.2 ppm, the;clinical significance of these
changes is questionable (Linn et al., 1983b; 1984a).  The fact that some
hyper-reactive individuals may be responsive to such low SOg levels cannot
be dismissed, however, given that an SQ£ concentration of 0,25 ppm was
sufficient to nearly double SRaw over baseline in the most sensitive subject
(Bethel et al., 1985).
     g)  Cpjnb 1 n_e d Relationships/Subject V a r i a b 11 i ty
     A number of the more  recent studies developed exposure/response
relationships over various concentration and ventilation ranges while others
examined the influence of  various subject-related and environmental factors.
Although individual studies fix various important factors to permit within
study  comparisons, it is more difficult to compare directly the results
from different investigations.  One  approach suggested in an earlier staff
assessment  (Cohen, 1983) and used by Kleinman  (1984) and Linn et al. (1983b),

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                                     18

normalizes studies according to effective oral dose rate.  The results of
such an analysis applied to both recent and earlier S02 studies are shown
in Figure 3-1.  As illustrated, reasonably consistent results are derived
from the various controlled S02 asthmatic studies when adjustments are made
for differences in ventilation rates and oral/nasal breathing patterns by
expressing the results in terms of the oral dose rates of S02.  Earlier
analyses also found a good consistency among then available studies using
similar surrogates of "effective dose" (Kleinman, 1984; Linn et a!., 1983b),
     This relationship can be used to estimate responses for exposures of
interest not yet tested.  For example, it is of interest to determine whether
large responses might occur in asthmatics at high concentrations, e.g., 2 ppm,
while at lower ventilation rates typical  of everyday activities.   Assuming
oronasal ventilation for "mouth" breathers (Niinamaa et al., 1981), oral  Ve
would be about 4 to 7 L/min at rest to light activity and the predicted
mean increase in SRaw for 2 ppm would be approximately 0 to 70%,
     The consistency among group mean responses represented in Figure 3-1
masks the substantial variability among individual  asthmatics, both within and
among studies.  Among the most useful studies for examining this  variability
is the work of Roger et al. (1985) and companion analysis by Horstman
et al.  (1986).  The study covers a wide range of concentrations (0,25 to
2 ppm), includes a substantial number of subjects (28) who were not pre-
selected for S02 sensitivity, and presents individual  exposure-response
data.  The highlighting in Figure 3-1 shows that the group mean results from
Roger et al.  are representative of the range of values for all  SOg/asthmatic
studies.  The range of subject responses from this  work is illustrated in
Figure 3-2, reproduced from the Horstman et al. (1986) report. The points
represent a logarithmic linear interpolation of exposure-response relationships

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CO
<
  400
  35Q  -
  300  -
  25O
  200 -
  150 -
  100 -
   50
                                                      n
                                              D
                                                                                   IT =  0.73
               0.25 ppm
               0 ppm
                                                              D
                                                                  1.0 ppm
                    chamber or facemask
                    study

                    mouthpiece study
       0
                                 ~T~

                                 2O
                                      T
T
                 4O                  60

ORAL AIRWAY SO2  DOSE RATE (ug/min)
                               80
Figure 3-1.  Combined $03  dose/response relationships*  Includes recent and  earlier  controlled studies of
exercising or hyperventilating asthmatics with SRaw reported.  Points respresent  group mean responses
significantly different  from baseline vs.  normalized oral-dose rate (S02 concentration x oral Ve).  Oral Ve
estimates for freebreathing from Niinimaa et al. (1981).  The results of Roger  et al.  (1985) are highlighted at
specific concentrations  (Ve total = 42 1/min) for orientation.  Despite uncertainties  in estimating the oral Ve
the results suggest reasonably good consistency among three laboratories with no  apparent difference between 5
and 10 minute exposures  and no tendency for mouthpiece studies to overstate  response when appropriate adjustments
for ventilation are made.

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Cohen, J. (1983) Analysis of SO2 Controlled Human Data.   Memorandum to
     John Haines, Ambient Standards Branch, Office of Air Quality Planning
     and Standards, U.S. EPA, Research Triangle Park, N.C.,  September 6,  1983,

Cohen, J. (1984) Assessing Asthmatic Responses to SOg:  Summary of Expert
     Opinions.  Memorandum to John Bachmann, Ambient Standards  Branch,
     Office of Air Quality Planning and Standards, U.S.  EPA, Research
     Triangle Park, N.C., February 27, 1984.

Committee on Public Works, U.S. Senate (1974)  A Legislative  History of the
     Clean Air Amendments.  Volume 1,   Serial  no. 93-18.   U.S.  Government
     Printing Office, Washington, D.C. prepared by the Environmental  Policy
     Division of the Congressional  Research Services of  the  Library of
     Congress.

CEC [Commission of the European Communities] (1983)  Report on the EC
     epidemiology survey on the relationship between air  pollution and
     respiratory health in primary school  children.  Brussels, Belgium:
     Environmental  Research Programme.

Dassen, W.;  Brunekreef, B.; Hoek, G.;  Hofschreuder,  P.; Staatsen, B.;
     deQroot, H.; Schouten, E.; Biersteker, K. (1986)  Decline  in
     children's pulmonary function during  an air pollution episode.
     J. Air Pollut. Control Assoc.  (in press),

D.C. Cir. (1980)  Lead Industries Association, Inc.  v. EPA,  F.  2d,  14
     ERC 1906 (O.C. Cir.) Cert. Denied -49  U.S.L.W, 3428  December  8,  1980.

D.C. Cir. (1981)  American Petroleum Institute v. Costle,  Nos.  79-1104
     et_. al_, (D.C.  Cir.) September 3,  1981.

Deal, E. C.; McFadden, E. R.; Ingram,  R. H.; Jaeger, J.  J. (1979b)  Hyperpnea
     and heat flux: initial reaction sequence  in exercise-induced asthma.  J.
     Appl. Physio!. 46: 476-483.

Oockery, D.  W.; Ware, J. H.; Ferris, B. G., Jr.; Speizer,  F.  £.;  Cook,  N.  R.;
     Herman, S. M.  (1982) Change in pulmonary  function in  children  associated
     with air pollution episodes, J. Air Pollut. Control  Assoc. 32:  937-942.

Dodge, R. (1983) The respiratory health and lung function  of Anglo-American
     children in a smelter town. Am. Rev.  Respir. Dis. 127:  158-161.

Dodge, R.; Solomon, P.; Moyers, J.; Hayes, C^  (1985) A longitudinal  study  of
     children exposed to sulfur oxides. Am. J. Epidemic!.  121:  720-736.

EPA [U.S. Environmental Protection Agency] (1982a)  Review of the National
     Ambient Air Quality Standards for Sulfur  Oxides:  Assessment of
     Scientific and Technical Information  (QAQPS Staff Paper) Office of
     Air Quality Planning and Standards, Research Triangle Park,  N,C.
     EPA-45Q/5-82-G07.  Available from NT IS, Springfield,  VA; PB  84-102920.

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                                     21
for each subject to determine the S02 exposure producing a 100% increase in
SRaw over exercise in clean air (termed PC [SQ^]).   The resulting cumulative
plot is useful in estimating the likelihood of a possibly clinically significant
response (doubling of SRaw) in mild asthmatics exposed at moderate exercise
(or ventilation) to particular S0£ concentrations.
     h) Recent Epidemio_1 ogical Ev idence
     The literature contains little epidemiologic evidence regarding the
relationship between peak SOg levels and asthma.  Early epidemiological
analyses of asthma incidence reported in the 1982 criteria document were
based on daily averages of S0£ and substantially confounded by the presence
of other pollutants.  A more recent study (Goldstein and Weinstein, 1986),
however, has examined the relationship between incidence of emergency room
visits  for asthma in three New York City hospitals from 1969 to 1972 and
hourly  S02 peaks.  Adjustments were made for seasonal, epidemic, day-of-
week, and lag effects, as well as for the long-term downward trend in S02
levels  in N.Y.C. over the study years.  Temperature, other pollutants, and
pollen  counts were not included.  No significant association was found
between days with "high" hourly SC>2 measurements (> 0.1, 0.3, and rarely
0.5 ppm) and days with elevated asthma visits.  There are several factors
that would have made detecting any associations difficult, including 1) (as
noted by the  authors) centralized, rooftop monitors may represent population
exposure too crudely to detect an effect; 2) hourly $02 levels may not
detect  rapid  responses such  as those observed in human studies in which
exercising asthmatics respond quickly to brief 5-10 minute S02 peaks whose
effects diminish within an hour;  3) less than 2% of all days had hourly 502
levels  higher than 0.5 ppm,  which substantially limits the statistical
power  related to examining high exposure situations; 4) actual hour of the
day for emergency room visits was not  readily available, so the analysis was

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                                 22
 done on a daily level  that  overlooked the timing  of the  S02  peaks  and
 asthma visits within  the days.   The authors  note  that  visits not  influenced
 by a pollution peak on a day would  have  been included  among  all  visits
 examined in relation  to that peak thus serving  to attenuate  any  relation
 that may be present;  and 5)  confounding  influences of  normally encountered
 agents or stresses in  the urban  environment  that  asthmatics  are  susceptible
 to could not have been readily controlled as in controlled exposure  studies.
 Additional  uncertainties regarding  the definition of elevated asthma days,
 the use of 14-day averages  to detrend the time  series  structure  of hospital
 admissions, and controls for day-of-the-week effect require  further examination.
 The authors conclude  that the results do not rule out  a  relationship between
 asthma and ambient S02 and  that  additional study  is needed on the individual
 exposure-response level  over time in order to determine  whether  the effects
 observed in the controlled  laboratory studies can be detected in free-living
 populations.
 2.  Short-term Exposures
      The principal basis for developing  quantitative assessments of acute
'effects of ambient exposures of  SOg on a daily  basis remains community
 epidemiological  studies. Such studies can provide strong evidence for the
 existence of pollution effects resulting from community  exposures.  The
 major limitations of  the epidemiological  studies  are discussed in the
 CD, CD addendum, as well as  the  1982 staff paper.
      Recognizing these limitations, the  discussion in  the 1982 staff paper
 outlined those studies cited by  the CD as providing the  most  reliable
 quantitative information as  well as other studies that provide useful

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                                    23


information on the relative importance  of S02 without allowing derivation

of specific levels.  These included a set of British studies of mortality

and morbidity.  The CD addendum identifies several  more recent analyses of

the London mortality data and one U.S.  morbidity study as providing the

most useful new information on the short-term SOg exposures.  These

studies are summarized in Table 3-1.  The more full description and evalua-

tion of these studies contained in Section III of the companion draft PM

staff paper addendum (EPA, 1986b) will  not be repeated here.  The discussion

will focus on the relative importance of S02 as compared with particulate

matter in producing the observed effects.

     With respect to the daily mortality studies, the CO addendum states

that:

     "the following conclusions appear warranted based on the earlier
     criteria review (U.S. EPA, 1982b) and present evaluation of newly
     available analyses of the London mortality experience:   (1) Markedly
     increased mortality occurred, mainly among the elderly and chronically
     ill, in association with BS and SOg concentrations above 1000 ug/rn  ,
     especially during episodes when such pollutant elevations occurred for
     several consecutive days; (2) During such episodes coincident high
     humidity or fog was also likely important, possibly by providing
     conditions leading to formation of ^$04 or other acidic aerosols;
     (3)  Increased risk of mortality is associated with exposure to BS and
     S02  levels in the range of 500 to 1000- yg/m, for SO^ most clearly at
     concentrations in excess of - 700 ug/m3; (4) Convincing evidence
     indicates that relatively small but statistically significant increases
     in the risk of mortality exist at BS (but not S02) levels below 500
     M9/m^» with no indications of any specific threshold level having been
     demonstrated at lower concentrations of BS (e.g., at <_ 150 ug/m^).
     However, precise quantitative specification of the lower PM levels
     associated with mortality is not possible, nor can one rule out
   •  potential contributions of other possible confounding variables at
     these low PM levels"  (COA, p. 3-9).

     Because of the high colinearity between 8S and S02 levels during the

study period, it has been difficult to readily separate the effects of the

two  pollutants on mortality.  The CD addendum states that attempts by

Mazumdar  et al.  (1982) using nested quartile analysis were only partially

successful given the substantial covariation that  remained between the

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                     TABLE 3-1.  SUMMARY OF RECENT  (1982-86) EPIOEMIOLOGICAL STUDIES PROVIDING MOST USEFUL
                                CONCENTRATION/RESPONSE INFORMATION FOR SHORT-TERM S02 EXPOSURES
Observed
Effects
Time
Observed Concentration Range
PH(pg/nr)         S02(ug/nr)  Comments
                                                   Study
Increases in
daily mortality
in metropolitan
London
Short-term
reductions in
luny function
in 330 school
children,
Steubenville,
OH
Short-term
reductions in
lung function
in 179 school
children in
the
Netherlands
{Ijmond)
1958-1972   <500 BS*          >500
winters            24-hr averages
Four
separate
study
periods of
3 weeks
following
pollution
"episodes"
in 1978-1980
1) 420 TSP           280
2) 270 TSP           460
3) 220 TSP           170
4) 160 TSP           190
(max 24 averages for
"alert" or "sham"
episode)
Before,
during, af-
ter pollu-
tion epi-
sode Nov.
1984-Feb.
1985
 200-250 TSP      200-250
 and RSP
 (050 < 3.5
  Mm)
      24-hr average
                              Recently published  studies  reinforce 1982  CD,
                              SP conclusions  regarding  likelihood  of  increased
                              mortality at 500 to 1000  ug/m  for BS and  SOp,
                              with no clearly defined threshold  for BS in  the
                              range of 150 to 500 pg/rn3.   Nature of relation-
                              ships vary significantly  with model, iazurndar
                              et al. infer no association < 700  pg/nr S02,  but
                              methodology for separating  pollutants questioned
                              in CDA.
                              Recent unpublished  analyses confirm  major
                              findings of the published studies  with  advanced
                              statistical techniques  accounting  for auto-
                              correlation and temperature effects. Schwartz
                              and Marcus findings suggest significant
                              association for BS  at lowest levels  (<10G  pg/m3
                              BS), but not for S02 below  about 500 pg/nr.
                                                   Mazumdar et
                                                   1982, 1983;
                                                   Ostro 1984
                                                                                                              Shumway et a
                                                                                                              1983, Schwan
                                                                                                              and Marcus,
                                                                                                              1986
First 3 episodes: small (21-3%) but significant    Dockery et al
reversible declines in FVC up to 2-3 weeks after   1982
peak.  Less consistent results for FEV.  No
significant effects after 4th "sham" episode.
Baseline measurements for 1st, 4th taken on days
with high pollution.  Linear regression of pooled
data for 330 children indicate significantly more
negative slopes in functions vs. TSP and SOg across
ranges (10-270 ug/m3, 0-28U pg/m3, respectively).
Higher response in some children.

Small (3-6%) reversible declines in several        Dassen et
measures of airway function (FVC, FEVj, MEF)       al., 1986
during episode and 5 days later.  No effect
after 26 days or shortly after a day when TS|,
RSP and S02 levels all averaged 100-150 pg/m3.
Separate sub-groups of children tested on each
day.  Peak TSP levels possibly understated.
*British Smoke (BS) is a pseudo-mass  indicator related to small particle (size less than a nominal 4.5 um) darkness
 (CD, pp. 1-88 to 1-90).

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                                     2b

pollutants in the highest and lowest quartiles  (COA,  p.  3-5).   Based  on
regression analyses using the highest pollution days, the authors  concluded,
however, that the mortality/pollution association was almost entirely due
to smoke with a possible S02 effect at higher concentrations (above 700
Mg/m3),
     Schwartz and Marcus (1986)* examined further the suggestion that the
effects of smoke are separable from those of SOg in this data set.  In
regressions involving both pollutants, the colinearity between the two
tended to deflate the apparent significance of both.   However, the overall
results for all years combined and for those individual  years with lower
correlations between BS and S02 (r < 0.9) show that the mortality effects
of BS remain significant and relatively large even when S02 is included  in
the model, while the inclusion of BS in the model reduces the SO2 coefficients
to insignificant values.  This analysis cannot, however, be used to exclude
an independent effect of SOg at higher concentrations.
     Besides the uncertainties that remain in separating the effects of  SOg
and PM, various issues are still unresolved regarding these London data
including a possible threshold for PM-mortality associations, varying
coefficients obtained with different subsets of data and models, the effects
of unmeasured  variables such as demographic change over time and indoor
air pollution, and the appropriate statistical  methods to account for long-
term seasonal  trends in mortality  (Wyzga et a!., 1985).
 *This  paper and a summary memorandum (Marcus and Schwartz, 1986), are
 reprinted in full as Appendix A to the Criteria Document Addendum.  Although
 not  published, the paper was presented to the CASAC and the public for
 review at the October 15-16, 1986 meeting.  Copies were made available to
 the  public at the time of the meeting.  Subsequently, EPA received and
 considered comments on this study from industry and environmental groups
 and  from members of the scientific community.

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                                    26
     While the possibility of small increases in the risk of mortality at
S02 levels less than the "likely effects level" (500 ug/m3 or 0.19 ppm)
cannot be dismissed conclusively, the available analyses of London mortality
data provide little basis to determine whether 24-hour concentrations
of S02 below this level may have accounted for any of the observed association
between mortality and pollution.  Because significant quantities of S02
are unlikely to penetrate to the tracheobronchial  region at lower con-
centrations without increased ventilation, the mechanisms by which 862
could contribute to excess mortality in ill or otherwise sensitive popula-
tions are limited.  Peak levels in London at the time of these studies were
undoubtedly, well in excess of the 24-hour values,  but at lower daily concen-
trations were less likely to affect even individuals with hyperreactive air-
ways.  The capacity of fog particles to "carry" untransformed S02 is limited.
At present, it appears more,likely that the role of SQg, in the presence of
smoke, involved transformation products such as acidic fine particles.
     Other recent studies discussed in the CD addendum and in the PM staff
paper addendum examined pollutant/mortality relationships in more contemporary
atmospheres in New York City, Pittsburgh, and Athens, Greece.  The Ozkaynak
at al. (1985) reanalysis of 14 years of N.Y.C. data (1963-76) found signifi-
cant associations between excess daily mortality and PM, S02 and temperature.
Differences in the rate of change of S02 and PM indicators during the study
period allowed estimation of their separate effects.  In joint regression
analysis across all years, PM indicators (coefficient of haze and visibility
extinction coefficient) together accounted for significantly greater excess
mortality than did S02.  As the CD addendum notes, however, these findings
must be considered preliminary for risk assessment purposes.
     The work of Mazumdar and Sussman (1983) in Pittsburgh and that of
Hatzakis et al, (1986) in Athens, however, found conflicting results.  The

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                                     27
first found a significant association between participate matter and excess
deaths in Pittsburgh, but no effect of SOg, while the Athens study found an
association with S02 but not with smoke measurements.  The CD addendum
points out that limitations in both studies with respect to measurement of
particulate matter as well as methodological difficulties prevent drawing
meaningful conclusions from these studies with respect to the effects of
particulate matter and SOg.
     b)  Morbidity
     Previous conclusions regarding morbidity effects of short-term PM/S02
exposures were primarily based on studies of bronchitic subjects in London
from the 1950's through the early 1970's.  Findings related to more
contemporary conditions are presented by Dockery et al. (1982) and Dassen
et al.  (1986) and summarized in Table 3-1.  The CD addendum concludes that
the repeated measurements of lung function by Dockery et al. showed
statistically significant but physiologically small and apparently reversible
declines of FVC and FEVg>7§ levels associated with short-term increases in
PM and SOa air pollution  (CDA, pp. 3-16, 3-19).  The small, reversible
decrements appear to persist for up to 3-4 weeks after episodic exposures
to these pollutants across a wide range of concentrations with no clear
delineation of a threshold defined by the authors or by the CD addendum.
A staff assessment of that study is contained in the draft  PM staff paper
addendum  (EPA, 1986b).  The following additional points are relevant in
assessing the implications of Dockery et al.  (1982) for SQ2 concentration/
response relationships.
     1) Of the 4 study periods in Steubenville, the most significant declines
in FEVQ^yij (4% on average) were observed following the episode with the highest
                   *3
SOg  level  (455 ug/m  , 24  hr. avg).  This observation is, however, confounded

-------
                                     28

because pollution levels during baseline measurements for this period were
among the lowest for any of the four study periods.
     2) No significant effects on lung function were reported in the Fall
1980 study, when 24-hour SQ2 levels reached 190 ug/m .   Significant lung
function declines were measured following a pollution episode in the Spring
1980 study when S02 was lower (169 ug/nr maximum), suggesting any pollution
related effect was more attributable to particles.
     3) When data for all 4 study periods were pooled and lung function was
regressed on TSP and SOg levels - assuming the relationship was linear across
all studies -- similar results were obtained for both pollutants.
     A similar study of the effects on children of episodic exposures
to particulate matter and S02 conducted in the Netherlands by Dassen et al.
(1986) produced results similar to those of Dockery et  al.  Pulmonary function
values measured during an air pollution episode in which both 24-hour average
PM (as TSP or RSP*) and S02 levels reached 200 to 250 ug/m3 were significantly
lower (3-5%) than baseline values measured 1-2 months earlier in a group of
Dutch school children.  Lung function parameters that showed significant
declines included FVC and FEV, as well as measures of small airway function
(e.g., maximum rnid-expiratory flow, maximum flow at 50% of vital  capacity).
Declines from baseline were observed 16 days after the  episode in a different
subset of children, but not after 25 days in yet a third subgroup.  Shortly
before the last set of measurements, 24-hour averages of both PM (as TSP or
RSP) and S02 reached between 100-150 ug/m3, suggesting  that these levels-were
not associated with observable functional effects (CDA, p. 3-17).
*Respirable Suspended Particles, reportedly Dgp <_ 3.5 urn by cyclone sampler.

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                                   29
     Although comparison of the Netherlands study with the Steubenville
episodes must be done with considerable caution, the absolute magnitude of
functional response in the Netherlands episode was comparable or greater
than that for any of the four Steubenville episodes, while the peak S02
levels  (200 to 250 ug/m3) were lower than two of those episodes.  Thus, the
relative magnitude of the effect appears to be better related to the
concentration of small particles (EPA, 1986b).
     In summary, the more quantitative epidemiological evidence from London
suggests that effects may occur at SOg levels at or above 0,19 ppm (500 ug/m3),
24-hour average, in combination with elevated particle levels.  Additional
evidence suggests the possibility of short-term, reversible declines in
lung function at SOg levels above approximately 250-450 pg/m  (0.1Q-.18 ppm).
Whether any of these effects are due  (in part) to $02 alone, formation of
sulfuric acid or other irritant aerosols, particles alone, or peak SOg
values  well above the daily mean cannot be determined unequivocally.
3.   Chronic Exposures
     Table 3-2 summarizes the most useful of the recent studies that have
examined the long-term effects of exposures to S02» in the presence of
particles, on respiratory mechanics, symptoms, and  illness.  Other, less
reliable, studies are evaluated in Appendix 3 of the PM staff paper addendum
(CEC,  1983; Muhling et al., 1985; Wojtyniak et a!., 1986).  Several cross-
sectional studies report  significant associations between long-term S02
exposures and effects in  populations of adults and  children  (PAARC, 1982a,b;
Chapman et a!.,  1985; Ware et al., 1986; Dodge, 1983; Dodge et al., 1985).
     The  CD  addendum  (p.  3-49 to 3-50) concludes that these new studies provide
evidence  for:   1) increased respiratory symptoms among young adults in
association with annual  average SOg levels of 115 ug/m^  (Chapman et al.,

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          Table 3-2.  SUMMARY OF RECENT (1982-86) EPlOEMiOLOtiiCAL STUDIES PKOVID1NU MOST USEFUL CUNCENTKATIUN/RESPUNSt
                                           INFORMATION ON LONG-TERM EXPOSURES TO
Observed Effects
Time    Population
                  Observed Concentration Range
                  SU2 (M9/mJ)   W (My/m3)
a) Communities Dominated by Large Point Sources
Increased prevalence
of chronic phlegm,
cough
1976
 ~ 6,600 adults
in 4 Utah towns
at varying dis-
tances from large
copper smelter
115           70 TSP/14 $04,

  (5 yr average - 1971-76)
Increased prevalence
of cough
1979-
82
 ~ 700 3rd-6th
graders in 2
smelter and
2 control
communities in
Arizona
103           51 TSP/9-10 504

      (3 yr average)
   Multiple Urban Area Comparisons
Increased prevalence
of cough, expectoration, 1974-
lower respiratory        76
illness in men.
Upper respiratory
disease in children. Re-
duced lung function in
adults and children.
        - 20,000 adults
       and children  in
       20 areas  of 7
       cities and 1  in-
       dustrial  region
       in France
                  13-127
              20-150  Smoke
              45-240 "Oust"
                         (3 yr average)
                               Comments
                                  Study
3 cleaner communities had 5-yr.   Chapman
S02 between 11-35 M9/»  » 6-       et al.»
8 ug/iiT S04; little gradient      1085
across towns In TSP (50-7U M8/m3).
Results more consistent in non-
smokers, wome,n; consistent with
previous 1970 survey.  No lung
function measurements.  Any ef-
fects of S02 likely attributable
to high short-term peaks.

High short-term peaks in 1 smelter Dodge,
town (repeated 3-hr. avgs. ~ 1.0   1983;
ppm)» as well as 2nd smelter area  Dodge
with elevated cough (avg. 24 hr    al.» 1985
max ~ 440 yg/«r; 3 yr avg. S02
 - 50 Mg/m3, 28 pg/m3 TSP}. 2
control areas had 3-yr S0^> <
14 M9/MT. 4-7 pg/raj SU4, 58-
60 ug/uij TSP.  No trend with
pollution in shortness of breath,
wheeze, sputum production, lung
function
                                                                                                        u>
                                                                                                        o
Significant effects found only     PAARC
with S0;>; PM measurements of      1982a,b
questionable comparibility (COA,
p. 3-43).  Inconsistent trends
within cities.  No control for
parental smoking in children;
uncertain control far season;
apparently incomplete statistical
analysis.

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                                     31
1983); 2)  increased prevalence of cough  in  children  (but  not  lung  function
changes) being associated with intermittent exposures to  mean peak 3-hr S02
levels of ~ 1.0 ppm or annual  average levels of » 103 ug/tn3 (Dodge et  al.,
1985); and 3) symptoms of lower respiratory disease  and decrements in  lung
function in adults possibly associated with annual  average SOg levels  ranging
without evident threshold from about 25 to 130 ug/m3 (PAARC»  1982a,b).  In
addition, the PAARC study suggests that upper respiratory disease  and  lung
function decrements in children may also be associated with annual average
SOg levels across the above range.
     Some questions must be raised regarding the PAARC analysis, however:
(I) SQ2 and PM indices were only tested in separate regressions resulting
in potentially confounded results, especially given the remarkably low
colinearity in the 2 pollutants;  (2) The positive associations between S0£
and lung function were significant for only one of the two SQ2 measurement
methods used and are apparently dominated by a large difference i'n Rouen
(an industrial city) between the $62 levels as measured by the two methods;
(3) The large within-city and between-city differences as separate sources
of variability were not assessed, possibly greatly reducing the statistical
significance of estimated effects in this very large study.  These and
other uncertainties related to aerometry, the lack of control for parental
smoking (for children), in controls for seasonal effects, and the counter-
intuitive results for N02 further limit the confidence to be placed in
the present  results.
      Correlations, and conclusions, from the Ware et al. (1986) study are  weakened
by the  relatively low illness rates in one area  (Carondolet, St.  Louis)
during  periods of relatively high SOg levels and by the fact that after S02
levels  declined there (from 184 (jg/m3 in 1976 to 88 pg/m3 in 1977) and TSP

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                                   32
dropped only slightly (125 ug/m3 to 104 ug/m3), illness rates increased
slightly.  Otherwise, reduced ventilatory function has been found to be
significantly related to elevated SQg levels in only the PAARC study and
possibly in the recent van der Lende et al. (1986) report, although the
latter findings are considered too preliminary for risk assessment purposes.
Similarly, the Schenker et al, (1983) study suggests increased risk of
wheeze (but not cough or phlegm) associated with elevated SQg concentrations
but specific effect levels are difficult to identify (CDA, p. 3-40).
     Many of these studies in which high long-term SOg concentrations  have
been measured and correlated with health effects were conducted in areas
around major point sources of S02 emissions (e.g., copper smelters,
coal-fired power plants).  It is therefore  likely that the populations studied
were exposed to repeated high short-term peak concentrations  of S02» primary
sulfuric acid, and other stack related particles.  In light of the con-
trolled human and animal exposure studies on S02 and sulfuric acid discussed
previously in this paper and in the 1982 PM staff paper (EPA, 1982cj,  it
appears likely that the effects associated  with SOg in these  studies were
at least in part related to intermittent, acute respiratory insults.  None of
these studies, however, have attempted to separately analyze  those individuals
expected to be most responsive to short-term $03 or other exposures, i.e.,
asthmatics and atopies.

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                               33 -

IV.  FACTORS TO BE CONSIDERED IN SELECTING PRIMARY STANDARDS FOR SULFUR
     OXIDES

     This section, drawing upon the previous summary of newly available

scientific information, enumerates key factors that should be considered

by the Administrator in decisions on the primary standards for sulfur

oxides.  The staff conclusions and recommendations on the most appropriate

policy options update and supplement those made in the 1982 staff assessment.

Where the original conclusions and recommendations and supporting rationale

are unchanged by the newly available information, they are summarized

without restating the supporting discussion.  Particular emphasis is placed

on aspects of the new information that amend or revise the original

assessment.  The key standard components discussed are the levels and

averaging times for the primary standards.  In addition, a summary assessment

of the relative protection afforded by alternative standard combinations is

presented.

A,   Levels and Averaging Times of the Standards

     1.  General Considerations

     The major scientific basis for selecting S02 standards that have an

adequate margin of safety comes from controlled human exposures and

community epidemiological .studies, with mechanistic support from toxicological,

deposition, and air chemistry investigations.  The limitations of available

controlled  human studies for quantitative evaluation of ambient exposures

of populations are summarized in the CD and in the CD addendum.  Such studies

provide accurate measurements of specific pollutant exposures, but are

limited in  exposure regimes, numbers and sensitivity of subjects, and   .  -

severity of effects tested, and may involve artifacts not representative of

ambient exposures.  Community epidemiological studies, while representing

real world  conditions, can only provide associations between a complex

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pollutant mix and a particular set of observable health endpoints.  It
follows that, although the scientific literature provides substantial
information on the potential  health risks associated with various levels
and exposure patterns of $02» selection of appropriate levels, form, and
averaging times remains largely a public health policy judgment.
     The following sections present a brief staff assessment of how the
concentration/response relationships suggested by the most significant
controlled human and epidemiological studies in the CO addendum supplement
the quantitative information previously assessed in the 1982 staff paper,
and indicate how these studies may be applied in decision-making on standards
for SOg.  The presentation also outlines a qualitative assessment of the
key factors that affect the margin of safety associated with the ranges of
standards derived from these studies.  This assessment includes identification
of those aspects of the qualitative literature that should be considered in
establishing standards that provide an adequate margin of safety.  Peak
(< 1-hour), short-term (<_ 24-hour), and long-term (annual),  exposures  are
discussed separately.
     2.  Peak _(< 1-hour) Exposures
     a)  Deri vation of Ranges of Interest from Cont rol1ed Human Exposu re
         Studies
     Table 4-1 presents an updated staff assessment of the controlled  human
studies most useful in developing a range of interest for selecting a
1-hour S02 standard.  Both recently published studies and those assessed in
the 1982 staff paper are included.  The table focuses on those studies
involving free breathing (chamber) or faeemask exposures, which provide the
closest approximation of natural  breathing.  Studies in which subjects
breathed through mouthpieces have also been considered.   Although caution
is necessary in extrapolating mouthpiece study results to ambient conditions,

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                                               35

              Table 4-1.  UPDATED STAFF ASSESSMENT  OF KEY CONTROLLED HUMAN STUDIES
     SO 2
Concentration
(5-60 minutes)  Observed Effects1
                                   Comments/Implications
1-2 ppm
Substantial changes in 8 of 12
subjects ( A SRaw 100-600%)
exposed to 2 ppm.  At 1 ppm,
functional changes ( A SRaw 170-
200%), symptoms in free
breathing asthmatics at
moderate exercise2
Effects range from moderate to incapacitate
for some individuals.  At 2 ppm, 80% of mil
asthmatics could experience at least a
doubling of SRaw.  Some might not tolerate
exposure at moderate exercise.  Approx. 60%
at 1 ppm could experience at least a doubli:
of SRaw.^  Some asthmatic mouth breathers
have significant bronchoconstriction at 2 p
even at light activity.	
0.6-0.75 ppm
Functional changes ( A SRaw 120-
260%), symptoms in free breath-
ing asthmatics at light-moderate
exercise*
Effects indicative of clinical  significance
on average, changes were mild to moderate
although severe for some individuals; 25-50'
of mild, free-breathing asthmatics at
moderate exercise could experience at least
a doubling of airwAy resistance.3	
0.5 ppm
Significant functional changes
( A SRaw 50-100%), symptoms
in free breathing asthmatics at
moderate, but not at light
exercise.5  At heavy exercise,
A SRaw 220-240%.6
On average, mild responses at moderate or
higher exercise, symptoms possibly of
clinical significance; severe responses for
some individuals.  About 20-25% could ex-
perience at least a doubling in airway
resistance.
0.4 ppm
Functional changes ( A SRaw 70%),
symptoms in free breathing
asthmatics at moderate-
heavy exercise7	
Lowest level of clinically significant
response for some free breathers.  Approx.
of mild, free breathing asthmatics could,ex
perience a doubling in airway resistance.3
0.1-0.3 ppm     No effects in free breathing
                asthmatics at light exercise.
                Slight but not significant
                functional changes in free-
                breathing subjects at moderate-
                heavy exercise (0.25 ppm)6, but
	      not at lower levels.'
                                   Significant effects unlikely at moderate
                                   exercise.  Effects of S02 indistinguishable
                                   at heavy exercise.  Possibility of more
                                   significant responses in small  percentage
                                   of sensitive asthmatics at 0.28 ppm.3
^•Unless otherwise noted, ( A SRaw	%) reflects group mean increase over clean air control  at
 rest.  Light, moderate, heavy exercise refers to ventilation rates approximating _< 35 L/min,
 40-45 L/min, and 2. 50 L/min} respectively.  Effects reflect results from range of moderate
 temperature/humidity conditions (i.e., 7-26°C, 36-90% RH).   Studies at 0.5-0.6 ppm indicate
 that exercise-induced bronchoconstriction associated with cold and/or dry air exacerbates
 response to S02 while warm, humid air mitigates asthmatic responses relative to moderate
 conditions.
2Schacter et al. (1984); Roger et al. (1985); Horstman et al. (1986).
•JHorstman et al., (1986).
^Hackney et al. (1984); Schacter et al. (1984); Linn et al.  (1983a,b,  1984a,b,c, 1985a).
^Kirkpatrick et al. (1982); Linn et al. (1984b); Roger et al. (1985);  Schacter et al.  (1984).
5Bethel et al. (1983a,b; 1985).
7Linn et al. (1983b, 1984a).

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                                  36
It does not appear that substantial differences exist in SQg-induced responses
for the different breathing modes when account is made for the partitioning
of oral and nasal airflow components in oronasal breathing (see Appendix A).
Inferences made in the "implications" column are derived from observations
made by the investigators or in the CD addendum.  The percentage of asthmatics
showing a potentially clinically significant increase in airway resistance
(100%) is derived from Horstman at al. (1986) (See Figure 3-2).
     Table 4-1 indicates that functional  changes and symptoms are likely
in a large percentage of freely breathing asthmatics exposed  to 5 to 10
minute peaks of S02 between 1 and 2 ppm while involved in light to moderate
exercise (Ve ~ 30-50 L/min), comparable to daily activities such as climbing
stairs and light bicycling or jogging.  At comparable exercise rates
(Ve - 4U to 48 L/min), Linn et al. (1983atb) found "clinically and physiologically
significant responses" in free breathing young adult asthmatics exposed to
0.75 ppm and to 0.6 ppm S02.  Several studies report significant asthmatic
responses at 0.5 ppm with oronasal (free or facemask) breathing at moderate-
heavy exercise (Ve - 40-60 L/min) (Kirkpatrick et al., 1982;  Bethel  et  al.,
1983b; .Roger .et. al.., 1985) but no substantial symptomatic or  functional
effects at lower ventilation rates (27-40 L/min) (Linn et al., 1982; Bethel
et al., 1983b; Roger et al., 1985; Schacter et al., 1984).
     Asthmatics exposed to 0.4 ppm S02 at a moderate to heavy exercise  rate
(Ve ~ 48 L/min) showed on average a moderate increase in SRaw and a mild
increase in group mean symptom score, with substantial bronchoconstriction
in some individuals and one subject requiring medication to relieve
symptoms (Linn et al., 1983b).  Studies of free breathing exposures at  lower

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                                  37

concentrations (0.1 to 0.3 ppm)  suggest marginal,  if any,  group responses
only with 0.25 ppm at heavy exercise (50-60 L/min).   Any effect of S02 is
negligible compared to exercise at these levels (Linn et al.,  1984b;  Bethel
et al., 1985).  The CD addendum concludes from these observations that
"some SQg-sensitive asthmatics are at risk of experiencing clinically
significant (i.e., symptomatic) bronchoconstriction  requiring  termination
of activity and/or medical intervention when exposed to $03 concentrations of
0.4 to 0.5 ppm or greater when this exposure is accompanied by at least
moderate activity" (CDA, pp. 5-10).
     The 1982 staff paper outlined several considerations that are
important in evaluating these results in the context of decision making on
a standard to limit peak (5-10 minute) $02 exposures.  The following discussion
represents an update of those considerations.
     1) Health Significance of the Observed or Anticipated Effects
     Although little controversy exists that a full  asthma attack represents
an adverse health effect, the relative significance  of some of the less severe
responses observed in the above controlled human studies is open to question.
Based on the 1982 CD discussion of these matters,  the staff paper con-
cluded that the results of these studies begin to  be of some concern
when bronchoconstriction is accompanied by noticeable symptoms.  This is an
imprecise criterion, however, as not all studies report symptoms and symptom
reports are not always a reliable indicator of clinical status.  The CO
Addendum identifies at least four variables frequently measured that can be
used to classify the medical significance of responses observed in the
studies (see Figure 4-1).  These variables are a)  change in SRaw; b) duration
of effect of SQ2; c) changes in spirornetry, chiefly  FEV^Q; and d) types of
symptoms and relative discomfort.  As noted in the CD Addendum, "This table is

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GRADE OF
RESPONSE
CHANGE
IN SRAW
DURATION
OF
EFFECT
CHANGE IN
SPIROMETRY
FEVi.o. FVC
SYMPTOMS
NONE
NO
CHANGE
NA
NO
CHANGE
NO
RESPIRATORY
SYMPTOMS
MILD
INCREASE
LESS THAN
1OO%
SPONTANEOUS
RECOVERY
15%*
OBVIOUS WHEEZE*
MARKED CHEST
TIGHTNESS
BREATHING DISTRESS
INCAPACI-
TATING
INCREASES
»2OO%*
EMERGENCY
TREATMENT
REQUIRED
DECREASE
»15%*
SEVERE
BREATHING
DISTRESS*
                                                                                                             UJ
                                                                                                             00
• STATISTICALLY SIGNIFICANT CHANGE
       Figure 4-1.  Gradation of physiological  responses to S(>2  (CDA, Figure 7).

-------
                                     39

not intended to provide a quantitative description of what does  or does not
constitute an adverse health effect but is primarily intended to demonstrate
that there are an array of responses and to assist the reader in judging the
relative severity of the different responses which are described" (COA, p.
4-8).
     The scientific literature does not provide sufficient information
to specify an SOg concentration at which the observed effects can themselves
be considered adverse or serve as indicators of potentially more serious
consequences.  In making such a judgment, the Administrator should consider,
among other factors, the following:
     a)  In almost all cases, the bronchoconstriction and symptoms observed
appear to have been transient and reversible.  Sheppard et al, (1983),
however, reported that for two subjects, exposure to 0.5 ppm S02 via mouth-
piece with hyperventilation produced severe bronchoconstriction  that lasted
longer than 45 minutes.  In other studies, asthmatic subjects have been
removed from the chambers because of severe responses accompanying free
breathing exposures at 0.5 ppm and higher (Roger et al., 1985).   In other
studies, some subjects needed bronchodilator medication after exposure to
0.4-0.6 ppm (Linn et al., 1983b, 1984a,b).  Although direct evidence of
long-term consequences from repeated peak exposures is not available, the
possibility of such effects cannot be ruled out.
     b) At concentrations less than 0.4 ppm with free breathing, group mean
functional changes were moderate to small (A SWaw ~ 0 to 70% over baseline)
and within the range of variability observed for day to day changes in many
asthmatics.  At 0.6-0.75 ppm, group mean effects were more substantial
(A SRaw - 200% over baseline).

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     c) Most studies utilized mild, young adult or adolescent, non-smoking
asthmatic volunteers.  Furthermore, the subjects were exposed only when they
were asymptomatic and without apparent respiratory tract infections or
allergic responses.  Even among the otherwise well defined groups of
relatively mild asthmatics studied, there was great variability in the
magnitude of bronchoconstriction induced by S02-  As illustrated by the
data derived from Roger et al. (1985)  in Figure 3-2, the SOg concentration
necessary to increase SRaw by 100% or  more in freely breathing asthmatics
at 42 L/min was 0,75 ppm for 50% of the subjects, and ranged between ap-
proximately 0.3 and 1.4 ppm in 80% of  the subjects.  Even more sensitive in-
dividuals may exist in the population  of "mild" asthmatics.   Individuals
with more severe asthma may also be more sensitive to SOg-induced broncho-
constriction, but the evidence on this issue is inadequate.   The conse-
quences of any particular functional  change in a more severe asthmatic
is thought to be of greater concern than in a mild asthmatic.  However,
more severe asthmatics may be somewhat protected from SOg because of their
greater reliance on medication and their reduced tolerance to sustained
levels of moderate to high exercise.
     d) Although the reported responses are not generally interpreted as
overt asthma attacks, the combination  of bronchoconstriction and symptoms
might be perceived by some subjects as a "mild" attack;  this could result
in discomfort, the need for medication, and curtailment  of desired physical
activities.  According to Linn et al,  (1983b), the responses of their
subjects at 0.6 ppm "might be judged  to show adversity in that the subjects

-------
                                  41

sense of well  being was clearly diminished,  their degree of air-flow obstruction
seemed to impair physical  performance meaningfully,  and  drug treatment  was
clinically indicated in a few.   On the other hand, possibly arguing against
a judgment of adversity, are the observations that the effects  were quickly
reversible, were similar to effects produced by exercise even in clean  air,
and did not prevent the subjects from carrying out their duties (completing
the exposure protocol)."
     The staff obtained additional guidance on the physiological or health
significance of asthmatic responses in the controlled exposure  studies
through discussions with a number of experts in the field (Cohen, 1984).
Some experts felt that the relatively mild,  transient, and reversible
effects are not of physiological significance given the current widespread
use of effective medication.  In contrast, others felt that despite
asthmatics1 sensory accommodation and learning to manage attacks through
medication or altered activity, even subtle functional changes  are
significant and potentially serious especially when accompanied by
symptoms.  Several pointed out that there may be persistent, undetected
effects (e.g., residual obstruction) associated with.even "mild" episodes
which may increase airway reactivity and predispose the individual to
further insults (e.g., infections, other bronchoconstrictive agents).
Furthermore, these experts agreed that any asthmatic experience is
alarming and in different degrees, disabling.  They felt that the effects
observed at 0.5 ppm SOg would, at a minimum, affect an individual's
lifestyle by causing discomfort, an increase in their medication usage,
or discontinuance or restriction of their activity.

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                                   42
     2) Relative Effect of S02 Exposure Compared to Exercise, Other Stimuli;
     Exercise-induced bronchoconstrietion, without pollutant exposure,
is a relatively common occurrence for many asthmatics and SOg represents
one of many potentially encountered stimuli  that can cause asthmatic
reactions (see SP, pp. 66-67).  Consistent with previous findings discussed
in the 1982 staff paper, recent studies find that S02 enhances the broncho-
constrictive effects due to exercise.  Roger et al. (1985) report that  the
effects of moderate exercise (Ve ~ 42 L/min) in inducing bronchoconstrietion
is roughly equal to that of 0.5 ppm S02 while the effects of 0.25 ppm S02
on asthmatics are insignificant compared to  those caused by moderate-heavy
exercise.  The exercise rate in this study is roughly equivalent  to light
jogging or climbing several flights of stairs (SP,  Appendix A).
     Cold (< 6°C) and/or dry air has been found to exacerbate the effects
of S02 in exercising asthmatics, producing effects  greater than those
seen at normal temperatures.  S02 at concentrations as low as U.3 ppm
may measurably potentiate the effect of cold air (Linn et al., I984b) which
may be possible in ambient winter conditions in the U.S.  On the  other
hand, effects with warm, humid temperatures  are less than those seen in
conditions typical of most laboratory studies.
3)   Exposure Considerations
     Peak 1-hour SC>2 levels in excess of 0,5 ppm are rare with current
U.S. air quality, and almost always occur only  in the vicinity of
major point sources.  Shorter term (5 to 10  minute) peaks at these levels
are somewhat more common, but no systematic  data exist.   Moreover, indoor
SOg levels are almost always substantially lower than outdoor levels (EPA,
1982b; pp. 5-117).  Thus, effects appear likely for situations involving

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                                      43
  asthmatics undergoing light to moderate exercise outdoors relatively near
  (<  10 km) sources of S02 in conditions resulting in peak (> 0.5 ppm, 5 to 10
  minutes) SOg levels;  Staff estimates of the probability of such exposures
  near large sources under alternative standards are summarized in the next
  section  (IV.B).  Asthmatics may also be exposed to more frequent peaks of limited
  durations (< 30 seconds to 2 minutes) around numerous smaller industrial and
  commercial sources (Section IIB).  It is not currently possible to determine
.  whether  exposures of such limited duration would produce effects approaching
  those seen at the 5 to 10 minute exposures used in most of the studies to date.
      To  the extent such sources produce repeated frequent short-term peaks,
  the findings of temporary adaptation response may be of some significance.
  Within a single day, repeated episodes of exercise with elevated SOg
  concentrations would be expected to produce mitigated responses.  Since
  tolerance appears to be short-lived (<5 hrs.), however, it would not afford
  protection against S02 on subsequent days, nor necessarily^on the same day.
      Some data suggest that rapid rises in SOg levels, such as those involved
  in  many  of the controlled studies, are more likely to produce effects than
  are more gradual rises.  As discussed in the 1982 staff paper, however, a
  rapid rise could result from a) movement from indoors to outdoors, b) onset
  of  exercise resulting in a rapid rise in SOg at sensitive respiratory tract
  receptors, c) movement into an area of peak levels (by vehicle or otherwise),
  as  well  as, d)  an actual rapid increase in ambient levels at a point.
  4)   Variance about the 1-hour average
      The controlled studies discussed in Section III indicate that effects
  occur within 5-10 minutes but do not necessarily worsen with continued
  exposure to SOg over the course of an hour.  Five and ten minute averages
  will vary about the 1-hour mean.  Thus, for an area just attaining
  a 1-hour standard of 0.5 ppm, 5 or 10 minute peaks would be higher.

-------
                                     44
Analyses of recent data (Section II), indicate that the peak is likely to
be within a factor of 2 (1.5 to 1.8 of the mean) or less than 1.0 ppm.
                                                          *
     Based on the above evaluation of the more recent studies and related
factors, the staff revises its original  recommended range of interest for a
possible 1-hour S0£ standard to 0.2 to U.5 ppm.  The lower bound of 0.2 ppm
represents a 1-hour level  for which maximum 5 to 10 minute peak exposures
are not likely to exceed 0.4 ppm, the lowest level  at which the CO Addendum
indicates a risk of clinically significant responses for asthmatics engaged
in moderate (or higher) activity levels.   Based on  normal  air quality
variations, a l-hour standard at the upper bound of the range of 0,5 ppm
would permit 5-10 minute peaks as high as- 1.0 ppm during the peak hours,
and would permit multiple hours in which  the 5-10 minute peak would exceed
0.5 ppm, even when the 1-hour average is  within this range.   The risk of
substantial effects with such exposures  is higher.
     Independent of frequency of exposure considerations,  1-hour concen-
trations at the high end of the above range may not previde a substantial
margin of safety for exercising asthmatics.  The low frequency with which
such peak values would occur in the presence of active sensitive subjects
is, however, a mitigating  factor that should be examined in  determining
the margin of safety provided by alternative standards.
     b)  AdditionalFactorsto be Considered in Evaluating Margin of
         Safety and Risks—Peak Exposures
     The data do not suggest other groups that are  more  sensitive than
asthmatics and atopies to  single peak exposures. To the extent that the
suggested range is protective of asthmatics and atopies, the risk of functional
effects in other sensitive individuals appears small.  Other effects of
concern (aggravation of bronchitis, increased respiratory  illnesses)  have
not been evaluated adequately in controlled human studies, but epidemiological

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                                     45


evidence suggests that they may result from repeated peak exposures  over

longer time periods.  Potential interactions of SOg and ozone have not been

investigated in the more recent literature.

     The potential pollutant interactions and other considerations listed

above should be considered in determining the need for and evaluating the

margin of safety provided by alternative 1-hour standards.

     3.  Short-Term (24-hour) Exposures

         a)  Derivation of Ranges of Interest from EpidemiologicalStudies

     An updated staff assessment of the most useful epidemiological  studies

for deriving ranges of interest for 24-hour standards is summarized in

Table 4-2 and discussed below.


 Table 4-2.  UPDATED STAFF ASSESSMENT OF SHORT-TERM EPIDEMIOLOGICAL STUDIES
                       Measured SQ9 - ug/irr (ppm) - 24 hour mean
Effects/
Study
Effects
Likely
Effects
Possible
No Effects
Observed
Daily Mortality
in London^
500-1000
(0.19-0.38)

—
—
Aggravation of
Bronchitis^
500-600
(0.19-0.23)

<500 (0.19)
—
Small , Reversible
Declines in
Children's Lung
Function-^
-

250-450
(0.10-0.13)
100-200
(0.04-0.08)
Combined
Effects
Levels
500 (0.19)

250 (0.10)
<200 (.08)
 ^Deviations in daily mortality during London winters (1958-1972).  Early
 winters dominated by high smoke and S02, principally from coal combustion
 emissions, and with frequent fogs (Martin and Bradley, 1960; Ware et al.,
 1981; Mazumdar et al., 1981, 1982; Schwartz and Marcus, 1986).
 2Examination of symptoms reported by bronchitics in London.  Studies
 conducted from the mid-1950's to the early 1970's (Lawther et a1.3 1970).
 3Studies of children in Steubenville (1978-80) and in the Netherlands
 (1985-86) before, during, and after pollution episodes characterized
 by  high particle and S02 levels (Dockery et al., 1982; Dassen et al., 1986).

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                                     46

     The "effects likely" row in Table 4-2 is unchanged from the 1982 assess-
ment.  The CD addendum relies on the original London mortality and bronchi tic
studies as those most appropriate in concluding that notable increases in
excess mortality and exacerbation of bronchi tic symptoms may occur above
500 M9/ni  BS and 502-  With regard to increased mortality, greater certainty
with respect to effects occurs when both pollutants exceed about 750
These estimates represent judgments of the most scientifically reliable
"effects levels" for daily smoke and SO 2 at least in the context of
historical London pollution episodes.
     Because of the severity of the health endpoints in these studies
and the need to provide an adequate margin of safety in standard setting,
it is important to determine whether the data suggest the possibility
of health risks below these "effects likely levels".  As discussed in the
CO addendum, the London mortality studies and reanalyses support the possibility
of effects due to particles below 500 ng/nP with no obvious threshold.
     The situation with respect to S0£, however, is less clear.   The 1982
CD notes that results from a selected group of subjects suggested that
500 M9/m^ SO 2 (and 250 gg/nr BS) may not be absolute thresholds  for the most
sensitive bronchitis patients, although the lead author of the study strongly
objects to this interpretation (Lawther, 1986).  On the other hand, the 1982
staff assessment previously concluded that the available evidence on daily
mortality did not suggest a significant risk of increased mortality for
exposures to $02 alone at concentrations below the likely effects levels.
     The recent London mortality reanalyses provide differing results
regarding the effects of 503.  Shumway et al . (1983) did not attempt to
separate the effects of the two pollutants and found that their  association

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                                     47





with daily increases in mortality were nearly identical  with no apparent



threshold.  Mazumdar et al. (1982) found no consistent trend in mortality



with increasing S02 below 700 ug/m3 (0.27 ppm) and that the component of



London mortality explained by pollution in the 1958-72 winters is almost



entirely due to smoke across all levels considered,  For days with 8S and



S02 below 500 ug/m3, the association between mortality and pollution



persisted for smoke and not SOg.  Schwartz and Marcus (1986) in joint



regressions for these winters found BS was significantly associated



with mortality, independent of SO2 effects.  While the effects of SO 2 and



BS cannot clearly be separated due to the high degree of their covarianee



in this data set, it does not appear that the recently published analyses



suggest a revision to the previous assessment, which concluded there was



not a significant risk of increased daily mortality with S02^alone below



the effects likely levels.



     The studies of school children in Table 4-2 exposed to peak-Si^ and



particle concentrations during pollution episodes suggest small, but significant,



reversible declines in lung function..  The studies suggest the possibility



of effects below the low end of the original range of interest (36b ug/m^ or



0.14 ppm) down to levels as low as approximately 250 pg/m^ (0.10 ppm)



with more certainty at levels around 450 M9/m3 (0.18 ppm).  Again, it is



difficult to distinguish the effects of the two pollutants though a more



consistent trend of reduced lung function with higher TSP, and not S02»



was reported by Oockery et al.  (1982).  Given that SOg alone has not been



observed to cause altered clearance or lung function in animals or humans

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                                  48



in controlled laboratory conditions  without very high short-term peaks


(> 1-5 ppm) (EPA, 1982a,b), it may be that the observed declines in lung


function during and after the pollution episodes were due to the elevated


particle levels (including the transformation products of 503)  either


acting alone or in the presence of SOg, rather than SOg alone.   Alternatively,


very high peak S02 concentrations on the order of minutes may have  accounted


for the lung function decrements, though this does not seem likely.


     Therefore, caution should be applied in using the recent episode studies


in the context of evaluating the range of interest for S(>2 alone.   While effects


may be associated with levels between 250-450 ug/m^ (0.10-0.18  ppm),  it  is


questionable to what extent $02 was  a factor in causing the observed  responses.

     In summary, the available data  indicate that the upper bound for

                                                                   •3
the range of interest for 24-hour S02 standards remains at 500  ug/nr


where effects appear to be likely.  Although consideration should be  given


to a lower bound of 250 ug/m^ (0.10  ppm), it is not clear whether important


effects are caused by SOg at levels  below the current standard  level


(365 Mg/m^» 0.14 ppm) which was previously judged - and still  appears -


to provide adequate protection.


     b)  Summaryof Factors to be Considered in Evaluating Margin of


         Safety — Short-Term Exposures


     The 1982 staff paper identified a number, of factors to be  considered


in developing a 24-hour standard with a margin of safety.  The  staff  finds


that this original discussion (SP, pp. 75-78) is still  appropriate.  In


summary, the factors include:


     1)  Interaction with ozone, particles, and other pollutants as well


         as fog.


     2)  Relative exposure in the U.S. compared to the British  studies.

-------
                                     49

     3)   Risk for other sensitive groups  and effects  not  evaluated  in  the
         more quantitative data,  and
     4)   Whether the 24-hour standard acts  alone or in  concert  with a
         new 1-hour standard.
     4.   Long-Term (Annual) Exposures
     Based on the 1982 assessment, the staff concluded  that although
the possibility of effects from continuous  low-level  exposures  to S02
could not be ruled out, no quantitative rationale could be offered  to
support a specific range of interest for an annual  standard given the
inconclusive nature of the available epidemiological  data.  As  discussed
in Section III, several recent community studies suggest increased  risk
of respiratory symptoms (cough, phlegm production,  wheeze) in populations
(children and adults) exposed to high (>100 ug/m3), long-term levels of S02l
with and without high particle concentrations.  The majority of these
studies were conducted in areas subjected to intermittent short-term peak
S02 concentrations resulting from point source emissions (Chapman et al.,
1985; Dodge, 1983; Dodge et al., 1985; Schenker et al., 1983).   A major
concern, therefore, is whether repeated S02 peaks permitted by  24-hour or
1-hour standard ranges in area-source dominated population centers  might,
after some long time period, result in increased risk of the effects noted,
along with other effects suggested by animal data (EPA  1982a,b).
     One recent study  (PAARC, 1982a,b) demonstrating associations between
S02 and respiratory health effects did not  focus on point-source dominated
exposures.   Increased  respiratory symptoms  and disease  in adults and children
were associated with S02, but not particles, across a range from 25 to
130 Mg/m3 with no apparent threshold (CDA,  p. 3-55).   In addition,
unlike in any other study, associations between S02 and reduced lung function

-------
                                  50

were detected.  As noted in Section III, a number of questions regarding the
aerometry,. statistical analyses, and interpretation of this work limit
the reliance that can be placed on the conclusions of this study at present.
     While no single study may provide strong evidence for substantial
risks, there does appear to be some consistency across results indicating
a possibility of respiratory impacts associated with either low-level,
long-term exposures to SOg or, more certainly, with repeated exposures to
peak S02 levels over long periods.  In essence, the recent studies do add
support to previous staff recommendations to retain an annual  primary
standard.  This recommendation was in part based on the finding that
elimination or substantial  relaxation of the current annual  standard
would result in increased exposures to large numbers of people in several
heavily populated urban centers (Frank and Thrall, 1982),   Such exposures
could lead to increased risks of health effects that are not readily
measured in controlled studies but for which there is qualitative evidence,
summarized in the 1982 staff paper.  These possible effects  include effects
on clearance and other host defense systems, and_to a lesser extent,
potential mutagenicity or co-carcinogenicity of $62 (SP, pp. 78-79).  In
addition, the long-term standard serves to limit emissions from numerous
smaller sources that "have recently been found to produce brief short-term
peaks (< 30 seconds to 2 minutes)  that are of potential  concern to
asthmatics (see Section 118 above).  Pending resolution of the issues
raised by the new studies,  the staff recommends maintaining  an annual
standard at about the current level of 0.03 ppm (80 ug/m^).
B.   Analysis of Relative Protection Afforded by Alternative Standards
     An essential consideration in evaluating potential  standards is the
relative protection afforded by standards with different averaging times

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                                     51

and levels.  A preliminary staff assessment of this issue is  presented in
the 1982 SP (pp. 79-83, Appendix D).   This assessment,  based  on  analysis  of
air quality data (Frank and Thrall, 1982;  Johnson,  1982), air quality
modeling (Burton et al., 1982), and source/population information  (Anderson,
1982), found that no single averaging time (annual, 24-hr, 3-hr, 1-hr)
would provide the same degree of protection and control  afforded by the
other averaging times in all situations.   The current 24-hour standard would
significantly limit 1-hour peaks in the range of interest from occurring  in
most population oriented sites, but would allow multiple exceedances of
these values in many point source oriented sites.  Similarly, the 24-hour
standard limits high annual values in most, but not all  sites of interest.
The current 3-hour secondary standard limits 1-hour peaks even more than
the 24-hour standard, but does not materially affect long-term urban values.
In essence, based on that preliminary analysis of alternative averaging times,
the staff concluded "that implementation of the current suite of $03 standards
(annual, 24-hour, 3-hour) provides substantial protection against the .direct
effects of S02  identified in the scientific literature" (SP,  pp. 82-83).
     Since closure on the 1982 staff paper, the staff has continued to
analyze relationships among averaging times and relative protection afforded.
Based on the above updated assessment of effects associated with both 24-
hour and annual exposures, the staff finds that the above conclusions
concerning protection provided by the current standards remain demonstrably
valid.  The staff has found the most critical aspect of examining the
relative (or alternative) standards to be in relation to peak exposures
associated with effects in asthmatics.  Over the past several years, the
staff has developed tools to permit analysis of substantially greater detail
than previously possible.  These tools and the results  of their application

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                                     52

to examine 1) current standards, 2) emissions typical of current conditions,
and 3) alternative standards are presented in detail in separate reports
(EPA, 1986c; 1986d).  The following discussion summarizes the major findings
from these reports.
     Population exposure simulations require detailed analyses of both air
quality and population patterns.  The EPA (1986d) describes a population
exposure study around four utility power plants each located in or near
an urban area.  The decision to focus that analysis on power plants was
guided by earlier studies (Frank and Thrall, 1982; Burton et al.» 1982)
which showed they were the source category most likely to produce high,
short-term levels of 502 in populated areas.  Other large sources, such
as smelters or Kraft pulp mills, however, can also produce such peaks,
A complete risk assessment would combine exposure results with detailed
exposure-response functions.  To reduce the complexity of this analytic
problem to a manageable size, the staff developed a benchmark called an
Exposure of Concern (EOC).  This benchmark permitted fixing a concentration,
averaging period, and exercise rate above which effects of concern could be
expected in some fraction of asthmatics,  Based on the health studies and
analyses described above, the benchmark EOC most often used was defined as
an asthmatic exposed at or above 0.5 ppm S02 for 5 minutes while at an
activity level associated with a ventilation rate at or above 35 L/minute.
At these levels, on the order of 26% of asthmatics might experience a
doubling of airway resistance (Figure 3-2).  In some of the work, other
concentration levels and averaging periods were also examined.  The
EOC defined above is not intended to define a threshold of response, but
rather as a level where a significant fraction of individuals so exposed
might experience potentially adverse effects.

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                                     53

     The air quality modeling estimated the probability that  the 5-minute
peak equalled or exceeded 0.5 ppm.   These probability estimates  of exceeding
a target level  (0.5 ppm)  provided the air quality basis for the  exposure
calculation.  The EPA's NAAQS Exposure Model  (NEM)  (Biller et al., 1981) was
modified to incorporate these probability estimates.   NEM is  designed to
simulate daily population movement around an urban area accounting
for travel patterns, activity levels, and microenvironment (e.g.,  indoor
vs. outdoor).  The population and travel data were specific to the urban
areas being studied.  The activities which are defined in NEM as "High"
correspond to ventilation >_ 35 L/minute.  The use of air quality probability
estimates meant that it was possible to express the exposure  results as  a
probability weighted distribution and allowed estimation of the expected
number of exposures.
     The findings of the exposure analysis are subject to a number of
uncertainties inherent in both air quality modeling and large population
simulations.  The results are conditioned by the analytic assumptions made.
The exposure analysis identifies some 16 separate sources of  uncertainty
                                        *
and error.  Among the more significant are:  1) Lacking activity pattern and
residential location data for asthmatics, it was assumed that the geographic
distributions, and activity patterns and ventilation rates for asthmatics
are the same as for the general population.  Although this may not be an
unreasonable assumption for most mild asthmatics, it undoubtedly overstates
the time spent at elevated ventilation rates for more severe  cases;
2) Power plants were assumed to operate at 100% capacity.  Sensitivity
analyses indicate that exposures are overestimated because of this assumption;
and 3) Although care was taken to select a representative sample of plants/
exposure regimes, only four power plants were modeled.  Nonetheless, despite

-------
                                     54
the caveats noted above as well  as others In the reports, the results do
provide an indication of both current exposures and those which might occur
under alternative standards around large utility power plants.
     The exposure analysis results in EPA (1986d) include air quality
levels, the expected number and  percent of asthmatics  living  in the vicinity
of each plant that experiences one or more EOC per year,  and  the highest
probability of an EOC for any single asthmatic.  Because  of variations  in
population around plants and the tendency for the maximum probability of
exposure to approach one under a variety of scenarios, the fraction (%)  of
asthmatics with one or more EOC/yr is the most useful  metric  for comparing
results around different plants.  This number is, however, somewhat sensitive
to the size of the area modeled  (EPA, 1986d).
     The results of the analysis of the fraction of asthmatics  with an  EOC
under 1) current emissions, and  2) maximum emissions assuming the current
standards are just met, are displayed in Figure 4-2.  With current emissions,
approximately 0,2 to 13% of resident asthmatics are predicted to experience
at least one 5-minute exposure to 0.5 ppm per year while  at moderate or
                              *
higher exercise.  With the exception of Eddystone, this represents on the
order of one to four thousand asthmatics (assuming 4%  of  the  population  is
asthmatic) for each plant.  With the exception of Eddystone,  the maximum
probability of an EOC for "most  exposed" individual  approaches  unity at  all
plants.  The results for just meeting the current standards are comparable
to the "current" case but with 3 of 4 plants showing increases  in predicted
EOC fraction.  In part, such increases are due to assumptions regarding
implementation, which reflect current practice in some areas  of the country,
but are less restrictive than more strict compliance requirements in practice
in other areas.  The 3-hour standard tends to be controlling  for large,  more
isolated plants, while the 24-hour standard controls in more  urban locations.

-------
      30
    CJ
    o
    LJ
      20
    LO
    u
      10  -
       0
                                                14.O*1
                  13.0
                                                                                   6ALLA8HER
                                                                                   PORTAGE DES  SIOUX
                                                                                   POTOMAC
                                                                                   EDDYSTONE
                                                                        M SECONDARY NAAOS CONTROL.!-INS
                    CURRENT EMISSIONS
CURRENT NAAQS
Figure 4-2.   Expected percentage  of  asthmatics with one exposure of concern (^0.5     SOg for 5 minutes^ "high"
activity)  per year In vicinity of four selected power plants.  For 1) current emissions and 2) just meeting
current S02  KAAQS assuming a 30 day  emission limit {EPA, 1986d).  The degree of protection varies significantly
with implementation approach.

-------
                                     56

     The results of the exposure analysis for alternative 1-hour standards
selected from the range of interest are illustrated in Figure 4-3.   Standards
in this range would reduce the HOC fraction to under 4% for all  plants modeled*
but still  do not eliminate all such exposures.  A standard of 0,4 ppm, for
example, would protect over 98% of potentially exposed asthmatics from an
EOC.  The maximum probability of an individual £OC for the range illustrated
is 0.1 to U.9.
     The results of the exposure analysis for utilities should be viewed
in light of the assumptions and uncertainties noted above.  In addition,
although utility power plants account for the majority of S02 emissions
in the U.S., recent work has shown that other smaller sources may also
produce peak exposures (Section II).  Around smaller sources (e.g.,  industrial
or commercial boilers), limited duration peaks in excess of 0.5  ppm  are due
either to low persistence meteorological events or, if the facility  has a
short stack, may be due to the phenomenon of building downwash.   In  either
event, the peaks are likely to be of very short duration (less than  30
seconds to two minutes).  Because the meteorological  events causing  the
peaks are not well  characterized and are not normally addressed  in standard
EPA dispersion models, a complete analysis of the situation around smaller
plants is not feasible.  Very rough estimates indicate that the  populations
at risk of an exposure in such situations may be large.  However, given the
very short duration of most such peaks, their health significance for
exercising asthmatics is uncertain.  Furthermore, it is not clear that
a 1-hour standard would further limit such exposures.
     In summary, the staff analysis of relative protection afforded  by
alternative standards results in the following conclusions:

-------
     5.0
     c.
     >»
    CJ
    a
    01
    CJ
    i
    i-
    w
     0.0
                      21
                   i.i
 i,3

^
                 0.5  ppm SOg for 5 minutes,  "high"

activity)  per year in vicinity of four selected power plants.   For just meeting alternative one hour standards

(EPA. 1986d).

-------
                                     58

     1)  The current standards provide substantial  protection against
         the effects identified as being associated with 24-hour and
         annual  exposures.
     2)  The current standards - as reflected by current emissions or emis-
         sions when the standards are just met with somewhat less restrictive
         implementation assumptions - also provide  some limit on peak SQ'i
         exposures of concern for asthmatics.  In some cases, however,
         up to 10 to 15% of the sensitive population could be exposed once
         a year to levels >_ 0.5 ppm for 5 minutes,  while at elevated
         ventilation,
     3)  The range of 1-hour standards analyzed. (0.25 to 0.5 ppm) would  provide
         increased protection against such exposures, limiting the fraction
         of asthmatics exposed to less than 4%.
C.  Summary of Staff Conclusions and Recommendations
     The major updated staff conclusions and recommendations made in Section
IV, A-B are briefly summarized below:
1)   The more recent data provide additional  support for the earlier staff
     recommendations regarding consideration of  a new 1-hour S02 standard.
     Based on an updated staff assessment of controlled human exposures
     to peak (minutes to hours) SOg concentrations, the staff has revised
     the range of potential  1-hour levels of interest to 0.2 to 0.5  ppm
     (525 to 1300 ug/m^).  The lower bound represents a 1-hour level  for
     which the maximum 5- to 10-minute peak exposures are unlikely to
     exceed 0.4 ppm, which is the lowest level where potentially
     significant responses in free (oronasal) breathing asthmatics have
     been reported in the CO addendum.  The upper bound of the range
     represents a 1-hour level for which 5- to 10-minute peak concentrations

-------
                                     59


     are unlikely to exceed 1 ppm, a concentration at which the risk of

     significant functional and symptomatic responses in exposed sensitive

     asthmatics and atopies appears high.  In evaluating these laboratory

     data in the context of decision making on possible 1-hour standards,

     the following considerations are important:  (a) the significance of

     the observed or anticipated responses to health, (b) the relative

     effect of S02 compared to normal day to day variations in asthmatics

     from exercise and other stimuli, (c) the low probability of exposures

     of exercising asthmatics to peak levels, and (d) 5^ to 10-minute peak

     exposures may be a factor of two greater than hourly averages.

          Independent of frequency of exposure consideration, the upper

     bound of the range contains little or no margin of safety for

     exposed sensitive individuals.  The limited geographical areas

     likely to be affected and low frequency of peak exposure to active

     asthmatics if the standard is met add to the margin of safety.  The

     data do not suggest other groups that are more sensitive than

     asthmatics to single peak exposures, but qualitative data suggest

     repeated peaks might produce effects of concern in other sensitive

     individuals.  Potential interactions of S02 and 03 have not been

     investigated in asthmatics.  The qualitative data, potential
i
     pollution interactions, and other considerations listed above

     should be considered in determining the need for and evaluating the

     margin of safety provided by alternative 1-hour standards.

 2)   Based on a staff assessment of the recent short-term epidemiological

     data, the original range of 24-hour SOg levels of interest - 0.14 to

     0.19 ppm (365 to 500 ug/m3) - still appears appropriate, although some

-------
     consideration could be given to the findings of physiological  changes
     of uncertain significance at levels as low as 0.1 ppm.   Earlier staff
     conclusions and recommendations concerning a 24-hour standard  (SP,
     pp. 85-86)  remain appropriate.
3)   The previous staff assessment concluded that although the possibility
     of effects  from continuous lower level  exposures to S02 cannot be
     ruled out,  no quantitative rationale could be offered to support a
     specific range of interest for  an annual  standard.   The more recent
     epidemiological data,  indicating associations between respiratory
     illnesses and symptoms and persistent exposures to  S02  in areas with
     long-term averages exceeding 100 Mg/m^, provide additional  support for
     the original recommendation for retaining arj annual  standard at or
     near the current level 0.03 ppm (80 ug/m^).   This recommendation was
     based in part on a finding that alternative short-term  standards would
     not prevent annual levels in excess of the current  standard in a
     limited number of heavily populated urban areas.  In addition, recent
     evidence suggests smaller sources in urban areas may produce short
     duration peaks of potential  concern.  The long-term standard often
     serves to limit the emissions of numerous smaller sources in such areas.
     Given the additional  information and the  possibility of both chronic  and
     acute effects from a large increase in population exposure, the staff
     recommends  maintaining the primary annual  standard  at its current
     level.
4)   Analyses of alternative averaging times and population  exposures
     suggest that:
     a)  The current standards provide substantial protection against
         the effects identified as being associated with 24-hour and
         annual  exposures.

-------
                                    61





     b)  The  current  standards-- as  reflected by current emissions or



        emissions  when  the  standards are just met with somewhat less



        restrictive  implementation  assumptions - also provide some limit



        on  peak  S02  exposures  of  concern for asthmatics.   In some cases,



        however, up  to  10 to 15%  of the sensitive population in the



        vicinity of  major sources could be exposed once a year to levels at



        or  above 0.5 ppm for 5 minutes, while at elevated  ventilation.



     c)  The  range  of 1-hour standards analyzed (0.25 to 0.5 ppm) provides



        increased  protection against such exposures, limiting the fraction



        of  asthmatics exposed  to  less than 4%.



     The relative protection afforded by current vs. alternative standards



as indicated  by current  and  ongoing  exposure analyses is an important



consideration in  determining what, if any, standard revisions may be necessary.

-------

-------
 APPENDIX A.   ANALYSIS  OF  DOSE-RESPONSE  RELATIONSHIPS  FROM  CONTROLLED S02
                      EXPOSURE STUDIES ON  ASTHMATICS
     The following discussion  describes  the  analyses  used  to  generate
Figure 3-1,  which plots results  from the various  controlled S02  exposure
studies on mild asthmatics.
     1)  The studies used are  summarized in  Table A-l.  To standardize
comparisons, only studies that reported  changes  in specific airway  resistance
(SRaw).  Unfortunately,  several  studies reporting significant declines
only for other lung function parameters  could  not be  not  represented
(e.g., Koenig et al., 1983b, 1985a;  Schacter et  al.,  1984).   Studies
involving unusual temperature  and/or humidity  conditions  (i.e.,  <  6°C, RH
< 40% or > 90%) were also excluded to avoid  the  interactive effects of
airway drying or cooling in  contributing to  bronchoconstriction.   In
addition, results at low 503 exposure levels (generally _<_ 0.25 ppm) where
changes in SRaw were not statistically different  from changes due  to
exercise alone were eliminated from the  analysis.  This would not  be
expected to bias the analysis  in the domain  where SRaw increases significantly
         %
with increased SOg exposure.  The regression line in  Figure 3-1
should not be extrapolated to  zero dose, since at 503 levels  below  0.25
ppm ( ~ 20 ug/min, oral airway dose rate)  exercise-induced constriction
dominates.
     2) The studies involved either 5- or 10-minute exposure  periods
with one exception.  Although  total  dose is  a  less satisfactory  predictor
of response than dose rate when  considering  longer exposure times  (e.g.,
1-hour) (Linn et al., 1982), no  consistent trend  can  be seen  in  comparing
responses to 3- vs. 5-minute vs.  10-minute exposures, which supports
findings of Linn et al., (1983b).

-------
                     Table A-l.   Summary of Data from SOg Controlled Asthmatic
                                Studies Used in Dose-Response Analysis
cue.
(ua/si'35
CM!.
TEW C/'H-
!W«JTES
t N

Vs
OWL Ue
GROWS*.
1300
1300
1970
630
2600
1300
1300
1300
1300
1970
1300
1300
2600
2600
1570
1300
1570
1040
800
800
1570
1570
630
1570
1300
2600
1570
1570
1970
1970
1370
0.5
0.5
0.7?
0.25
|
0.5
0,5
0.5
0.5
0.75
0.5
0.5
1
1
0.6
0.5
0.6
0.4
0.3
0,3
0.6
0,6
0.25
0.6
0.5
1
0.6,
"O.fi'
0.75
0.75
0.75
5
tr
10
10
s
3
10
10
f
ij
10
5
5
10
10
5
10
5
5
5
5
u
5
5
5
5
30
5
5
10
10
10
23/80
£3/80
23/80
23/80
£2/80
£3/82
23/80
£2/85
23/80
23/90
23/60
23/SO
26/70
26/70
22/15
26/70
21/80
23/85
7/80
21/80
21/20
21/60
23/36
5/85
23/41
26/70
7/60
23/85
£3/90
22/S5
22/85
6
7
23
7
6
3
7
24
9
14
6
9
£7
10
24
28
24
23
24
24
22
£2
- 19
24
10
10
24
23
23
£3
17
V
M

«
J»
M
«
»
N
N
F
F
C
C
C
C
c
C
C
C
C
C
C
C
C
r
LI
r
C
C
f*
C
0,04
0.041
0.04
0.03
0,031
0. 035
0,035
0.027
0.061
0.04
0.04
0.061
0.042
0.041
0.05
0.042
0.05
0.049
0.05
0.05
0.05
0,05
0,06
0.05
0. 06
0.041
0.05
0.048
0.04
0.0*
0, 045
0.04
0.041
0.04
0.03
0.031
0.035
0.035
0.027
0.061
0.04
0.019
0.038
0.02
0.02
0.027
0.02
0.027
0,023
0.027
0.027
0.027
0.0£7
0.032
0, 027
0.032
0.02
0,027
0. 023
0,019
0.019
0.0225
OWL Ve QBftL 302
A3/BiTi. UB/nin. yq/s-ifi.
MOUTH r)UTM
0.04
0.041
d.04
0.03
0.031
0.035
0.035
0,027
0.061
9,04
0,026
0.042
0.027
0.027
0,033
0.027
0.033
0.032
0.033
0.033
0.033
0.033
0.042
0.033
0,042
0.027
0.033
0, 032
0.026
0.026
'0.03
52
=;> 3
7B.fi
18.1
80,6
45,5
45.5
35.!
79.3
78.8
24.7
49.4
52
52
42.39
26
42.39
23.92
21.6
21.6
42.39
42.39
£0. 16
42.39
41.6
52
42.39
36.11
37.43
37.43
44.325
52
53.3
78. e
IB. 9
B<). 6
45.5
45.5
35.1.
79.3
78. i
33.6
54.5
70.2.
70.2
51.81
35.1
51; 85
33. £9
26.4
21.4
51.61
51. Bl
£6.45
51.81
54.6
70.2
51,61
50. £4
51.22
51.22
53, 1
< Slaw INCASE RE't^Ct
CLEWH SQ2/ Ki OVE1
EKERCISE -J.
15
5
S
o
0
f\
I)
35
£5
54
15
£5
*7
48
27
47
28
35
5S
28
20
10
77
3d
39
50
58
36
54
55
?
POSE "LEflWS
14!.
£3!
372
30
300
10*
i »'~j
%
306
321
69
£19
m
172
132
93
150
69
67
53
206
157
134
162
238
£33
207
IcO
!S6
241
£63
lit
;0£
3ES
30
300
!0i
'.15
51
28!
267
54
194
143
124
!05
46
122
34
2E
31
186
147
57
144
119
183
149
64
!32
IBS
-
*
KIRKPa^JCK dSBt'S
oCTuri "aatht
L!KN (JffiSb)
CLiCrin/jDA M tjoi **.
Pr* »„ I- •*H fi u ,4 jp I -jj /
(!?B!a»
3H--!5fi^D (1983)
CL£PSP^|) (icglfll
LIV»i n3S?a)
BETHEL nSB3bJ
LIW
KJRKMTWCK <;36c)
BETHEL flSaSs)
ROGER 11985)
KEWHL (193S5
LIW (!984a»
3D6tS (1985)
LIW (2984W
LIW (!383bl
LINN (1984b)
LINN (19a4bl
LINN <1985a)
LINN f!985i)
BETHEL (1965)
LIKN U9B4a)
iim 
-------
                                    A-3



     3) Given the almost complete absorption of S02 that occurs in the


moist surfaces of the nasal  airways, the oral  component of ventilation is


critical in determining the S02 dose that penetrates to the airways where


bronchomotor responses are triggered (Kleinman, 1984).  Data on the


partitioning between oral  and nasal  breathing under different exercise


levels  (Niinimaa et al., 1981; see 1982 staff paper, Appendix A) were used


to estimate the oral component of ventilation given the ventilation


rates  (Ve) reported by the investigators.  For example, Kirkpatrick et


al.  (1982) exposed asthmatics via mouthpiece to 0.5 ppm while exercising


at about 40 L/min.  Because a mouthpiece forces inspired air through the


oral cavity thereby bypassing the nasal airways, it can be assumed that
       *

the  oral Ve was 40 L/min resulting in an estimated 502 dose delivered via


the  oral airways of [1300 ug/m3  (0.5 ppm) x 0.04 m3/rnin (40 L/min)], or 52


ug/min.  The asthmatics in the Kehrl et al. (1986) study were exposed


free-breathing 1.0 ppm S02 while exercising at a ventilation rate of


approximately 41 L/min.  At this exercise level, most normal healthy


individuals breathing unencumbered augment the amount of air entering the


nasal  passages by inhaling some  air via the mouth so that the oral Ve


would  be approximately 20 L/min  (Niinimaa et al., 1981).  The oral airway


S02  dose is estimated as [2600 ug/m3 (1.0 ppm) x 0.02 m3/min (20 L/min)],


or 52  ug/min, which is identical to that in the Kirkpatrick study.


Interestingly, the  increases  in  airway  resistance over clean air/exercise


control in these studies were almost identical  (126% vs. 124%).


     For all calculations on  free breathing experiments, typical oral/nasal


breathing  patterns were used  as  determined by  Niinimaa et al.,  (1981) (see


1982 staff paper, Appendix A).   By assuming that all of the freebreathing


subjects were normal augmentors,. some underestimation of S02 dose likely

-------
                                    A-4

results, especially given indications of increased frequency of allergic
rhinitis and nasal congestion in asthmatics resulting in obligatory
mouth breathing. Variability in such conditions between different groups
of subjects may explain observed differences in responses between studies,
as evidenced by the failure to fully replicate the Kirkpatriek et al. (1982)
results under similar conditions but with fewer subjects with nasal
disorders (Bethel et al., 1983b).  An alternative approach is taken by
Kleinman (1984) who estimates population-weighted oral  Ve at different
activity levels.  A separate analysis (not illustrated), which used the
same group of data assuming subjects were habitual mouthbreathers,
produced no apparent improvements (r^ * 0.76).
     For the facemask experiment included in Bethel  et  al. (1983b),
actual  measurements of oral airflow through the masks were provided and
roughly matched Niinimaa et al.'s prediction for oronasa.1 breathing.  In
the Kirkpatrick et al. (1982) facemask study, it was assumed that free,
oronasal breathing was simulated.
     5) Changes in SRaw in response to SOg exposure while at exercise
over baseline measurements were used as opposed to changes in SRaw over
increases due to exercise alone in clean air.  Again, separate analysis
(not shown) using the latter measure yielded nearly identical results.
     6) A simple linear regression was fit to the data.  As mentioned, the
linear relationship should not be extended to lower SOg exposure levels
down to zero.

-------
                                  CASAC Closure Letter
                                                           SAB-CASAC-87-022

 r*.
  \          UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

  /                      .  WASHINGTON. D C.  20-SO
                            February 19, 1987
The Honorable Lee M. Thomas                   .                  ™e *o«'msT
Administrator
U.S. Environmental Protection
  Agency
Washington, DC  20460

Dear Mr. Thcaas:

     The Clean Air Scientific Advisory Committee (CASAC) has completed
its review of the 1986 Addendum to the 1982 staff Paper on Sulfur Oxides
(Review of the National Anbient Air duality -Standards for Sulfur Oxides;
Updated AssessmenC^^tentif^                            ...... prepared by
the Agency's Office, of Air "Quality. Planning and Standards (QAQPS) .

     The Committee unanimously concludes that this document is consistent
in all significant respects with the scientific evidence presented and
interpreted in the combined Air Quality Criteria Document for Particulate
Matter/Sulfur Oxides  (1982) and its 1986 Addendum, on which CASAC issued
its closure letter on December 15 , 1986.  The Conraittee beliefs that the
1986 Addendum to the 1982 Staff Paper on Sulfur Oxides provides you with
the kind and amount of technical guidance that will be needed to make
appropriate decisions with respect to the standards.  The Conmittee's
major findings and conclusions concerning the various scientific issues
and studies discussed in the Staff Paper Addendum are contained in the
attached report.            |

     Thank you for the opportunity to present the Committee's views on
this important public health and welfare issue.
                                   Sincerely,
                                   Morton Lippmann/ Ph.D.
                                   Chairman
                                   Clean Air Scientific Advisory
                                      Conmittee
cc:   A. Janes Barnes
      Gerald Emison
      Lester Grant
      Vaun Newill
      John O'Connor
      Craig Potter
      Terry Yosie

-------
                                                             SA&-CASAC-87-L
               SUMMARY OF MAJOR SCIENTIFIC ISSUES AND CASAC
                  CONCLUSIONS ON THE 1986 DRAFT ADDENDUM
                  TO THE 1982 SULFUR OXIDES STAFF PAPER
     The Conmittee found the technical discussions contained in the Staff
Paper Addendum to ba scientifically thorough and acceptable, subject to
minor editorial revisions.  This document is consistent in all significant
respects with the scientific evidence presented in the 1982 combined Air
Quality Criteria Document for Particulate Matter/Sulfur Oxides and its 1986
Addendum, on which the Conroittee issued its closure letter on Decanter 15,
1986.

Scientific .Basis for Primary Standards,

     The Comnittee addressed the scientific basis for a 1-hour, 24-hour,
and annual primary standards at some length in its August 26, 1983 closure
letter on the 1982 Sulfur Oxides Staff-Paper.  That letter was based on
the scientific literature which had been published up to 1982.  The present <
review has examined the more recently published studies.                   t

     It is clear that no single study of 303 can fully address the range of
public health issues that arise during the standard setting process.  The
Agency has conpleted a thorough analysis of the strengths and weaknesses of
various studies and has derived its recommended ranges of interest by
evaluating the weight of the evidence.  The Coranittee endorses this approach.

     The Ccranittee wishes to content on several major issues concerning the
scientific data that are available.  These issues include:

     * Itecent studies more clearly implicate particulate matter than SO2
       as a longer-term public health concern at low exposure levels.

     • A majority of Conraittee members believe that the effects reported
       in the clinical studies of asthmatics represent effects of
       significant public health concern.

     * The exposure uncertainties associated with a 1-hour standard are
       quite large.  The relationship between the frequency of short-terra
       peak exposures and various scenarios of asthmatic responses  is not
       well understood.  Both EPA and the electric power  industry are
       conducting further analyses of a series of exposure assessment
       issues.  Such analyses have the potential to increase  the collective
       understanding of the relationship between SC>2 exposures and  responses
       observed in subgroups of the general peculation.

     • The number of asthmatics vulnerable  to peak exposures near electric
       power plants, given  the protection afforded by  the  current standards,
       represents a small number of people.  Although  the  Clean Air Act
       requires that sensitive population groups receive protection,  the
       size of such groups  has not been defined.  CASAC believes  that this
       issue represents a legal/policy matter and has  no  specific  scientific
       advice to provide on it.

-------
                                     -2-
     CASAC's advice on primary standards for three averaging times is presented
below:

          1-Hour Standard - It is our conclusion that a large/ consistent
     data base exists to document the bronc*oconstrictive response in mild
     to moderate asthmatics subjected in clinical chanters to short-term,       _  -
     low levels of sulfur dioxide while exercising.  There is, however, no
     scientific basis at present to support or dispute the hypothesis that
     individuals participating in the SC>2 clinical studies are surrogates
     for more sensitive asthmatics.  Estimates of the size of the asthmatic
     population that experience exposures to short-term peaks of SC>2
     (0.2 - 0.5 parts per million (ppm) S02 for 5-10 minutes) during light
     to moderate exercise, and that can be expected to exhibit a broncho-
     eonstrictive response, varies from 5,000 to 50,000.

          The majority of the Committee believes that the scientific evidence
     supporting the establishment of.'a new 1-hour standard is stronger than
     it was in 1983.  As a result, and in view of the significance of the
     effects reported in these clinical studies, there is strong, but not
     unanimous support for the recommendation that the Administrator consider
     establishing a new 1-hour standard for S02 exposures.  The Committee   ;
     agrees that the range suggested by EPA staff  (0.2 - 0.5 ppm) is        ?
     appropriate, with several members of the Committee suggesting a standard
     from the middle of this range.  The Committee concludes that there  is
     not a scientifically demonstrated need for a wide margin of safety  for a
     1-hour standard.

          24-Hour _Standard - The more recent studies presented and analyzed
     in the 1986 Staff Paper Addendum, in particular, the episodic lung
     function studies in children  (Doekery et al., and Dassen et al.)  serve
     to strengthen our previous conclusion that the rationale for reaffirming
     the 24-hour standard is appropriate.

          Annual Standard - The* Committee reaffirms its conclusion,  voiced  in
     its 1983 closure letter, that-there is no quantitative  basis for  retaining
     the current annual standard.  However, a decision to abolish the  annual
     standard must be considered in  the light of the total protection  that
     is to be offered by the suite of standards that will be established.

     The above recommendations reflect the consensus position of CASA.C.  Not
all CASAC reviewers agree with each  position adopted because of  the  uncertainties
associated with the existing scientific data.  However, a strong majority
supports each of the specific recommendations presented above, and  the entire
Committee agrees that this letter  represents the consensus position.

Secondary	Standards

     The 3-hour secondary standard was  not addressed at this review.

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                                   3

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Horstman, D. H.; Roger, L.  J.;  Kehrl,  H.  R.;  Hazucha,  M.  J.  (1986) Airway
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                                  TECHNICAL REPORT DATA
                           (Please read Instructions on the reverse before completing]
 REPORT NO.
    EPA-450/5-86-13
                             2,
                                                           3. RECIPIENT'S ACCESSION NO.
 TITLE ANDSUSTITLE
 Review  of  the National Ambient Air  Quality Standards
 for  Sulfur Oxides:„  Updated Assessment  of Scientific
 and  Technical Information Addendum  to  the 1982 OAQPS
             5. REPORT DATE
               December  1986
             6. PERFORMING ORGANIZATION CODE
                                                           8. PERFORMING ORGANIZATION REPORT NO.
                                                           10. PROGRAM ELEMENT NO.
. PERFORMING ORGANIZATION NAME AND ADDRESS
 Office of  Air and Radiation
 Office of  Air Quality Planning  and Standards
 U.  S.  Environmental Protection  Agency
 Research Triangle Park,  NC 27711
             11. CONTRACT/GRANT NO.
12. SPONSORING AGENCY NAME AND ADDRESS
             13. TYPE OF REPORT AND PERIOD COVERED
               Final	
                                                           14. SPONSORING AGENCY CODE
15. SUPPLEMENTARY NOTES
 S ABSTRACT
 This paper evaluates and  interprets the updated scientific and technical information
 that EPA staff believes is  most relevant to the review of primary (health) national am-
 bient air quality standards for sulfur oxides and  represents an update of previous
 staff conclusions and  recommendations in the 1982  sulfur oxides staff paper  to  incorpo-
 rate more recent information.   This assessment is  intended to bridge the gap between
 the scientific review  in  the EPA criteria document second addendum for particulate  mat-
 ter and sulfur oxides  and the judgments required of the Administrator in setting am-
 bient air quality standards for sulfur oxides.
 The major recommendations of the staff paper addendum include the following:   (1)  that
 the health data support  the need for sulfur dioxide (S02) standards; (2) that new data
 from controlled human  exposure studies on asthmatics and atopies warrant consideration
 of a new short-term (1-hour) standard;  (3) that the current primary and secondary
 standards (annual,  24-hour, and 3-hour) provide substantial protection against  effects
 associated with 24-hour  and annual exposures, and  some limit on peak exposures  of con-
 cern for asthmatics;   (4) that the relative'protection afforded by current vs.  alterna-
 tive standards is an important consideration in determining, what, if any, standards
 revisions may be necessary.
17.
                                KEY WORDS AND DOCUMENT ANALYSIS
a.
                  DESCRIPTORS
                                              b.lDENTIFIERS/OPEN ENDED TERMS
                           c. COSATi Field/Group
     Sulfur  Oxides
     Sulfur  Dioxide
     Air Pollution
     Particulate Matter
 Air Quality Standards
18. DISTRIBUTION STATEMENT
     Release  to  Public
19. SECURITY CLASS (This Report)
Unclassified
21. NO. OF PAGES
       88
                                              20. SECURITY CLASS (This page)
                           22. PRICE
EPA Form 2220-1 (Rev. 4-77)   PREVIOUS EDI TION is OBSOLETE;

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