450582007
              United States
              Environmental Protection
              Agency
              Office of Air Quality
              Planning and Standards
              Research Triangle Park NC 27711
EPA-450/5-82-007
November 1982
              Air
P/EPA
Review of the National
Ambient Air Quality
Standards for Sulfur Oxides:
Assessment of Scientific
and Technical Information
OAQPS 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
                           November 1982
                                                   0*1-V 4

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 The cover illustration shows two lateral views, represented schematically and by
 fluoroscope (x-ray), of the oral cavity during two breathing patterns. The top figures
 depict the mouth during typical oronasal breathing with a small air passage between
 the palate (P) and tongue (T). In this situation, much of the inhaled air enters through the
 the nose. The bottom figures depict hyperventilation, characterized by rapid oronasal
 breathing and an enlarged air space between the palate and tongue. Because the nose
 is very efficient in removing S02 , the relative penetration of S02 to more sensitive
 regions of the respiratory tract is largely dependent on the extent and character of the
 oral component of breathing under various conditions. This is an important
 consideration in evaluating controlled human exposure studies to SO 2 . which employ
 various types of  breathing and levels of exercise.
• Illustration courtesy of Dr. Donald Proctor.
         This report has been  reviewed by the Office of Air
         Quality  Planning and  Standards, EPA, and  approved
         for publication.  Mention  of trade names  or
         commercial  products Is not Intended to constitute
         endorsement or recommendation for use.

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REVIEW OF THE NATIONAL AMBIENT AIR QUALITY  STANDARDS  FOR  SULFUR  OXIDES:


           ASSESSMENT OF  SCIENTIFIC AND  TECHNICAL  INFORMATION
                           OAQPS  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
                             November,  1982

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                                    ii
                             ACKNOWLEDGEMENTS

     This staff paper is the product of the Office of Air Quality  Planning
and Standards (OAQPS).  The principal  authors include John Bachmann,
Jeff Cohen, Larry Zaragoza, and John Haines.  The report  includes  comments
from OAQPS, the Office of Research and Development, Office of Planning  and
Resource Management, 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  a number of
independent scientists,  by officials from the state agencies  of
California and Maine, by the Department of the  Interior,  and  the
Tennessee Valley Authority, and by environmental  and industrial groups
including the National Resources Defense Council,  the National  Audubon
Society, the Environmental Defense Fund, the Non-Ferrous  Smelter
Companies, the American  Petroleum Institute, and  the Utility  Air
Regulatory Group.

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                                   ill
                            TABLE OF CONTENTS

                                                                         Page
List of Figures  	    v
List of Tables 	   vi
Executi ve Summary 	  vi -j
  I.  Purpose 	    i
 II.  Background 	f	    1
III.  Approach 	    3
 IV.  Air Quality Considerations	    6
      A.  Chemical  and Physical Characteristics 	    6
      B.  Ambient Concentrations 	    7
  V.  Critical Elements in the Review of the Primary Standards 	   14
      A.  Mechanisms 	   14
      B.  Effects of Concern	   16
      C.  Sensitive Population Groups	   29
      D.  Concentration/Response Information 	   34
 VI.  Factors to  be Considered in Selecting Primary  Standards
      for Sulfur  Oxides 	   53
      A.  Pollutant Indicator, Averaging Times,  and  Form of
          the Standards 	   53
      B.  Level of  the Standard 	   60
      C.  Summary of Staff Conclusions  and  Recommendations  	   83
VII.  Critical Elements in the Review of the Secondary Standard	   88
      A.  Vegetation Damage 	   88
      B.  Materials  Damage 	   115
      C. .Personal  Comfort and Well-Being 	   124

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                                     iv
                                                                           Page
      D.  Acidic Deposition 	   125
      E.  Summary of Staff Conclusions and Recommendations 	    126
Appendix A.  Factors that Influence Penetration and Deposition
             of S02 	    A-l
      A.  Inhalation Patterns 	    A-l
      B.  Absorption by Particles	    A-5
      C.  Mechanisms of Toxicity 	    A-7
Appendix 8.  Evaluation of Evidence for Effects on
             Respiratory Mechanics and Symptoms 	    B-l
      A.  Controlled Human Exposure Studies of S02  Alone  	    B-l
      B.  Long-term Exposures to S02 Alone 	    B-6
      C.  SOg in Combination with Laboratory Particles,
          Other Gases	    B-6
      D.  Community Air Pollution	  B-10
Appendix C.  Pulmonary Function  Tests Used in Controlled
             Human Exposure Studies of $03 	    C-l
      A.  Introduction 	    C-l
      B.  Glossary of Terms 	    C-2
Appendix D.  Analysis  of Alternative Averaging Times and
             Exposure  	    D-l
      A.  Analysis of  SOg Air Quality Data 	    D-l
      B.  Modeling Analysis 	    D-7
      C.  Exposure Analysis 	  D-ll
Appendix E.  CASAC Closure Memorandum 	,	    E-l
References

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                                     LIST OF'FIGURES


Number                                   Title                                Page

4-1        Distribution of the Typical  Hour of Maximum SOg  among  153
           Monitoring Locations, 1975-1978 	    12

4-2        Monthly Arithmetic Mean SC>2  Concentrations  at  Nonurban  Sites
           in the Northeast	    12

6-1        Factors Needed to Render a Multiple-Exceedance Standard
           Equivalent to a Single Exceedance Standard  	    59

6-2        Proportion of Sites Recording a Given Annual Average S02
           Concentration, with 2 or more Short-Term S02 Concentrations
           Exceeding 0.5 ppm for 1-Hour or 0.14 ppm for 24  Hours	    80

6-3        Proportion of Sites Recording a Given Second Maximum 24-Hour
           Average Concentration, with  2 or more 1-Hour S02 Concentrations
           Exceeding 0.5 ppm 	    80

7-1        Concentration-Response Relationships for the Minimum Concen-
           tration of S02 required to produce  Foliar Injury 	   102

7-2        Corrosion Rate for Roofing and Siding (Large Sheets)	   122

7-3        Corrosion Rate for Wire Fencing 	   122

D-l        Basic Relationships Between  the Second Highest 1-Hour Value
           per Year and the Second Highest 24-Hour  Value  	   D-4

D-2        Location and Number of Expected Exceedances  per  Year of a
           1-Hour Average Value of 0.5  ppm for  a 1000 MW  Power Plant
           just Complying with a) the Current  24-Hour S02 Standard and
           b) the Current 3-Hour S02 Standard  	   D-8

D-3        Maximum 5 Concentrations  for a 1000  MW Power Plant just
           Complying with a)  the Current  24-Hour S02 Standard and
           b) the Current 3-Hour S02 Standard	   D-10

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                                          vi

                                 LIST OF  TABLES
  Number                               Title                                   Page
  1           Staff Assessment of Key Controlled Human Exposure Studies ......   xii
  2           Staff Assessment of Short -Term Epidemiological Studies .........   xiv
  4-la        Characterization of S02 Levels (in ppm) at Population-
             Oriented Monitoring Sites for Different Averaging Times .......     9
  4-lb        Approximate Conversion of ppm to pg/m^ ........................     9
  4-2        Characterization of S02 Levels (in ppm) at Source-
            Oriented Monitoring Sites for Different Averaging
            Ti mes  [[[    11
•  5-1        Effects of S02 on Respiratory Mechanics and Symptoms ......... .    20
  5-2        Major Sensitive Population Subgroups .............. ' ............    30
  5-3        Comparison of Responses in Normals, Atopies, and Asthmatics
            to S02 [[[    32
  5-4        Selected Controlled Human Studies of Quantitative
            Interest ..................... .................................    38
  5-5        Summary of Epidemiological Studies Providing Most Useful
            Concentration/Response Information for Short-Term S02
            Exposures [[[    43
  6-1        Staff Evaluation of Key Controlled Human Exposure Studies  .....    62
  6-2        Triggers of Asthmatic Attacks .................................    67
  6-3        Staff Assessment of Short -Term Epidemiological  Studies  ........    72
  7-1        Controlled S02 Exposure Studies ...............................     93
  7-2        Effects of Single 4-Hour S02  Exposure Mixtures  on Foliar
            Injury [[[     95
  7-3        Controlled Exposure Studies of Long-Term Exposures  to
            Pollutant Mixtures  ............................................     98
  7-4        Field Studies  of Chronic Ambient  S02  Exposures  ................    106
  7-5        Staff Assessment of Short-Term Vegetation  Studies .............    Ill
 A-l        Oronasal  Distribution  of Inspired Air .........................    A-4
 D-l        Current Status of Second High 1-Hour  Values  Versus  Second

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                                   vi i
                            EXECUTIVE SUMMARY

     This paper evaluates and interprets the available scientific and
technical information that the EPA staff believes is most relevant to
the  review of primary (health) and secondary (welfare) National Ambient
Air  Quality Standards (NAAQS) for sulfur oxides and presents staff
recommendations on alternative approaches to revising the standards.*
Review of the NAAQS is a periodic process instituted to ensure the
scientific adequacy of air quality standards and is required by Section
109  of the 1977 Clean Air Amendments.  The assessment in this staff
paper is intended to help bridge the gap between the scientific review
contained in the EPA criteria document "Air Quality Criteria for
Particulate Matter and Sulfur Oxides" and the judgments required of the
Administrator in setting ambient standards for sulfur oxides.  The staff
paper is, therefore, an important element in the standards review
process and provides an opportunity for public comment on proposed staff
recommendations before they are presented to the Administrator.  The
focus of this paper is on sulfur dioxide (S02), alone and in combination
with other pollutants.
     S02 is a rapidly diffusing reactive gas that i? quite soluble in
water.  It is emitted principally from combustion or processing of
sulfur containing fossil  fuels and ores.  S02 occurs in the atmosphere
with a variety of particles and other gases, and undergoes chemical  and
*The current standards for sulfur dioxide (SC>2)  are:   primary,  0.03 ppm
(80 Mg/m3) annual arithmetic mean and 0.14 ppm (365  yg/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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                                    VI11

 physical  interactions  with  them forming  sulfates and other transformation
 products.
      At elevated  concentrations, S02  can adversely affect human health,
 vegetation,  materials, economic  values, and personal comfort and well-
 being.   S02  and its transformation  products also are a major component
 of  pollution related acidic deposition and visibility degradation.  Long-
 term  average SOg  levels range from  less than 0.004 ppm in remote rural
 sites to  over 0.03 ppm in the most  polluted urban industrial  areas.  The
 highest short-term values are found in the vicinity (< 20 km) of major
 point sources.  At such sites, maximum short-term levels for 24-hour,  3-
 hour, and 1-hour averages can exceed 0.4 ppm,  1.4 ppm,  and 2.3 ppm,
 respectively.
 Primary Standards
     The staff has reviewed scientific and technical  information on the
known and potential  health effects  of S02 cited in  the  criteria  document.
The information includes  studies of mechanisms  of toxicity, effects of
high exposures to  SOg,  alone and in combination with  particles and  pollutant
gases, in controlled  human and animal  studies;  epidemiological studies of
community air pollution;  and air quality  information.  Based  on  this
review,  the  staff  derives  the  following conclusions:
1)  Due  to its high solubility,  $03 is readily  removed in the moist
    surfaces  of the nose and other  respiratory  passages.  With quiescent
    nasal  breathing, almost  all  inhaled SOg is  removed in the
    extrathoracic  (head) region.  This limits the potential for effects
    on the more sensitive  thoracic  regions of the respiratory tract.
    Factors that can increase penetration of S02 to these regions

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                                    ix

     include mouth and oronasal  breathing,  increased ventilation rates,
     and the presence of high levels of particles or fog droplets that
     may act as "carriers" for S02-
2)   Although S(>2 may produce effects through  several  mechanisms, the
     most striking acute effects observed appear to result  from
     stimulation of receptors in the tracheobronchial  region  leading to a
     reflex bronchoconstriction  mediated by the nervous  system.
3)   The major effects categories of concern associated  with  high
     exposures to S02 include:   (a)  sensory and other  non-respiratory
     responses, (b) effects on respiratory  mechanics and symptoms,
     (c) aggravation of existing respiratory and cardiovascular disease,
     (d) effects on clearance and other host defense mechanisms, and
     (e) mortality.
4)   The major subgroups of the  population  that appear likely to be most
     sensitive to the effects of 862 include:   (a) asthmatics,
     (b) individuals not diagnosed as asthmatic but with atopic disorders
     (e.g., allergies), and (c)  individuals with chronic obstructive
     pulmonary or cardiovascular disease.  Other subgroups  that may be
     somewhat sensitive include  the  elderly and children.
5)   Although a number of animal, controlled human, and  community
     epidemiological studies provide important qualitative  information on
     the range of possible responses to SOg, the most  useful
     concentration-response information comes  from a few very recent
     controlled human exposure studies and  a limited set of
     epidemiological studies reflecting British air pollution exposures
     in the 1960's and early 1970's.

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     Based on the scientific and technical review as well as policy
considerations, the staff makes the following recommendations and
conclusions with respect to primary S02 standards:
1)   Laboratory studies show that peak ambient levels of SOg, acting
     alone, can cause health effects in humans.  Consequently, a separate
     S02 standard is still appropriate.  Because the range of possible
     SOg pollution interactions may not be well captured by an
     S02-particle index, and because separate particle and $63 standards
     can be chosen with due consideration to potential interactive
     effects, the additional complexities involved  in specifying
     combination S02/particle standards do not appear warranted in
     terms  of public health protection.
2)   a)  Retention of a standard with  a 24-hour averaging time is
     recommended.
     b)  Support for an annual  standard at or near  current levels  is
     largely  qualitative.   Nevertheless,  because short-term standards
     would  not prevent  increases in annual  mean concentrations in  some
     heavily  populated  urban areas,  consideration should  be given  to
     retention of  a  primary  annual  standard for S02.
     c)  Based on  a  series  of  recent controlled human  studies,  considera-
     tion of  a new peak  (1-hour)  SC>2 standard is also  recommended.
     d)  The  24-hour  and potential  annual  and 1-hour standards  should all
     be expressed in  statistical  form;  the  decision on the  allowable
     number of exceedances for the 24-hour  and  potential  1-hour standard
     should be made  in conjunction with establishing levels for the
     standards.

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                                    XI
3)   a)  The staff assessment  of key  controlled  human  studies of peak
     (minutes to an hour)  SOg  exposures  is  summarized  in Table  1.  The table
     focuses on  those studies  involving  unencumbered or free breathing with
     exercise (chamber or  facemask studies) and  resting oral (mouthpiece)
     exposures.   In so doing,  the staff  recognizes that caution must be
     used in extending the results of these laboratory exposures to ambient
     conditions;  attention must  be paid  to the differences in natural
     oronasal  and mouthpiece breathing,  environmental conditions, and
     changes in  S02 concentration with time.  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 or above 0.5 ppm,
     changes in  functional measures are  accompanied by perceptible symptoms
     such  as wheezing,  shortness  of breath, and coughing.
     b)  Based on this  staff assessment, the range of 1-hour S02 levels of
     interest  is  0.25 to 0.75 ppm (650 to 2000 jig/m3).  The lower bound
     represents  a 1-hour level for which the maximum 5 to 10 minute peak
     exposures do not exceed 0.5  ppm, which is the lowest level  where
     potentially  significant responses in free (oronasal) breathing asthmatics
     have  been reported in the published literature as of this  writing.  The
     upper bound  of the range represents concentrations at which the risk
     of significant functional and symptomatic responses in exposed sensitive
     asthmatics and atopies appears high.  In evaluating these  data in the
     context of decision making on a possible 1-hour S02 standard,  the following
     considerations are important: (a) the significance of the  observed
     or anticipated responses to health, (b) the relative effect of S02

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                     TABLE 1.  STAFF ASSESSMENT OF KEY CONTROLLED HUMAN EXPOSURE STUDIES
SO,
Concentration  (5-60 minutes]
      Observed Effects
       Implications
   1 ppm
  0.75 ppm
  0.5 ppm
  0.25 ppm
Functional changes, possible
symptoms in resting asthmatics, oral
(facemask or mouthpiece) exposure.
Functional changes in free
breathing normal healthy
subjects, moderate to heavy  „
exercise.  No health effects.

Functional changes, symptoms in
free breathing (chamber) asthmatics,
moderate exercise.

Functional changes, symptoms
in oronasal (facemask) breathing,
asthmatics with moderate exercise
but not in asthmatics (chamber) with
light exercise.

No observed effect in free
breathing subjects.
Strong suggestion that at
this level even light exercise
for "mouth" breathing asthmatics
would result in comparable or
more marked changes.

Comparable oronasal exposures
in asthmatics, or atopies could
result in effects of significance.

Significant  effects in mild
asthmatics with moderate exercise.
Lowest level of significant
response for free breathing.
Significant effects unlikely.
                                                                                                                      H

                                                                                                                     "J
 Sheppard et al. (1980), Koenig et al.  (1980).  The second study used S0? in combination with saline
 aerosol.

2Stacy et al. (1981); Bates and Hazucha (1973).

3Sheppard et al. (1981a); Linn et al. (1982a); Koenig et al.  (1982a).

4Linn et al. (1982b).

5Kirkpatrick et al. (1982); Linn et al. (1982a).

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                                   xiii

      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 to three greater than hourly averages.
      Independent of frequency of exposure considerations, the upper bound
      of the range contains little or no margin of safety for exposed
      sensitive individuals.  However,  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.
      c)  The data do not suggest other groups that are more sensitive
      than asthmatics to single peak exposures, but qualitative  data
      suggest tnat repeated peaks might produce effects of concern in
      other sensitive individuals.   Potential interactions of S02 and 03
      have not been investigated in asthmatics and atopies.   The qualitative
      data, 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.
4)   a)  The staff assessment of the short-term (24-hour) epidemiological
     data is summarized in Table 2.  The  "effects  likely" row denotes
     concentration ranges  derived  from the criteria  document at or above
     which there appears greatest  certainty  that effects would  occur.
     The data do not,  however,  show evidence of  clear population
     thresholds,  but  suggest  that  effects  may be possible at levels  below
     those listed in  the "effects  likely"  row;  the evidence  and risks  at
     lower levels are,  however,  much less  certain.

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                                     xi v
       TABLE 2.  STAFF ASSESSMENT OF SHORT-TERM EPIDEMIOLOGICAL STUDIES
Effects/
Study
Effects Likely3
Effects Possible
Measured Sulfur Dioxide - ug/m3(ppm) -, 24 hour mean
Daily Mortality
in London1
500-1000(0.19-0.38)
Aggravation of
Bronchitis2
500-600(0.19-0.23)
< 500(0.19)
Combined Effects
Levels
500(0.19)
< 500(0.19)
^Deviations in daily mortality from mean levels examined in 3 studies  encompassing
 individual London winters of 1958-59 and 14 aggregate winters from  1958-72.   Early
 winters were dominated by high smoke and S02,  principally  from coal combustion
 emissions, and with frequent fogs (Martin and  Bradley, 1960; Ware et  al.,  1981;
 Mazundar et al., 1981).
Examination of symptoms reported by bronchitics in  London.  Studies conducted
 from the mid-1950's to the early 1970's (Lawther et al., 1970).
3CD, Table 14-8.
       b)  Based on this  staff  assessment,  the  range  of  24-hour S02  levels
       of interest are 0.14  to  0.19  ppm (365  to 500 ng/m3).   Under the
       conditions prevailing during  the London  studies  (high  particles,
       frequent  fogs,  winter),  the upper end  of the range  represents  levels
       at which  effects may  be  likely  according to the criteria document.  The
       risk of health  effects should be lower when translating these  results to
       U.S. settings with particle levels at  or below the  ambient standards.
       c)  The uncertainties with respect to  interactive effects with particles
       or other  pollutants and  nature  of effects are important margin of safety
       considerations.  In the  absence  of quantitative scientific evidence for
       a  well defined  "no effects" level, the level of the current standard is
       recommended  as  a lower bound.  This  level was previously judged to provide
       an  adequate  margin of safety  from the  same effects under consideration

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                                    XV

     here.  Qualitative data from animal  toxicology, controlled human studies
     and community epidemiology suggest risks of potential  effects  (e.g.,
     slowed clearance) as well as the existence of sensitive groups (e.g.,
     children) not evaluated in the more  quantitative studies.   These
     factors, as well as potential pollutant interactions,  exposure
     characteristics, and whether the 24-hour standard is intended to
     act as a surrogate for a 1-hour standard, should also  be considered
     in evaluating the margin of safety provided by 24-hour standards in
     the range of 0.14 to 0.19 ppm.
5)   Although the data are inconclusive and uncertain, the  possibility of
     effects from continuous lower level  exposures to SOg cannot be ruled
     out.  Given the lack of epidemiological  data suggesting long-term
     effects of S02 at or near the levels of the current  annual  standard,
     however, no quantitative rationale can be offered to support a
     specific range of interest for an annual  standard.   Nevertheless,
     air quality analyses summarized in Appendix D suggest  that  short-term
     standards in the ranges recommended  in this paper would not prevent
     annual levels in excess of the current standard in a limited number
     of heavily populated urban areas. Because of the possibility of
     effects from a large increase in  population exposure,  consideration
     should be given to maintaining a  primary  annual  standard at or above
     the level of the current standard.
6)   Analysis of alternative averaging times to date suggest that while
     any single standard might not be  a suitable surrogate  for other
     averaging times, implementation of the current  suite of primary and
     secondary S02 standards (annual,  24-hour,  3-hour) provides  substantial
     protection against the direct health  and  welfare  effects identified

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                                   xvi

     in the scientific literature as being associated with ground level
     S02 air quality.  This permits the consideration of reaffirming the
     existing S02 standards as a reasonable policy option, following the
     current criteria and standards review.  Factors favoring such an
     option include the substantial improvements likely in information on
     1-hour effects over the next few years, the uncertainties in long-term
     effects data, the possibility of substantial changes in S02 control
     strategies prompted by regional effects, and the.practical  advantages
     of not requiring premature formulation and implementation of a new
     S02 regulatory program associated with revising standards at this
     time.
Secondary Standards
     The staff examined information in the criteria document relevant to
the review of the secondary standards.  Categories of welfare effects
examined include effects on vegetation, materials, personal  comfort and
well-being, and acid deposition.   Major staff conclusions and
recommendations are summarized below.
1)   a)  Damage to vegetation by  S02,  resulting in economic  losses in
     commercial crops,  aesthetic  damage to cultivated trees,  shrubs and
     other ornamentals,  and reductions in  productivity,  species  richness
     and diversity in natural  ecosystems,  constitute effects  on  public
     welfare in impacted areas.   Such  effects are associated  with both
     peak  and short-term (minutes to hours)  and long-term (weeks to
     years) exposures to S02.
     b)  Given  the available data on  the acute effects  of S02 on plants
     (growth and yield  and  foliar injury),  a 3-hour standard  at  or below
     the level  of the current  secondary standard (0.5 ppm) may be needed

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                              xvii

to  protect  vegetation.  If a 1-hour primary standard is chosen that
provides equivalent or better protection, then the averaging time
and level of the secondary standard can be made equal to the primary
standard.   In the absence of a primary standard that provides adequate
protection  for vegetation, a 3-hour secondary standard is recommended.
c)   Available data on the effects of long-term S0£ exposures of
vascular plants (e.g., trees, shrubs, crops) suggest the possibility
of  changes  in species richness and diversity, reduced growth over
extended periods, and premature needle drop.  However,  these data
are weak and not developed well  enough to provide the principal
basis for selecting the level of a long-term SO? standard.  Existing
information, thus, cannot be used to show significant effects on
vascular plants at annual  SOg levels below the current  primary
annual standard,  but does  support the need to protect against the
effects of prolonged S02 exposure by limiting long-term S02
concentrations much above  this  level.
d)  Current long-term S02  concentrations  over large areas  of the
northeast exceed  levels  that  may be associated with effects on non-
vascular plants (e.g., lichens,  mosses).   Given uncertainties re-
garding the extent and importance of these potential  effects on
natural  ecosystems and the regional  character of the  exposures,  the
staff recommends  that  the  effects of SOg  on  non-vascular plants  be
considered in the larger  context of regional  acid deposition -
visibility - fine particle strategies.  As such,  no separate long-
term secondary standard  for non-vascular  plants is recommended at
this time.

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                                   XVTI1
 2)    a)   Elevated  long-term S02  concentrations  in the presence of
      moisture  can  damage  a  number of materials  including:  exposed
      metals, paints,  building materials, statuary, paper, leather, and
      textiles.   Control strategies have resulted in marked improvements
      in  long-term  S02 levels over the past 13 years, which the criteria
      document  associates  with substantial benefits.  While the available
      data are  limited and do not permit definitive findings with respect
      to  the potential  costs of S02 related material damage or provide
      clear quantitative relationships for the full range of potentially
      affected materials,  they generally support the need for limiting
      long-term SOg concentrations in urban areas.
      b)  Analysis of  existing air quality data suggests that without
      the primary annual standard, long-term urban air quality could
      deteriorate and  in a number of large urban areas might exceed the
      current annual standard.  Therefore,  consideration should be given
      to a long-term secondary SOg standard at or below the level  of the
      current annual primary standard of 0.03 ppm (80 ug/m3) to protect
      against materials damage effects.
3)    The staff concludes that a secondary  S02 standard is not needed to
     protect against  effects on personal  comfort and well-being.
4)   The available  scientific information  indicates  that the  current 3-
     hour and annual  standards  provide  reasonable protection  against  the
     direct  welfare effects  associated  with  ambient  S02-  In  essence,  the
     data support maintenance of  S02  standards  at or  below  levels  of  the
     current  standards.
5)   The acid  deposition issue  will not  be addressed  directly  in this
     review  of  the  sulfur  oxides  standards.

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 REVIEW OF THE NATIONAL AMBIENT AIR QUALITY STANDARDS FOR SULFUR OXIDES:
            ASSESSMENT OF SCIENTIFIC AND TECHNICAL INFORMATION
                            OAQPS STAFF PAPER

I.   PURPOSE
     This paper evaluates and interprets the most relevant  scientific
and technical information reviewed in the draft  EPA document  "Air
Quality Criteria for Particulate Matter and Sulfur Oxides"  (EPA, 1982a)
in order to better specify the critical  elements which  EPA  staff
believes should be considered in the possible revision  of the primary
and secondary National  Ambient Air Quality Standards (NAAQS)  for sulfur
oxides.  This assessment is intended to help bridge the gap between  the
scientific review contained in the criteria document and the  judgments
required of the Administrator in setting ambient standards  for sulfur
oxides.  As such, particular emphasis is placed  on identifying those
conclusions and uncertainties in the available scientific literature
that the staff believes should be considered in  selecting averaging
time, form, and level  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.
II.  BACKGROUND
     Since 1970 the Clean Air Act,  as amended, has provided authority
and guidance for the listing of certain  ambient  air pollutants  which may
endanger public health  or welfare and the setting and revising  of NAAQS
for those pollutants.   Primary standards  must be based  on health effects

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 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 standard, based on his judgment
 regarding the  implications of all the health effects evidence and the
 requirement that an adequate margin of safety be provided.
     Secondary ambient air quality standards must be adequate to protect
 the  public welfare from any known or anticipated adverse effects
 associated with the presence of a listed ambient air pollutant.  Welfare
 effects,  which are defined in section 302(h) of the Act, include effects
 on  vegetation, visibility, water, crops, man-made materials,  animals,
 economic  values and personal comfort and well-being.  In specifying a
 level or  levels for secondary standards  the Administrator must determine
 at which  point the effects become "adverse" and base his judgment on the
welfare effects criteria.
     The  current  primary standards for sulfur oxides (to protect public
health) are 0.03  parts per million (ppm  or 80 micrograms per  cubic meter

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 [yg/m3])  annual arithmetic mean, and 0.14 ppm (365 ug/m3), 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 yg/m3), 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,
 S02 is the  current indicator for the sulfur oxides standards.
      Preliminary drafts of this paper were reviewed by the Clean Air
 Scientific  Advisory Committee (CASAC) in April  and August, 1982.  This
 final product incorporates the suggestions and recommendations of the
 CASAC as well as other appropriate comments received on the initial
 drafts.  The CASAC closure letter on the staff paper (Goldstein,
 1983) is reproduced in Appendix E.
 III.  APPROACH
     The approach used in this paper is to assess  and integrate information
 derived from the criteria review in the context  of those critical  ele-
 ments which the staff believes should be considered in the review of the
 primary and secondary standards.   Particular attention is  drawn to those
 judgments that must be based on  the careful  interpretation of incomplete
 or uncertain evidence.  In such  instances,  the paper states the staff's
 evaluation of the evidence as it  relates to a specific judgment,  sets
 forth appropriate alternatives that should  be considered,  and recommends
 a course of action.
     Sections IV and V review and integrate important  scientific and
technical  information relevant to standard-setting.   Because sulfur
oxides are often studied  in  combination  with  particulate matter,  much of
the more important  literature has  already been assessed  in  the  companion

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staff paper on particulate matter (EPA, 19825).  Where possible,
pertinent references are made to the appendices of that paper with only
summaries in the main body of this paper.  Section IV presents relevant
features of historical and current U.S. air quality to-support discussions
of both primary and secondary standards.  Section V addresses the essen-
tial elements with regard to the primary standards; these include the
following:
     1)  identification of possible mechanisms of toxicity;
     2)  description of effects and judgments of critical effects
         of concern for standard-setting;
     3)  identification of most sensitive population groups;  and
     4)  discussion of controlled human and community studies re-
         lating level (s) and duration(s) of exposure to indicators
         of health effects.
     Drawing from the discussion in Sections IV and V, Section VI
identifies and assesses the factors the staff believes should be
considered in selecting averaging times, form, and level  of  primary
standards.  Preliminary staff recommendations on alternative  policy
options in each of these areas are also presented.
     Section VII examines information in the criteria document the staff
believes is most relevant with respect to secondary standards and
focuses on the direct  effects of S02 on vegetation, man-made  materials,
and personal  comfort and well-being.  Indirect effects on visibility  and
climate and acid deposition are not discussed.  The elements  addressed
include:
     1)  description of effects and judgment of the critical
         effects of concern for standard-setting;

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     2)  identification of causal mechanisms;
     3)  studies relating level(s) and duration(s) of exposure to
         indicators of effects; and
     4)  factors to be considered in selecting averaging times, form,
         and level  of secondary standards.
Preliminary staff recommendations on policy options for secondary
standards are also presented.
     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., $03) are not commonly found in the  atmosphere.   The effects  of
the principal atmospheric transformation products of SOg (i.e., sulfuric
acid and sulfates)  are discussed  in the companion staff paper  on  particu-
late matter.

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IV.  AIR QUALITY CONSIDERATIONS
     This section summarizes the relevant chemical  and physical
properties of S02 as it occurs in the ambient atmosphere and briefly
characterizes ambient S02 levels to provide perspective for subsequent
interpretation of health and welfare studies.  More detailed discussion
of these areas is contained in Chapters 2 and 5 of  the criteria  document
("CD", EPA, 1982a); supplemental analyses of air quality relationships
are also outlined in Appendix D.
A.   Chemical and Physical  Characteristics
     S02 is a rapidly diffusing reactive gas that is quite soluble in
water, readily dissolving to form sulfurous acid (H20'S02), a weak acid
that dissociates into hydrogen (H+), sulfite (SOj3), and bisulfite
(HS03") ions.  The solubility of S02 and the ratio  of sulfite to
bisulfite ions in aqueous solution increase significantly with
increasing pH (and local ammonia concentration).  The sulfite/bisulfite
ratio is about 1:1000 at a  pH of 7.4 (as in some body fluids) (CD, Figure 2-3).
Total dissolved S02 increases by a factor of about  104 from pH 3 to pH 7.
     SOg occurs in the ambient air with a variety of particles and
other gases.  The potential  chemical and physical interactions among these
numerous substances are complex and incompletely characterized (CD,  pp.
2-62 to 2-69).  The following generalizations are of some significance
in evaluating the health and welfare effects of S02 in complex mixtures:
1)   S02 is oxidized by a number of homogenous (gas-phase) and
     heterogeneous (liquid  or solid surface phase)  mechanisms to form
     sulfuric acid and, ultimately, other sulfates.  S02 may also
     reversibly dissolve in  or attach to particles  or may form stable
     sulfite complexes (CD,  pp.  2-38 to 2-40).

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2)   At low  relative humidities, ambient S02 may adsorb onto the
     surfaces of dry participate matter, but the extent of adsorbtion is
     limited by the available particle surface area.  Because fine mode
     (< 2.5 um) aerosols usually contain most of the available surface
     area, adsorbed S02 would most likely be found in the fine mode
     (CD, p. 2-71).  Except in the case of particles of unusually high
     surface/mass ratios, or in the presence of pollutants promoting
     oxidation to sulfate, the amount of SOg adsorbed onto dry particles
     may be only a small fraction of total fine particle mass (Schryer
     et al., 1980).
3)   At higher relative humidities, SOg will dissolve into available
     droplet aerosol.  S02 solubility in such droplets is greater with
     lower temperature and lower droplet acidity (e.g., with elevated
     ammonia levels).  Unless converted to sulfates, the SOg may be
     released from the droplet when it encounters lower gas phase S02
     concentrations.  At low ambient ammonia levels (< 1 part per billion
     [ppbj), the ultimate capacity for droplet absorption of S(>2 is
     limited to < 1% of droplet mass (Larson et al., 1978; Scott and
     Hobbs, 1967).   Because of their low pH, little interaction  would be
     expected between various ammonium sulfate or sulfuric acid  aerosols
     and S02-
B.   Ambient Concentrations
     S02 concentrations can be examined on three geographical  scales:
1) the vicinity (<  20 km) of major point sources, 2) urban areas, and
3) multi-county to  multi-state regions.  As indicated by the criteria
document (CD, Chapter 5), S02 levels in urban areas and near many point
sources have been markedly reduced by control  programs over the  past 10

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 to  15 years.  Current  (1979-80) S02 air quality data for approximately
 900 population- and source-oriented sites with continuous monitors are
 summarized  in Tables 4-1 and 4-2.  These sites reflect a more limited
 number  of counties and urban areas (approximately 500 total count'ies)
 with multiple S02 monitors. Annual SOg levels are less than 0.03 ppm
 (80 ug/m3)  in 99% of both site categories.  Although the distribution of
 annual  averages are similar in population- and source-oriented sites,
 short-term  concentrations (£24 hours) tend to be higher, at source
 oriented sites.  Less than 5% of population-oriented sites had second
 maximum 24-hour levels in excess of 0.14 ppm (370 yg/m3); over 5% of 24-
 hour second maxima at source-oriented sites exceeded this value.
 Similarily, less than 1% of population-oriented sites had second maximum
 3-hour  averages in excess of 0.5 ppm, while over 5% of second 3-hour
 maxima  at source-oriented sites exceeded 0.5 ppm.
     Tables 4-1 and 4-2 also contain two methods of displaying the 1-
 hour average SOg concentrations observed during 1979-80 at these
 sites.  The first method consists  of determining the distribution of
 maximum and second highest 1-hour  average concentrations.  This
 distribution corresponds with similar distributions at source- and
 population-oriented sites for 24-hour and 3-hour averages.   The  second
 approach gives the frequency distribution of the 99th percentile of  all
 hourly $03 values  at  these sites.
     As indicated  in  the tables, in  50%  of  the  sites,  the annual  maximum
 1-hour S02 concentration would  not exceed 0.16  ppm  (population-oriented)
to 0.32 ppm (source-oriented).  Maximum  hourly  levels  at  sites with  the
highest  concentrations  can  reach substantial  values  (0.7-2.3 ppm), but
such levels  occur  less  than  1%  of the  time  for  99%  of  all  sites.

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                  TABLE 4-la.  CHARACTERIZATION OF SO, LEVELS (IN PPM) AT POPULATION-ORIENTED
                                MONITORING SITES FOR DIFFERENT AVERAGING TIMES*
Distribution of the
Summary Statistic
Minimum
50th Percent! le
95th Percentile
99th Percentile
24-Hour Average
Annual
Average
0.00
0.01
0.02
0.03
Maximum
0.00
0.06
0.14
0.21
Second
Maximum
0.00
0.05
0.11
0.14
3-Hour Average
Maximum
0.00
0.12
0.34
0.45
Second
Maximum
0.00
0.11
0.28
0.40
Maximum
0.00
0.16
0.45
0.70
1-Hour Average
Second
Maximum
0.00
0.14
0.38
0.53
99th
Percentile
0.00
0.06
0.13
0.20
*Source:  1979-1980 SAROAD data base, 24- and 3-hour averages  derived from running averages.   Based on 761 site-years
at 521 sites.
                              TABLE 4-lb.   APPROXIMATE CONVERSION OF PPM TO yg/nT FOR S02
PPM
0.01
0.02
0.03
0.04
0.05
0.1
0.5
0.75
1.0
Approximate yg/m
25
50
80
100
130
260
1300
2000
2600

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                    TABLE 4-2.   CHARACTERIZATION OF SO, LEVELS  (IN PPM) AT SOURCE-ORIENTED
                                     MONITORING SITES FOR DIFFERENT AVERAGING TIMES*
24-Hour Average
Distribution of the
Summary Statistic
Minimum
50th Percentile
95 Percentile
99 percentile
Annual
Average
0.00
0.01
0.02
0.03
Maximum
0.00
0.07
0.23
0.41
Second
Maximum
0.00
0.06
0.18
0.28
3-Hour Average
Maximum
0.01
0.22
0.77
1.36
Second
Maximum
0.00
0.18
0.58
1.13
Maximum
0.01
0.32
1.33
2.30
1-Hour Average
Second
Maximum
0.00
0.27
1.00
1.62
99th
Percentile
0.00
0.08
0.27
0.49
*Source:  1979-1980 SAROAD data base,  24-and  3-hour  averages  derived  from  running  averages.   Based  on'581  site-years
at 364 sites.

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                                    11

      The typical  diurnal  behavior  of SOg  is shown  in Figure 4-1, which
 represents a frequency  distribution of maximum  hourly S02 concentrations
 at sites that are with  levels  among the nation's highest  (Frank et al.,
 1981).   Maximum SO-2  levels most  frequently occur in the late morning to
 early afternoon during  all seasons; this  may be of some interest in
 evaluating exposures  for  both  humans and  vegetation.  The pattern is
 consistent with elevated  emission  releases characteristic of major SOg
 emitters in combination with the diurnal  variance in atmospheric
 turbulence.   Substantial  variance  from this typical pattern can occur
 for sites  involving complex terrain, marked diurnal emissions trends, or
 other exceptional  atmospheric  flows and source operating characteristics
 (Frank et  al.,  1981).  On a seasonal basis, monthly average S02 levels
 tend to  be higher  in winter months in those areas affected by S02
 emissions  from  space heating,  but  like diurnal  patterns, seasonal
 variation  is  dependent on site-specific source,  terrain, and
 meteorological  characteristics (CD, p. 5-18).
      Although non-urban levels of S02 are substantially lower than those
 found in urban  or  source oriented sites,  in some areas  S02 levels  appear
 clearly  in excess  of those expected in most natural settings (< 0.004
 ppm,  CD, p. 5-5).   Data from the 54 station non-urban SURE network
 indicate that S02  concentrations, like those  of  its transformation
 products (sulfates),  are elevated on a regional  scale in large  portions
 of the northeastern U.S. (Figure 4-2).  .If the data from this  network
 are  representative, ground level  S02 concentrations in  large portions  of
the northeast (0.01-0.02 ppm,  or 25-50  yg/m3) are substantially  higher
than sulfate levels in the same region  (6-12 yg/m3), on  both  a  chemical
equivalent and mass concentration basis  (Mueller et  al.,  1980).  As

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                  TIME of OW, hr
               om              pm
               6   9  NOON 3   6   9   12
           I    I    I
          1st QUARTER
          2nd QUARTER
          3rd QUARTER-
          4th QUARTER
          ANNUAL
                           I
                               I
               6   9 NOON  369
              am             pm
                 TIME of DW. hr
12.
Figure 4-1.   Distribution of the  typical hour
of maximum SO, among 153 monitoring  locations,
1975-1978 (Fr&nk et al., 1981).   Sites from
EPA National Air Data Bank include all those
with 2:6000 hourly observations/year  with annual
average for at least 1  hour 21.0.03 ppm S0?.
                 Figure 4-2.  Monthly Arithmetic Mean Sulfur Dioxide
                 Concentrations at Nonurban Sites in the Northeast
                 (Mueller et al., 1980).

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                                    13

evidenced by the same network,  non-urban  average  and peak ozone  levels
were also elevated in this region.   Unlike S02, which on a  regional
scale is highest in winter months,  both ozone and sulfates  tend  to have
summer maxima.

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                                    14

 V.   CRITICAL ELEMENTS  IN THE REVIEW OF THE PRIMARY STANDARD
 A.   Mechanisms
     This  section discusses the factors that influence deposition and
 clearance  of S02 in the respiratory tract and outlines the mechanisms by
 which S02,  alone and in combination with other factors, may initiate
 physiological and pathological responses.  This discussion is intended
 to aid  interpretation of the role of S02 in producing responses observed
 in humans.
     1.  Deposition and Clearance
     An evaluation of the mechanisms by which S02, alone and in
 combination with particles, may affect human health must recognize the
 importance of deposition and clearance of S02 in the major regions of
 the respiratory tract.  As described in the criteria document, the
 respiratory tract can be classified according to three major regions:
 1) extrathoracic, including the passages of the nose,  mouth, nasal
 pharynx, oral pharynx, epiglottis, and larynx,  2) tracheobronchial,
 including the ciliated airways from the trachea to the terminal
 bronchioles, and 3) alveolar or pulmonary,  including the respiratory
 bronchioles, alveolar ducts and sacs,  atria,  and alveoli  (CD,  p. 1-52).
     Due to its high solubility in aqueous  solutions of near neutral
 acidity (e.g.,  physiological  fluids),  SC>2 is  readily absorbed  upon
 contact with the moist surfaces of the nose and other  upper respiratory
passages (CD, p. 1-54).   Deposition of S02  in the airways  of the upper
extrathoracic region determines how much SOg  is available  for
penetration to  the  more  sensitive  larynx and  the tracheobronchial  and
alveolar regions.  S02 (1  to  50 ppm)  is almost  completely  absorbed
(_> 99%)  by  nasal  removal under resting conditions  in both  man  and

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                                     15
 laboratory animals  (Frank  et  al.,  1969;  Speizer and  Frank,  1966b;
 Brain,  1970).   No evidence for  decreased nasal removal was  found even
 after six hours at  25  ppm  (Andersen  et al.,  1974).
      Factors that can  increase  penetration and deposition of S02 in the
 respiratory tract over that observed for quiescent nasal breathing
 include mouth  and oronasal  breathing, increased ventilation rates, and
 the  presence of airborne particles that  may  act as "carriers" for SOg.
 These factors,  critical in the  interpretation of studies of the health
 effects of SC>2,  are summarized  briefly in Appendix A.
      Although  most  inspired S02 appears  to be readily absorbed into
 moist upper respiratory tract surfaces,  about 15 and 30% of inhaled S02
 is expired in  resting  human subjects for nose and mouth (only)
 breathing,  respectively (Melville, 1970).  The results of Speizer and
 Frank  (1966b)  suggest that the expiration may be the result of partial
 desorption  of  inhaled S02-  Absorbed S02 is rapidly transferred into the
 circulatory system from all regions of the respiratory tract,  a small
 fraction of which may be desorbed into the alveolar region  from the
blood (Frank et al., 1967).
     In body fluids, S02 rapidly forms  a solution  of bisulfite and  (in
smaller quantities)  sulfite.  Animal  and in vitro  studies  indicate  that
these substances can reversibly  react with compounds  containing
disulfide  linkages (e.g.,  proteins) to  form S-sulfonate (sulfonation
reaction)  (Guunnison and Palmes, 1973).   The  predominant metabolic  fate
of the sulfur/sulfonate complex  appears  to be oxidation to  sulfate  as
mediated by the enzyme  sulfite oxidase  and excretion  in urine  (Gunnison
and Palmes, 1973; Yokoyama  et  al.,  1971).

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                                    16

     2.  Mechanisms of Toxicity
     SC>2 may produce physiological and, ultimately, pathological effects
by mechanisms that depend upon amount and site of deposition, reactions
with biological materials, and sensitivity of the affected region.  The
major mechanisms of potential interest in S02 toxicity are discussed in
Appendix A.  They can be briefly categorized as follows:
     a)  irritation of tissues or nerve receptors leading to
         airway/functional changes;
     b)  alteration of clearance and other host defense mechanisms;
     c)  tissue irritation or damage leading to morphological
         alterations; and
     d)  reactions with important cellular constituents.
B.   Effects of Concern
     This section identifies and describes the principal  effects that
may be associated with S02, alone and in combination with other
pollutants.  Evidence for such associations is drawn from animal
toxicology, controlled human exposure and community epidemiological
studies.*  Based on these data, as summarized in the criteria document,
the following effect areas appear to be of most interest:
     1)  sensory and other non-respiratory responses;
     2)  respiratory mechanics and symptoms;
     3)  aggravation of existing respiratory  and cardiovascular
         disease;
     4)  clearance and other host defense mechanisms;
*Frequent reference is made to previous staff evaluations of these data
as presented in Appendix B of the companion staff paper on particulate matter
(EPA, 1982b).

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                                     17

      5)  potential  mutagenesis/carcinogenesis;  and
      6)  mortality.
 The major implications of the available  literature  related  to each  of
 these effects areas are summarized  below.
      1.  Sensory and Other Non-Respiratory Responses
      Sensory and certain other  non-respiratory  responses to sulfur
 oxides have been studied in controlled human exposures.  In Soviet
 tests, the average  odor threshold for S02 was 0.8 to 1 ppm  (Dubrovskaya,
 1957).  In controlled U.S.  tests, the odor threshold was 0.47 ppm (A.D.
 Little,  Inc. 1968).   Under  more typical conditions, most individuals
 would probably  be less  responsive to such levels (CD, p. 13-5).  The
 sensitivity of  the  eye  to  light during dark and light adaptation is
 increased  by short-term SOg exposures as low as 0.23 to 0.34 ppm
 (Dubrovskaya, 1957;  Shalamberidze, 1967).  Electroencephalographic
 measurements  of  alpha rhythms show an interruption of these brain waves
 at 20-second  SOg  exposures  of 0.3 to 1 ppm (Bushtueva,  1962).
     These  effects of sulfur oxides have no known implications  for
 health, and  near  these threshold levels bear little  obvious relation to
 personal comfort  and well-being.  Given the odor thresholds, it  is
 possible that subjects might detect the presence of  S02 at  levels on the
 order  of 1 ppm SOg in controlled human studies  involving nose  breathing,
 making truly double blind experiments difficult.
     2.   Respiratory Mechanics and Symptoms
     Effects on respiratory mechanics can  range  from mild transient
 changes of little apparent direct  health  consequence to  incapacitating
 impairment of breathing.  Symptomatic effects also vary  in  severity,  but
at minimum, indicate a biological  response.

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                                     18

      a)  S02 Alone
      Few animal studies have evaluated the acute effects of S02 exposure
 on pulmonary mechanics (CD, Table 12-3).  The most sensitive species
 tested is the guinea pig; the lowest 1-hour exposure to produce an
 increase in flow resistance in any animals tested was 0.16 ppm (Amdur
 and Underhill, 1970).  Sensitivity varies with experiment and later
 studies in the same laboratory found no responses at higher levels (0.2
 to 0.8 ppm) (Amdur et al., 1978b).  The collective experience of guinea
• pig exposures to S02 alone suggests the following:
 1)   Response of individual animals varies widely,  with on the order of
      10% of animals tested from 1964-1974 considered as "susceptible"
      (Amdur, 1964, 1973,  1974).
 2)   Negative findings below 1 ppm in later years may be due to
      differences in strains of animals (CD, pp.  12-15 to 12-16).
 3)   The time course of guinea pig response (response increased with
      exposure, slow to recover) appears different from the short-term
      responses seen in resting humans and cats and  dogs (Corn et  al.,
      1972;  Frank and Speizer,  1965;  Nadel  et al., 1965).   .
 4)   The lowest level  at  which response occurs is substantially below
      those  seen for other animals  and humans where  exposure was also
      through predominantly quiescent  nasal  breathing.
 5)   Exposure conditions  (intrapleural  catheter,  restraints,  nasal
      breathing,  effects of prior anesthesia) may  increase  or otherwise
      alter  response (MAS,  1978,  p.  7-14).
 In essence,  it is  clear that the guinea pig results  should be
 interpreted  cautiously  when drawing qualitative conclusions  with  respect
 to effects  in  humans.

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                                    19

     A number of controlled human exposure studies have examined the
acute effects of S02, alone and in combination with other pollutants, on
respiratory function and on subjective symptoms indicating discomfort.
The more important findings of a collection of such studies are summarized
1n Table 5-1.  The studies vary in a number of characteristics (e.g.,
exposure mode, exercise levels) that are important when considering more
quantitative observations than are intended in this section.  These as
well as other studies of interest are more fully discussed in  Chapter 13
of the criteria document and in Appendix B of this paper.  Those most
useful for quantitative conclusions are also discussed in Section V-D of
this paper.
     Key conclusions with respect to the effects of SC>2 derived from the
evaluation in Appendix B include:
1)   The major observed response to short-term exposures to S02 appears
     to be bronchoconstriction, usually evidenced in increased airway
     resistance and decreased expiratory flow rates.  Asthmatics, and to
     a lesser extent, atopic individuals with allergic responses but no
     clinical manifestations of asthma, are substantially more sensitive
     to these effects.  Significant increases in airway resistance and
     occurrence of symptoms such as shortness of breath and wheezing
     have occurred in short-term mouthpiece,  face mask and/or  free
     breathing exposures to 0.5 to 0.75 ppm S02 with moderate  exercise
     (Sheppard et al., 1981a; Kirkpatrick et  al., 1982;  Linn et al.,
     1982a,b), but not at rest or with light  exercise (Sheppard et al.,
     1981a; Linn et al., 1982a).
2)   The time course of S02 induced reflex bronchoconstriction varies
     with exercise, method, and duration of exposure,  and subject

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 Exposure
                                Observations*
                                                                                          References
   He'd 11 hy_Subjec ts

 5 ppiu SO.,, 3-180 minutes,
 mostly  resting, various
 routes
 1-4 ppin SO.,  3-30 minutes,
 mostly resting, various
 rou tes
 0.37-0.75 ppm SO?, 15-180
 minutes,  various routes,
 activities
 Host studies  report changes in function measurements,
 bronchoconstriction.  Increased symptoms: throat
 irritation and dryness, cough.
 Mixed  results; some subjects appear more sensitive;
 some changes  in function measurements indicating
 bronchoconstriction (e.g., increased airway resistance,
 decreased HEFR, MMFR); some subjects report symptoms
 such as  throat irritation; usually greater response
 with oral breathing, exercise.

 5  studies - No effects on function, symptoms,
 equal  to or less than 0.5 ppm SO-.

 2  studies - Decrease In MEFR, FVC. FEV, n, HMFR at
 0.75 ppm, free breathing with moderate't« heavy exercise.
Amdur et al.  (1953); Andersen et  al.  (1974);  Frank  et  al.
(1962); Kreisman et al.  (1976); Lawther et al.  (1975);
Melville (1970); Nadel et  al.  (1965);  Newhouse  et al.  (1978);
Sheppard et al. (1980);  Sim and Pattle (1957);  Snell and
Luchsinger (1969); Tonono  (1961)

Amdur et al.  (1953); Burton et al.  (1969); Frank et al.
(1962); Kreisnan et al.  (1976); Lawther et al.  (1975);
Melville (1970); Nadel et  al.  (1965);  Sim and Pattle (1957);
Sheppard et al. (1980);  Snell  and Luchsinger  (1969);
Tomono (1961); Koenig et al.  (1982b)
Bates and Hazucha  (1973); Bedi  et  al.  (1979);  Bell  et  al.
(1977); Horvath and Folinsbee (1977);  Jaeger et al.  (1979);
Snell and Luchsinger  (1969); Stacy et  al.  (1981)
   Atopic Subjects

 1  ppm SO,, with  and without
 1  Pig/or NaCl  (0.9  MO) drop-
 lets.   Rest and  exercise,
 10 to 40 minutes
  Asthmatic Subjects

1-5 ppm SO., 5-150 minutes,
mostly at rest, oral
exposures
1 ppm SO, + 1 mg/mj NaCl
(0.9 unO'droplets. RH 75S.
oral, rest and exercise,
40-60 minutes

0.25 to 0.75 ppm SO.. 5-60
minutes,light to moderate
exercise, free breathing
(chamber or face mask)
0.1-0.5 ppm SO., 5-180
minutes, various activity
levels, oral exposures
At rest, I of 7 subjects had increased airway resistance.
With exercise, decreased flow and other parameters
suggesting effects in central and small airways.
No difference between S0? + NaCl, S02 alone.
Sheppard et al. (1981a); Koenig et al.  (1982a)
                                                                  ro
                                                                  o
Harked changes In respiratory function In most subjects
(airway resistance,  others).   Numbers reporting
wheezing, shortness  of breath, dyspnea Increase with
dose, exercise; some require  medication.

Decreased flow, other parameters suggesting effects In
central and small airways;  with exercise  5 of B
experienced wheezing, 3 of  8  shortness of breath.
No effect at 0.25 ppm.  At 0.5 ppn,  no response at
lowest exercise rate;  with higher exercise, oronasal
(face mask) exposure resulted In increased airway
resistance in all subjects, symptoms in 4 of 6.
At 0.75 ppm and moderate exercise, chamber exposure
resulted in significant increase In both symptoms
and airway resistance; functional effects
less than those for similar mouthpiece exposures.

Incremental increases  in airway resistance in some
subjects at all levels, slight change in MMFR,
resting subjects; wheezing, shortness of breath in
some subjects;  potentiated by exercise.
Sheppard et al. (1980); Sheppard et al. (1981a);
Kirkpatrick et al.. (1982)
Koenig et al. (1980. 1981)
Linn et al. (1982a.b); Klrkpatrick et al. (1982)
Jaeger et al. (1979); Sheppard et al. (1981a); Linn et  al.
(1982a); Klrkpatrick et al. (1982)
*lun«j function tests listed here are briefly described In Appendix C.

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                                    21

     sensitivity.  In normal resting subjects, maximal response is rapid
     (5-10 minutes) and decreases quickly following exposures.  Recovery
     may be delayed after exercise and appears longer for sensitive
     asthmatics and subjects with apparent bronchial obstruction
     (Sheppard et al., 1981a; Gokemeijer et al., 1973).
3)   Preliminary evidence suggests S02 may increase sensitivity to
     subsequent challenge by other bronchoconstrictors (Islam et al.,
     1972; Reichel, 1972).  This might explain the as yet unreplicated
     finding of delayed symptomatic response following S02 exposure
     (Jaeger et al.,  1979).
4)   A gradual rise in SOg exposure appears less likely to result  in
     reflex bronchoconstriction than a rapid "step function" increase
     (Andersen et al., 1974; Schachter,  1982).  In the ambient
     environment, such an increase might occur by moving from indoors to
     outdoors or by a meandering source  plume.  Because the response is
     probably more dependent on dose at  sensitive receptors than on
     ambient S02 levels,  the onset of  exercise may also produce a  "step
     function" increase in "effective" SOg  levels at these receptors;
     this is evidenced by the marked increase  in airway resistance
     following exercise,  even in subjects who  were just previously
     exposed to the same  level  at rest for  30  minutes  at  levels (0.5 or
     0.75 ppm) that did not produce functional changes  (e.g.,  Stacy et
     al., 1981;  Koenig et al.,  1982a).
5)   Longer-term studies  (6 hours to 6 days) have found no effects of
     continuous  exposure  to 0.3 ppm S02  in  apparently  resting  normal
     subjects  or subjects with  prior airway  impairment  but provide some
     evidence  of changes  in nasal  cross-sectional  area  and pulmonary

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                                    22

     function changes at 1 ppm (Andersen  et  al.,  1974;  Weir  and
     Bromberg, 1972).  Suggestion of a progressive decrease  in functions
     was observed at 3 ppm.  In these extended studies, impaired  or
     bronchitic subjects did not appear more sensitive.than  normals,  but
     this is confounded by large day-to-day  variation  in baseline lung
     function (Weir and Bromberg, 1972) or use of medication and
     incomplete reporting of techniques (Reichel, 1972).
6)   Chronic animal studies provide no evidence supporting concern over
     direct SOg effects on respiratory mechanics  of long-term average
     exposures to even high ambient levels (CD, Table  12-3). Repeated
     peak exposures, however, have not been  properly assessed.
7)   Although particles may potentiate the effect of S02 by  increased
     penetration or chemical  reaction, controlled human exposures have
     found mixed results, with little convincing  evidence that such
     enhancement occurs for laboratory aerosol  conditions at realistic
     peak aerosol  levels (Appendix B). Ambient conditions that might
     tend to maximize interactions between S02 and particles (cold
     temperatures, fog droplets,  substantial  NOg, NH3)  have  not been
     systematically examined in the laboratory.
8)   Combinations  of SOg and other atmospheric gases (principally 03)
     have also produced mixed results. One  study (Bates and Hazucha,
     1973) reported marked synergism for  S02 plus 03,  both at 0.37 ppm,
     but follow-up work in several  laboratories failed  to confirm the
     initial  findings.  The weight of evidence suggests some reason for
     caution with  respect to mixtures of  S02,  03, and  sulfates, but the
     issue is unresolved (CD, p.  13-52).

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                                    23

 9)    A  number  of  long-term community air pollution studies (Table B-3,
      EPA,  1982b)  have found that populations living in areas with high
      SOg and particles tend to have a higher prevalence of respiratory
      symptoms  and lower lung functions than those living in areas with
      lower pollution levels.  The data do not, however, permit clear
      identification of the importance of S02 in the pollution mix.  Some
      cross-sectional (Neri et al., 1975; Becklake et al., 1978) and
      longitudinal studies (Van der Lende, 1973, 1975,  1981) provide weak
      qualitative  evidence of effects associated with differences in SOg
      levels, although in the presence of particles.
          Two series of studies (Lawther et al., 1974a,b,c; Dockery et
      al.,  1981) provide qualitative evidence of lung function decrements
      in adults and children in response to  episodic  increases in S02
      levels in combination with particles.
      3-  Aggravation of Existing Respiratory and Cardiovascular Disease
     SOg induced bronchoconstriction or other acute  responses described
above clearly aggravate asthmatics  in  laboratory situations and might
also aggravate those with  other respiratory ailments and  cardiovascular
disease. A number of community  observational  studies  (Table B-4,  EPA,
1982b) of episodic as well  as  more  moderate acute exposures to high
levels of SOg in combination with  particulate matter qualitatively
suggest that  these exposures aggravate  the  conditions of  cardiovascular
patients and  individuals with  bronchitis, emphysema, pneumonia,  and
influenza.  The relative importance  of  S02  in these pollutant  exposures
is difficult  to specify.
     Epidemiological  support for aggravation  of  asthma  by SC>2  is  weak
(CD, p.  14-34).   In  addition to the  usual problems associated with

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                                    24

community epidemiological studies (CD, Section 14.1), studies of
asthmatics are confounded by limited numbers of subjects, use of
medication, and multiple stimuli other than air pollution that may
affect response.  In addition, no studies have measured short-term
(<_ 1 hr) peak levels most likely to be responsible for any effects.
Because 1-hour maxima tend to be highest in the vicinity of strong point
sources, the study of asthmatics by Cohen et al. (1972) conducted near a
coal-fired power plant is of most direct relevance to the controlled
human results.  Although the results do suggest an SOg (and particulate
matter) effect on the frequency of attacks, potential biases and other
methodological difficulties with the study (CD, p. 14-33) and the lack
of 1-hour S02 data make unequivocal  conclusions impossible.
     4.  Clearance and Other Host Defense Mechanisms
     Major host defense mechanisms potentially affected by S02 include
clearance of particles and other foreign matter from the respiratory
tract and other respiratory system related defenses against infectious
agents.
     Few controlled human studies have examined the effects of S02 on
clearance.  Extended nasal  exposure  (4 to 6 hours) to 5 and 25 ppm S02,
alone and in combination with (2 or  10 mg/m^)  "inert" particles,
significantly reduced nasal  mucous flow rates  in resting healthy adult
subjects (Andersen et al.,  1974, 1977, 1981).   The effects of particles
were additive at most.  Mucous flow  was also reduced at 1 ppm S02, but
not significantly so (Andersen et al., 1974).   An interesting
observation in the earlier study was an abnormally nigh (4 of 15)
incidence of colds within one week of S02 exposures of 1, 5, and 25 ppm
on successive days.   The evidence did not relate this increase to S02

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                                     25

 exposures.   This anecdotal  result  prompted  a  follow-up  study  (Andersen
 et al., 1977)  in which  S02  exposed and  control groups were subjected to
 experimentally induced  rhinovirus  infection.  The S02 exposed group had
 no increase in the  number of colds  and  had  fewer symptoms.  The
 significance of this  finding with  regard to cold incidence is made
 questionable by the fact that virus was innoculated into a region of the
 nose  previously known not to be affected by S02 induced reduction in
 clearance.   The innoculated region  is out of the mainstream sites of
 deposition  for both airborne virus  and S02  (Andersen et al., 1977).  A
 related anecdotal result of interest is the observation of Weir and
 Bromberg (1972)  that  recovery from mild upper respiratory infections was
 slower  for  subjects exposed to 5 ppm S02 for several days than for
 control  subjects.   Statistical evaluation was not possible due to the
 small number of  subjects.
     Wolff  et  al. (1975a,b) and Newhouse et al.  (1978) have examined the
 effects  of  single acute exposures to S02 on tracheobronchial  mucociliary
 clearance.   At  5 ppm, S02 produced only a transient acceleration in
 tracheobronchial clearance in normal, healthy subjects for oral, resting
 exposures of 1 to 2 hours.  Significantly increased clearance was found
 for a 2.5 to 3 hour exposure that included a 30 minute exercise
 period.  Exercise alone increased clearance but the rate for  those
 undergoing exercise and SC>2  was  significantly faster.   Unfortunately,  no
 published studies have examined  S02 induced effects  on clearance in
 sensitive subjects or the effects of repeated peak  exposures  in  humans.
     Animal  studies  have examined the effects  of  both  short-  and long-
term S02 exposures on  clearance  and other host defense mechanisms  (CD,
Table 12-4).  Unlike the animal-human comparisons observed  for sulfuric

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                                    26
 acid  (e.g.,  Leikauf et al., 1981), donkeys appear far less sensitive to
 acute S02  exposures than are humans, with no response at 25 ppm
 (Spiegelman  et  al., 1968).  Rats may be more sensitive (Ferin and Leach,
 1973).   Of particular interest is the finding that prolonged, repeated
 exposures  (1.5  to 7 hours/day) to relatively low levels may result in
 clearance  effects (Ferin and Leach, 1973; Hirsch et al., 1975).  Ferin
 and Leach  (1973) exposed rats to 0.1, 1 or 20 ppm S02 for 7 hr/day, 5
 days/wk  for  10  and 25 days as an indicator of "integrated alveolar
 clearance."  S02 at 0.1 ppm accelerated clearance at 10 and 23 days, but
 1  ppm accelerated clearance at 10 days, had no.significant effect at 18
 to 20 days,  and depressed clearance at 25 days.  Twenty ppm depressed
 clearance  after 11 days.  The mechanisms by which S02 might affect
 apparent alveolar clearance is unclear, but would not appear to be
 related to penetration and direct effects on alveolar macrophages or
 cilia  beat frequency (Fraser et al., 1968).  Hirsch et al. (1975) found
 that  tracheal mucous flow was slowed in beagles exposed to 1 ppm S02 for
 1.5 hours  twice a day, 5 days a week,  for 1 year.  Clearance was
 examined only once (24 hours after exposure) and not measured prior to
 exposure.  Thus, the time to produce an effect is unclear, and the
 extent of  the depression is called into question.  In essence, the
 results of S02 on clearance suggest some concern over repeated peaks,
 but confirmatory testing is needed.
     As discussed in Section V-A and Tables 12-4 and 12-13 of the
 criteria document,  the effects of weekly to 3-month exposures to high
 levels of S02 appear to affect antiviral  defenses but not  susceptibility
to bacterial  infection.   Some suggestion of effects of S02 and carbon on
pulmonary immune responses  exists (Zarkower,  1972)  but their mechanisms
were considered puzzling.

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                                     27

      Community epidemlological  studies (Holland  and  Reid,  1965;  Lambert
 and Reid, 1970) of elevated SOg  in  combination with  particles  suggest
 that long-term exposures  may be  associated with  an increase in the
 prevalence of bronchitis.   Although  the  role of  SOg  versus sulfuric acid
 or other particles is  not  clear, animal  studies  suggesting effects of
 repeated S02  peaks on  clearance  provide  some basis for S02
 involvemen.t.   Community studies  (Table B-7, EPA, 1982b) also suggest
 increased infectious disease during  pollution episodes and in children
 and adults living  in areas  of higher S02/particle pollution.  Again, the
 relative role of SOg in such  responses is unclear.
      5.   Possible  Mutagenesis/Carcinogenesis
      S02 and  bisulfite have  been reported to be mutagenic in microbial
 test  systems  (CD,  Table 12-15) at acidic pH.  Potential mechanisms
 (e.g., reaction with nucleic acids,  free radical  production) are
 outlined in Appendix A.  The relevance of the microbial results to whole
 animals  is unclear.  Negative results have been reported for mammalian
 cells and  insects  (CD, Table 12-15).  The criteria document concludes
 that  "On the  basis of present evidence, one cannot decide whether or not
 bisulfite, and hence S02,  is a mutagen in mammals" (CD, p. 12-77).
     Two studies have examined the  potential  carcinogenicity  of S02
 alone.   Lifetime exposures of rats to 10 ppm S02  for  6 hr/day  produced
 no squamous cell carcinoma (Laskin et al.,  1976).  Peacock and  Spence
 (1967) as reanalyzed by EPA (CD,  Appendix,  Chapter 12),  found  a
 significant increase in primary  lung carcinoma  in female  mice  and
primary lung adenomas in male and female  mice.  Unfortunately,  the data
do not permit  calculation  of exposure level, which was in  the nature of
intermittent peaks  (high concentration  unspecified, 5 minutes,  5

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                                    28

days/wk) for 300 days.  The combination of 10 mg/rn^ benzo(a)pyrene (BaP)
and SOg produced no lung tumors in hamsters but a significant increase
in lung carcinoma in rats (Laskin et al., 1970).  A follow-up study in
rats found that lifetime exposure to S02 (10 ppm, 6 hr/day) alone and
BaP (10 mg/m3, 1 hr/day) alone produced no significant change in tumors,
but various combinations of S02 and BaP did result in increased lung
tumors (Laskin et al., 1976).  The criteria document concludes that it
is difficult to interpret the studies of carcinogenicity, "However, SOg
must remain suspect as a carcinogen or cocarcinogen in view of these
reanalyses and the positive results of mutagenicity assays" (CD, p. 12-
78).
   Retrospective community epidemiological  studies of cancer (Appendix
B.5, EPA, 1982b) have focused on areas with high particles (especially
BaP) pollution.  Nevertheless, S02 levels were also high in most areas
examined.  In essence, most studies find that cigarette smoking is the
dominant cause of lung cancer, but some small portion of the observed
gradient in urban/rural cancer rates in smokers and non-smokers may have
been related to high historical levels of community air pollution.
Available studies neither prove nor negate the possibility that S02,
alone or acting with particulate carcinogens, may have contributed to
cancer.
     6.  Mortality
     A number of epidemiological studies have demonstrated an
association between peak S02 and particulate pollution and increased
mortality rates (Table B-10, EPA, 1982b).  Observations during the
severe pollution episodes in Europe and the U.S. suggest that most of

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                                     29

 the pollution-related  deaths were  among the elderly and those with
 chronic cardiopulmonary  disease.
      Because  of  the  high correlation between S02 and particle levels
 during these  study periods, the relative importance of these pollutants
 are difficult to distinguish.  The combination of elevated levels of S02
 and particles with fog in the urban smog episodes likely resulted in
 increased penetration of S02 or its irritant transformation products.
 Whether S02,  alone or in combination with particles, increased mortality
 during "episodic" as well as "non-episodic" conditions is unknown.
 Several  analyses of daily mortality in London, New York City, and
 Pittsburgh suggest, however, that associations between air pollution and
 mortality are primarily due to particles and not S02 (Mazumdar et al.,
 1981;  Schimmel and Murawski, 1976;  Mazumdar and Sussman, 1981).   Although
 these  studies employed refined statistical  techniques, the criteria
 document indicates that they cannot clearly separate the effects of S02
 and particles nor rule out possible interactive effects between  the
 pollutants, humidity, and other factors  (CD,  p. 14-53).
 C.   Sensitive Population Groups
     This section identifies the  major  groups  most  likely  to  be  among
 the most sensitive to the effects of  S02,  based principally on material
 presented in Sections A and  B.  Available  estimates  of the size  of each
 of these groups  in the U.S.  population are  also given.   Table 5-2
 draws upon information  from  epidemiological, toxicological, and
 controlled human  research in summarizing the observations  that have
 identified various  subgroups and possible explanations  for their
sensitivity.   Much  individual  variation exists  among the subgroups.

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                                             TABLE 5-2.  MAJOR SENSITIVE POPULATION SUBGROUPS*
 ubgroup/
 isease Characteristics
 sthmatics
  recurrent episodes of
  cough, wheezing, and
  breathlessness result-
  ing from reversible
  airway obstruction
  caused by bronchial
  constriction, bronchial
  wall swelling, and
  accumulated secretions
  (NIAID.  1979)
 ndividuals with
non-asthmatic
atopic disorders.
  g., hay fever, other
allergies
- clinical hyper-sensitivity
  state, or allergy, to a
  variety of environmental
  antigens (NIAID. 1979)
Individuals with
chronic obstructive
pulmonary diseases


  • Bronchitis - chronic
    inflammation of
    the trachea and
    bronchus with recurrent
    cough and sputum
    (Fishman. 1980)
  • Bronchiectasis - chroni
    dilatation of bronchi
    (Fishman, 1980)
  • Emphysema - unevenly
    distended lung
    air-sacs, usually with
    loss of lung tissue
    (Fishman, 1980)
opulation Estimates
.300.000
derived from prevalence
stlmate of NIAID, 1979
nd applied to 1982
.5. population)
20.000.000
(derived from prevalence
estimates of Johnson,
1982b and applied to 1982
U.S. population)
                             7.800,000 (DHEM.  1973)
                           Rationale  (or Criteria)
- Hyperreactlve airways
  (Boushey et al.. 1980)
  Hyperreactlve airways
  (Boushey et al..  1980)
                              Mucus hypersecution and
                              blocked airways may worsen
                              effects of S02-Induced
                              bronchospasm.
                                                            Enlarged  airspaces  Increase
                                                            blood  flow resistance  throug
                                                            the  pulmonary capillary net-
                                                            work.  Increasing cardiac
                                                            stress.
                                                             Observation/Associations Supporting  Increased Sensitivity
                                                                                         Exaggerated bronchoconstrlctlon In asthmatics exposed briefly
                                                                                         to SO..  Effects at SO, levels up to an order of "?9n1tude
                                                                                          owerzthan In normal subjects (Sheppard et al.. 1980. 1981a;
                                                                                         Linn et al.. 1982a.b; Koenig et al., 1982a).

                                                                                          Longer recovery to normal  lung  function required  In
                                                                                          exercising asthmatics following brief  SO, exposure
                                                                                          (Sheppard et al.,  1981a;  Koenig et al., 1981).
                                                                                          Increased bronchoconstrlctlon after SO. In atopic
                                                                                          Individuals without asthma compared with normal  subjects
                                                                                          (Stacy et al..  1981; Koenig et al.. 1982a;
                                                                                          Sheppard et al., 1980)

                                                                                          Numerous Investigators have found Individuals (10-201 of
                                                                                          subjects) substantially more responsive to S02 than the rest
                                                                                          of the group (CD. p. 13-20).
                                                                                                    GO
                                                                                                    o
                                  Many of the deaths and Illnesses during and after air
                                  pollution episodes were among people with pre-existing
                                  obstructive diseases (Martin. 1964; Martin and Bradley.  1960;
                                  Ministry of Health. 1954; Lawther et al.. 1970).

                                  Longer recovery to normal lung function required In
                                  bronchltlcs following brief SO. exposure
                                  (Gokemeljer et al.. 1973).
 •Other Identifiable groups  that may  have enhanced sensitivity to S02 Include Individuals with cardiovascular disease, the elderly, and children
  and adolescents  (see text).

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                                     31

 Moreover, some of these groups may be at lower risks,  as in the case of
 patients confined to indoor environments with lower than ambient SOg
 levels.
      Asthmatics are substantially more sensitive to a  brief exposure to
 S02 than are normal subjects.   Table 5-3 provides a quantitative
 comparison of the relative sensitivity to S02 of asthmatics,  atopies,
 and normal  individuals  as  indicated  by pulmonary function tests.  Asthma
 is a common disease that affects  approximately  9.3  million  people in
 the U.S. (NIAID,  1979), although  higher estimates have been made  (Dodge
 and Burrows,  1981).
      Increased sensitivity  to  S02, less marked  than  in asthmatics (Table
 5-3),  has  also been  noted among atopic  individuals without any clinical
 signs  of asthma  (Koenig et  al., 1982a;  Stacy  et  al., 1981; Sheppard  et
 al.,  1980).   Koenig  et al.  (1982a) suggest that  hyperreactive atopies
 with exercise  induced bronchospasm (EIB), who,  in one study, made up
 about  41% of the allergic persons under age 18  (Kawabori  et al., 1976),
 should perhaps be categorized as having subclinical asthma.   The
 undetected presence of asymptomatic atopies in studies  of presumed
 "normal" subjects may account for the recurrent finding of subjects
 "hyperreactive" to S02 who generally  make up 10-20% of  the study group
 (CD, p.  13-20).  A similar incidence  of susceptible individuals  has  been
observed in animal studies  (CD, pp. 12-15 to 12-16). Temporary  but
marked airway hyperreactivity occurs  in otherwise normal  subjects with
viral respiratory infection (Boushey  et al.,  1980).
     Other diseases, which  may  or  may not be  associated with  asthma
appear to be important factors  in  the predisposition of certain
individuals to the harmful  effects of high S02/particulate matter

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                                      32
TABLE 5-3.   COMPARISON OF RESPONSES IN NORMALS,  ATOPICS,  AND ASTHMATICS TO S02
a)  SO, Alone1 (Sheppard et al.,  1980;  1981a)
Concentration (ppm)

5
3
1
.5
% Change
Normals
18*
-3
-4
NA
in Specific Airway
Atopies
33*
1.5
2.5
NA-
Resistance (SRaw)
Asthmatics
126*
76*
25*
-vO
*Significantly different from baseline (p < 0.05).   Asthmatics,  but not
 atopies, are significantly different from normals.

^Adult subjects at rest.  Oral-mouthpiece exposure, 10 minutes.
b)  1 ppm S02 + l.mg/m3 NaCl1  (Koenig et al., 1982a)

Pulmonary
Functional
Value
RT (3Hz)
Vmax50
w
max75
FEV1.0
FRC
Percent

Normals
3.0
-8.0
-7.0
-6.0
10
Change in Functional Value
Atopies
with EIB
41*
-29*
-44*
-18*
0.3
Extrinsic
Asthmatics
67*
-44*
-50*
-23*
7.0
*Significantly different from baseline.
 Adolescent subjects, measurements made after 10 minutes of moderate exercise.
 Oral-mouthpiece exposure, 30 minutes at rest, followed by 5-7 minutes
 break, followed by  10 minutes exercise.

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                                     33

 combinations.  The history of catastrophic pollution  episodes  as  well  as
 the lesser episodes in London have  clearly indicated  that  chronically
 ill individuals,  especially those with cardiovascular and  obstructive
 respiratory diseases,  and the elderly, were more  severely  affected  than
 the general population.   Whether  these groups would also be  sensitive  to
 SOg alone is not  clear.   Bronchitics are  reported to  be among  the most
 sensitive to elevated  S02 and particles  (Lawther et al., 1970).   In
 limited  multi-day  clinical  tests  however,  subjects with minor  and more
 serious  obstructive disease were  not clearly more sensitive to S02 than
 normals  (Weir and  Bromberg, 1972; Reichel,  1972).  Subjects with
 obstructed airways (e.g.,  bronchitics) may, however,  require a
 substantially  longer recovery time to  baseline function following brief
 exposure  to S02 than normal subjects (Gokemeijer et al., 1973).
     Children  are  generally more active outdoors and contain a somewhat
 higher percentage  of asthmatics and atopies (NIAID, 1979).   Enhanced
 sensitivity  and prolonged effects have been noted among children exposed
 to  high levels of  ambient SO? and particulate pollution (Lebowitz  et
 al., 1972;  Douglas  and Waller, 1966; Colley et al., 1973;  Kiernan  et
 al., 1976;  Becklake et al., 1978), but the effects cannot  be attributed
 to  a single pollutant.  Moderate episodes of SOg (with particles)  have
 been associated with depression of lung function in children (Dockery
 et  al., 1981).
     Based on limited studies, about 15% of healthy young adults tested
appear to be habitual "mouth", or  oronasal breathers under  the
conditions of the  tests (Saibene et  al., 1978;  Niinimaa et  al., 1981).
Because the subjects and  test  procedures used  could have affected  the
results,  extrapolation  of this estimate to the  general  population,

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                                    34

including sensitive subjects, is uncertain.  Anyone, however, may
temporarily shift to oronasal breathing during exercise, conversation,
singing, or illness with related nasal congestion.  The decreased nasal
cross sectional area caused by high S02 levels (Andersen et al., 1974)
might itself result in increased oronasal breathing.  While all mouth
breathers may not have comparable sensitivity to S02, mouth breathers in
sensitive groups (e.g., asthmatics or atopies) are likely to be at
greater risk of effect.  Because allergic subjects often have nasal
obstruction, the proportion of "mouth" breathers in such groups may  be
of equal or greater magnitude to that observed in healthy subjects.
     People with sulfite oxidase enzyme deficiency who are unable to
detoxify S02 and/or sulfite for subsequent excretion are very few in
the U.S. (Cohen et al., 1973).  Because the condition has serious.
clinical implications  regardless of SOg exposure (Mudd et al., 1967;
Irreverre et al., 1967; Shih et al., 1977) it may be irrelevant for
present consideration.  Other individuals with an intermediate enzyme
deficiency (heterozygotes) may be at an increased risk, especially with
chronic exposure to S02-  Although intermediate levels of sulfite
oxidase activity in the liver of humans has been reported (Shih et al.,
1977) the frequency of the heterozygote gene is not known.
D.   Concentration/Response Information
     As outlined in Section B, responses to S02,  alone or in combination
with other pollutants  have been examined in roughly three time scales:
1) peak exposures (minutes-hours), 2) short-term exposures (hours-days),
and 3) long-term exposures (months-years).  Although a number of animal,
controlled human, and  community studies provide important qualitative
information on  the range of possible responses to S02 on these time-

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                                     35
 scales, only a more limited set of controlled human and epidemiological
 studies are of principal  interest in examining concentration-response
 relationships in humans.   The following review summarizes  those studies
 cited by the criteria document as providing the most reliable
 quantitative information  as well  as  a few other studies that provide
 reasonable evidence of exposure-response relationships  without  allowing
 derivation of specific levels.  A further assessment of these studies  as
 applied to selecting alternative  levels  for air quality standards  is
 presented in Section VI.
      1.  Peak Exposures
      The best information  on  the  effects  of relatively  brief (minutes-
 hours)  peak  exposures  to S02  is derived  from studies  of exposure of
 humans  under controlled laboratory conditions.   The  importance and
 limitations  of  controlled  human exposure  studies are  discussed in
 Section 13.1 of  the  criteria  document.  Such  studies  can provide
 accurate measurement of responses, exposure  levels and  conditions for a
 single  pollutant or  simple  combinations of  pollutants,  and produce
 useful  concentration-response relationships for a variety of subjects.
 Important  limitations  include:  1) ethical  considerations reduce the
 exposure  regimes and types of sensitive subjects studied; 2) the number
 of subjects  per test is limited; 3) repeated peak exposures and other
 longer-term  exposures usually cannot be done; 4) only a small  number of
 possible combinations of environmental variables and subject-related
 variables  can be examined; 5) laboratory studies may induce physical  or
 psychological artifacts; 6) to date,  only a limited number  of  endpoints
 (usually respiratory mechanics and symptoms) have been measured;  and,  7)
 functional measurements used vary  from study to study, making
quantitative comparisons difficult.

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                                    36

     a)  Normal Subjects (< 5 ppm)
     Concentration-response information for SOg exposures of 1 to 5 ppm
in resting healthy subjects is summarized in the criteria document and
in Table 5-1.  Both oral (mouthpiece) and nasal exposures have been
studied.  Although a few isolated cases of sensitivity to SOg have been
found, it is not clear that such subjects are not atopic and or
undiagnosed asthmatics.  Accordingly, the criteria document concludes:
"...available evidence points to 5.0 ppm (13.1 mg/m3) as being the
most probable lowest observed effect level  for induction of
bronchoconstriction effects in healthy adults exposed to S02 while at
rest"  (CD, p. 13-48).
     Exercise and oral breathing increases fractional penetration and
total dose of S02 (Section V.A.) and therefore results in effects at
lower ambient concentrations.  Based on the work of Lawther et al.
(1975), Melville (1970), Snell and Luchsinger (1969), and Koenig et al.
(1982b), the criteria document concludes that induction of pulmonary
mechanical effects may occur at S02 concentrations _>_ 1 to 3 ppm in
exercising healthy subjects.  Most of these studies involved forced oral
breathing, in some cases with light exercise.
     Table 5-4 summarizes the results of a  selected group of controlled
human studies involving peak (_<_ 1 to 3 hours) exposures to S02 levels at
or below 1.0 ppm.   When comparing these results for quantitative
purposes, it is important to note the sensitivity of the subjects
(normal, atopic, asthmatic), the exposure mode (chamber, oral-mouthpiece
and/or nose clip,  oronasal, or nasal) and exercise status.  Most of the
studies involved a rather rapid (step function) increase in S02
exposure.  The importance of each of these  factors is discussed in the

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                                     37

 criteria document  (CD,  Chapters  11,  13) and  in Section V-B and Appendix
 A of this paper.   The comments column of the table provides some
 interpretation  of  the functional testing results, based upon the general
 nature of the tests  as  summarized in Appendix C and discussions in the
 criteria document  (Section 13.6).
      Studies  involving  exercising healthy adults and free breathing
 (chamber) exposures  are summarized in Table  5-4.  Bates and Hazucha
 (1973)  found  decreases  in several parameters indicative of airway
 constriction  with  0.75  ppm exposure of adults under intermittent light
 exercise (minute ventilation (Ve) ~ 25 1/min).  Due to the limited
 number  of subjects,  group mean changes were  not statistically
 significant and the  results are preliminary.  Stacy et al. (1981) used
 the  same exposure  regime but with a single exercise period of heavy
 exercise (Ve  ~ 60  1/min) sufficient to induce oronasal breathing.
 Indications of large airway constriction were significant, with a trend
 toward  changes in  smaller airways.   Responses were greater in subjects
 reacting positively to allergen skin tests,  suggesting that some of
 these healthy subjects were atopic  (but  without asthma).   The criteria
 document  concludes that  these studies provide weak evidence of S02-
 induced  bronchospasm in  free breathing exercising  healthy  normal
 individuals at levels of 0.75 ppm (CD, p.  13-49).   As  noted by the
 authors  and by the criteria document (CD,  p.  13-51), the  relatively
 small (8-20%) reversible changes  in  functional  parameters  observed  in
 these studies are not likely  to be  of any  health significance  in  the
 normal healthy adults tested.   The  principal  significance  of  these
 studies  is to indicate levels  and conditions  at which  comparable  or more
marked functional  changes  might  be expected  in  more sensitive

-------
TABLE 5-1.  SELECTED CONTROLLED HUMAN STUDIES OF QUANTITATIVE INTEREST
(.onifntr.it ions
No. iiw1_ Snl. Jet U
0. f> (i|Mn







0.7S p| HII



17 c nil(1
. J / - . D ppm


Dui.ilii.il

1^0 minutt-s







l?(l minutes







lype Sulij4'f.ls

 ."> 1/min)
*'


15 minute exercise
period, tnd of first
hour V - 60 1/min
e

exercise
V • 30 \/min
e

Ui serv.it ions?

Trend toward decrease in WFR (8-10i), H[FR,n..(20i ),
FVC.FEV. n (8-101) No change in CC.
1 .U





Significant increase in KHW, (mean •*• I5'Z),
trend toward decreased FI.F FEV/FVC;
maximal after 1 hr. No change in other
parameters, symptoms. Positive allergen
skin test subjects more responsive.
mixed.


(..-.•m-m-.

S»n(t)fs t-> possible constriction in
l.iMl<» airways, constriction in
inlennedidte to small airways as
measured by HHFR but nut in small
•tirways as measured by CC. Effect
increased through 1.5 hours. No
health viunif icance to normal subjects.

Indicates large airway constriction.
possible small airway constriction.
Consistent with Bates and lla/ucha
findings. Effects not of health
significance to normal subjects.
Indicates no effects in large or
small airways. No detectable
health effects.


Ki'lnence

Dates and llazucha
(19/1)






Stacy et al. (1981)



Horvath «nd Folinsbee,
(1977); (tedl et al.
(19/9; 1982); Bates and
Hazucha (1973); Bell
et al. (1977 )
Asthmatics and Atopies
'«•



1 ppm


1 ppM SO,
'1 •«)/iii:"l«dCI
droplet aerosol
1 |i.» SO, i
1 imj/M1 (l,,f 1
droplet aerosol



1.0 ppm S0?
with and without
druplet aerosol



0.71 ppm








10 minutes



5 minutes


60 Minutes
10 minutes
at rest;
S-7 minute
break; 10
minutes
enerrise

30 minutes
al rest;5-7
10 minutes
exercise


10 minutes
plus3







7 normals
7 atopies
(seasonal rhinitis)
7 asthmatics


6 asthmatics
adults

9 Extrinsic
asthmatics
(adolescents)
R extrinsic
asthmotics
(adolescents)



8 a topic
adolescents
asthmatics)



23 asthmatics








Oral-
mouthpiece



Oral-
mouthpiece

Oral-
facemask
(no mouthpiece)
Oral-
mouthpiece




Oral-
mouthpiece




l)0ral-
mouthpiece
2) Chamber






Resting



f xercise.
V - 31 l/min-
and hyperventilation

Resting
Rest, then
txen ise; we- .10
V >. 5? 1/min1



Rest, then
exercise .
V ^24-56 1/min




Exert is ing
V;v 40 1/min
*•







asthmatics had chest tightening, wheezing.


Harked increase (mean > 3001) In SRaw In all
subjects. Dyspnea and wheezing in all subjects.
Time course of response differs from resting
• subjects.
Signi Meant decrease in V M V ,,
(mean ^ 8-141) after 30 mTflulifV. • hVWgnUicant
change In R,. FRC, FfV, Q. No symptoms.
Post exercise (4-5 minutes)--si
-------
                                         TABLE  5-4.    SELECTED  CONTROLLED  HUMAN  STUDIES  OF  QUANTITATIVE   INTEREST
                                                                                          (Continued)
 ConLentrdtion-.      Duration      lype  Subjects
                                    Exposure
                                    Nude
                                                                     ExercKt?
                                                                     Status
 05 W*           10 minutes     7 asthmatics
 0-5 PP™           10 minutes     5  asthmatics
 05 W»            60 minutes     24 asthmatics
                   S minutes      6 asthmatics
0.5 ppm
0.25 ppm


0.25 ppm
0.1 ppm
                   ISO minutes    40 normals,
                                 40 mild
                                 asthmatics
10 minutes      7 asthmatics


60 minutes      24 asthmatics
                  10 minutes
                                 2  asthmatics
                                 selected for
                                 sensitivity at
                                 0.25, 0.5 ppm
                                                      Oral-
                                                      mouthpiece
                                                      Oral-
                                                      mouthpiece
                                                      Chamber
                                                      (nasal)
                                                      Doral-
                                                      mouthpiece
                                                      2)oronasal-
                                                      facemask
                                                      3)nasal-
                                                      facemask
                                                      mouth occluded
                                   Oral-
                                   chamber «ith
                                   nose clip
                                                   Oral-
                                                   mouthplece
                                   Oral-
                                   mouthpiece
                                                     OExercising ,
                                                     »e  •«.  35  1/min5

                                                     2)Resting

                                                     Exercising
                                                     V.  -v  27  l/«iin
                                                     Intermittent
                                                     exercise
                                                     alternating with
                                                     rest 110 Kin.)
                                                     V. -v 27 1/min
                                                    Exercising
                                                    V  •  40 1/min
                                                    Resting
Exercising  K
Ve ' 30 1/min5

Intermittent
exercise
alternating
with, rest
(10 minutes)
Ve -^ 27 l/mtn

Exercising  ,.
V  •>. 35 1/min
                                                                                              Significant Increase  (mean = 1151) In SRaw
                                                                                              (all 7 subjects  responded) with exercise.
                                                                                              Shortness of breath and wheezing reported  in 3
                                                                                              subjects.  No change  in SRaw after resting exposure.

                                                                                              Increase in SRaw (mean = 401 over post
                                                                                              exercise control)  in 4 subjects.  One subject
                                                                                              (with largest Increase In SRaw) reported
                                                                                              increase in respiratory syi«ptoms(unspecif1ed).


                                                                                              No significant changes In SRaw or FVC.   No
                                                                                              Increase In symptoms.  No delayed symptoms.
 Oral: Significant increase in  SRaw  (mean = 901)
 all subjects responded.   Five  subjects reported
 shortness of breath,  the sixth reported throat
 irritation; 3 subjects coughed.  No symptoms during
 sham (humidified air).
 Orunasal: Significant increase in SRaw (mean -vSOS)
 all subjects responded.   Four  subjects reported
 shortness of breath,  nose and  throat irritation,
 2 had no symptoms.
 Nasal: Significant  Increase in SRaw (mean i28Z)
 5 subjects responded. One subject  reported
 shortness of breath,  two reported nose and throat
 irritation.  Oral SRaw significantly greater than
 nasat.  Other differences between exposure routes
 not statistically significant.

 No functional  changes in 39 of 40 normals.
 One "normal" 1} yr. old  had decreased MHFR
 (181), Increased Raw  (301).  after exposure.
 Small  decrease (2.71) in MMFR  In asthmatics.
 Delayed symptoms (3 subjects).

 Significant Increase  In  SRaw (mean  • 301);  3 c
 7 subjects showed Increase.  No symptoms.

No significant change In SRaw  or FVC.   No
 increase In symptoms  during exposure.
No delayed symptoms.
                                                                                             Significant, but  small (unqualified)
                                                                                             increase In SRaw  in both subjects.
                                                                                             No symptoms.
                                                                               Indicates constriction in  large airways.
                                                                               Symptoms suggestive of clinical
                                                                               significance.
                                                                              Statistics not given.   Indicates
                                                                              constriction in large airways.
                                                                              Symptoms suggestive of clinical
                                                                              significance.   Generally consistent
                                                                              with Sheppard  et al., 1981 above.

                                                                              Indicates no effects on large or
                                                                              small airways,  symptoms.  No
                                                                              detectable health effects.  Suggests
                                                                              decreased effects of nasal vs.
                                                                              mouthpiece exposures, somewhat smaller
                                                                              ventllation.

                                                                              Indicates constriction in large
                                                                              airways Is diminished by nasal, oronasal
                                                                              breathing, but under these conditions
                                                                              bronchoconstriction remains.   Symptoms
                                                                              suggestive of  clinical significance,
                                                                              increase going from nasal  tu oronasal
                                                                              to oral.
                                                                                                                                                                                                Sheppard et al.
                                                                                                                                                                                                (1911 la)
                                                                                                                                                                                                Linn et al. (I982a
                                                                                                                                                                                               Linn et al. (I982<
                                                                                                                                                                             Kirkpatrick et al.
                                                                                                                                                                             (1982)
 Small changes in NNFR less  than dlumal
 variation, no clinical  significance.  The
 "normal- responder nay  have been an un-
 diagnosed asthmatic.  Delayed nocturnal
 responses not replicated In other studies.

 Small change in  large airways; health
 significance In  these subjects unclear.

 Indicates no effects  on large or small
 airways, symptoms.  No detectable
 health effects.   Suggests decreased
effect of nasal mouthpiece (Sheppard
et al.,  1981) exposure, somewhat
smaller ventilation, high humidity.

Small  change  In  large airways;  health
significance  In  these subjects  unclear.
                                                                                                                                                                                             Jaeger et  al. (1979
                                                                                                                                                                                             Sheppard et al.
                                                                                                                                                                                             (I98la)

                                                                                                                                                                                             Linn et al. (I982a)
                                                                                               Sheppard et a).
                                                                                               (I98la)
Exercise i
otherwise
                                                                             activities,  corresponding to  these rates.  Unless
                  feiV" tCM? ",'•  t0ta'  mil"fte Vent11atfon <».)'  s« Tal>^  A-'  '»••                    ,                       e ra
                  fied, ventilation  rates given represent approximate mean  values derived from  Information presented In the study.

  See Appendix C  for a brief description of various  functional tests listed here.   Percentage  changes Hsted here  represent changes  in
  cjroup mean over comparable clean  air  exposure situation.                                               "siio nere  represent cnanges  in

  Exposure continued while pulmonary  function tests were administered.
  Kcwnig (19B2).

-------
                                    40

subjects.  The remaining chamber studies of exercising healthy adults
indicate that functional changes are not expected in such subjects at
S02 levels £0.5 ppm (CD, p. 13-49).
     b)  Asthmatics and Atopies (1 ppm)
     Asthmatics and, to a lesser extent, atopic subjects appear
significantly more sensitive than normals to SOg induced
bronchoconstriction.  This is illustrated most clearly in the work of
Sheppard et al. (1980) for S02 alone and Koenig et al. (1982a) for S02
and salt aerosol, both of which provide comparative responses of the
three groups under comparable exposure conditions.
     Five studies in Table 5-4 have examined the effect of S02 on
asthmatics and atopies.  Activity levels include resting to moderate
levels of exercise and ventilation rates.  All studies used mouthpieces,
which tend to result in greater effects than would be expected for
normal breathing and otherwise similar exposures.  Thus, effects should
not be directly extrapolated to ambient settings without accounting for
differences in ventilation and oral  configuration.  The Koenig group
used S02 and 1 mg/m  salt droplet aerosol,  which complicated assessment
of the role of S02-  Nevertheless, empirical results and physico-
chemical considerations suggest the effects of the combination are
largely, if not exclusively, due to S02 alone.  Results in atopies
suggest no significant difference between S02 alone and the combination
aerosol (Koenig et al., 1982a).  Moreover,  for this NaCl/S02 exposure
combination, less than 1% of the S02 would  be expected to dissolve in
the droplet (Section IV), severely limiting the potential for increased
S02 penetration by a "carrier" mechanism.  No sulfuric acid formation is
likely to have occurred (McJilton et al., 1976).

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                                     41

      The five studies of 1 ppm S02 (by two separate groups) are
 qualitatively consistent.  Despite the somewhat large inter- and intra-
 subject variability in functional  parameters noted in these asthmatic
 subjects, it is clear that all  studies found statistically  and possibly
 clinically significant changes  in  respiratory mechanics.  As expected,
 increased ventilation through exercise (or hyperventilation) resulted in
 marked increases in airway resistance  and  perceptible breathing
 difficulties.  Under the ventilation rates,  humidity  and temperatures
 used in these studies,  no evidence  existed of exercise induced
 bronchospasm (EIB)  in clean  air.  The  most notable  changes were reported
 by Sheppard  et  al.  (1981a) for  asthmatics  after 10  minutes of  moderate
 exercise and mouthpiece  exposure.   Although  direct, quantitative
 comparisons  are  not  possible due to different measurements,  the
 responses  in asthmatics  observed by Koenig et al.  (1982a) appear to be
 less  severe  (but still significant), even  though higher exercise rates
 and longer exposure  durations were  involved.  The lower response might
 be related to differences in subjects,  measurement parameters, or the
 fact  that Koenig's subjects were exposed at  rest for 30 minutes prior to
 exercise exposure while Sheppard's subjects  received S02 and exercise
 simultaneously.  Of  note, however,  is that Koenig still observed
 significant  functional changes and symptoms after exercise exposure,
 even  after 30 minutes of "conditioning" at this relatively high
 concentration.  Functional parameters had not returned to baseline
 values even 20 minutes after exercise.
     c)  Asthmatics   (0.75 ppm)
     One recent study has examined  the  response of  exercising asthmatics
to natural oronasal  and mouthpiece  exposures (10 minutes)  to  0.75 ppm

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                                     42

 S02 (Linn et al.,  1982b).   Although  exercise  levels  (Ve ~ 40  1/min) were
 lower than used in the study of normal  subjects  by Stacy et al.  (1981),
 functional responses of free breathing asthmatics to 10 minute exposures
 were about an order of magnitude or  more greater.  For  mouthpiece
 exposures, functional responses (SRaw, FEV^g. PEFR, V^^g,  Vmx25)
 were consistent with those reported  in the 1.0 ppm S02  mouthpiece
 studies of asthmatics discussed above.  For unencumbered breathing,
 specific airway resistance (SRaw) also increased substantially over
.clean air controls, but the increase was about 55% of that observed for
 mouthpiece breathing, presumably reflecting a decrease  in S02
 penetration with oronasal  breathing.  Based on measured ventilation
 patterns (Table A-l), under the conditions of this study, the oral
 ventilation rate for oronasal  breathing would be about  50-65% of that
 for mouthpiece breathing.   Decrements in other functional parameters
 (e.g., FEVj^g, Vmax5o) were somewhat smaller  for unencumbered than for
 mouthpiece breathing, but  the differences were not statistically
 significant.  This study found a substantial  increase in SRaw (55%) in
 clean, humidified  air at room temperature. This increase at  Ve ~ 40
 1/min is not consistent with the much smaller exercise  induced
 bronchoconstriction reported by Kirkpatrick et al.  (1982) and Deal et
 al. (1979).
      Coincident with changes in lung function following S02 exposure was
 a marked increse in symptom scores based on 11 sympto.m  types  measured.
 Unlike SRaw, symptom responses were  not significantly mitigated by unencumbered
 breathing relative to mouthpiece breathing.  Symptoms or functional
 measurements were  not reported on an individual  basis.   The authors did
 observe "excess" responders and noted the removal of one sensitive subject

-------
                                     43

 from the group average because his  plethysmograph  readings went  off  the
 scale of the instrument following both mouthpiece  and  unencumbered exposures
 to S02-   Linn et  al.  (1982b)  concluded.that  "...our  results  are  consistent
 with the possibility  of a  'high-risk'  subpopulation  of asthmatics in whom
 upper respiratory defenses  are ineffective,  suggested  by Sheppard et al.
 Even with effective upper respiratory  defenses, many young adult asthmatics
 clearly  can  be expected to  show clinically and physiologically significant
 responses to S02  at concentrations  of  0.75 ppm or  less."
      d)   Asthmatics (0.5 ppm)
      Four studies in  Table  5-4 examined 7 different exposures to 0.5 ppm
 S02.   The Jaeger  et al.  (1979) work is somewhat unique in the number of
 subjects,  exercise status (all at rest), and duration  of exposure.  The
 major finding  is  a very  small, but  statistically significant difference
 in  airway  constriction  in resting asthmatics, breathing orally with nose
 clips, but no  change  in  normals.  The small change is of no known health
 significance,  but much  larger functional responses in one,  apparently
 atopic normal  adolescent, and delayed symptomatic responses in this
 subject and two asthmatics were considered by the authors as indicative
 of  possible concern.  Although delayed responses are mechanistically
 plausible if SOg  sensitizes  asthmatics to subsequent bronchoconstrictive
 challenge  (Reichel, 1972),  the issue has not  been systematically
 investigated and other studies have  not yet confirmed unequivocal
 delayed responses  following  S02 exposures (Linn  et  al., 1982a,b;
Koenig et al., 1981).
     The other studies of 0.5  ppm SOg  involve averaging times of  5  to
60 minutes, with varying exercise  rates and exposure  modes.   The  most
pronounced functional  and symptomatic  responses  were  observed by

-------
                                    44

Sheppard et al. (1981a) for moderate exercise (35 1/nrin) and mouthpiece
exposure.  The results of the pilot experiment by Linn et al. (1982a)
(exposure identical with somewhat lower exercise, Ve ~ 27 1/min) and of
the oral exposures of Kirkpatrick et al. (1982) (higher exercise,
shorter duration) are qualitatively similar to the Sheppard work, but
the responses appear somewhat smaller in the more recent studies.
Varying exercise regimes, subject sensitivity, and exposure duration
appear sufficient to account for the observed differences.  These
studies indicate that oral (mouthpiece) exposure with light to moderate
exercise can result in effects of concern in asthmatics (CD, p. 13-
51).  They also suggest the possibility of similar responses at exercise
levels high enough to result in comparable oral ventilation rates with
free breathing.  Because use of a mouthpiece decreases oral resistance
to breathing, however (CD, p. 11-11; Cole et al., 1982), it has been
speculated that mouthpiece exposures tend to overstate S02 effects with
free breathing, even with comparable oral flow rates (Proctor, 1981).
     Two studies (Linn et al., 1982a; Kirkpatrick et al., 1982) used
exposure systems that more reliably simulate natural breathing
conditions.  Linn et al. (1982a) found no response to 0.5 ppm S02 in a
chamber exposure. At the exercise levels used by Linn et al., 85% of
typical populations would be exclusively nasal breathing, but 15% (mouth
breathers) would have oral ventilation rates on the order of 15 1/min,
or close to the rate that might be observed for resting mouthpiece
breathing (Niinimaa et al., 1981).  Based on the negative results of
Sheppard et al. (1981a) in resting asthmatics, no substantial effects
would be expected under the exposure regime used by Linn et al.
(1982a).  with a higher total ventilation rate (40 1/min), Kirkpatrick

-------
                                     45

 found marked responses  after  5  minute face mask exposures to
 0.5 ppm S02.  Both  studies  found  evidence of exercise induced
 bronchoconstriction in  clean  air  (SRaw  increase ~ 15%).  Given the
 conditions  and exercise levels, EIB  of  this magnitude or less is
 consistent  with the work of Deal  et  al.  (1979).
      Although  not precisely duplicating ambient conditions, no evidence
 suggests that  face  masks would  result in marked increases in penetration
 of  S02  over that obtained for natural oronasal breathing.  If the
 asthmatics  in  the Kirkpatrick study were similar to the "mouth
 breathing"  subjects  in  the Niinimaa study, the oral  component of
 ventilation  (27  1/min) would be virtually identical  to that used in the
 Linn  pilot  study.   Perhaps fortuitously, the increases in airway
 resistance  over  clean air/exercise control in these  studies are also
 quantitatively  similar  (50% versus 40%).  In essence, these studies
 indicate the possibility of significant  increases  in airway resistance
 and symptoms in  free breathing asthmatics after short (5 to 10 minute)
 exposures to 0.5 ppm SOg, but only with  moderate or  higher exercise
 levels.  The Kirkpatrick study further permits  direct comparisons of oral
 only, oronasal   (facemask),  and nasal  only exposures  at similar exercise
 levels.  All three routes result in significant increases  in
 bronchoconstriction  suggesting that at high  enough ventilation rates,
 the effective fraction of SOg removed by the  nose decreases,  permitting
 increased penetration.
     e)  Asthmatics  (< 0.25  ppm)
     Two studies in  Table 5-4 examined exposure of asthmatics  to  S02
 levels of _<  0.25 ppm.  Sheppard  et al. (1981a)  found evidence  of
bronchoconstriction  in 3 of  7  subjects with exercise and mouthpiece

-------
                                    46

exposures at 0.25 ppm and in the two most sensitive subjects,  small  (as
indicated by graph) changes at 0.1 ppm.  The significance of these small
changes, unaccompanied by symptoms, is unclear.  Linn et al. (1982a)
found no response for free breathing asthmatics at 0.25 ppm S02.
     2.  Short-term Exposures
     The few controlled human studies that have examined S02 exposures
over periods of several hours to days are of limited quantitative value
due to unrealistic exposure levels and patterns, limited or unreported
activity levels, restricted numbers of endpoints measured, and in one
case, confounding influence of medication and limited description of
procedures and results (Appendix B).  Weir and Bromberg (1972) found  no
evidence of long-term functional changes (tests of large and small
airways, gas exchange region) or symptoms in 12 healthy subjects and  7
smokers with early signs of small airway impairment following  continuous  5
and 4 day exposures to 0.3 ppm S02.  Exercise, if any, was not reported.
Effects on nasal cross sectional area and mucociliary clearance, suggested
by 6-hour exposures to higher levels (1 ppm, Andersen et al.,  1974),  were
not examined.  Functional parameters in the smokers were highly variable
under sham conditions, limiting evaluation of potential S02 responses.  The
study indicates that exposure to a constant level of S02 at 0.3 ppm results
in no pulmonary function changes in normal adults or smokers with signs of
impaired small airways.  Effects of similar exposures to other sensitive
groups or effects of more realistic variations about the mean  S02 levels
have not been assessed.
     The principal  basis for developing quantitative assessments of acute
effects of ambient exposures of S02 on a daily basis is community
epidemiological studies.  Such studies can provide strong evidence for  the

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                                     47

 existence of pollution effects resulting from community exposures.   The
 major limitations of epidemiological  studies as  discussed in Section 14.1.1
 of the criteria document include:   1}   inadequate  and  inconsistent
 measurement of the exposure burden  of  individuals;  2)  variability in the
 measurement of health endpoints  (e.g.,  lung  function,  hospital
 admissions, frequency of symptoms)  and  in  the sensitivity of populations
 studied;  3) failure to fully  control for confounding,  or  covarying
 factors,  such as  cigarette  smoking  and  socioeconomic status;  4)
 difficulty in distinguishing  the effects of  SOg  from particulate matter
 and other pollutants,  and;  5)  inability  to establish a  causal
 relationship, or  negate one,  based  on statistical associations.
      Recognizing  these limitations, the  following discussion  outlines
 those studies cited by the  criteria document  as  providing the most
 reliable  quantitative  information as well as  other studies that provide
 useful information  on  the relative  importance of SOg without  allowing
 derivation of specific levels.  Epidemiological evidence for
 quantitative  assessment  of  SC>2 is drawn from the same limited set of
 British studies previously  evaluated in the particulate matter staff
 paper  (EPA, 1982b).  These  studies are summarized in Table 5-5.  The
 description and evaluation  contained in Section V-D of the particulate
 matter staff  paper will not be repeated here.  The  discussion will  focus
 on the relative importance of SOg in producing the  observed effects.
     The early London mortality studies (Martin and Bradley,  1960;
Martin, 1964; Ware et al., 1981)  found marked associations among smoke,
S02, and mortality in the concentration ranges indicated in Table 5-5.
The presence of dense fog may have  been particularly important in these
winters.   These studies did  not attempt  to  separate the effects  of

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                                    TABLE 5-5.   SUMMARY OF EPIDEMIOLOGICAL STUDIES PROVIDING MOST USEFUL
                                                CONCENTRATION/RESPONSE INFORMATION FOR SHORT-TERM S0? EXPOSURES
Observed
Effects
Clear increases
in daily mortal-
ity
Likely increases
in daily mortal-
ity
Daily worsening
of health status
in bronchi tics
Time
1958-60
winters
1958-60
winters
1958-72
winters
1954-68
winters
Population
Metropolitan
London
Metropolitan
London
180, and later
= 1000 chronic
bronchitic
patients,
London
24-Hr Levels Where Effects
Are Likely (CD, Table 14-7)
BS (as ug/m3)*
>. 1000
500-1000
250-500
S02 (pg/m3)
> 1000
TO. 38 ppm)
500-1000
(0.19-0.38 ppm)
500-600
(0.19-0.23 ppm)
Comments
1958-59 winter episodes. Unusually
foggy with peak pollution. (Lawther,
1963; Holland et al., 1979).
"Greatest certainty" of Increases with
BS, SO, > 750 gg/m , but Indications of
small Increases with BS < 500 ug/m
(CD, Table 14-7). Significant
correlation most consistent for smoke.
Well designed. Peak values above daily
average may have been Important. Mini-
mum levels for any "significant" re-
sponse were 250 ug/m BS, 500 pg/m
SO,; significant associations among
sensitive subgroup at lower levels
(Lawther et al., 1970).
Study
Martin and Bradley
(1960)
Martin (1964)
Martin and Bradley
(1960)
Martin (1964)
Ware et al. (1981)
Mazumdar et al .
(1981)
Lawther et al. (1970)
Lawther (1958)
*British Smoke - A pseudo-mass indicator related  to  small  particle (^4.5 urn)  darkness  (i.e.,  carbon content).   Mass relationships approximate.

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                                    49

 from particulate matter.   In their analysis of 14 London winters,
 Mazumdar et  al.  (1981) attempted to partition the effects of the two
 pollutants using two approaches:  1) categorizing mortality by quartiles
 of  pollutant levels  (e.g., 4 ranges of smoke levels within each of 4
 ranges  of S02); and 2) regression in models that considered smoke and
 S02,  their squares and their interactions separately and jointly.
      Examination of the quartile analyses shows that for the limited
 number  of comparisons where concentration of one pollutant is held
 relatively constant while the other varies, there is a clear tendency
 for mortality to rise with increasing smoke, but no consistent rise in
 mortality with increasing S02 levels.  In the regression analysis, when
 pollutants were considered separately, both S02 and smoke were
 significantly associated with mortality.  When the pollutants were
 considered together, only smoke is consistently positively and
 significantly associated with mortality.  The coefficient for S02 is
 positive  (nonsignificant) for the episodic (> 500 yg/m3 smoke and S02)
 period.
     On the  basis of their analysis,  the authors conclude that smoke
 (particles),  but not S02, is influential  in causing mortality and that
 no evidence of synergism was found.   They further developed  dose-
 response models for smoke, but  not SOg,  which extended to smoke levels
 below 500 pg/m3.  The criteria  document  cautions  that  "serious questions
 can be  raised regarding specific details  concerning the quartile
 analysis used and the validity  of reported conclusions regarding the
 separation of BS from S02 effects" (CD,  p. 14-21).   It seems  reasonable
to conclude,  however,  that while the  14-winter  analyses suggests the
possibility  of small  increases  in the  risk of mortality at smoke levels

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                                    50

 less than the  "likely effects level" (500 iig/m3), the published analyses
 provide  no such suggestion for S02 exposures below the likely effects
 levels listed  in the criteria document.  Further examination of the
 London data  set and available analyses appear warranted before more
 definitive conclusions can be reached.
     Other time-series analyses of daily variation in mortality and
 pollution in New York City between 1963 and 1972 indicate weak but
 positive associations between non-episodic mortality and-daily levels of
 particles, but not S02 (Schimmel and Murawski, 1976; Schimtnel, 1978).
 The criteria document states that these latter analyses "create serious
 doubt regarding reported associations between mortality and non-episodic
 SOg levels present in New York City during the 1963 to 1972 period" (CD,
 p. 14-26).  Unfortunately, reliance on a single, central Manhattan
 monitoring station as an estimate of pollutant exposures for the entire
 New York City area "precludes clear quantitative statements regarding
 possible effect or no-effect levels based on these results" (CD, p. 14-
 26).
   •  The work of Lawther et al.  (1970) on bronchitics is widely regarded
 as being among the most reliable investigations of the effects of
 particles and S02 on morbidity.   The levels  indicated in Table 5-5 are,
 in the authors' judgment, the lowest leading to any significant response.
 They suggested that the reported aggravations in health may have
 reflected the effects of brief exposures to  the maximum concentration
 occurring during the day.  These peaks were  several  times the 24-hour
 averages, but,  because of the wide dispersion of subjects and the
 variation in the magnitude and timing of such peaks  across the study
areas,  the impact  of peak values could not  be examined directly.

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                                     51
 Moreover,  it  is  possible  that  repeated  variations in exposures during
 the day  may have lead to  effects not accounted for by single daily peak
 exposures.
     Of  some  interest in  this  regard is the study by the same group
 (Lawther et al.,  1973, 1974a,b,c) of acute decrements in ventilatory
 function in four healthy  adults and two bronchitics.  Responses were
 associated'with  variations in  pollutant levels measured at their place
 of  work  or treatment (St. Bartholomew's Hospital).  After multiple
 regression to remove time trend effects, S02 concentrations explained
 the largest proportion of residual  variance in peak flow rates, with
 clearest association shown after walking exercise in heavy pollution.
 Quantitative conclusions  from this  study are not possible.
     Two additional morbidity studies involved hospital  and emergency
 room visits in London (Martin, 1964) and Steubenville,  Ohio (Samet et
 al., 1981).  Although both suggest  associations between  admissions and
 exposures to particles and SOg, neither used as sensitive a health index
 for quantitative purposes as did Lawther's group.
     In  summary, the more quantitative epidemiological  studies  suggest
 that effects may occur at S02 levels at or above 0.19 ppm (500  ug/m3),
 24-hour average, in combination with elevated particle  levels.   The
 strongest evidence relates to effects  on bronchitics.  Whether  the
 effects are due (in part)  to S02 alone,  heterogeneous formation  of
sulfuric acid  or other  irritant aerosol, particles  alone,  peak  values,
or repeated variations  around the daily  mean  cannot  be unequivocally
determined.

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                                    52

     3.  Chronic Exposures
     The relationship between long-term exposure to air pollution and
health has been extensively studied, but few of the studies provide
sound data or consistent findings sufficient to make quantitative
conclusions, especially regarding SOg.  Geographic comparisons of
morbidity (Appendix B.5, EPA, 1982b) and mortality rates among
populations suffer from many limitations (CD, Section 14.1.1.1 and
p. 14-35).  There are no studies that are useful in delineating
quantitative relationships between chronic exposures to sulfur oxides
and mortality, while only one quantitative study of chronic morbidity
effects possibly involving SOg has been identified in the criteria
document.  The results of this study are outlined below.
     Lunn et al. (1967, 1970) studied respiratory disease and lung
function of school  children in four areas of differing pollution levels
in Sheffield, England.  At age 5, both chronic upper respiratory
infections and lower respiratory tract illnesses were associated with
residence in more polluted areas.  The criteria document notes that the
effects were likely with annual  S02 levels of 131-275 ug/m3 (0.07-0.1
ppm) S02 in combination with 230-301 ug/m3 smoke (CD, Table 14-8).  The
criteria document concludes that "no-effect" annual  levels of S02 or
smoke cannot be determined from a follow-up study conducted by the same
investigators (Lunn et al., 1970; CD, p. 14-49).

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                                     53

 VI.  FACTORS TO BE CONSIDERED  IN  SELECTING"PRIMARY  STANDARDS  FOR  SULFUR
      OXIDES
      This section, drawing  upon the  previous  evaluation of  scientific
 information, outlines  the key  factors  that  should be considered by the
 Administrator in deciding what pollutant  indicator  to use for sulfur
 oxides,  establishing the level of primary standards, and designating
 appropriate averaging  times and frequency criteria.  Preliminary  staff
 recommendations on the most appropriate policy options in each of these
 interrelated areas are presented.
 A.   Pollutant Indicator, Averaging Times, and Form  of the Standards
      1.   Pollutant  Indicator
      Elevated levels of S02 associated with health effects in historical
 episodes  were always accompanied by high levels of particles.  As
 discussed in  previous  sections, it has been difficult to separate the
 effects of  S02  and particles in these cases, and either or both
 pollutants  might have  been surrogates for some hitherto unidentified
 "active agent."  Based on laboratory studies,  particles  may  increase
 respiratory tract penetration of absorbed S02  or otherwise enhance
 toxicity  by chemical or physical  transformations.   Combined
 S02/particulate matter indicators  have been  suggested to account  for
 these potential interactions.
     In its previous assessment (EPA, 1982b),  the  staff  with CASAC
 concurrence, recommended  a  separate  standard for particles but  left  open
the possibility of linking  S02  standards  to  particle levels.   In
evaluating this possibility,  the following factors  should  be
 considered:
 1)   Recent  evidence from controlled  human studies  shows that S02  acting
     alone can, at realistic peak  concentrations, produce  substantial

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                                     54
      decrements In pulmonary function and increase respiratory  symptoms
      in exercising asthmatics (Section V-B).
 2)   In contemporary U.S. atmospheres, TSP, PM^*,  and  fine  particle
      readings all  may be poor indicators  of those  aerosols most  likely
      to interact with S02-   The acidity of sulfuric acid  and other
      ambient sulfates, major components of fine  particle  mass, precludes
      substantial  additional  adsorption of S02-   The presence of  fog, low
      temperature,  and high  humidity,  which are not  necessarily
      associated with high particle mass,  are more  likely  to  lead to
      interactions  (Section  IV).
 3)   The particulate matter  standard  should ensure  that particle levels
      are lower  than  those likely to be associated with health effects,
      alone  or in the presence of SOg.   The principal transformation
      products of SOg/particle interactions (i.e., sulfates)  form a major
      component  of PMio and,  as such,  are  included in the  recommended
      particle standards  (EPA, 1982b).
 4)    Although the issue  is unresolved,  SC>2 may interact in an additive
      or  synergistic  manner with other  criteria pollutants, notably
      ozone.
 5)    Sources of high S02  levels often are well  controlled with respect
      to  primary particulate matter,  and many  sources of particles emit
      no  S02.
      Given the health effects data,  it appears  that a" separate S02
standard is appropriate, whether or  not a  combination standard is also
*Particles less than a nominal  10 ym,  termed "Thoracic  Particles"  in  the
particulate matter staff paper  (EPA,  1982).   PM10  is  the  indicator recommended
by the staff and by CASAC for use in  revised standards  for  particulate  matter.

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                                    55
adopted.  In view of the above considerations,  it is not clear that a
combination standard would result in any improvement in health
protection over separate standards for S02 and  particles,  each chosen
with due consideration of the potential for interactive effects.   Unless
health related advantages can be identified,  the additional  complexities
involved in specifying and implementing combination S02/particle
standards do not appear warranted.
     2.  Averaging Time(s)
     The current averaging times for the sulfur oxides  primary NAAQS are
annual and 24-hour; they were based on available epidemiological
studies.  The studies outlined in Section V still  provide  qualitative
and quantitative support for short-term standards,  but  do  not  provide
clear quantitative support for the current annual  standard.  Although
some studies suggest the possibility of effects associated with long-
term exposures to community air pollution containing SOg and particles,
data on respiratory tract deposition (Appendix  A),  long-term animal,  and
community studies (Appendix B) indicate that  any such effects  are  more
likely to be the result of exposures to repeated short-term  peaks  than
of continuous lower level exposures.  The possibility of effects from
such lower level  exposures cannot, however, be  ruled out.  In  the
absence of more quantitative data, it appears appropriate  to base  the
decision on whether to retain an annual  average S02 standard on the
long-term air quality that is anticipated as  a  result of the
implementation of short-term standards.   Under  the  current standards,
maintenance of the 24-hour standard results in  attainment  of the annual
standard in the vast majority of sites.   Nevertheless,  air quality
analyses indicate that the exceptions where the annual  standard is

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                                     56

 "controlling"  include  heavily populated urban areas such as New York
 City,  Chicago,  and  Philadelphia  (Frank and Thrall, 1982).  Thus,
 although  the health data are limited, the potential for increased
 exposure  in populated  areas suggests that it is appropriate to consider
 retaining an annual  average standard.
     Qualitative and quantitative  (Table 5-5) studies support a 24-hour
 averaging time.  Some  epidemiological investigators (Lawther et al.,
 1970)  have speculated  that the observed health effects might be largely
 due to short-term peaks on the order of an hour.  While controlled human
 exposures  to peak levels clearly indicate functional  and symptomatic
 responses, these studies cannot capture the full range of exposures,
 potential  effects,  and sensitive groups examined in the acute
 epidemiological studies.  Therefore, retention of a 24-hour averaging
 time is appropriate.
     Both  animal and controlled human studies (Table  5-1)  have reported
 respiratory responses to peak S02 exposures  lasting minutes to hours.
 The more quantitative controlled human studies (Table 5-4)  provide
 evidence sufficient to warrant  consideration of an additional  shorter
 averaging  time for SC>2 standards.  Most of the studies indicating
 effects of concern involve averaging times of 1-hour  or less.   Based on
 practical   considerations related to monitoring,  modeling, data
 manipulation and storage,  and implementation, the staff recommends
 consideration  of a 1-hour  averaging time  in  addition  to the 24-hour
 period.  In considering the level  of a 1-hour standard,  the range  of
 shorter-term (5-10 minute)  peak  levels associated with 1-hour  averages
should be  recognized, because effects have been  observed following
controlled exposures as brief as  5  to 10 minutes.

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                                    57

     3.  Form of the Standard
     The staff recommends that the 24-hour and possible 1-hour and
annual standards be stated in a statistical form rather-than a
deterministic form (the current 24-hour standard is not to be exceeded
more than once per year).  For the short-term standards this could be
accomplished by either:  1) setting a standard where an allowable number
of exceedances of the standard level would be expressed as an average or
expected number per year, or, 2) setting a standard where a given
percent of-the daily maximum hourly values would be expected to be less
than or equal to the standard level.  The emissions reductions to be
achieved in the required control program would be based on a statistical
analysis of the monitoring or modeling data over a multi-year period
(e.g., the preceding 3-year period).  In the case of the possible annual
standard, this would be accomplished by determining an expected value
based on multi-year monitoring data.
     The statistical  form can offer a more stable target  for control
programs and, with reasonably complete data, is less sensitive to truly
unusual meteorological  conditions than the deterministic  form.  The
general limitations of  the deterministic form are discussed more fully
elsewhere (Biller and Feagans, 1981).   Recognition of these limitations
has led EPA to promulgate or propose statistical  forms for the ozone and
carbon monoxide standards.
     For the purposes of this paper, ranges for standards presented
later will  assume a statistical  form.   Alternative numbers of
exceedances may be desirable and should be considered. Multiple
exceedances are helpful in that  they permit more  stable portions of the
air quality distribution to be used as implementation targets.  In so
doing, the interaction  between multiple exceedance alternatives and the
level of the standards  can be specified (Frank and Thrall, 1982).

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                                     58

      Two general  approaches  to  establishing multiple exceedance
 standards include:
 1)   Establish  a  standard  level  and  permit more exceedances of that
      level.   With this  approach,' increasing the number of exceedances
      increases  the  risk associated with just attaining the standard.
 2)   Allow more exceedances, but  adjust the level of the standard
      downward so  as to  provide  health protection roughly equivalent to
      that associated with  a  single exceedance.
      Figure 6-1 illustrates  the  relationship between standard level and
 exceedances for 24-hour S02  values based on the empirical data, and
 several  assumed log normal distributions (Frank and Thrall, 1982).  For
 example,  the  figure shows that a  standard with five allowable
 exceedances has an average ratio  of 0.67.  This means that on the
 average,  the  level of a  24-hour standard with five allowable exceedances
 should be  67  percent of  the  level associated with a standard with one
 allowable  exceedance in  order to provide the same degree of protection.
 If this  average adjustment factor of 0.67 were employed,  however,
 approximately half of the locations that would just meet  this standard
would exceed the level  associated with the standard with  one allowable
exceedance.   If protection equal to or greater than that  associated with
a single exceedance standard was desired at 90% of the  sites,  the figure
indicates that the appropriate ratio would be 0.44,  resulting in  a lower
standard level.   In this case about 90%  of the sites might  be
controlling to a greater extent  than  might be required  under a single
exceedance standard.  Trade-offs among risks,  degree of over-control,
and the robustness of  air quality targets  should  be  considered when
deciding upon  the  number of exceedances.   Comparable analyses  have also
been prepared  for  alternative 1-hour  standards  (Frank and Thrall,  1982).

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                        59
                  Number of allowable exceedances

               34567
i.U
0.9
0.8

0.7

0.5
0.1

0.3


0.2
0.1
-
.

-
1. 1
V':->-A I 1
VN,*^VX- **~*J
N * «
i
Box Plot
r— 90th percentile



i


J** *".. + *
i n^
h— 75th percentile

•—Median
' — Arithmetic average


Reference:
[standard
geometric
deviation
* ~~ 2.1
"* 2.8
"" 3.6
1



:?5th percentile
10th percentile
Figure 6-1.  Factors needed to  render  a  Multiple-Exceedance
Standard Equivalent to a Single  Exceedance  Standard
(Frank and Thrall, 1982).  The  box  plots are  based on 130
site-years with maximum 24-hour  value  >  0.12  ppm;  the dotted
lines are derived from lognormal distributions  and are
presented for comparative purposes.

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                                    60

B.   Level of the Standard
     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 Section
V-D and in the criteria document (Section 13.1).  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 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 SC>2, selection
of appropriate levels, frequency criteria, and averaging times remains
largely a public health policy judgment.
     The following sections present a brief staff assessment of the
concentration/response relationships suggested by the most significant
controlled human studies and epidemiological studies in the criteria
document and indicate how these studies may be applied in developing
ranges  for decision-making on standards for S02.   The presentation also
outlines a qualitative assessment  of the key factors,  based on
contemporary U.S.  exposures,  that  affect the margin  of safety  associated

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                                    61

with the ranges of standards derived from these studies.  This includes
identification of those important aspects of the qualitative human and
animal studies as summarized in Section V that should be incorporated
into margin of safety considerations.  Peak (< 1-hour),  short-term
(£ 24-hour), and long-term (annual), exposures are discussed separately.
     2.  Peak (< 1-hour) Exposjres
     a)  Derivation of Ranges of Interest from Controlled Human Exposure
         Studies                                     ~~~~~
     Controlled human studies providing useful quantitative information
on peak SOg exposures are summarized in Section V-D and  Table 5-4.
Although all of these studies provide important information,  many
involved use of a mouthpiece or nose clip.  As the criteria document
points out with regard to quantitative results in these  studies,
"caution should be employed in regard to any attempted extrapolation of
these observed quantitative exposure-effect relationships to what might
be expected under ambient conditions" (CD, p.  13-50). With due regard
to this guidance, Table 6-1 presents a preliminary staff assessment of
the controlled human studies most useful  in developing a range of
interest for selecting a 1-hour SOg standard.   The table focuses on
those studies involving free breathing (chamber or facemask)  exposures
and resting oral exposures.  The former studies provide  the closest
approximation of free breathing; the latter involve low  ( ~ 10 1/min)
oral  ventilation rates which would be exceeded in "mouth" breathers by
oronasal breathing with even light to moderate exercise  (Table A-l).
Although the oral component of breathing may be different for oronasal
and mouthpiece breathing at comparable flow rates (Cole  et al.,  1982),
it is both prudent and consistent with the available SOg studies to
assume that no substantial  differences exist in 503 induced responses

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                     TABLE 6-1.  STAFF ASSESSMENT OF KEY CONTROLLED HUMAN EXPOSURE STUDIES
so2
Concentration  (5-60 minutes)
      Observed Effects
                                                 Implications
   1 ppm
  0.75 ppm
  0.5 ppm
  0.25 ppm
Functional changes, possible
symptoms in resting asthmatics, oral
(facemask or mouthpiece) exposure.
Functional changes in free
breathing normal healthy
subjects, moderate to heavy  ?
exercise.  No health effects.

Functional changes, symptoms in
free breathing (chamber) asthmatics,
moderate exercise.

Functional changes, symptoms
in oronasal (facemask) breathing,
asthmatics with moderate exercise
but not in asthmatics (chamber) with
light exercise.

No observed effect in free
breathing subjects.
Strong suggestion that at
this level even light exercise
for "mouth" breathing asthmatics
would result in comparable or
more marked changes.

Comparable oronasal exposures
in asthmatics, or atopies could   ,
result in effects of significance.

Significant  effects in mild
asthmatics with moderate exercise.
Lowest level of significant
response for free breathing.
Significant effects unlikely.
                                                                                                                    en
                                                                                                                    ro
 Sheppard et al. (1980), Koenig et al.  (1980).   The second study used SO, in combination with saline
 aerosol.                                                               '
2
 Stacy et al. (1981); Bates and Hazucha (1973).

 Sheppard et al. (1981a); Linn et al.  (1982a);  Koenig et al.  (1982a).

4Linn et al. (1982b).

5Kirkpatrick et al.  (1982); Linn et al.  (1982a).

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                                    63

for these breathing modes.  Inferences made in the "implications" column
are supported by those mouthpiece studies that demonstrate the high
sensitivity of asthmatics and atopies to S02 and the substantial
enhancement of response in these subjects with increased ventilation.
     The table indicates that functional changes and symptoms  are likely
in "mouth" breathing asthmatics exposed to short-term peaks of 1  ppm S02
while involved in everyday activities such as walking outdoors.   The
finding of functional changes in free breathing normals  with moderate to
heavy exercise (Ve ~ 60 1/min) at 0.75 ppm SOg suggests  that asthmatics
and atopies, who are substantially more sensitive than normals (Table
5-3; CD, p. 13-50), would experience significant responses if  engaged in
exercise producing similar ventilation rates (e.g.,  moderate jogging).
Indeed, even with a lower exercise rate (Ve ~ 40 1/min), Linn  et  al.
(1982b) found "clinically and physiologically significant" responses in
free breathing young adult asthmatics at 0.75 ppm SOg.  Results at 0.5
ppm SOg are mixed, but do suggest effects in asthmatics  with moderate
exercise (Ve ~ 42 1/min), such as light jogging.  This is the  lowest
level of response for free breathing reported in the published
literature as of this writing.  Studies of oronasal  breathing  (Appendix
A) suggest that with higher exercise (50-60 1/min),  oral ventilation
rates (35 1/min) would be equivalent to those in the mouthpiece
exposures of 0.25 ppm S02 which produced small  increases in airway
resistance in some asthmatics; no perceptible symptoms would be expected
(Sheppard et al., 1981a).
     In evaluating these results in the context of decision-making on
possible standards, the following considerations are important:

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                                    64

 1)   The Significance of the Observed or Anticipated Effects to Health.
     Little controversy exists that a full asthma attack
 represents an adverse health effect.  In the extreme case, status
 asthmaticus. which occurs in as many as 10% of adults hospitalized
 for asthma (Senior and Lefrak, 1980), the situation can be life
 threatening.  In less extreme cases, day to day activities must be
 terminated until medication that relieves the symptoms and eases
 breathing can be administered.  Even though relief is-usually rapid
 following medication, an insult that requires the use of medication
 to permit routine functioning might well be considered an adverse
 health effect.
     The controlled human exposure studies of S02 discussed above
were designed to avoid precipitating serious asthma attacks or
 irreversible effects in exposed subjects.  The question arises,
 then, as to whether the observed responses themselves represent
 adverse effects or serve as indicators of potentially more serious
 consequences for larger populations exposed in ambient settings.
     The criteria document concludes that temporary small  changes
 in pulmonary function observed in normal adults are of less concern
than functional  changes and symptoms observed in asthmatics.   The
document summarizes the issue as follows (CD,  p. 13-51):
     Probably  of most concern are marked increases (> 10 percent)
     in airway resistance and symptomatic effects (wheezing,
     dyspnea)  observed by Sheppard et  al. (1981a) in  a group  of
     mild asthmatics with oral  exposure  via mouthpiece to  0.5 ppm
     (1.3 mg/nv3) sulfur dioxide during exercise.  A recent article
     (Fischl et  al.,  1981)  and accompanying editorial  (Franklin,
     1981)  in  the medical  literature discuss  the inclusion of
     indices of  airway obstruction and presenting symptoms such as
     wheezing  and dyspnea among factors  to be  considered  in
     attempting  to  predict  the need for  hospitalization  of asthma
     patients  following initial  emergency room treatment  (e.g.,
     bronchodilator therapy,  etc.)  for asthmatic attacks.

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                                    65

     Based on this criteria document discussion,  it appears that the
results of studies listed in Table 6-1 begin to be of some concern to
health when bronchoconstriction is accompanied by noticable symptoms.
This occurs for exercising asthmatics exposed to  S02 levels at or above
0.5 ppm.  The scientific literature does not, however,  provide
sufficient information to specify a concentration at which effects of
concern should be considered adverse.  In making  such a judgment,  the
Administrator should consider the discussion above and the following
additional factors:
     a)  In all cases, the bronchoconstriction and symptoms were
     transient and reversible.  The data do not provide direct
     evidence of long-term consequences  from repeated peak
     exposures, but  the possibility of such effects cannot be  ruled
     out.
     b)  Particularly at lower concentrations with free breathing
     functional changes were moderate to small  (A SRaw  ~ 0 to  50%)
     and within the  range of variability observed for day to day
     changes in many asthmatics.   At 0.75 ppm,  effects  were more
     substantial  (A  SRaw ~ 180%)  (Table  5-4).
     c)  Most studies utilized mild, young-adult  or adolescent
     asthmatics.   Even with the limited  number of subjects studied
     to date, some individuals appear particularly sensitive,
     exhibiting functional  changes  and symptoms markedly  greater
     than average.  Even more sensitive  individuals  may exist  in the
     population of "mild" asthmatics;  those with  more severe asthma  may
     also be more sensitive to S02  induced  bronchoconstriction.

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                                    66

     d)  Although the reported responses cannot be interpreted as
     overt asthma attacks, the combination of bronchospasm and
     symptoms might be perceived by some subjects as a "mild"
     attack; this could well result in curtailment of desired
     physical activities.
     e)  It is unclear whether psychological  factors can induce
     asthma attacks (NIAID, 1979).  If they can, however,  perception
     of symptoms and bronchospasm induced by  SOg could trigger more
     serious consequences in suggestible subjects.
     f)  Given the limited combination of concentrations,  subjects,
     activity levels,  and other environmental  conditions studied to
     date,  firm conclusions about situations  in which SOg  would
     likely induce asthma attacks are not possible.   Even  if it is
     judged that the functional and symptomatic effects seen in
     available studies are not themselves adverse, they could be
     considered as possible indicators of more serious attacks that
     are clearly adverse.
2)   Relative Effect of SOg Exposure Compared  to Exercise,  Other
     Stimuli.
     One of the tests  used in  characterizing  asthmatics is  evidence of
     exercise induced  bronchospasm (EIB).  The phenomenon  has been
     extensively investigated  (e.g., Deal et  al.,  1979) and appears to
     be related to temperature and relative humidity.of inspired air.
     Under  the exercise and other test conditions  (  ~ 20°C,  70-95%  RH) of
     most SOg  studies,  EIB is  usually  small (increase in SRaw <_ 15%)
     (Linn  et  al., 1982a;  Sheppard et  al.,  1981a;  Deal  et  al.,  1979);
     Linn et  al.  (1982b)  observed a  somewhat larger  group mean  EIB

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                                       67

      (SRaw ~ 55%).   At low temperatures and  humidities  (-12°C, 0% RH)

      more substantial  increases  in  airway resistance can  occur (Deal et
      al., 1979).  Under these environmental  conditions, the  EIB found  by
      Deal et al.  (1979) (A SRaw  ~ 40%) with  clean air mouthpiece
      breathing is smaller than the  increase  in  airway resistance (50%
      over exercise  control) seen  by Kirkpatrick  with facemask  exposure
      to  0.5 ppm S02 at the same exercise rate.   Thus, although EIB alone
      may limit the  maximal exercise rate of  asthmatics, S02  enhances the
      effect, further limiting activity or increasing the  risk  of a more
      serious response.  The combination of SOg,  exercise, and  cold dry
      air has not yet been tested.

      A number of other stimuli may  induce bronchoconstriction  in
asthmatics  (Table 6-2).   This does  not diminish  the importance of
responses potentially  induced by  peak  S02 levels.


           TABLE 6-2.   TRIGGERS OF ASTHMATIC ATTACKS (NIAID,  1979)
                         I.  Known
                           Al Allergen
                           B) Drugs
                             1) Allergy
                             2) Aspirin intolerance
                             3) Pharmacologic effects
                           0 Exercise
                           D) Industrial (avocational and occupational exposure)
                           E) Infections
                           F) Reflexes

                         II.  Probable
                           Al Air pollutants
                           Bl Chemical irritants
                           Cl Sinusitis
                           Dl Vasculitis (periarteritisl

                        III.  Possible
                           Al Emotions
                           Bl Endocrinologic imbalance
                           0 Weather

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                                    68

3)   Probability of Most Sensitive Exposures
     Peak 1-hour SOg 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 (Tables 4-1,  4-2; Appendix D).  Shorter term (5
     to 10 minute)  peaks at  these  levels may  be somewhat more common,
     but no systematic  data  exist.   Moreover, indoor  S02 levels are
     almost always  substantially lower than outdoor levels  (CD, p. 5-
     117).  Thus, effects appear likely only  for situations  involving
     asthmatics undergoing light to moderate  exercise outdoors  relatively
     near (< 10 km) major point sources in conditions resulting in peak
     (> 0.5 ppm, 5  to 10 minutes)  S02  levels.   Preliminary  analyses
     (Appendix 0) suggest that  several  hundred  thousand asthmatics and
     atopies may live in the vicinity  of such sources, but  because the
     frequency and  extent of levels in excess of 0.5  ppm is  low, the
     probability that an exercising asthmatic will be located in the same
     time and area  with  such peaks  appears small.  Quantitative analyses
     of the frequency of occurrence of such exposures are not yet available.
  .   Although under current  air quality conditions, such situations must
     be infrequent,  they present the possibility of significant health
     effects.
          Some data suggest  that rapid rises  in  S02 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
     Section V-B, however, the  rapid rise might  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.

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                                     69
 4)   Variance about the 1-hour  average.
      The controlled studies  in  Table 5-4  indicate that effects occur
      within 5-10 minutes  but do not  necessarily worsen with continued
      exposure 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 will be
      higher.   Based on  typical  distributions, the peak is likely to be
      within a factor of 1.4 to  2.4, or less than 1.2 ppm (Larsen, 1968;
      Burton and Thrall, 1982).  As the ratio of 5-minute to 1-hour
      concentrations  increases,  the geographical extent of the peak tends
      to  decrease.

      Based  on  the above evaluation of the studies and related factors,
the staff believes that an appropriate range of interest for a possible
1-hour S02  standard  is 0.25 to 0.75 ppm.   The lower bound of 0.25 ppm
represents  a 1-hour  level for which maximum 5 to 10 minute peak exposures
are not  likely  to exceed 0.5 ppm,  the lowest level  where potentially
significant responses in asthmatics have  been observed with free breathing,
but with a  facemask.  Although  mouthpiece experiments  suggest  the possibility
of modest functional changes produced by  10 minute  exposures to 0.25 ppm
S02, with moderate exercise, the effects  themselves  are not clearly  of
health significance.  Furthermore,  heavy  exercise rates are required to
produce comparable or greater oral  ventilation  for  free breathing,  reducing
the probability of exposure  to  this condition.   The  upper  bound of the
range (0.75 ppm) represents  a level  at which  (based  on  the  results in
free breathing asthmatics  and normals, the increased sensitivity  of
asthmatics and atopies  in  mouthpiece  experiments, and the  results of

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                                    70

 oronasal exposures at 0.5 ppm), the risk of effects appears high.  Based
 on  normal air quality variations a 1-hour standard of 0.75 ppm would
 permit  5-10 minute peaks in excess of 1 to 2 ppm during the peak hours,
 and would permit multiple hours in which the 5-10 minute peak would
 exceed  0.5 to 0.75 ppm, even when the 1-hour average is within this
 range.
      Independent of frequency of exposure considerations, 1-hour
 concentrations at the high end of the above range would provide little
 margin  of safety for exercising asthmatics.  The low frequency with
 which such peak values would occur in the presence of active sensitive
 subjects tends to enhance the margin of safety.
      b)  Additional factors to be considered in evaluating margin of
         safety and risks - peak exposures
     Additional factors that should be considered in evaluating a margin
 of  safety for a 1-hour standard include:
      i)  Interaction with Other Pollutants
     The -studies in Table 6-1 were done with S02 alone.  As discussed in
 Section V, additive or greater than additive responses might occur where
 peak S02 levels occur in combination with 03 or particles.  The
 available data do not provide clear evidence for synergism in either
 case, but controlled exposures have not examined such combinations in
 sensitive asthmatics.  Because peak S02 exposures occur during morning
 to early afternoon hours (Figure 4-1),  combinations with 03 at or near
 the standard level  (0.12 ppm) are possible.   Because peak S02 levels
 near combustion sources will  be accompanied  by  high NOX levels,
 simultaneous peaks of S02 and 03 near these  sources are not likely.
Significant  health related  interactions between S02 and N02 have not
been demonstrated.

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                                    71

      ii)   Risks for Other Sensitive Groups. Effects Not Evaluated
      Based on the available data, asthmatics and atopies appear to be
the most sensitive segments of the population with respect to peak S02
induced functional changes.  To the extent the suggested range is
protective of these groups, the risk of functional effects in other
groups appears small.  The other major effects of concern (changes in
clearance, aggravation of bronchitis, genetic toxicity, and mortality)
have  not been evaluated adequately in controlled human studies, but may
result from repeated peak exposures over longer time periods.  These are
addressed  in the following sections.
      3.  Short-term (24-hour) Exposures
      a)  Derivation of Ranges of Interest from Epidemiological  Studies
     Although a number of epidemiological investigations provide
qualitative evidence for the effects of short-term exposure to  S02 in
combination with particles,  the criteria document indicates that those
most useful for developing quantitative conclusions include a series of
studies and reanalyses of daily mortality in London (Martin and Bradley,
1960; Martin, 1964;  Ware et  al.,  1981;  Mazumdar et al., 1981; CD,  p. 14-
16 to 14-24)  and studies of  bronchitis  patients in London  (Lawther et
al., 1970).  These studies are briefly  evaluated in Section V-D (Table
5-5).  The staff assessment  of these studies for deriving  ranges  of
interest for  24-hour S02 standards is summarized in Table  6-3 and
discussed below.
     The London  mortality studies  have  been  characterized  by  the
criteria document  as  suggesting that  notable increases  in  excess
mortality ocurred  in  the range of  500-1000  pg/m3 British Smoke  (BS)  and
S02 (0.19-0.38 ppm)  and are  most  likely  when both pollutants  exceeded

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                                      72
       TABLE 6-3.  STAFF ASSESSMENT OF SHORT-TERM EPIDEMIOLOGICAL STUDIES
Effects/
Study
Effects Likely3
Effects Possible
Measured Sulfur Dioxide - u9/m3(ppni) - 24 hour mean
Daily Mortality
in London 1
500-1000(0.19-0.38)
Aggravation of
Bronchitis2
500-600(0.19-0.23)
< 500(0.19)
Combined Effects
Levels
500(0.19)
< 500(0.19)
Deviations in daily mortality from mean levels examined in  3 studies  encompassing
 individual London winters of 1958-59 and 14 aggregate winters from 1958-72.   Early
 winters were dominated by high smoke and S02,  principally from coal combustion
 emissions, and with frequent fogs (Martin and  Bradley, 1960; Ware  et  al.,  1981;
 Mazundar et al., 1981).
Examination of symptoms reported by bronchitics in  London.   Studies conducted
 from the mid-1950's to the early 1970's (Lawther et al.,  1970).
3CD, Table 14-8.
  about 750 pg/m3 (0.29 ppm S02).   As  indicated  in  Table  6-3,  these
  estimates represent  judgments  of  the most  scientifically  reliable
  "effects  likely levels"  for  daily S02 (and BS)  and  mortality,  at least
  in the context  of historical London  pollution  exposures.  Because of the
  severity  of the health endpoint and  the  need to provide an adequate
  margin of safety in  standard setting,  it is important to  determine
  whether the data support  the possibility of health  risks  below these
  "effects  likely levels."   As discussed in  the  criteria  document  (CD,
  Section 14.3.1.2)  and the particulate matter staff  pa'per  (EPA, 1982b),
  the London  mortality  studies and  reanalyses do  support  the possibility
  of a monotonic  dose-response for  particles, with  no obvious  "threshold"
  at 500 ug/m3.

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                                    73

      The  situation with respect to S02, however, is much less clear.
When  S02  alone  is compared with daily mortality deviations, an apparent
association persists at levels below 500 yg/m3 or 0.19 ppm (Ware et al.,
1981; Mazumdar  et al., 1981).  However, if attempts are made to account
for particles and weather variables, the association between mortality
and pollution on non-episodic days (BS, S02 < 500 yg/m3) persists for
smoke but not for S02 {Mazumdar et al., 1981).  This analysis also
questions the role of higher S02 levels (> 500 yg/m3 or 0.19 ppm) with
respect to mortality effects.  The criteria document concludes, however,
that the effects of S02 and BS at these higher concentrations cannot
clearly be separated (CD,  p. 14-24).  Table 6-3 reflects the staff
conclusion of Section V-D, namely that the published evidence does not
suggest a significant risk of increased mortality for exposures to S02
alone at concentrations below the likely effects levels listed in the
criteria document.
     Lawther's studies  of  bronchitic patients  began during periods of
high pollution  (1954) and  continued through the time when levels  were
considerably lower (e.g.,  1967-68;  mean winter S02, 204 yg/m3,  0.08 ppm;
BS, 68 yg/m3).  Lawther et al.  (1970)  found an association  between peak
pollution and health status  of  bronchitics  and that responses declined
as controls reduced pollutant  levels.   Because of the nature  of the
study, effects were related  to  peak daily  concentrations, but the
authors felt the effects were more  likely  the  result of brief exposures
to short-term peaks "several-times  the 24-hour average." While this
suggestion is  plausible, the available data do not  permit any quantitative
evaluation.   The mechanisms  of  aggravation  of  bronchitis might  involve
responses (e.g., slowed  clearance)  other than  the functional  changes

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                                     74

 observed  in  asthmatics.  Thus, 1-hour standards based on protecting
 asthmatics might  not be adequate for bronchitics.  Therefore, 24-hour, or to
 a  lesser  extent,  longer-term pollutant averages, should be used to indicate
 the  possibility of  repeated short-term levels of concern.  Lawtheir's
 suggestion that 24-hour averages of 250 yg/m3 smoke and 500 yg/m3 (0.19 ppm)
 SOg  represent  "the  minimum pollution leading to any significant reponse"
 appears reasonable, although the possibility that short-term peaks of
 concern may  occur at lower 24-hour levels cannot be discounted.  The
 criteria  document notes that a summary of results for selected patients for
 the  winter 1967-68  (Table III, Lawther et al., 1970) suggests a statistically
 significant  correlation between S02  (as well as smoke, sulfuric acid, and
 temperature) and symptom scores for a winter with only one day of S02 > 500
 yg/m3  (0.19  ppm) and BS >_ 250 yg/m3.  While such simple correlations
 do not demonstrate  effects at lower levels, they do suggest that 500 yg/m3
 (0.19 ppm) S02 (and 250 yg/m3 BS) may not be absolute thresholds for
 the  most  sensitive  bronchitis patients (CD, p. 14-53).
     Both the mortality and bronchitic studies represent population
 groups among the most sensitive to pollutant effects.  Taken together,
 as in Table  6-3, the studies indicate that effects are likely with S02
 levels at or above 500 yg/m3 (0.19 ppm) in the presence of smoke levels
of 250 yg/m3 to 500 yg/m3.   Thus, 500 yg/m3 (0.19 ppm) represents an
 upper bound for the range of interest for 24-hour S02 standards.
Although the data suggest that effects may be possible at  lower levels
and, therefore, a need to include an adequate margin of safety below the
more certain effects levels,  the  studies  provide no scientific basis for
establishing a lower bound  for a  range of interest for 24-hour S02
standards.  In the absence  of such  data,  it seems  reasonable to

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                                    75
recommend the level of the current standard (365 pg/m^ or 0.14 ppm) as a
lower bound.   This level was previously judged to provide an adequate
margin of safety from the effects under consideration here.  Although
the effects of S02 cannot be unequivocally separated from particles, for
reasons specified in Section VI-A, a separate SOg standard is
desirable.  For days in which particulate matter approaches the high end
of the recommended range (350 yg/m3 as PM10; EpA, 1982b), simultaneous
SOg levels'at the high end of the above range (0.19 ppm) would provide no
clear margin of safety.  With lower particle levels, the margin of safety
increases.
     b)  Additional Factors to be Considered in Evaluating Margin of
         Safety — Short-term Exposures
     The range of interest was derived from British data representing
two effects categories and London pollution from 1958 to 1972.  In
considering standards within this range the following additional  factors
should be considered:
     i)  Interactions with Other Pollutants or Conditions
     As noted above,  interactions with expected maximum particle
concentrations have been taken into account to establish the range of
interest.  Interactions of S02 with ozone and other photochemical
oxidants have not been evaluated on a  daily basis.   The results of
short-term (2-hour) studies at high SOg and 03 levels do not permit
clear conclusions (Appendix B).
     Based on the experiences in London and other areas and solubility .
considerations,  conditions involving low temperature, high humidity fogs
with substantial  ammonia, with or without high primary particles, might
exacerbate the effects of S02-

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                                    76

      ii)   Relative Exposure
      Based on measurement of indoor exposures and ventilation reported
 by  Lawther et al.  (1970), indoor pollutant exposures in British
 residences more closely tracked outdoor levels than is-the case in more
 tightly sealed U.S. residences.  Thus, for comparable outdoor concentrations,
 the overall exposure to maximum 24-hour outdoor pollution was likely to
 have been  greater in urban areas of Great Britain than in contemporary
 U.S. exposure situations.  Since many of the more sensitive individuals
 may  be confined indoors, the extent of increased mortality or symptoms
 would tend to be lower in the U.S. than observed at comparable levels in
 British studies.
      i ii)   Risks for Other Sensitive Groups, Effects not Evaluated
      Based on the evaluation of toxicological, controlled human,  and
 qualitative epidemiological  data, Section V-B and Table 5-2 identify a
 number of  effects that would be observed or anticipated to occur  in
 sensitive  groups as a result of such exposures.   The studies used to
 derive the  range addressed:   1) premature mortality in very sensitive
 individuals with chronic respiratory and cardiovascular diseases,
 individuals with influenza,  and the elderly;  and 2) morbidity (aggravation
 of disease) in bronchitic patients.  Because it  is reasonable to  expect
 morbidity  at or below levels at which  mortality  occurs in these sensitive
 groups,  the London  mortality studies,  which involved a large population,
 also may be considered as a  relatively sensitive indicator of morbidity
 risks.  Thus,  to the  extent  that  the London data suggest  a risk of small
 increases  in mortality at levels  as low as  0.19  ppm,  some risk of morbidity
is possible at or somewhat below  this  level.   This risk  should be considered
in evaluating  potential  standards.

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                                    77

     Other  groups not expressly addressed by the short-term British
 studies are children and asthmatics.  Daily exposures to particles and
 S02 appear  to be associated with increased symptoms of respiratory
 disease, particularly in sensitive children (Lebowitz et al., 1972).
 Repeated peak S(>2 exposures might reduce resistance to infection by
 slowing nasal or other mucociliary clearance rates (Section V-B).  Other
 qualitative studies suggest possible small effects of repeated peak or
 24-hour exposures to SOg on lung function in children in contemporary
 North American cities (Becklake et al., 1978;  Dockery et al., 1981).
 The significance of these preliminary findings is unclear at this time,
 and no reason exists to suggest important effects below the range of
 interest.   Potential effects on sensitive asthmatics are most likely
 related to  peak exposures and are addressed by the recommendations with
 regard to a 1-hour standard.
     The above discussion addresses,  in part,  several  of the major
 effects categories of expected effects of SOg  outlined in Section V-B.
With respect to those not addressed:   1) Qualitative evidence summarized
 in that section suggests that repeated acute exposures to high levels of
 S02 and community air pollution may  affect clearance and other host-
 defense mechanisms,  possibly resulting in increased infections and
disease.  2)  The question  of potential  mutagenesis/carcinogenesis of SOg
alone or in combination  with carcinogens (BaP)  is unresolved.   The
available toxicological  data mostly  involve extended repeated  exposures
to very high exposures,  but do not permit quantitative evaluation.
Epidemiological  studies  indicate that  cigarette smoking is  the major
determiniant of lung cancer,  but do not  rule out the possibility  of a

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                                    78

small effect of high historical levels of air pollution.  Both peak (1-
hour) and short-term (24-hour) ranges would maintain these as well as
annual SOg concentrations in U.S. cities to levels well below these
historical values, but would not prevent long-term air quality in some
heavily populated areas from deteriorating to levels above those allowed
under current standards (Frank and Thrall, 1982).
     Studies of hospital admissions or emergency room visits, although a
crude indicator of morbidity, sometimes can provide some suggestion of
the effects of pollution on several of the above categories.  The
results of Samet et al. (1981), although essentially negative, provide a
suggestion of a very small, but statistically significant, association
between emergency room visits for respiratory diseases and SOg levels
between 2 to 369 yg/m3 (0.001-0.14 ppm) and TSP levels in the range of
14 to 700 yg/m3.
     4.  Long-Term (Annual) Exposures
     As discussed in Section V, despite a number of studies of long-term
community exposures of  S02 in combination with particles and other
pollutants, the criteria document concludes that there is little
quantitative data useful  in developing long-term concentration response
relationships for SOg.   Based on the work of Lunn et al. (1967,  1970)
long-term S02 levels should be maintained below 0.07 ppm (180 ug/m3),  a
level  not approached in contemporary U.S. atmospheres.  The health basis
for limiting annual  SOg levels beyond those permitted by shorter-term
standards is suggested  by  the more qualitative evidence summarized in
Section V-B and also outlined in the previous section.  These potential
effects of interest  for which quantitative data are not available
include effects on  clearance and other host defense systems,  and,  to  a

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                                    79

 lesser extent, potential mutagenicity or co-carcinogenicity of S02.  The
 major concern is whether repeated S02 peaks permitted by 24-hour or 1-
 hour ranges in area-source dominated populations centers might, after
 some long time period, result in increased risk of such effects.  While
 the available data do not provide strong evidence for substantial risks
 on an individual basis, the analysis of Frank and Thrall (1982) suggests
 that elimination or substantial relaxation of the current annual
 standard could result in increased exposures to large numbers of people
 in several heavily populated urban centers.  The potentially large
 increase in exposed individuals and the qualitative evidence for effects
 should be considered in deciding whether to maintain an annual  standard
 at or above the current level  of 0.03 ppm (80 ug/m3).
     5.  Relationships Among Averaging Times
     An important consideration in evaluating potential  standards are
 the interrelationships among 1-hour, 24-hour, and annual averaging
 times.  Although several  recent analyses are available (Frank and
 Thrall, 1982;  Burton et al., 1982; MES,  1982) information in this area
 remains incomplete.  Data from the approximately 900 sites  used in
 Tables 4-1 and 4-2 show that attainment  of the current annual  standard
 (0.03 ppm S02) would not  prevent multiple exceedances of the lower bound
 of the recommended ranges for  both 1-hour and 24-hour standards (Figure
 6-2).  This figure indicates that a  national  annual  standard would
 probably not be a useful  surrogate for shorter term standards without
 being unnecessarily restrictive in some  areas.  Conversely,  as  noted
above and in Appendix D,  current and alternative shorter term standards
 (24-hour, 3-hour, 1-hour) would not  prevent  long-term levels from
exceeding the  current annual standard  in some population-oriented sites

-------
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a
UJ
a  «•«
  ••"
                                      J
                                                       -24-HOUR DATA
-I-HOUR DATA
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                                     81
 which are few in  number,  but  represent substantial .numbers of people
 potentially  exposed  (Frank  and Thrall, 1982).
      It  is also apparent  that a 1-hour standard would not guarantee
 attainment of the 24-hour standard at all site types.  For example,
 analysis  of  continuous S02  data at population oriented sites in 4 major
 urban areas  suggests that attainment of a 0.5 ppm 1-hour maximum
 standard  in  these areas would result in a 24-hour maximum of 0.21 ppm
 (550  yg/m3)  (Johnson, 1982a).  The situation is reversed at many sites
 dominated  by  large point  sources (Frank and Thrall, 1982).
      The question of whether a 24-hour standard is a useful surrogate
 for 1-hour effects has been examined by air quality and modeling
 analyses  (Appendix D).  The adequacy of a 24-hour surrogate depends on
 site  type, level  and number of exceedances considered adequate for
 protecting health, and the degree of over-control  required vs a 1-hour
 standard.  Figure 6-3 shows the proportion of sites with second 1-hour
 maxima in excess of 0.5 ppm as a function of second 24-hour maxima for
 the 900 sites noted above.  These data indicate that with attainment  of the
 current 24-hour standard,  over 40% of the sites would have second hourly
 maxima in excess of 0.5 ppm.  An even higher proportion  of sites can  be
 expected to have second hourly maxima in  excess of 0.25  ppm.   The air
 quality and modeling analyses  summarized  in  Appendix D suggest  that the
 current 24-hour standard effectively  limits  1-hour maxima at  population-
 oriented sites.  At many sites dominated  by  strong point  sources,  however,
the current 24-hour standard would  be a useful  surrogate  for  a  1-hour
 standard only if multiple  (2 to  over  20/yr)  exceedances  of SOg  levels  in
the range of  0.5 to 0.75 ppm were  considered acceptable.   Even  a more
stringent 24-hour  standard of  0.12  ppm would not substantially  improve

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                                    82
1-hour air quality at many sites with high 1-hour values.  Still  tighter
24-hour surrogates would be overly stringent at sites with currently
acceptable air quality.  Relaxing the 24-hour standard to a level in the
upper portion of the range of interest (0.16 to 0.19 ppm) could permit a
substantially larger number of sites with second maximum hourly values in
excess of 0.75 ppm.
     The simulation modeling of large point sources of SOg (1000  megawatt
power plant) suggests that the current secondary 3-hour standard  provides
substantially better protection against 1-hour peaks than does the 24-hour
standard, and might itself be a useful surrogate.  In this simulation,
the worst site is predicted to experience 3 to 4 expected exceedances/year
of 0.5 ppm and only 1 expected exceedance per year of 0.75 ppm.  The air
quality analysis of Frank and Thrall (1982) does not suggest substantially
improved protection with the 3-hour standard, but because it is based on
only 1 or 2 monitors per source, the air quality analysis is less reliable
on this point.
     The .analysis of air quality relationships suggests that no single
averaging time will provide the same degree of protection and control
afforded by the other averaging times in all  situations.   The current
24-hour standard would prevent 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  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,  while additional
analyses of alternative averaging times are needed,  the work to date

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                                    83
 suggests that implementation of the current suite of SOg standards
 (annual, 24-hour, 3-hour) provides substantial protection against the
 direct effects of S02 identified in the scientific literature.  This
 permits consideration of reaffirming the existing S02 standards as a
 reasonable policy option following the current criteria and standards
 review.
 C.   Summary of Staff Conclusions and Recommendations
     The major staff conclusions and recommendations made in Section VI,
 A-B are briefly summarized below:
 1)   Laboratory studies show that peak ambient levels of SOg, acting
     alone, can cause health effects in humans.   Consequently, a
     separate S02 standard is still  appropriate.   The additional
     complexities involved in specifying combination S02/particle
     standards do not appear warranted in terms  of public health
     protection.
2)   Support for  an  annual  standard  at or near current  levels is largely
     qualitative.  Nevertheless,  because short-term standards alone  would
     not  prevent  increases  in annual  mean concentrations  in  some heavily
     populated urban areas,  consideration should  be  given to retention
     of a primary annual  standard for  S02-   Based on  a  series of recent
     controlled human studies,  consideration of a new peak  (1-hour)  S02
     standard is  also recommended.   The 24-hour and  potential  annual  and
     1-hour standards should all  be  expressed  in  statistical  form; the
     decision on  the allowable  number  of  exceedances  for  the 24-hour  and
     potential  1-hour standard  should  be  made  in  conjunction with
     establishing a  level for the  standards.

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                                    84

3)   Based on a staff assessment  of  controlled  human  exposures to peak
     (minutes to hours)  S02  concentrations,  the range of  1-hour SOg
     levels of interest  is 0.25 to 0.75  ppm  (650 to 2000  yg/m3).
     The lower bound represents a 1-hour level  for which  the maximum
     5 to 10 minute peak exposures do  not exceed 0.5  ppm, which is
     the lowest level  where  potentially  significant responses in free
     (oronasal) breathing asthmatics have been  reported in the published
     literature as  of this writing.  The upper  bound  of the range represents
     concentrations 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  to three 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

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                                    85

     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.
4)   Based on a staff assessment  of  the short-term epidemiological  data,
     the range of 24-hour S02 levels of interest are 0.14  to  0.19 ppm
     (365 to 500 yg/m3).   Under the  conditions  prevailing  during the
     London studies  (high particles, frequent fogs,  winter),  the upper
     end of the range represents  levels at which effects may  be likely
     according to the criteria document.  The risk  of health  effects
     should be lower when translating these  results  to U.S. settings
     with particle levels at  or below the ambient  standards.
          The uncertainties with  respect to  interactive effects with
     particles or other pollutants and the nature  of  effects  are
     important margin of  safety considerations.   In  the absence of
     quantitative scientific  evidence for a  level where effects are
     unlikely,  the level  of the current  standard  is  recommended as a
     lower bound.  This level  was previously  judged  to  provide an
     adequate margin  of safety  from  the  same  effect:  under consideration
     here.   Qualitative data  from animal toxicology,  controlled human
     studies and  community epidemiology  suggest  risks  of potential
     effects (e.g.,  slowed clearance)  as well as the  existence of
     sensitive  groups  (e.g.,  children)  not evaluated  in the more
     quantitative  studies.  These factors as well as  potential pollutant
     interactions, exposure characteristics and whether the 24-hour
     standard is  intended to  act as  a  surrogate for a 1-hour standard,

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                                    86
     should also be considered in evaluating the margin of safety
     associated with alternative standards in the range of 0.14 to 0.19
     ppm.
5)   Although the data are inconclusive and uncertain,  the possibility
     of effects from continuous lower level exposures to SOg cannot be
     ruled out.  Given the lack of epidemiological  data suggesting long-
     term effects of S02 at or near the levels of the current annual
     standard, however, no quantitative rationale can be offered to
     support a specific range of interest for. an annual standard.
     Nevertheless, air quality analyses summarized  in Appendix D suggest
     that short-term standards in the ranges recommended in this paper
     would not prevent annual levels in excess of the current standard
     in a limited number of heavily populated urban areas.   Because of
     the possibility of effects from a large increase in population
     exposure, consideration should be given to maintaining a primary
     annual  standard at or above the level  of the current standard.
6)   Analyses of alternative averaging times to date suggest that
     while any single standard might not be a suitable  surrogate for
     other averaging times, implementation  of the current suite  of
     primary and secondary S02 standards (annual, 24-hour,  3-hour)
     provides substantial  protection against the direct health  and
     welfare (see Section  VII) effects identified in the scientific
     literature as being associated with ground level S02  air quality.
     This permits the consideration of reaffirming  the  existing  S02
     standards as a reasonable policy  option,  following the current
     criteria and standards review.  Factors  favoring such  an option
     include the substantial  improvements  likely  in  information  on
     1-hour  effects over the  next  few  years,  the  uncertainties in

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                               87

long-term effects data, the possibility of substantial  changes in S02
control strategies prompted by regional effects,  and the practical
advantages of not requiring premature formulation and implementation
of a new S02 regulatory program associated with revising standards
at this time.

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                                    88

VII. CRITICAL ELEMENTS IN THE REVIEW OF THE SECONDARY STANDARD
     This section discusses information drawn from the criteria document
that appears most relevant in the review and possible revision of
secondary standards for sulfur oxides.  Three major categories of
welfare effects are examined.  Within each category, the paper presents
1) a brief summary of relevant scientific information, 2) an evaluation
of potential quantitative relationships between S02 and effects, and
3) a staff assessment of whether the available information suggests
consideration of secondary standards that differ from the recommended
primary standards.  Preliminary staff recommendations on policy options
for secondary standards are also presented.
A.   Vegetation Damage
     1.  Nature of Effects and Factors Affecting Plant Sensitivity
     Plant responses to S02 exposure may result in physiological and
biochemical effects, foliar injury, and reductions in growth and
yield.  The specific response varies with the pollutant concentration,
duration of exposure, and is enhanced or mitigated by certain biological
and environmental factors.
     Information on the mechanisms of toxicity of S02 suggests that
plant responses are strongly linked to the penetration of SO? and
accumulation of sulfite and bisulfite within plant cells.  Since sulfate
is considered to be much less toxic than sulfite and bisulfite, toxic
effects are believed to occur when the rate of accumulation exceeds the
rate of conversion of bisulfite and sulfite to sulfate (Thomas, 1951).
     In general, there is a progression of effects that can be expected
following either short-term or long-term (repeated peak or continuous)
exposure.  At the lowest reported response levels, short-term exposures

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                                     89
 tend to be associated with potentially reversible physiological effects
 (e.g., gas exchange rates, enzyme activities).  As exposure levels
 increase, foliar injury and reductions in growth and yield may result.
 However, reductions in growth and yield are not always accompanied by
 foliar injury, and conversely,  foliar injury is not always a  reliable
 indicator of growth and yield (CD, p. 8-11).
      More specifically, the types of  effects can be summarized as
 follows:
      a)  Physiological  and Biochemical  Effects
      Physiological  and  biochemical  changes  may  be  expected to  precede
 the development  of  foliar  injury  and  changes in  growth  and yield.
 Although  foliar  injury  is  the most  obvious  effect  of  S02 on plants, it
 is  only the end  result  of  a  series  of events  that  have  occurred at the
 sub-cellular  level  of biological  organization.   Initial changes in
 photosynthetic and  transpiration  rates and  biochemical  status  (e.g.,
 enzyme  activities,  metabolite concentrations) are  subtle responses that
 may  be  followed  by  more severe measures of plant injury (CD, p. 8-5).
     b)  Foliar  Injury
     Foliar injury  appears to be associated with the penetration of SOg
 to substomatal cavities where damage to mesophyll cells may lead to
 collapse of tissues and changes in leaf color (NAS, 1978;  Mclaughlin et
 al., 1979; Evans and Miller, 1975).  Short-term exposure to SOg produces
 foliar injury, which varies in appearance from ivory to white  in most
 broadleaf plants to darker colors  (e.g., brown, red) in other  plants
 such as conifers (CD, p. 8-10).  Long-term exposure to S02  is
characterized by chlorotic  spots or mottling.  Leaves  are most  sensitive
to S02 exposure just after  growth  to full  development  (NAS, 1978, p.
105).

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                                    90

     c)  Growth and Yield
     Effects of S02 exposure on growth and yield have been examined,  to
some extent, in both short-term and long-term exposure studies.
Although increases in foliar injury and decreases in growth and yield
tend to occur simultaneously when S02 exposures are sufficiently high,
foliar injury is an imprecise measure of the effect of S02 on growth  and
yield parameters.  For example, studies using soybeans report that
growth and yield reductions occur with minimal or no accompanying foliar
injury (Reinert and Weber, 1980) and it is possible to have foliar
injury with no apparent effect on crop yield (Heagle et al., 1974).
     Although plant damage may follow long-term exposures, enhanced
growth has also been reported when soil sulfur is not sufficient to meet
plant needs and atmospheric S02 levels are low (CD, pp. 8-7 to 8-10).
Noggle and Jones (1979) conclude that low to moderate levels of
atmospheric S02 can be beneficial for agricultural  crops in areas with
sulfur deficient soils.  In natural ecosystems, however, S02 induced
increases (or decreases) in plant growth can affect species richness  and
diversity and might reduce the stability and productivity of such
ecosystems (CD, pp. 7-9 to 7-13).  Thus, increased  yield in natural
ecosystems is not always beneficial (CD, pp. 8-9 to 8-10).
     The extent, severity, and type of plant response to S02 exposure
varies with plant genetics, the condition of the plant itself,  and
environmental conditions.  The inherent susceptibility of plants to S02
varies greatly among plant species and even among cultivars, varieties,
or clones of the same species (CD, pp. 8-12 to 8-14).   In general, the
influence of genetics on plant susceptibility is stable and does not
change unless selection, mutation, or hybridization occurs (-NAS, 1978,

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                                     91
 pp.  101-103;  Wilson  and  Bossert,  1971).  Other important factors
 affecting the severity of  damage  which should be considered include:
 1)    The stage of  growth at the time of plant exposure  (NAS, 1978, pp.
      104-105);
 2)    The plant's nutrient  and water status; the later is particularly
      important because plants are less physiologically active and more
      resistant to  gas exchanges (including pollutant gases) when
      stressed for water; and
 3)    Environmental conditions such as the presence or absence of other
      pollutants, soil moisture (Hill et al., 1974; Zimmerman and
      Crocker,  1934), wind  speed (Ashenden and Mansfield, 1977),
      temperature (Heck and Dunning, 1978),  light (Thomas and Hendricks,
      1956) and  relative  humidity  (Mclaughlin and Taylor, 1981).
      2.  Quantitative Relationships
      The following general  criteria were used to select those studies
most  relevant to evaluating quantitative relationships:
1)    Exposure  regimes should be at or near  realistic levels anticipated
      in the ambient environment.   The following  levels  were used as  a
      guide:  short-term exposures  (minutes  to hours) <  1 ppm (2600
      yg/m3); and, long-term exposures (weeks to years)  < 0.1  ppm (260
      ug/m3).
2)    Exposure and growth  conditions  must  be adequately  defined.
3)   Plant response should  be  expressed  so  that effects  on  exposed
     plants can be  compared to control plants.
Finally, exposure studies not  meeting the above criteria  may  be  included
if discussion of their validity and  significance  is  an  important  part of
assessing evidence.

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                                    92

     Quantitative information on plant response to S02 exposure is drawn
from controlled and ambient exposure studies.  The strengths and
weaknesses of both are outlined below.
     a)  Controlled Exposure Studies
     Controlled exposure studies are comprised of greenhouse, environmental
chamber, and field chamber studies.  Although a common characteristic of
these studies is to control plant exposure to pollutants, controlled
exposure studies also allow for the control of other environmental variables.
Since field chambers allow plants to be grown and exposed under conditions
that approximate actual field conditions, experiments employing field
chambers are generally considered to reasonably simulate plant growth in
the field.  Controlled exposure systems have some inherent problems that
complicate extrapolation of experimental  results to actual field conditions.
For example, most of these studies have exposed plants at wind speeds
that are lower than those experienced under field conditions.  This is
expected to reduce pollutant uptake and plant sensitivity (Ashenden and
Mansfield, 1977; Nobel, 1974).  On the other hand, investigators typically
attempt to optimize growth conditions (e.g., soil  fertilization, moisture),
which should generally increase plant sensitivity  to pollution.
     i)  SO? Alone
     The most relevant short-term and long-term exposure studies of the
effects of SOg alone are listed in Table  7-1.  The short-term studies
suggest that plants'are affected by S02 exposures  of 1.5 to 4 hours
duration.  Although some early studies reported foliar injury in
agronomic crops following single 1-hour exposures  to less than 1 ppm
(NAS,  1978; Zimmerman and Crocker, 1934),  more recent studies have not
evaluated the effect of single hour exposures on other biological

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             93
TABLE 7-1.
Concentration
ppm (»g/m )
Short-tern
0.2S (660)
0.50 (1300)
0.50 (1300)

.
0.54 (1915)
0.75 (1965)
0.79 (2070)
1.0 (2600)


1.0 (2620)
Long-term
0.05 (130)
0.06 (160)
(see text)
0.067 (190)
0.068 (190)
0.05 (131)
to 0.2 (524)
Exposure Duration/
Growth Conditions*

2 Hours
1.5 Noun
2 Hours


4 Hours
1 .5 Hours
2 Exposures
Environmental Chamber
4 Hours
2 Hours


1.5 Hours
2 Exposures
Environmental Chamber
8 Hours/day
5 Days/week
5 weeks
68 days continuously
Plants were grown 1n
closed top field
chambers and potted
In an artificial
soil mixture.
26 weeks continuous
closed outdoor chambers
winter growth
open sided greenhouse
Exposures.of 0.11
(290 ug/nr) for 4 to
20 weeks from 9:30 a.m.
Monday through
5:00 p.m. Friday
10 weeks continuously
Closed top field
chambers
Results

Foliar Injury In 7 pine species.
No significant change 1n fresh shoot weight or
Increase In foliar Injury (soybean).
No effects In 3 begonia cultlvars; 2 snap-
dragon cultlvars.
Reductions 1n shoot Might In 1 of 3 petunia
cultlvars; 1 of 2 coleus cultlvars.
Reduction In flower number In 1 of 3 petunia
cultlvars.
Foliar Injury 1n 50% of the leaves exposed 1n
Red Kidney Beans. Concentrations es low as
0.4 ppm produced 4i foliar Injury and 100:
foliar Injury was observed at 1.6 ppm sulfur
dioxide.
Slight but not statistically significant
reduction 1n dry root weight of oats. Authors
suggest "threshold."
Foliar Injury 1n 501 of the leaves exposed 1n
tempo beans. The lowest concentration producing
foliar Injury was 0.6 ppm. At 1.6 ppm where
82: of the leaf surface area was Injured.
Reductions 1n shoot weight 1n 1 of 3 petunia
cultlvars; 2 of 2 coleus cultlvars; 1 of 2
snapdragon cultlvars.
Reductions 1n flower number 1n 2 of 3 petunia
cultlvars; 1 of 2 coleus cultlvars.
No effect 1n 3 begonia cultlvars.
191 reduction 1n top dry might for oat
plants harvested at 28 days.
Reductions 1n root fresh and dry weights
of radish plants (Cherry Bel1e--a sensitive
cultlvar).
SOS reduction 1n foliar weight of alfalfa.
Other measures of plant growth were also
depressed.
Decreases In the dry weight of living leaves
(SOS), dry weight of stubble (551) and
other growth Indices 1n S23 ryegrass.
No effect In wild clones.
Reductions In dry weight of green leaves of
2 grasses ranging from about 25 to 40*4 at 20
weeks and other reductions 1n growth were also
observed between 4 and 20 weeks.
Potted grafts of old spruce showed a
reduction 1n CO, uptake which was well
correlated with decreases 1n both annual
growth ring width and wood density. Beech
seedlings exposed during winter to SO.
displayed progressive decreases 1n terminal
bud viability the following spring that
were attributed to S02 exposure.
References

Berry (1971, 1974)
Heagle and Johnson (1979)
Aded-ipe et al. (1972)


Jacobson and Colavlto
(1976)
Heck and Dunning (1978)
Jacobson and Colavlto
(1976)
Adedlpe et al. (1972)


Heck and Dunning (1978)
Mngey et al. (1973b)
Neely et al. (1977)
Bell and Clough (1973)
Ashenden (1.979)
Keller (1978, 1980)
'Plants nere grown under greenhouse conditions unless otherwise Indicated.

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                                    94
endpoints.  Studies in Table 7-1 indicate that conifer seedlings are
particularly sensitive to SOg exposure—a factor which may affect seedling
survival.  In addition to those studies reporting foliar injury, Adedipe
et al.  (1972) found that reductions in flower growth and development may
also  occur at relatively low exposure regimes (e.g., 0.5 ppm for 2 hours).
      The long-term exposure studies in Table 7-1 do not necessarily
utilize realistic fluctuations in concentration during long-term
exposures.  The studies on tree species (Keller, 1978, 1980), ryegrass
(Bell and Clough, 1973), and radish (Tingey et al., 1971b) were designed
to maintain continuous uniform exposure to S02-  The studies by Keller
(1978, 1980) are regarded as careful work demonstrating how extended
exposure to S02, in sufficient amounts to depress photosynthesis, can
reduce plant growth.  The study by Tingey and coworkers (1971b)
reporting reductions in radish harvest parameters is of particular
interest because it found that plants may be affected at relatively low
exposure .levels.  The median concentration (0.06 ppm) in the study by
Neely and coworkers (1977) apparently included repeated peak
exposures.  In this study, the highest single hour daylight
concentration during the growing season reached 0.60 ppm S02 and the
second and third highest peak 1-hour daylight concentrations were 0.42
and 0.40 ppm S02, respectively (Neely, 1982).  Consequently, in this
study, it is not possible to determine the relative importance of
repeated peak versus long-term low-level  exposure.
     ii)  Pollutant Mixtures
     Studies of the effects of pollutant  mixtures show that plants may
exhibit  different types of responses which are influenced by several

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                                     95

 variables and are difficult  to  predict.  Three general kinds of
 responses may follow  plant exposure  to mixtures of S02 and one or more
 other pollutants.
 1)    Additive responses.  An additive response is a response that would
      be  predicted from the effects of individual pollutants alone.  For
      example, if  a 2-hour exposure to either of two pollutants each at
      0.10 ppm caused  10 percent foliar injury, 20 percent foliar injury
      would be expected following simultaneous exposure to both
      pollutants.
 2)    Greater  than additive or "synergistic" responses.  One example of a
      "synergistic response" is one in which there is no foliar injury
      from exposure to either pollutant alone and foliar injury is
      observed  following simultaneous exposure to both pollutants.
      Within the context of plant responses to pollutant exposure a
      "synergistic" response refers only to the degree of response and
      does  not  imply anything about potential mechanism(s) of injury.
 3)    Less  than additive or "antagonistic" responses.   Antagonistic
      responses are expected when exposures are high  and effects  are
      relatively pronounced.
Two of these three kinds  of responses are found to  some degree  in the
experimental  results  using various combinations of  S02 and 03  or  NOg
shown in Table 7-2.  At lower concentrations (e.g., 0.10  ppm NOg  and
0.05 ppm S02), little if  any  increase in  foliar injury is  observed.   As
concentrations are raised (e.g., 0.10 ppm N02  and 0.10 ppm $02),  the
increase in foliar injury is  greater  than additive.  At higher
concentrations, foliar injury increases for  the S02 and 03  but not for
the S02 and N02 exposure  mixtures.  The variability of response at

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                                          96
                   TABLE 7-2.  EFFECTS OF SINGLE 4-HOUR S0?
                               EXPOSURE MIXTURES ON FOLIAR^INJURY
a)
0
Species
Alfalfa6
Broccol i
Cabbage
Radish
Tomato
Tobacco
(Bell W3)
b)
2
Species
Pinto Beans
Oats
Radish
Soybean
Tobacco
(Bell W3)
Tomato
Percent
Ozone/Sulfur Dioxide
0/0.10 0.10/0.10 0
2 24
1 34
0 22
0 50
0 50
0 95
1 n
Leaf Injury '
Concentration
.10/0.25 0.
21
11
14
22
10
88
(ppm/ppm)
10/0.50
60
19
54
46
13
96
0/0.50
19
0
0
1
0
0
Percent Foliar Injury '
Nitrogen Dioxide/Sulfur Dioxide (ppm/ppm)
0.10/0.05 0.10/0.10 0.
0 11
0 27
1 27
1 35
9 11
0 1
15/0.10 0.
24
12
24
20
18
17
20/0.20
16
10
6
9
4
0
0.15/0.20
4
0
4
1
6
0
]Source:   Tingey et al.  (1973a).

2Alfalfa (Medicago sativa.  L.  cv.  Vernal),  broccoli  (Brassica oleracea botrytis.
 L.,  cv.  Calabrese),  cabbage (Brassica oleracea capitata.  L.  cv.  All  Season),  radish
 (Raphnus sativus, L.  cv.  Cherry Belle),  tomato Lycopersicon  esculentum,  Mill,  cv.
 Roma VF), and tobacco (Nicotiana tabacum,  L.  cv.  Bell  VL).   Pinto beans  (Phaseolus
 vulgaris L.,  cv Pinto),  oats  (Avena sativa L., cv.  Clintland 64), soybeanTGIycine
 max^L.,  Merr.,  cv. Hark),  tobacco (Nicotiana  tabacum L.,  cv.  Bel  W3).

3Source:   Tingey et al.  (1971a).
Average foliar injury resulting from 0.10 ppm 03 only was 2% alfala,  7% radish,
40% tobacco, and no foliar injury for the other three species.

Concentrations below either 2 ppm nitrogen dioxide or 0.50 ppm sulfur dioxide alone
produced no foliar injury.

Sensitive cultivar.
5

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                                     97

 higher concentrations of N02 and S02 is  not  readily  explained.   This
 reduced response at higher exposures is  unlike that  observed  for the  03
 and S02 mixtures and may be related  to.stomatal  closure, which would
 reduce pollutant influx into leaves.  Although both  of these  studies
 reported pronounced synergism at  concentrations  below the thresholds  for
 single pollutants,  some other studies  examining  plant response to
 similar pollutant mixtures  have not  found synergistic effects at  levels
 significantly  below the thresholds for the single pollutants  (e.g.,
 Bennett et  al.,  1975;  Heagle  and  Johnson, 1979).
     An additional  complication arises when assessing controlled
 exposure studies of pollutant mixtures in that exposure regimes employed
 are  not necessarily representative of those occurring in the ambient
 environment.   For example, peak 03 concentrations are unlikely to occur
 simultaneously with peak N02 and S02 concentrations near combustion
 sources  because NO, which is released along with N02, is effective at
 scavenging 63.
     Table 7-3 summarizes plant responses following long-term exposure
 to pollutant mixtures.  The lack  of an effect of S02 on  soybean yield in
 the  higher exposure regime in the Heagle  et  al.  (1974)  study is
 unexpected in view of the decrease in growth  reported by  Tingey  and
 coworkers.  This may have occurred because  different  measures  of
 productivity were used and because the measurements  were  not taken at
 the same stage of growth.  The Red Kidney Bean study  was  designed to
 introduce an increment of 0.10 ppm (260 u9/m3) S02 with 50 percent non-
 filtered air in the  South Coast Air Basin.  Oshima  (1978) reports that
the 03  concentrations in the exposure chambers with  50 percent non-
filtered air probably reached 0.15 ppm (294 ug/m3), 0.12  (235  yg/m3),

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                        TABLE 7-3.  CONTROLLED EXPOSURE STUDIES OF LONG-TERM EXPOSURES TO POLLUTANT MIXTURES
Concentration
ppm (ug/m )
u^ rr 	 \ r" Jl 	 ; 	 1 	 ,_
0.05 (98) 0,+
0.05 (131) SO,
\ / 2



0.05 (98) 0,+
0.05 (131) SO,
c.


0.10 (262) S02+
partially
f i 1 tered
ambient air
containing 0,*
0.10 (200 0,+
0.10 (260) 502



Exposure
Period 	
8 hrs/day
5 days/week
18 days



8 hrs/day
5 days/week
5 weeks


6 hrs/day
on 45 days
over 11
weeks

6 hrs/day
133 days
(continuous-
ly)

Response
Synergistic




Additive/
Antagonistic



Synergistic




Additive
(No SO,)
i


Comments
Greenhouse grown soybeans displayed reductions
in top weight (21%), root fresh (24%) and dry
(20%) weights and shoot-root fresh and dry weight
ratios. No effect on top dry weight or plant
height. Plant growth was not affected by either
pollutant alone.
Greenhouse grown radishes displayed less than
additive reductions in plant fresh weight, and
root dry weights. Additive reductions were
observed for leaf fresh and dry weights. Exposure
to either S02 or 0, alone affected plant growth.
Approximately a 33% reduction in total seed weight
of Red Kidney Bean when compared with ambient air
having 50% of the ambient 0, removed. Plants
were grown in pots placed in the field inside
special design closed top field chambers.
No effect in soybeans from sulfur dioxide alone or
combination with 0, (different from the effects of
Oo alone) plant growth, and foliar injury. Plants
were grown in the ground and exposed in closed
field chambers.
Reference
Tingey et al.
(1973b)




Tingey et al.
(1971b)



Oshima (1978)




Heagle et al.
(1974)



                                                                                                                          ID
                                                                                                                          O>
*See text.

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                                    99

 and  0.12  (235  ug/m3) ppm on the highest, second highest, and third
 highest 03 days,  respectively.  Exposure regimes reported in the Oshima
 study would  violate the current 03 standard (0.12 ppm, 1-hour average,
 not  to be exceeded more than once per year, statistical form) and the
 exposure regime used in the study by Heagle and coworkers probably would
 have violated the standard.
     In summary, short-term and long-term exposure studies of pollutant
 mixtures provide mixed results that are difficult to interpret.
 Although these studies indicate that pollutant mixtures can produce
 effects that are greater than additive (especially at low exposure
 levels), additional  research is needed to resolve reported differences.
     i1i)  Zonal Air Pollution System Exposure Studies
     The Zonal Air Pollution System (ZAPS)  is  a relatively recent
development in controlled exposure systems  that allows plants to be
 grown without the use of chambers.  The ZAPS system releases controlled
amounts of S02 from a pipe upwind  of the vegetation.   Plant  response to
different exposure levels are examined by placing plants  and S02 monitors
at different  distances  downwind of the ZAPS release pipe.   It is difficult
to characterize exposure regimes  in ZAPS studies  for  two  reasons:
1)   Estimates of plant exposure are subject to uncertainty.   The number
     of monitors are  limited and concentrations at  each location are not
     continuously monitored.   Furthermore,  the  close  proximity  of the
     vegetation to the  release point of  S02 and variations in
     meteorological conditions  and canopy structure also  increase the
     uncertainties associated  with plant  exposure  (Miller  et  al.,
     1980).

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                                   100

2)   Other pollutants are not excluded in this exposure system and
     could, if present, influence plant response.
     The most extensive ZAPS S02 exposure studies have been conducted by
Miller and coworkers.  In one study using repeated exposures Tasting 4.5
hours, significant reductions in the yield of soybeans ranged from 6.4
percent at 0.09 ppm SOg to 45 percent at 0.79 ppm (Sprugel et al.,
1980).  Although ambient 03 levels may have exceeded 0.10 ppm on more
than one occasion, it is not possible to attribute any effect on
soybeans to 03 exposure alone.  Within this study, exposure to 5
different mean S02 concentrations between 0.09 (240 ug/m3) and 0.36 ppm
(940 yg/m3) for 18 repeated 4.5 hour exposures reduced yield from 6.4 to
19 percent.  No single 3-hour average S02 concentration in these studies
exceeded 0.5 ppm.  The consistency of results over a two year period at
different geographical locations supports these findings.
     b)  Ambient Exposure Studies
     Field observations of plant response in agronomic settings and
natural ecosystems show that S02 exposure can increase foliar injury,
decrease plant growth and yield, and decrease the richness and diversity
of plants.  Ambient exposure studies have three major advantages over
controlled exposure studies:   1) plants  are exposed and grown under
conditions that occur in  the ambient air;   2)  large sample sizes can be
collected; and 3) only field observations  can demonstrate long-term
changes in plant communities resulting from SOg exposures.  On the other
hand,  it  is  more difficult to define actual  exposure conditions (i.e.,
frequency, concentration,  duration),  and  to ascribe  the observed plant
responses  to S02 alone.

-------

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                                   101
     i)  Short-Term Exposures
     The criteria document cites ambient exposure studies.  These
studies are important because tfrey provide:
1)   quantitative estimates of short-term SOg exposure and observations of
     plant response,
2)   the only available data on plant responses to short-term exposures
     in the field observed near point emission sources, and
3)   observations on larger numbers of species than would be practical
     in laboratory settings.
     The ambient exposure studies of Dreisinger and McGovern (1970)  and
Mclaughlin and Lee (1974) provide the most extensive observations of
foliar injury in the vicinity of major point sources of S02 (CD,  pp. 8-
19 to 8-24).  Observations of minimum concentrations required to  produce
foliar injury in these studies are limited by the number of S02
monitors, location of individual plant species, and distribution  of  S02
exposures (i.e., concentration, frequency, exposure duration).
     Figure 7-1 shows concentration-response curves for foliar injury
that have been developed from observations on a variety of agricultural
crops, trees, and native vegetation from the 1970 to 1973 growing
seasons.  This figure does not represent the percent of foliar injury,
but the cumulative percent of affected species (i.e., those species  in
which some foliar injury was observed in conjunction with air quality
measurements) for a given concentration of SOg.  Plotted lines were
fitted by eye.
     The data shown in Figure 7-la were collected in the vicinity of a
coal fired power plant in the southeastern U.S. from 1970 to 1973.
Following review of these data, Mclaughlin and Lee concluded that most
species in the area "are not visibly affected by sulfur dioxide when

-------
                                                   CUMULATIVE PERCENT OF AFFECTEO'SPECIES
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-------
                                   103

 peak  (about a 3-minute average), 1-hour average, and 3-hour average
 sulfur  dioxide concentrations do not exceed 1.0, 0.50 and 0.20 ppm,
 respectively."  Similarity Dreisinger and McGovern concluded that S02
 concentrations should not exceed 0.70 ppm for 1-hour, 0.40 ppm for 2
 hours,  0.26 ppm for 4 hours and 0.18 ppm for 8 hours under relatively
 sensitive conditions.  However, review of their data indicates at least
 several species developed foliar injury following exposure to
 concentrations below those reported above.
      For both studies, all species were not exposed and injured during
 any specific fumigation event, and plants were'not always in the most
 sensitive condition during each exposure (e.g., exposures when stomates
 were  open).  In the Mclaughlin and Lee study,  the greatest percentage of
 affected species following a single exposure is about 20 percent.
      The data plotted in Figure 7-1 provide relatively consistent
 concentration-response relationships indicating that the number of
 plants  showing first signs of foliar injury affected within a given
 concentration range approximates a normal distribution.  The slope of
 the lines for the Dreisinger and McGovern data appear to be steeper than
 the slope of the lines for the Mclaughlin and  Lee data, suggesting that
 differences in peak to mean S02 ratios,  plants exposed, and
 environmental  conditions may have affected plant response in different
 situations.  Reports of increased foliar injury when peak to mean ratios
 are high suggest that peak rather than mean concentrations are probably
 of greatest importance.  Dreisinger and  McGovern report that plants are
 most  sensitive during periods  of warm,  humid weather that are favorable
for plant  growth.

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                                    104

      Several  limitations that should be considered when evaluating these
 data  are  listed  below.
 1)    Although these plots show that the concentration required to
      produce  foliar injury decreases with Increasing duration, it is not
      possible to establish definitively which averaging period is best
      linked to the production of foliar injury.
 2)    It is not possible from these data to derive specific estimates of
      the  amount  of leaf surface affected or reductions in growth and
      yield for individual species.
 3)    The  data shown in Figure 7-1 have only incorporated results from
      species that were affected by known S02 concentrations.  In the
      Mclaughlin  and Lee study SOg related foliar injury was observed in
      a total of  196 species over a 20 year period.  No foliar injury was
      reported in 23 additional  species.   Figure 7-1 does not reflect
      data on the other plants affected by S02 in the Mclaughlin and Lee
      study because the specific SOg exposures listed are only associated
     with 84 of the 196 affected species.   Of a total .of 39 species
      observed in the Dreisinger and McGovern study, only 2 species
      exhibited no foliar injury at the observed concentrations.
      ii)  Long-Term Exposures
     Most field studies of  long-term S02 exposures have  focused on
natural ecosystems.   Unlike short-term exposures studies,  observational
studies of long-term SOg exposure typically  focus on  different  biological
endpoints including  the richness  and diversity  of species  in an area,
seedling survival,  premature  leaf drop,  and  reduced growth (Linzon,  1978;
Rosenberg'et al., 1979;  Winner  and Bewley, 1978a,b).

-------
                                  105

     Although the importance of short-term peaks relative to long-term
averages in producing effects remains unclear, observational studies
provide strong support that long-term S02 exposures can affect the
diversity and richness of species.  A study of species composition in
the vicinity of a 25-year old coal fired power plant demonstrates
reductions in the number of vascular* plant per unit area and species
diversity (Rosenberg et al., 1979).  Similarly, Winner and Bewley
(1978a,b) report that both vascular plants and mosses show a marked
increase in understory species diversity with increasing distance from
the source.  The criteria document notes "changes in moss communities
were conspicuous and included decreasing values for moss canopy
coverage, moss carpet depth, dry weight, capsule number, and for the
frequency of physiologically active versus inactive moss plants" (CD, p.
8-47).
     Table 7-4 summarizes results of long-term ambient S02 exposures.  A
difficulty in interpreting long-term ambient exposure studies is
determining whether short-term peaks or long-term concentrations are
most closely associated with the effects observed.  In the Canadian
studies on White Pine, Linzon indicates that the maximum 30 minute S02
concentrations are estimated to be about 2.5 ppm at the West Bay site
and 1.0 ppm at the Portage Bay site.  Since concentrations even below
these levels may cause foliar injury and other effects following short-
term exposures, the effects observed at the West Bay site may be
associated with repeated peak rather than long-term low-level
exposures.  However, both the author of the study and the criteria
document associate the effects observed with long-term exposure average
concentrations of 0.045 ppm S02 for the West Bay site and 0.017 ppm S02
*Vascular plants (e.g., agricultural  crops,  trees,  shrubs)  are characterized
by a vascular system that is used in  the movement  of water  and other  materials
to different parts of the plant.   Conversely,  non-vascular  plants  (e.g.,
lichens, mosses) lack a vascular  system.

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                             TABLE 7-4.  FIELD STUDIES OF CHRONIC AMBIENT S02 EXPOSURES

Source/Location
Vascular Plants:
Nickel-Copper Smelters/
Sudbury District
Ontario, Canada
(study on White Pine)
West Bay
(19 miles N.E.)



Portage Bay
(25 miles N.E.)



Grassy to Emerald Lake
(40-43 miles N.E.)


Lake Hatimenda
(93 miles W)

Non-Vascular Plants:
Coal Fired Power Plant/
Ohio


Industrial Pollution/
England and Males





Exposure, ppm
(Duration)





0.045*
(10 year average)

•

0.017*
(10 year average)



0.008*
(10 year average)


0.001
(5 month growth
season- 1971)
control for above

0.020
(Annual Average)



0.03 to 0.06
0.02 to 0.03
0.01 to 0.02
0.005 to 0.01
<0.005
[Annual Averages)

Effects





1.3% reduction in net tree volume and
a 2.6% annual average mortality rate,
foliar injury was observed on foliage
from both the current year and
previous years.
0.5% loss in net tree volume and a 2.5%
annual average mortality rate, foliar
injury on current year needles developed
slowly and injury from the previous
year was apparent.
A 1.8* increase in net annual tree
volume and a 1.4% annual average
mortality rate, little foliar injury
was apparent.
A 2.1% increase in net annual tree
volume and a 0.5% annual average mortality
rate.


Two lichen species absent. The
distribution of more resistant became
apparent at annual average concentrations
of 0.025 ppm S02.
% reduction in the number of tolerant
lichen epiphytes:
95
62
24
13
0 .


References





Linzon (1971, 1978)














Showman (1975)


Hawksworth and Rose
(1970)
LeBlanc and Rao (1975)




•Exposures probably included some heavy metals (e.g.,  As,  Cu) that are found in smelter emissions (Chapter 4).
                                                                                                                                     o
                                                                                                                                     cr>

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                                   107

for the Portage Bay site.  As shown in Table 7-4, Linzon (1978)
indicates that there are differences in the effects observed as
distances are increased from the smelter and thus, peak concentrations
are reduced.  The nature of the effects observed suggests that they may
be associated with either continuous or repeated peak S02 exposures
(Linzon, 1978).  The presence of metals may have affected plant  response
or sensitivity in this study.
     Long-term ambient exposure studies show that the community
composition of non-vascular plants* can be affected by exposure  to long-
term low-levels of S02-  Results of these studies are summarized in
Table 7-4.  Similarly, non-vascular plants are also reported to  have
responded to long-term S02 levels between 0.005 and 0.03 ppm near
Sudbury, Canada (LeBlanc and Rao, 1975).  In contrast to vascular
plants, there are several reasons that non-vascular plants are more
sensitive to S02 and that long-term and not short-term exposures are
probably associated with the effects observed at low long-term S02
exposure levels, including:
1)   Sulfur metabolites cannot be eliminated through translocation
     (Nieboer et al., 1976).  Lichen mapping studies have repeatedly
     shown associations between changes in plant communities and the
     accumulation of sulfur metabolites (CD, p. 8-53).
2)   Pollutants cannot be excluded during periods of high pollutant
     levels because they lack both epidermis and stomata (Nieboer et
     al., 1976).
3)   Non-vascular plants probably have less buffering capacity than
     vascular plants (Nieboer et al., 1976).
*See footnote on page 105.

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                                    108

 For these reasons,  non-vascular plant  communities  appear  to  be  more
 sensitive to long-term low-level  S02 exposures  than  vascular plants.
 Although investigators have  associated effects  in  lichens with  long-term
 low-level exposures,  the relative importance of repeated  pollution
 episodes as compared  with  continuous exposure to low S02  levels cannot
 be determined at  this time.
      Non-vascular plants vary widely in their distribution across the
 U.S.  and serve a  variety of  functions  in a number of different
 environments  from the desert to coniferous forests.  Non-vascular plants
 affect  survival of other plant species  (CD, pp. 7-9 to 7-13).  In some
 areas,  non-vascular plants participate in the process of  soil formation,
 prevent  erosion,  play  a  role in succession, and can be an important food
 source  for  foraging animals when other vegetation is scarce  (Linzon,
 1978; Winner  et al.,  1978).  Non-vascular plants can also play an
 important role  in influencing the movement of materials within the
 ecosystem.  For example, lichens fix 5 to 20 percent of the total
 nitrogen  requirement  (2 to 11 kg nitrogen/ha) for Douglas fir, the
 dominant producer in northwestern coniferous forests (Denison, 1973).
     3.  Staff Recommendations
     S02 induced damage to commercial  crops, cultivated ornamentals  and
marked changes in natural ecosystems clearly may affect public
welfare.  If the recommended  ranges of  the primary  standards  do  not
provide adequate protection,  the staff  recommends consideration  of
vegetation effects in  evaluating the need  for both  short-  and long-term
secondary standards.
     a)  Short-Term  Exposures
     Controlled exposure and  field observation  studies  of  the responses
of vascular plants to  S02 exposure provide  support  for  continuation  of  a

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                                   109
short-term standard to protect vegetation.  These studies show a
progression of effects following S(>2 exposure from physiological and
biochemical changes to foliar injury and decreases in growth and
yield.  The original 3-hour S02 standard (0.50 ppm), promulgated in
1970, is apparently based on foliar injury in Mountain Ash following
a single controlled exposure to 0.54 ppm (1400 ug/m3) (DHEW, 1970).  This
standard was maintained in 1973 following a review of the secondary SOg
standards where additional foliar injury data provided added support for
plant injury to SOa exposure (38 FR 25678; EPA, 1973).  '
     Available evidence shows that plant responses vary with both
concentration and time.  Controlled exposure studies examining plant
response to S02 show that concentration is generally more important in
the production of plant responses which emphasizes the importance of
peak exposures (CD, p. 8-15; Mclaughlin et al., 1979).  However, as
exposure periods are extended, concentrations required to produce
effects diminish.  Comparison of levels associated with plant injury and
ambient variations in SOg concentrations with time indicate levels that
are reported to injure vegetation are only expected in the vicinity of
point sources.  The occurrence of peak S02 levels between mid-morning
and early afternoon, a time when stomates are typically open, increases
the likelihood that plants will be injured  by ambient fumigations near
point sources.  Because meteorological conditions and emission rates
vary with time, maximum S02 concentrations producing effects following
short-term exposures should be associated with short-term fumigation
periods from less than an hour up to several hours.  Controlled exposure
studies (Table 7-5) demonstrate that plants can be affected by S02
exposure for 2 to 4 hours.  Thus an averaging period of 3 hours would be
a reasonable choice.

-------
                                    110

      The level  of a revised  standard would depend on the extent to which
 anticipated effects would  be considered to be adverse.  ZAPS field
 studies  on soybeans suggest  multiple peak SOg exposures that do not
 exceed the level  of the current 3-hour secondary standard can result in
 reduced  growth  and yield.  Although few controlled exposure studies at
 low  exposure regimes have  been performed to date, these studies indicate
 that single exposures that would not violate the current S02 standard
 can  increase foliar injury (See Table 7-5) and affect growth and yield
 (i.e., 2  hours  at  0.5 ppm).  Foliar injury data from ambient exposure
 studies  show greater continuity of response concentrations because of
 the  larger  number  of observations.  The concentrations associated with
 foliar injury for  the ambient exposure studies in Table 7-5 were derived
 from the  observations plotted in Figure 7-1.   In each case, the
 concentration associated with foliar injury corresponds with the
 concentration associated with producing foliar injury in about  20
 percent of the species affected.  Although foliar injury may be caused
 by natural phenomena (e.g., insect damage, unfavorable weather,  and
 nutrient  stress), increases in foliar injury  reduces  the aesthetic value
 of natural vegetation and ornamental  plants,  as  well  as, the commercial
 value of  some leafy agricultural  crops  (e.g.,  spinach).
     While the acute studies  by Tingey  and co-workers (1971a,b)
on pollutant mixtures of  S02, NOg,  and  03  suggest that  exposures  below
current standard levels may affect  foliar  injury, the results of  these.
studies do not agree with  some other work  reporting that foliar  injury
occurs only at higher concentrations  (e.g., Bennett et  al.,  1975;  Heagle
and Johnson, 1979).  Ambient  exposure studies  near point sources  shown
in Figure 7-1, where mixtures of NOg and 03 might be  expected to  be

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                    TABLE 7-5.   STAFF ASSESSMENT  OF  SHORT-TERM VEGETATION  STUDIES
Averaging
Period
Controlled Exposure
Results L	
Ambient?Exposure
Results^ 	
1-Hour
2-Hour
3-Hour
4-Hour
0.25 ppm - Foliar Injury
0.50 ppm - Reduced Growth and
           Productivity
0.40 ppm - Foliar Injury
                                        0.50 ppm - 20% Foliar Injury
0.40 ppm - 20% Foliar Injury
                                        0.32 ppm - 20% Foliar Injury
Derived from Adedipe et al.  (1972),  Berry (1971,  1974), Jacobson and Colavito, (1976) and Heck
and Dunning (1979).  All results from single exposures at stated level and averaging time (See Table 7-1).

2Derived from Dreisinger and  McGovern (1970) and Mclaughlin and Lee (19.74).  Values provided in
this column are for concentrations that are associated with foliar injury following a single exposure.
Values shown have been interpolated from Figure 7-1.

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                                    112
 present  with  S02  in  low ambient concentrations, suggest that plant
 response is not much different from the response that would be expected
 for S02  exposure  alone.   In essence, these data do not readily support a
 combination standard at this time.
     Based on the available data, a 3-hour secondary standard at or
 below  the level of the current standard may be needed to protect
 vegetation.   A range of 0.4 to 0.5 ppm (1050 to 1300 pg/m3) would be
 roughly  equivalent to the lowest reported exposure regime affecting
 growth and productivity.  Such a standard would not be expected to
 prevent  against all  foliar injury but should protect over half of
 exposed  species against foliar injury even during "sensitive" exposure
 periods.  Available  air quality information indicates that such
 concentrations would  only be expected to occur in the immediate vicinity
 of point  sources  (Burton et al.,  1982;  Frank and Thrall,  1982).
 Although  cultivated crops may be  equally sensitive in different regions
 if plant water status- is not stressed,  natural  ecosystems  would be
 expected to be less sensitive in  arid regions  (e.g.,  southwestern U.S.)
 where soil moisture and relative  humidity  tend  to be  lower.   Given the
 available information, 1-hour standards  in the  middle and  lower portions
 of the range of interest for a primary  standard (0.25 to 0.75 ppm) may
 provide equivalent or better protection  for vegetation  than  the current
 3-hour standard;  in  this case,  the  secondary standard may  be set  equivalent
to the primary standard.   In the absence of a primary standard  that
provides  adequate  protection the staff  recommends  a 3-hour secondary
standard.

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                                   113

     b)  Long-Term Exposures
     Available evidence suggests that long-term exposure to S02
may affect foliar injury, growth, productivity, and the number's and
density of species present in plant communities.
     Studies on the effects of vascular plants suggest that long-term
exposures may reduce productivity, cause premature leaf drop, and
otherwise affect plants.  Although the investigations by Tingey and co-
workers (1971b) and Keller (1978, 1980) suggest decreases in measures of
productivity following exposure to 0.05 ppm (131 pg/m ) S02, other
studies have not reported similar effects until slightly higher
levels.  Several ambient exposure studies examining effects on vascular
plants have effectively demonstrated changes in species richness and
diversity, but do not provide specific levels that can be associated
with such changes (e.g., Rosenberg et al., 1979).  However, reductions
in tree volume and increased mortality in White Pine have been
associated with 10 year average SOg concentrations as low as 0.017 ppm
(45 yg/m^).  Nevertheless, it is unclear if these effects were most
clearly associated with repeated peak or the long-term average exposures
(CD, p. 8-19).  The presence of metals may have affected plant response
in this study.  The reported damage at the Portage Bay site showed
little injury associated with acute exposure.  Moreover, peak half hour
concentrations (< 1 ppm, 2600 ug/m^) reported by Linzon near the Portage
Bay site indicate that the second highest 3-hour concentration probably
did not exceed the current secondary standard level  of 0.5 ppm (1300
ug/m3).  Thus, it is unlikely that effects observed in this study can be
attributed to a short-term exposure.  Although these data suggest that
long-term S02 levels may affect vascular plants, the data are not well

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                                    114

 enough developed to provide the principal  basis  for selecting a  level
 for a long-term secondary standard but do  suggest  the  need  to limit
 long-term S02 levels.
      Mapping studies of non-vascular  plant  responses provide
 convincing evidence that non-vascular plants may be affected  by  S02 at
 low levels.  Although  non-vascular plants display  both visible injury
 and changes in community composition,  available studies suggest  that
 species  diversity  appears  to be  the most sensitive  index of non-vascular
 plant response (LeBlanc and Rao, 1975).  As Table  7-4 shows,  non-
 vascular plants  may  be  injured by  exposure to annual arithmetic  mean
 concentrations of  S02 from as low  as 0.005 ppm (13  ug/m3) to  about 0.06
 ppm (160 ug/m3); the later concentration can eliminate most species of
 epiphitic lichens  (LeBlanc and Rao, 1975).
      If  the data of Mueller et al.  (1980) (See Figure 4-2) are indeed
 representative of  regional S02 levels in the northeast quadrant,  then
 existing  studies suggest that current non-urban S02 levels may have
 effects  on  the richness and diversity of non-vascular plants primarily
 in  the northeast where  rainfall, relative humidity, and soil moisture
 are relatively high.  Assuming that the deposition  and accumulation of
 sulfur in non-vascular plants is an important  parameter that affects
 plant response, the deposition of S02 (northeast  seasonal  concentrations
 of ~ 25 to 50 yg/m3) may be even more important than sulfate (northeast
 seasonal  concentrations of ~ 6 to 12 yg/m3)  deposition  in  determining
 the response of non-vascular plants to sulfur  oxides.   To the extent
that the contribution of non-vascular  plants to the stability  and
productivity is considered to  be  important,  reductions  in  regional  S02

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                                   115

 levels  in the northeast may be warranted.  Other uncertainties in the
 exposure-response relationships of non-vascular plants that should be
 recognized include:
 1)   Since many non-vascular plants live deep within the canopy of their
     environment, current monitoring efforts may overestimate actual
     concentrations experienced by non-vascular plants.
 2)   Although existing studies associate effects with long-term averages
     and indicate that the mechanism of toxicity is associated with
     accumulation of sulfur in tissues, the importance of repeated
     episodes on plant response cannot be eliminated at this time.
 Since regional loadings of atmospheric sulfur is a problem that will be
 addressed during future actions on visibility (EPA, 1982b) and acidic
 deposition, the staff recommends that any action on the regional  effects
 of S02  on non-vascular plants be deferred until that time.
 B.  Materials Damage
     1.  Nature of Effects
     S02 alone or in conjunction with hygroscopic and other active
 components of particulate matter contributes to the physical damage of a
 wide range of materials.  SOg has been associated with the corrosion of
 ferrous and non-ferrous metals, degradation of zinc and other protective
 coatings, and with the deterioration of inorganic building materials
 (e.g.,  concrete and limestone), as well as paper, leather goods,  works of
 historical interest, and certain textiles.  SOg is corrosive in the
 presence of moisture because of its electrolytic properties that  enhance
 electrochemical  corrosion and because of its acidity.  In addition to
 moisture, other factors that affect the extent of S02 induced damage
 include temperature, sunlight,  wind speed, protective measures taken, as
well  as the level  of SOg to which the material  is exposed.

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                                   116

     Sulfur dioxide-induced materials damage becomes economically
 significant, and thus is most likely to affect public welfare only when
 one or more of the following conditions are met:
 1)   the service life of the material is impaired or prematurely ended;
 2)   the frequency of maintenance tasks must be Increased; or
 3)   the quantity or quality of the service rendered by the affected
     object is diminished (Gillette, 1975).
 As discussed in the criteria document (CD, Chapter 10), the evidence on
 the effects of SOg on materials is drawn from field and laboratory
 studies.  In addition, estimates of the economic loss associated with
 SOg damage have been made.  The key findings from these assessments are
 presented below:
 1)   The evidence presented in the criteria document clearly establishes
     that SC>2 (at humidities commonly exceeded in large regions of the
     U.S.) can accelerate the corrosion of exposed ferrous metals (Upham
     1967; Haynie and Upham, 1971; Haynie and Upham, 1974).  With the
     exception of weathering steel, these findings have little practical
     significance however, since ferrous metals are normally
     protected by paint,  zinc,  or by  addition of alloys when exposed
     outdoors.   Such  measures  reduce  corrosion  and in the  case of paints
     enhance the  aesthetic appearance of materials.   Certain non-ferrous
     metals such  as  aluminum and copper,  however,  are relatively
     unaffected by  levels of S02 currently  observed  in  the ambient  air.
     (Fink et  al.,  1971;  Abe et  al.,  1971).
2)   Both field and  laboratory  studies  have  shown  that  zinc corrosion is
     accelerated  by SOg and  that time of  wetness,  SOg concentration,  and
     surface geometry  are determining factors  (Guttman,  1968;  Haynie  et

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                                   117

     al., 1976; Haynie, 1980).  Such findings are potentially
     significant because of the use of zinc as protective coatings for
     ferrous metals.
3)   Controlled exposure chamber'studies by Campbell  et al.  (1974) and
     Spence et al. (1975) have examined the effects of SO2 on several
     exterior paints.  The results from these studies suggest that
     coatings, which do not contain aluminum or magnesium silicates or
     calcium carbonate or combinations thereof, are relatively
     unaffected by S02 at concentrations up to 1.0 ppm after exposure
     periods of 400, 700, and 1000 hours.  For an oil base house paint
     which contained magnesium silicate, Spence et al. (1975) reported
     statistically significant errosion at 0.03 ppm S02 after exposure
     periods of nominally 250, 500 and 1000 hours which they attributed
     to the effects of S02 and relative humidity.  Unfortunately,  their
     exposure study of acrylic latex house paint had  to be terminated
     before completion of the exposure cycle.  As a result,  data on this
     widely used coating are not available at S02 concentrations (< 1.0
     ppm) that are more relevant to current ambient conditions.   The
     investigators cautioned that  their findings for  one coating should
     not be generalized to an entire class of paints  because of
     differences in paint formulations.
4)   The studies cited in the criteria document (CD,  pp. 10-34 to 10-37)
     primarily show that S02 can react with calcareous materials and,
     thus, cause deterioration of  inorganic materials such  as concrete,
     marble, and limestone used in buildings, monuments, and some
     statuary.  These studies have not fully investigated the relative

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                                   118

     contribution of S02 as compared to other components of acidic
     deposition (wet and dry) as well as other physical  and biological
     agents.
5)   The studies of the effects of SOg on textile,  leather and paper
     goods are less relevant since these materials  are not typically
     exposed for long periods in the ambient environment.   The preservation
     of documents and old books is, however, of concern  to libraries and
     museums (CD, p. 10-37).
6)   The criteria document concludes that the dollar  value of  SOg
     associated material  damage in 1970 ranged from $450 million to  $1.4
     billion in 1978 dollars.  It was also estimated  that  the  reduction
     in the average annual  S02 ambient levels in  U.S.  urban areas  from
     1970 to 1978 resulted in a total  U.S. annual benefit  for  1978 of
     approximately $0.4 billion dollars (CD, p.  10-71).  These
     estimates, however,  must be viewed with caution  since they provide
     only a crude indication of the costs  associated with  S02  materials
     damage.  Some of the limitations  inherent  in the  underlying
     estimates  include:
     a)  the lack  of reliable damage  functions  for  the full  range  of
         materials that may  be affected by S02;
     b)  uncertainty as to quantities  and  distribution of  materials  in
         place, and the level  of  S02  as well  as the environmental
         conditions  (i.e., relative humidity) to which they may have
         been exposed;
     c)  uncertainty as to whether the  useful life of the materials was
         actually  impaired;  and
     d)  inadequate  consideration of substitution possibilities.

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                                    119

      2.  Mechanisms and Quantitative Relationships
      Of the materials potentially affected by SOg, the most accurate
 damage functions have been developed for zinc coated materials-.  Based
 on these functions, it is possible to relate the corrosion of zinc to
 varying concentrations of SOg under different environmental conditions.
 S02 induced damage to zinc coatings may also be economically significant
 because zinc is used as a coating for ferrous metals that are to be
 exposed in the ambient air.  Haynie (1974) attributed 90 percent of the
'Fink et al. (1971) nationwide estimate of exterior metal corrosion costs
 (some $1.4 billion) to the corrosion of galvanized (zinc coated) steel.
 On the other hand, Stankunas et al. (1981) in their survey of Boston,
 Massachusetts, found far less than the average per capita amount of bare
 galvanized metal exposed.  They reported an annual cost due to SOg corrosion
 of only $335,000 for the Boston metropolitan area.  No attempt was made
 to extrapolate this to a national  estimate.  They attributed their findings
 to development of new coatings that adhere to galvanized metals and which
 are aesthetically more pleasing and afford additional  protection.
      Zinc is anodic with respect to steel  and,  thus,  when .zinc and steel
 are in contact with an electrolyte, the electrolytic cell provides
 current to protect the steel  from corrosion while some oxidation of the
 zinc occurs (CD, p. 10-23).   In addition,  zinc  naturally forms a
 protective film of zinc carbonate  which reduces  the rate of corrosion.
 SOg or other acidic gases,  in the  presence of moistupe,  however,
 destroys  or prevents the film from forming,  thus resulting in the
 acceleration of the corrosion process.
      Reporting on the  work  of a number  of  investigators,  the criteria
 document  identified several  factors that  influence the corrosion rate of

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                                   120

zinc coated materials.  These include:  the time the material surface is
wet, SC>2 concentration, wind speed, and geometry of the exposed
surface.  The latter factor controls delivery of S02 to the material
surface and, in part, explains why certain surfaces such as zinc coated
chain link fences exhibit higher corrosion rates than zinc coated siding
and roofing materials.
     Haynie (1980) incorporated these factors into the following
mathematical expression to determine the corrosion rate for galvanized
materials (zinc coated) under various conditions:
     Cz = 2.32 tw + 0.0134 V0-781 (S02) tw, for small sheets       (7-1)
     Cz = 2.32 tw + 0.0082 V0-781 (S02) tw, for large sheets       (7-2)
     Cz = 2.32 tw + 0.0183 V0-781 (S02) tw> for wire fence         (7-3)
     where:
          Cz = corrosion (ym)
          tw = time of wetness (years)
          V  = wind velocity (m/s)
                                                 o
         S02 = sulfur dioxide concentration (yg/nr)
To determine the time of wetness when the average  relative humidity  is
known, Haynie, 1980 developed the following relationship:
     f = (1-k) RH
         100-k (RH)                                                (7-4)
     where:
        f = fraction of time relative humidity  exceeds the
            critical  value (90% for zinc sulfate)
       RH = average relative humidity
        k = an empirical  constant less than unity  (k = 0.86)
     Based on  equations 7-2, 7-3, and 7-4,  the  annual  rate of corrosion
for zinc coated roofing,  siding,  and  wire fence can be plotted as  shown

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 in Figures 7-2 and 7-3.  This assumes a typical relative humidity of 70%
 for inland areas east of the Mississippi River, 80% for the seacoast,
 and 30% for desert areas as in California and Arizona.  Under these
 conditions, the fractional time of wetness is 0.25 for inland eastern
 states, 0.35 for the seacoast, and 0.057 for desert areas.  A typical
 wind speed of 4 meters per second (9 mph) was used.
     It is evident from Figures 7-2 and 7-3 that relative humidity as
 well as SOg can significantly effect the corrosion of zinc coated
 materials.  This must be considered in estimating potential nationwide
 damages to these materials.
     An additional consideration in making such estimates is whether the
 service life of the zinc coated material have been impaired or
 prematurely ended.  This is a function of the coating thickness and
 prevailing maintenance practice.  Gillette (1975) reported that coating
 thickness varies with intended use, ranging from 26 pm for building
 accessories and wire fencing to 85 pm for pole line hardware. The work
 of Bird (1977) and Haynie (1980),  however, suggest coating thickness on
 a given piece of material can vary as much as +_ 40 percent.  For wire
 fencing, the product expected to be most sensitive to corrosion, this
means the first rust could occur after 16 urn of corrosion.  Using Figure
 7-3, it can be estimated that first rust may occur in wire fencing after
 10, 13, or 17 years of exposure at 70 percent relative humidity and
 long-term mean SOg concentrations  of  0.03, 0.02, and 0.01 ppm (80, 50,
25 pg/m3), respectively.  In the absence of S02, first rust would not
occur until  28 years of exposure at 70 percent relative humidity.   Thus,
it can  be concluded that S02-related  damage for this material  can occur

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  I
   t  2
                  100
                 (0.04)
 200
(0.08)
 300
(0.11)
 400
(0.15)
         Annual Mean SO, Concentrations, pg/m  (ppm)
 100
(0.04)
 200
(0.08)
 300
(0.11)
 400
(0.15)
                                                   Annual  Mean SO^ Concentrations, ug/m  (ppm)
Figure 7-2.  Corrosion Rate for Roofing and Siding (Large Sheets).
Relationships based on Equations 7-2 and 7-4 (Haynie, 1980).
                                                  Figure 7-3.   Corrosion Rate for Wire Fencing.
                                                  Relationship's based on Equations 7-3 and 7-4
                                                  (Haynie,  1980).

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                                    123

 down to and at  background  SOg  concentrations  found  in the eastern United
 States.  For other  zinc  coated products, with different surface
 geometries  and/or coating  thicknesses, the time period required for
 first rust  will  be  longer.
      Depending  on the prevailing maintenance practices, the material
 could be painted when rust first appears to provide extended protection
 or  be allowed to deteriorate further until the substrate is damaged to
 the point that  replacement is  necessary.  Both approaches are commonly
 employed (Stankunas et al., 1981).  This uncertainty with respect to
 response coupled with the absence of accurate determinations of the
 amount  of materials actually exposed under varying conditions has
 precluded development of complete and accurate national cost estimates.
 The work of  Stankunas et al. (1981), however, suggests that such costs
 may  be  significant assuming other major metropolitan areas in the country
 experience  similar costs ($335,000 per year) as estimated for Boston.
 The  1976 annual S02 values in Boston ranged from 15 to 48 ug/m3
 (Stankunas et al., 1980).
      3.  Staff Recommendations
     The association of SOg with damage to a number of materials suggests
 that economically important impacts may result at elevated long-term SOg
 concentrations.  Control  strategies have resulted in marked improvements
 in  long-term S02 levels  over the past 13 years,  which the criteria  document
 associates with substantial benefits (CD, pp.  5-16,  10-71).   While  the
 available data are limited and do not permit definitive findings with
 respect to the potential  costs or provide clear  quantitative relationships
 for the full range of potentially affected materials,  they  generally
support the need for limiting long-term $03 concentrations  in  urban
areas.

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                                   124

     Analysis of existing air quality data (Frank and Thrall, 1982)
suggests that without a primary annual standard long-term urban air
quality could deteriorate and in a number of large urban areas might
exceed the current annual standard.  Therefore, consideration should be
given to a long-term secondary SO2 standard at or below the level  of the
current annual primary standard of 0.03 ppm (80 ug/m^) to protect
against materials damage effects.
C.   Personal Comfort and Well-Being
     1.  Description of Effects, Quantitative Data
     In addition to the health effects discussed in Sections V-B,  short-
term exposures to SOg may also be associated with other perceived
responses that may not be related to health; examples include odor
perception, eye, nose, or throat irritation, and other non-respiratory
sensory responses.  As summarized in Section V-B.l, the available  data
indicate that S02 is not detected by human senses at levels below  1 ppm
except under controlled conditions that either tend to underestimate the
threshold of detection, or use indicators of unknown relevance to
personal comfort and well-being (e.g., brain alpha rhythms, eye
sensitivity to light).
     A number of investigators have noted subjective perceptions of
irritative or painful  effects such as eye, nose,  or throat  irritation
and cough associated with short-term SOg exposures above 5  ppm (Lehmann,
1893; Yamada, 1905;  Greenwald, 1954;  Amdur et al., 1953) and as low as
0.5 ppm among asthmatics (Kirkpatrick et al., 1982).   Healthy subjects
exposed for 6 hours  to S02 had a "threshold of discomfort"  at 1 ppm
(Andersen et al., 1974).  The addition of 2 mg/m3 "inert" plastic  dust

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                                    125

 to  this  S02  level  increased the level of discomfort and the incidence of
 throat and nose  irritation  (Andersen et al., 1981).  Symptoms such as
 wheezing and shortness of breath have been observed among asthmatics
 after short-term exposures to 0.5 ppm SOg  (Table 5-1).  These symptoms
 are clearly  indications of personal discomfort but they are accompanied
 by  substantial functional responses and are of apparent relevance to
 health  (CD,  p. 13-51).  As such they are not considered here.
     2.   Staff Recommendations
     Because the effects relevant solely to personal comfort and well-
 being are generally associated with short-term S02 levels above the
 range of interest  for the primary standard (0.25-0.75 ppm), there is no
 support  for  a secondary standard based on personal comfort and well-
 being.
 D.   Acidic  Deposition
     On  August 20-21, 1981, the Clean Air Scientific Advisory Committee
 (CASAC)  concluded that the issue of acidic deposition was so complex and
 important that a significantly expanded and separate document would be
 necessary if NAAQS were to be selected as a regulatory mechanism for
 control   of acidic deposition.  CASAC noted that a fundamental  problem of
 addresing acidic deposition in a criteria document is that it is
 produced by  several pollutants (including oxides of nitrogen,  oxides of
 sulfur,   and  acidic fine particles).   Consequently, a document on acidic
 deposition would include various pollutants contributing to wet and dry
 deposition.   The Committee also recommended that a revised version of
the acidic deposition chapter be retained in the particulate
matter/sulfur oxides and nitrogen  oxides  criteria documents.  In

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                                   126
response to these recommendations,  EPA is  in the process  of developing
an acidic deposition document that  will  provide a more comprehensive
treatment of this subject.   Thus, the Issue will  not  be addressed
directly in this staff paper.
E.   Summary of Staff Conclusions and Recommendations
     Major staff conclusions and recommendations  with respect  to
secondary standards  (Section VII.A-D) are  summarized  below:
1)   a)  Damage to vegetation by 302  resulting  in economic  losses in
     commercial crops, aesthetic damage  to cultivated trees, shrubs  and
     other ornamentals,  and reductions in  productivity, species richness
     and diversity in natural  ecosystems constitute effects  on public
     welfare in impacted areas.  Such effects are associated with both
     short-term (minutes to hours)  and long-term  (weeks to years)
     exposures  to SOg.
     b)  Given  the available data on  the acute  effects  of S02  on  plants
     (growth and yield and  foliar injury),  a 3-hour standard at or below
     the level  of the current  secondary  standard  (0.5  ppm) may be needed
     to protect vegetation.   If  a 1-hour primary  standard is chosen  that
     provides equivalent or better  protection,  then the averaging time
     and level  of the secondary  standard can be made  equal to the
     primary standard.  In  the absence of  a primary standard that
     provides adequate protection for  vegetation,  a 3-hour secondary
     standard is recommended.
     c)  Available data  on  the effects of  long-term S02 exposures of
     vascular plants  (e.g.,  trees,  shrubs) suggest the possibility of
     changes in species  richness and  diversity, reduced growth over
     extended periods, and  premature needle drop.  However,  these data

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                                   127
     are weak and not developed well  enough to provide the principal
     basis for selecting the level  of a long-term SOg standard.   Thus,
     existing information cannot be used to show significant effects  at
     annual S02 levels below the current primary annual  standard, but
     does support the need to protect against the effects of prolonged
     S02 exposure by limiting long-term S02 concentrations much  above
     this level.
     d)  Current long-term S02 concentrations over large'areas of the
     northeast exceed levels that may be associated with effects on non-
     vascular plants (e.g., lichens,  mosses).  Given uncertainties
     regarding the extent and importance of these potential  effects on
     natural  ecosystems and the regional character of the exposures,  the
     staff recommends that the effects of S02 on non-vascular plants  be
     considered in the larger context of regional  acidic deposition -
     visibility - fine particle strategies.  As such, no separate long-
     term secondary standard for non-vascular plants is  recommended at
     this time.
2}   a)  Elevated long-term S02 concentrations in  the presence of
     moisture can damage a number of  materials including:   exposed
     metals,  paints, building materials, statuary,  paper,  leather, and
     textiles.  Control  strategies  have resulted in marked improvements
     in long-term S02 levels over the past 13 years, which the criteria
     document associates with substantial  benefits.  While the available
     data are limited and do not permit definitive  findings  with respect
     to the potential  costs of S02  related material  damage or provide
     clear quantitative  relationships for the full  range of  potentially

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                                   128
     affected materials, they generally support the need for limiting
     long-term S02 concentrations in urban areas.
     b)  Analysis of existing air quality data suggests that without the
     primary annual standard, long-term urban air quality could
     deteriorate and in a number of large urban areas might exceed the
     current annual standard.  Therefore, consideration should be given
     to a -long-term secondary S02 standard at or below the level  of the
     current annual primary standard of 0.03 ppm (80 ug/m3) to protect
     against material  damage effects.
3)   The staff concludes that a secondary SOg standard is not needed to
     protect against effects on personal  comfort and well-being.
4)   The available scientific information indicates that the current 3-
     hour and annual  standards provide reasonable protection against the
     direct welfare effects associated with ambient S02 in general.  In
     essence, the data support maintenance of SOg standards at or below
     levels of the current  standards.
5)   The acidic deposition  issue will not be addressed directly in the
     review of the sulfur oxides standards.

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 APPENDIX A.   FACTORS THAT  INFLUENCE PENETRATION AND DEPOSITION OF SO?
              AND MECHANISMS OF TOXICITY
      This material  briefly summarizes subject-related and environmental
 factors  that  affect  penetration and deposition of S02,.,and mechanisms of
 toxicity.  This material supports the discussion in Section V.A. of this
 paper.
 A.   Inhalation Patterns
      SOg  (1  to 50 ppm) is almost completely absorbed.^ 99%) by the
 nasal passages under resting conditions in both man and laboratory
 animals  (Frank et al., 1969; Speizer and Frank, 1966b; Andersen et al.,
 1974; Brain,  1970).  One study in rabbits also found nearly complete
 nasal absorption (95-99%) for 10 to 100 ppm SOe, but reported a decrease
 in nasal removal to as little as 40% at lower S02 levels (0.1 ppm)
 (Strandberg,  1964).  The reason for the apparent difference in absorption
 rate at 0.1 ppm S02 is not clear, although methodological  difficulties
may have influenced the results.  Comparable measurements  (< 0.1 ppm)
have not been made in humans,  but the criteria document concludes that
nasal removal at lower S02 levels should be similar to that at 21 1 ppm
 (CD, p. 1-54).
      Subject-related factors  that can increase penetration of S02 over
that observed for quiescent nasal  breathing include mouth  and oronasal
breathing and increased ventilation rates.  Forced mouth breathing has
been shown to increase S02 penetration significantly in animals (Frank
et al., 1969).  Although  direct  measurements  of S02 penetration for
mouth or oronasal  breathing are  not available in  humans, measurements of
increases in  expired  S02  (Melville,  1970)  and bronchoconstriction
(Speizer and  Frank,  1966a;  Melville,  1970;  Snell  and Luchsinger,  1969)

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                                       A-2

for mouth only versus nasal breathing provide strong indirect evidence
of increased penetration with oral breathing through a mouthpiece with
the nose occluded.  In these studies, the increased bronchoconstrictive
responses for resting oral versus nasal exposure are most marked at high
concentrations (15 to 28 ppm), and not always statistically significant
at lower levels (0.5 to 10 ppm).  Comparisons between mouthpiece and
nasal or oronasal  breathing in exercising asthmatics (0.5 ppm SOg)
indicate that bronchoconstriction increases when going from nasal  to
oronasal to mouthpiece breathing (Kirkpatrick et al., 1982; Linn et al.,
1982a,b).  These results indicate a parallel increase in S02 penetration
with route of inhalation, and also suggest nasal removal is less than
complete at high ventilation rates.  There remains, however, some question
whether studies using mouthpiece or nose clips overstate oral  penetration
of S02 under free  breathing conditions and comparable oral  ventilation
rates (Cole et al., 1982).  Direct measurements of S02 penetration under
these conditions are not available in animals or humans.  These  matters
are of some interest in quantitative evaluations of the numerous controlled
human S02 experiments that involve mouth only exposures and the  use of
nose clips.
      Except in the case of blockage of the nasal  passages  by  mucus or
other obstruction, typical "mouth breathing" is better characterized as
oronasal breathing, since the larger portion of the inspired air does
pass through the nose.  Under test conditions, about 15% of subjects studied
to date appear to  be habitual  oronasal  or mouth only breathers  (Saibene et al.,
1978; Niinimaa et  al., 1981).   Anyone may shift to oronasal  breathing during
conversation, singing, illness with nasal  congestion,  or exercise.   High levels

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                                       A-3

 of S02 may  increase  nasal  airflow  resistance to the extent that the oral
 portion of  breathing is  increased  (Andersen et al., 1974).  Most
 individuals shift  to oronasal breathing at flow rates greater than 30-35
 1/min  (Niinimaa  et al.,  1981), which is roughly equivalent to moderate
 exercise as in walking briskly or  bicycling (Cotes, 1979).  At this
 ventilation rate,  about  43% of the inspired air bypasses the nose
 (Niinimaa et  al.,  1981).  Table A-l summarizes ventilation patterns
 observed in "mouth"  breathers and  normal subjects.
       Exercise or  its analogue, deep breathing, can increase penetration
 of S02 both through  increased ventilation and by causing a shift to
 oronasal  breathing.   Increasing nasal flow rate from 3.5 1/min to 35
 1/min  increased tracheal  penetration of SOg in dogs from 0.01% to about
 3.2% (Frank et al.,  1969).  In the same experiments, the combination of
 changing  from nose to mouth only breathing and increasing ventilation
 rate from 3.5 to 35  1/min increased tracheal  penetration of SOg from
 0.01%  to  about 70%.  Theoretical  (Aharonson,  1976) and empirical  (Brain,
 1970)  evidence indicates  that besides increasing penetration of SOg,
 higher  ventilation rates  result in increased  deposition  of S02 into the
 mucosal lining of the upper airways.   A number of  human  studies generally
 support the notion that increased ventilation  results  in increased
 penetration and deposition as indicated by  enhanced functional  responses
 and/or increased symptoms (Kreisman et  al., 1976;  Lawther et  al.,  1975;
 Sheppard et al.,  1981a; Stacy et  al.,  1981).   Of particular interest in
this regard is the similarity in  both the time  course  and magnitude of
S02-induced bronchoconstriction  observed under  modified  hyperventilation
and under exercise (Sheppard  et  al.,  1981a).

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                                              TABLE A-l.  ORONASAL DISTRIBUTION OF INSPIRED AIR
Ventilation
Rate (1/min)
5
10
15
20
30
35.3*
40
45
50
60
80
90
Normal Breathers
Nasal Volume (1/min) Mouth Volume (l/m1n)
5 0
10 0
15 0
20 0
30 0
19.8 15.5
21 19
22.5 22.5
23 27
28 32
32 48
36.5 53.5
"Mouth-Only" Breathers
Nasal Volume (l/m1n) Mouth Volume (l/m1n)
4 1
6 4
8 7
9 11
12 18
13 22
14 26
15 30
17 33
18 42
23 57
~ ~
Representative
Activity2
Sleep
Standing
Walking normally
(2 mph)
Walking slow (1 mph),
carrying 10 Ib. load
Walking quickly (4 mph)
Climbing 3 flights of
stairs, light cycling
and snow shoveling
Light jogging, tennis
(singles)
Climbing 4 Tights of
stairs, moderate cycling,
chopping wood
Light uphill running
(8.6% grade), gymnastics
Moderate Jogging (7 mph)
Heavy cycling, climbing
7 flights of stairs
Heavy exercise,
e.g., basketball, running
(11 mph)
 From Nlinlmaa et al.  (1981)

 From NAS (1958); Morehouse and Miller (1948); Karpovlch (1953);  Rossler et al.  (1960);  Zenz (1975);  and Cotes (1979).   Activities are derived from
 average maximal oxygen consumption and a range of ventllatory  rates  at each activity for healthy men.   Because there 1s great variation In breathing
 requirements among people, these can only be considered as approximations.

*Point at which normal breathers switch from nasal only breathing to  oronasal  breathing.

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                                        A-5

       Most studies investigating the effects  of exercise  or hyperventi-
 lation used mouth only exposure to S02;  the penetration of  SOg  and
 resultant effects for exercise related  oronasal  breathing are,  as expected,
 somewhat lower than that  reported for mouth only breathing,  at  comparable
 total  ventilation rates (Kirkpatrlck et  al.,  1982;  Linn et  al.,  1982a).
 B.     Absorption  by Particles
       An additional  factor  hypothesized  to increase penetration  of S02 is
 absorption onto particles capable of penetrating to the thoracic regions
 (CD, p.  11-37  to  11-38).  Direct  measurements of the extent  to which
 penetration  might increase  are not  available.  -Theoretical  considerations
 summarized in  Section  IV-A  suggest  that  at realistic peak levels of
 particle/S02 combinations (_< 1000 ug/m3),  only  a relatively  small amount
 of  S02 can be  attached  to or dissolved in  particles.  Nevertheless, both
 animal and human  studies have  sometimes  reported apparent "synergistic"
 increases  in responses  to exposures  to S(>2 and certain aerosols  (CD,
 Tables 12-11 and  13-14).  In some cases, the .increased response  is
 attributed to  the  formation of  sulfuric  acid by  catalytic metals (Amdur
 and Underhill,  1968), but the  combinations of S02 and water droplets or
 NaCl aerosols  used  in most animal and human studies  are unlikely to
 produce  an enhanced response through an  oxidation mechanism  (McJilton et
 al., 1976).  In this case, droplet aerosols containing H+, HS03", S02,
 NH3, and dissolved electrolyte penetrate the thoracic region and result
 in discrete "hot spot" deposition characteristic of particles as well  as
the more diffuse gas deposition from S02 released from the droplet  in
deeper regions.
      The mixed results observed with regard  to potentiation of  S02
effects by non-catalytic dry particles and droplet aerosols  appear

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                                       A-6

 consistent with the extent to which those particles can increase S02
 penetration.  S02 absorption by dry aerosols is limited by particle
 surface area and the amount absorbed is likely to be a small fraction of
 particle mass, particularly for coarse particles.  High concentrations
 (60 mg/m3) of coarse (6 to 8 ym) .NaCl aerosols did not increase response
 to 5 ppm S02 in humans (Snell and Luchsinger, 1969).  In animal experiments,
 10 mg/m3 of dry submicrometer NaCl potentiated response to 2 ppm S02,
 but 4 mg/m3 of the same aerosol was insufficient to enhance effects (Amdur, 1961).
 In human studies, high levels of submicrometer NaCl (> 7 mg/m3) have either
 enhanced (Toyama, 1964) or failed to enhance (Frank et al., 1964) S02 effects.
 Humidity was not reported in these studies.
      An equivalent mass of neutral pH droplet aerosols can absorb more
 S02 than can dry particles and thus increase response.  This was apparently
 shown in animal  exposures to dry and droplet NaCl  aerosols by McJilton
 et al. (1976), and suggested in human studies by the distilled water-S02
 combinations used by Snell and Luchsinger (1969),   Conditions that favor
 increased S02 penetration through  dissolution in droplets  include:
 1) Higher droplet pH resulting from increased ammonia levels in chambers
'(as in animal  studies)  or in ambient air  can dramatically  increase
 dissolved S02.  Higher  ammonia concentrations in the mouth (Larson et
 al., 1982)  may thus  actually increase effective  penetration of S02
 levels by increasing S02 solubility (CD,  p.  2-67).   Conversely,
sulfuric acid droplets  absorb little $02;   2) High  humidity - this
favors formation  of  hygroscopic aerosols  or  fog  droplets;   3) Low temperature  -
S02 is more soluble  at  colder temperatures;  and   4)  High droplet aerosol
concentration.

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                                       A-7

C.   Mechanisms of Toxicity
      The major mechanisms of potential interest in S02 toxicity can be
categorized as outlined below:
      1.   Irritation of tissues or nerve receptors leading to airway
           functional changes
      Rapid bronchoconstriction (airway narrowing) is the major response
to short-term (< 1-hour) exposures to S02 at realistic peak ambient
levels  (CD, p. 1-57).  In both human and animal studies, it appears that
this response results from stimulation of irritant or "cough" receptors
located in the larynx, trachea, and more central bronchii and a reflex
contraction of bronchial smooth muscles, as mediated by neural pathways
involving the vagus nerve (Widdicombe, 1954; Nadel et al., 1965; Sheppard
et al., 1981a).  The relative importance of the potentially responsible
agent(s) (H20'S02, sulfite, bisulfite, or hydrogen ion) is not known with
certainty.  The mechanism(s) of action may include reaction of dissolved
SOg or one of the products of hydration with nerve endings (NAS, 1978,  p.
7-10), or irritation of surrounding tissues leading to release of agents
that act on nearby receptors or are transported by the blood (CD, p. 12-14).
      The mechanism by which airway constriction occurs for a particular
species may be influenced by the underlying state of health, time course
of exposure,  and concentration, which may be more important than duration
of exposure (CD, p. 12-76).   Direct action by S02 or locally released
agents is most likely involved in  the reflex bronchoconstriction that
develops within minutes and tends  to subside after 10 to 15 minutes or
at the end of exposure (Corn et al., 1972;  Frank and Speizer,  1965;
Frank et al., 1964, Melville, 1970).  Recent evidence suggests that SOg

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                                       A-8

might trigger reflex bronchospasm in asthmatics by stimulating the
release of mediators (e.g., histamine) from mast cells (Sheppard et al.,
1981b).  Induced release of humoral agents with delayed action or increased
secretion or pooling of mucus might be responsible for the progressive
airway narrowing associated with continued exposure in guinea pigs over
a period of hours (Amdur, 1959) and, after intermediate time periods
(hours - days), in humans (Andersen et al., 1974; Weir and Bromberg,
1972).  In contrast to rapid recovery of normal humans to short-term
peaks noted above, responses in guinea pigs may require an hour or more
to return to normal  values (Amdur, 1959).
      Although evidence is not conclusive, peak or prolonged S02 exposure
may also increase sensitivity of bronchial receptors to subsequent
irritation by other bronchoconstrictive agents, as suggested by small  to
moderate increases in reactivity to acetylcholine in dogs (Islam et al.,
1972) and humans (Reichel, 1972) following S02 exposures.  At high
concentrations (17 ppm), S(>2 produces a transient depression in respiratory
rates in mice, possibly mediated through a neural  reflex following
stimulation of receptors in the nasal region (Alarie,  1973).  Available
data do not suggest  this is an important mechanism in  human responses  to
peak ambient levels.
      Because the smooth muscles involved in reflex bronchoconstriction
fatigue or become adjusted to altered tone over time and because long-
term penetration of  S02 to the tracheobronchial region is limited by
upper airway removal, chronic exposure to SC>2 alone is not likely to
cause permanent changes in bronchial  tone (CD, p.  12-19).  Indeed,  long-
term exposures, alone (< 5 ppm S02)  and in combination with dry fly ash

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                                        A-9

 or sulfuric acid in animals  have not  produced notable changes  in  respiratory
 function (Alarie et al.,  1970,  1972,  1973, 1975).   Repeated  peak  exposures
 have not been adequately  tested.
       2.   Alteration  of  clearance  and  other  host  defense  systems
       This  may result  in  increased  susceptibility  to  infection or contribute
 to chronic  respiratory disease.   The  effect of SOg on clearance apparently
 varies with region  of  the respiratory tract,  species, and  nature of
 exposure.  SOg may  affect clearance rates  by  affecting physicochemical
'properties  of the mucus,  increasing mucous secretion, damage to cilia,
 or altering deposition patterns  through bronchoconstriction.  S02 (5
 ppm) decreased nasal mucous  flow rates  in  3^  to 6-hour human exposures
 (Andersen et al., 1974).   The implications of this response  for susceptibility
 to infection are, however, unclear  (Andersen  et al.,  1977).  Short-term
 oral exposure to 5  ppm S02 during exercise enhances exercise induced
 increases in tracheobronchial clearance in healthy adults  (Wolff et al.,
 1975a;  Newhouse et  al., 1978), but  no effects are  seen at  rest (Wolff et
 al., 1975b).  Effects  of  repeated peak  and long-term  exposures in animals
 suggest a biphasic  response; slightly accelerated  clearance  and no
 change  after several days followed  by increasingly decreased clearance
 with time or higher SO^ levels  (Spiegelman et al.,  1968; Ferin and
 Leach,  1973; Hirsch et  al.,  1975).  Similar biphasic  responses have been
 noted for sulfuric  acid (at  lower concentration  than  SOg)  and cigarette
 smoke (Leikauf et al.,  1981).  Because  SOg effects orr clearance may also
 be mediated through a  reflex response (Wolff  et  al.,  1975a), clearance
 may be  affected in  airways distal to  the site of S02  deposition.
      Because little S02  penetrates to  the pulmonary  region, substantial
 direct  effects on pulmonary macrophages are not  expected;  none have been

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                                       A-10

 observed  (Katz and Laskin, 1976).  From limited infectivity work in
 animals,  it  appears that susceptibility to bacterial infection is not
 affected  by  high S02 concentrations (5 ppm for up to 3 months) (Ehrlich
 et al., 1978).  Antiviral defenses were Impaired by S02 in mice, but
                                 • •"»»-»
 only at high levels (7 to 10 ppm) for 7 days (Fairchild et al., 1972;
 Lebowitz  and Fairchild, 1973).  Long-term exposure to 2 ppm alone and in
 combination with 560 pg/m3 of carbon dust for 192 days altered pulmonary
 and systemic immune systems (Zarkower, 1972).  Effects of the combined
 exposure were at most additive and dominated by carbon.
      3.  Tissue irritation or damage leading to morphological alterations
      Because most SC>2 is deposited in the upper.airways, the potential
 for damage is greatest in the upper respiratory passages (Giddens and
 Fairchild, 1972; Hirsch et al., 1975).  High concentrations (repeated
 peaks of 50 ppm) produced damage to the mucous secreting cells in the
 bronchial airways of rats (Reid, 1970).  At lower long-term exposures
 (0.14 to 5.1 ppm), S02 alone and in combination with dry fly ash particles
 produced no significant morphological  alterations  in bronchial airways
 or alveolar regions of monkeys (Alarie et al., 1972).
      4.  Reactions with important  cellular constituents
      The three major reactions of  bisulfite (e.g.,  from dissolved S02)
with biological materials include sulfonation,  auto-oxidation, and
 addition to cytosine (CD, p.  1-57).  A number of in  vitro studies have
 suggested that these reactions may  result  in effects on enzyme systems,
 but, because major in  vivo studies  of  these endpoints  have not been
 conducted, no evidence exists  indicating  effects in  whole animals or
humans (CD, p.  12-7).  Production of free  radicals  during auto-oxidation
 (CD, p. 12-4) and the  reaction with cytosine in DNA  are mechanisms by

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                                       A-ll

which bisulfite might induce mutation (Shapiro, 1977).  SC>2 and bisulfite
are mutagenic in microbial systems at acid pH, but cytotoxicity, rather
than mutagenicity, is the most common response of cultured animal  or
human cells (Thompson and Pace, 1962; Kikigawa and lizuka, 1972).,
Animal studies using high concentrations provide some suggestion that
S02 might be a carcinogen or co-carcinogen with benzo-a-pyrene.  (Peacock
and Spence, 1967; Laskin et al., 1970, 1976).  The evidence is, however,
inconclusive (CD, p. 12-78).

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 APPENDIX B.   EVALUATION OF  EVIDENCE  FOR  EFFECTS  ON  RESPIRATORY MECHANICS
              AND SYMPTOMS
       This section  discusses  and  evaluates  the key  studies  providing
 information  on  the  effects  of S02, alone and  in  combination with other
 pollutants,  on  respiratory  mechanics and symptoms.
 A.  Controlled  Human  Studies  of S02  Alone
      Although differences in  aspects such as  respiratory function
 indicators,  subject activity  levels, and routes  of  exposure make direct
 comparisons  difficult,  the  major  observed response  to short-term exposures
 of S02 appears  to be  bronchoconstriction, usually evidenced in increased
 pulmonary  flow  resistance or  impaired forced  expiratory flow rates. The
 data  indicate that most  healthy adult subjects respond to short-term S02
 exposures  of 5  ppm or more  (Table 5-1, Section V; CD, p. 13-48).  At
 lower levels, (1-4 ppm)  results are  more  mixed, with a number of studies
 reporting  otherwise normal  individual "hyperreactors."  At  1 ppm, Frank
 et  al.  (1962) reported a significant increase in pulmonary  flow resistance
 in  one  of  11  subjects during exposures lasting 15 minutes.  Also at 1
 ppm,  Andersen et  al.  (1974) found a  small but progressive decrease in
 forced  expiratory flow  (FEF25_75%) and forced expiratory volume (FEV^g)
 and an  increase in nasal flow resistance in 15 adults exposed for 6
 hours.  With  intermittent exercise,  levels of 0.75 ppm S02  resulted in
 decreases  in several functional parameters in apparently healthy  adults
 (Bates  and Hazucha, 1973; Stacy et al.,  1981). The major responders in
the Stacy work might have been defined as mild atopies.   Other  work
 indicates that such individuals are substantially more responsive to S02
than normal subjects (Koenig et al.,  1982a,b;  Sheppard et  al.,  1981a).
      Asthmatic  subjects appear to respond to S02 at levels  an  order of
magnitude lower  than do  healthy adults.   Several  studies  in  Table 5-1

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                                       B-2

 (Section V-B of main text) report marked changes in functional measurements
 after  short-term  (_< 1 hour) oral (mouthpiece) exposure at rest and
 during exercise at levels of 1-5 ppm with symptoms such as wheezing and
 shortness of breath increasing with concentration.  A number of subjects
 were reportedly unable to tolerate these exposures.  Symptomatic responses
 are reported at levels as low as 0.5 ppm for 10 minutes (Sheppard et
 al., 1981a; Kirkpatrick et al., 1982).  Decreased functional measurements
 can occur for oral (mouthpiece) exposures of 0.25 to 0.5 ppm with exercise
 (Sheppard et al., 1981a).  In this study, the two most sensitive asthmatic
 subjects exibited increased airway resistance (without symptoms) for
 mouthpiece breathing and exercise at levels of 0.1 ppm.
       A number of studies suggest that acute reflex respiratory mechanical
 changes induced by S02 take place within a relatively short period of
 time,  on the order of 1 to 5 minutes (e.g., Frank et al.,  1964; Melville,
 1970;  Lawther et al.,  1975).   Deep breathing accompanying  exercise can
 temporarily reverse this bronchoconstriction (Nadel and Tierny, 1961)
 and can delay the onset of respiratory changes (Sheppard et al., 1981a)
 and otherwise lengthen the period in which decrements occur (Bates and
 Hazucha, 1973).   Responses are usually maximal  within 10 minutes,  and may
 decrease somewhat and/or remain about constant for exposures of up to
 one hour (Melville,  1970).  This is  in contrast to the steady increase
 in resistance reported for guinea pigs over similar periods (Amdur,
 1959).
      After short-term exposures, recovery  to normal  functional  values
 can occur rapidly, in  as little as  5 minutes in normal  resting subjects
 (Lawther et al., 1975),  but  may take 30-60  minutes for exposures involving
exercise (Bates  and  Hazucha,  1973),  asthmatic subjects  with  exercise

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                                       B-3

 (Sheppard  et  al.,  1981a; Koenig et al., 1981), or other sensitive subjects
 (Lawther et al., 1975; Gokemeijer et al., 1973).  In one study, (Jaeger
 et  al., 1979)  symptomatic responses  (wheezing and shortness of breath)
 observed in three  sensitive subjects (out of 80) did not occur until the
 evening following  a quiescent oral (nose clips) 3-hour exposure to 0.5
 ppm S02.   In  this  study, only very small decreases in one functional
 response were seen immediately following exposure in most subjects and
 it  is  not  clear how S02, acting alone, could have produced such a delayed
 response.  Nevertheless, of the three reactors, two were asthmatics who
 had been free  of wheezing for several months before the experiment and
 one (non-diagnosed) had never experienced wheezing previously, suggesting
 some involvement of the exposures.  One plausible explanation is suggested
 by  the observations of Islam et al. (1972) and Reichel  (1972), outlined
 in  Section V-A, namely that S02 may sensitize airways to subsequent
 bronchoconstrictive challenge. Thus,  in this case, the attacks might
 have been proximally caused by post-experimental  exposures  to other
 substances.  Additional work is needed to determine the extent to  which
 such S02 levels may increase airway sensitivity.
      Three controlled studies of longer S02 exposures  (> 3 hrs to days)
 suggest the possibility of somewhat different respiratory responses.
Andersen et al. (1974) found that chamber (mostly  at  rest,  nasal breathing)
exposure to 1  ppm S02 produced a  progressive decrease in  forced expiratory
flow (FEF25_75^) and to a lesser  (nonsignificant)  extent  FEV-| ^ over a
six hour period.  Changes were slight after  1 to 3 hours  and  were  small but
significantly  larger for  one parameter  (FEF25_75%), after 6 hours.   There was
some suggestion of  a  carry  over of  functional  decrement after exposure
into the next  day  ( =  18 hours), although  the carry  over was more convincing

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                                       B-4

 after a  similar  5  ppm,  6 hour exposure.  Some slight discomfort and
 symptoms were  noted  at  this higher concentration.
       Weir  and Bromberg (1972) exposed 12 healthy subjects and a selected
 group of seven otherwise healthy smokers with evidence of early small
                                              t >•
 airway functional  impairment for 5 and 4 days respectively to 0.3, 1,
 and  3 ppm of SOg.  Subjects were free breathing and may have exercised,
 but  such occurrences were not reported.  No effects were noted at the
 0.3  ppm  level  in either group.  In the healthy group, small but significant
 decreases in compliance were noted at 1 and 3 ppm.  These changes were
 maximal  at  the first measurement (24 hours), decreased to insignificant
 levels over the next several days, and finally increased again after 120
 hours  in the 3 ppm exposure group.  Recovery to normal  values was complete
 48 hours after exposure.  The authors suggest that the early changes
were  the result of the  reflex bronchoconstriction observed in short-term
 studies, an effect which can diminish with continued exposure.  The
 later effects, they argue,  may represent  a different mechanism of damage.
 Responses in the impaired group were reported to be so variable under
 both  controlled and exposure conditions that consistent responses
 (mechanics  or  symptoms) to  SOg were not detectable.   Under the conditions
of study (steady multiday  exposures,  mostly  resting) the impaired group
was not more sensitive to the  effects of  SOg.
      Reichel   (1972)  reported  a  gradual,  but not  statistically significant
increase in intrathoracic  gas  volume  in normal  subjects exposed for 6
days to 7.7 ppm S02-   No trends  in  airway resistance were  noted.   All
subjects complained of various symptoms such as  rhinitis,  conjunctivitis
and throat irritation.   In  this  study,  the frequency of increased  obstructive
bronchial reactions to acetylcholine  increased  as  a  result  of the  exposure.

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                                    B-5

Bronchitic patients were also exposed but to lower levels (1.5 to 3.8 ppm
S02, 4 or 6 days).  One of the groups with more serious obstructive disease
appeared to show a decrease in total resistance but no statistics are given
and the discussion suggests that no responses were seen.  The results on
bronchitics are confounded because the patients had to be treated by
medicative therapy during the exposure; thus conclusions about their relative
sensitivity at these exposures are not possible.
      In these long-term studies, S02 exposures were increased gradually
from control to maximum levels over a period of hours.  This apparently
reduces the chance of more severe bronchoconstriction observed in short-
term studies after abrupt increases in concentration over a period of
seconds.  Andersen et al. (1974), for example, observed that subjects slowly
brought to 5 ppm reported only mild discomfort while the investigators
entering the 5 ppm chamber from clean air felt "strong discomfort and a
cough which was difficult to suppress but disappeared after a few minutes."
The time course of flow reduction during free breathing chamber exposures
to 0.75 ppm SOg observed by Bates and Hazucha (1973) and Stacy et al.
(1981) suggest that the rapid rise in ventilation brought on by the
onset of intermittent exercise may be equivalent to a sharp increase in
concentration.  In the Bates study, MEFR5Q% continued to decrease throughout
a 2-hour exposure with periodic exercise.  In the Stacy study, subjects
were exposed at rest for 45 minutes to 0.75 ppm S02 before beginning
exercise.  Based orl previous work on resting healthy adults, it is
highly unlikely that constrictive effects would have been observed
during the resting exposure.  Despite this extended exposure prior to
exercise,  airway resistance still increased significantly following a
15-minute exercise period.  This is consistent with expectations in that

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                                       B-6

 even  though  external S02 levels remained constant, the effective concentration
 at  sensitive receptors increased rapidly with the increased oronasal
 ventilation  associated with exercise.
 B.  Long-term Exposures to S02 Alone
     As discussed in Section V-A, long-term exposures of laboratory
 animals to moderate SOg levels have not generally been observed to
 produce decrements in respiratory mechanics (CD, Table 12-3).  The only
 exception is  the work of Lewis et al. (1969, 1973), who found increased
 pulmonary flow resistance and decreased lung compliance in dogs exposed
 to  5.1 ppm SOg, 21 hours a day for 225 days.  After 620 days, nitrogen
 washout increased, but the other functional parameters were no longer
 significantly different.  This high level  exposure of apparently resting
 animals used  in this and most animal studies may not adequately assess
 the potential long-term effects associated with repeated peak exposure
 and intermittent exercise characteristic of human exposures.
 C.  S02 in Combination with Laboratory Particles, Other Gases
     The interaction of S02 with particles and with pollutant gases has
 been variously reported to produce responses on respiratory mechanics
 and symptoms sometimes  exceeding those attributable to the two agents
 administered separately,  and sometimes not.  Enhanced responses may
 arise from physical  sorption of S02 on or  in particles permitting  enhanced
 respiratory penetration of the gas (Appendix A), chemical  reactions to
 form irritant pollutants  (e.g., stable sulfites or sulfuric acid),  and
 deposition and combined actions of S02 and particles  or pollutant  gases
 in various sites in  the respiratory tract.
      Amdur and coworkers  studied  combinations of S02 and  particles in
the guinea pig model  already shown  to  be quite sensitive to both S02 and

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                                       B-7

 sulfates.  The  results of fine aerosol/502 mixtures at low humidity,
 typically  administered for an hour, can be summarized as follows:
 1)  soluble catalytic aerosols (containing manganese, ferrous iron, or
 vanadium)  potentiated the response to S02 by reactions in the chamber or
 in  the  animal that apparently formed a more irritant aerosol (e.g.,
 sulfuric acid or  sulfite complex); 2) certain salt aerosols (NaCl, KC1,
 NH4$CN) potentiated SOg response in order of increasing S02 solubility,
 but only at unrealistic levels (10 mg/m3) (Amdur and Underhill, 1968);
 3)  combinations of S02 and the most common atmospheric sulfate species
 (ammonium  sulfates, sulfuric acid) produced additive responses (Amdur et
 al., 1978a), and; 4) S02 and insoluble dry aerosols (carbon, activated
 charcoal,  fly ash, ferric oxide, manganese dioxide, and motor oil)
 produced,  at most, additive responses (Amdur and Underhill, 1968; Costa
 and Amdur, 1979).
      As noted, the Amdur studies were apparently conducted at low
 relative humidity (< 70%).   Work on guinea pigs by McJilton et al. (1976)
 found no response to a one hour exposure to S02 (1 ppm) and sodium
 chloride (1 mg/m3) aerosol  at low relative humidity (RH),  but a marked
 potentiation at high RH (80%) that allowed droplet formation.  Droplet
 pH prior to exposure was 3.8 with no detectable sulfate formation.
 Chamber ammonia, which might have increased S02 solubility in the droplets,
was not measured.
      A few controlled human studies have examined combinations of 862
 and particulate matter,  chiefly  sodium chloride,  water  droplet  aerosols,
and carbon particles.   Dry  salt/S02 combinations  support the McJilton et
al.  (1973)  results in  animals,  that is,  moderate  levels (_< 1000 pg/m3)
of dry  salt particles  do not potentiate  the  effect of S02  (Frank  et al.,

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                                       B-8

 1964;  Burton  et  al.,  1969; Snell and Luchsinger, 1969).  Some Japanese
 work  suggest  a possible  potentiation by dry salt (Toyama, 1962; Nakamura,
 1964),  but  these studies used high salt (7 mg/m3) or S02 (9 ppm) levels,
 and,  according to the criteria document (p. 13-27) and MAS (1978) used
 inadequate  functional measurements.  In contrast to McJilton and Frank,
 however, Koenig  et al. (1982a,b) found no evidence of potentiation in
 humans  using  virtually the same S02/NaCl droplet aerosol.  Possibly,
 this disparity is due to the presence of ammonia in the animal chamber,
 but not in  the human exposure.
      The results of Snell and Luchsinger (1969), provide some controlled
 human evidence that water droplet aerosols may potentiate the effect of
 S02 by  increased penetration and/or hot spot deposition.  Increased
 effects were suggested for S02/water droplet aerosol  combinations,  but
the resultant decrease in pulmonary function was independent  of S02
 concentration; thus enhancement occurred only at lower S02 levels  (<_ 1 ppm),
 Unfortunately, water droplet levels could  not be estimated,  ammonia
 levels are  not known, and the functional measurement  techniques used are
of questionable validity  (CD, p.  13-51;  Kreisman et al., 1976).
      Andersen et al. (1981)  examined  nasal  exposure  to combinations of
S02 (1 or 5 ppm)  and a coarse (2-15 ym)  plastic dust  (2 or  10  mg/m3)
with and without  a surface coating  of  vanadium oxide.   Effects on nasal
mucous flows,  nasal  air flow  resistance, forced expiratory  flow
 (FEF25-75%) and symptomatic discomfort were,  at most,  additive.  This  is
not suprising  since most  of the coarse aerosol  did not  penetrate the
nose and adsorption  of S02 on dry insoluble  aerosols  (e.g., carbon)  is
probably minimal  (Schryrer et al.,  1980).

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                                       B-9

     In summary, although particles may potentiate the effect of S02 by
increased penetration or chemical reaction, controlled human exposures
have found mixed results, with little convincing evidence that-such
enhancement occurs for laboratory aerosol conditions at realistic peak
aerosol levels.  Ambient conditions that might tend to maximize interactions
between SOg and particles (cold temperatures, fog droplets, substantial
N02, NH3) have not been systematically examined in the laboratory.
     Long-term exposures to S02 in combination with particulate pollutants
have been conducted only in animals, and are evaluated in Appendix B
(Table B-8) of the particulate matter staff paper (EPA, 1982b).  These
studies in general have either found no lasting mechanical responses or
the functional decrements appear less important than underlying damage;
deep lung damage in such cases (Gillespie et al., 1980) does not appear
related to the S02 component of the mixtures (EPA, 1982b).
     Combinations of S02 and other atmospheric gases have produced mixed
results.  Bates and Hazucha (1973) first reported synergistic functional
responses to S02 + 03 (0.37 ppm each), but follow up studies in other
laboratories and with other investigators (Bell et al., 19.77; Horvath
and Folinsbee, 1977; Bedi  et al., 1979) did not confirm these results.
Follow-up measurements by Bell et al. (1977) suggested that the system
used in the original study may have produced ultrafine sulfuric acid and
other sulfate aerosol formation (total sulfates as high as 200 yg/m3)
and may have permitted intrusion of ambient particles.  The result of a
follow up study by Kleinman et al. (1981) with 0.4 ppm SOg, 03 and 100
yg/m3 sulfuric acid/ammonium sulfate aerosol found,  however, only a
small  incremental  response over ozone alone; the increment was much
smaller than observed by Hazucha and Bates.  A recent Japanese study

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                                        B-10
 (Kagawa and Tsuru, 1979)  reports  that  exposures  to  S02  + 03,  (0.15  ppm
 each) results in a greater than additive  increase in  airway  resistance,
 but not to the extent seen by  Hazucha  and Bates.  The finding  of  small
 significant responses in  this  study  may be  related  to differences in
 methods of statistical  analyses (Bedi  et  al., 1982).  In sunwary, the
 available evidence on synergism between 03  and S02  or 03, S02, and
 sulfates suggests reason  for caution,  but the question  is unresolved.
 Combinations of S02 with  N02 and  03  at both high and  low levels (CD,
 Table 13-5)  resulted in no enhancement of functional  changes (Linn et
 al.,  1980;  von  Nieding et  al., 1979).
 D.  Community Air Pollution
      Qualitative  examination of short-term respiratory mechanical  changes
 in  people exposed to  fluctuating ambient levels of S02 and particles are
 limited  to two  epidemiological investigations.  Lawther et al. (1974a,b,c)
 made  daily measurements of  lung function on four normal  subjects for five
years, and two  bronchitics for one winter in London.  Daily variations in
 lung  function were  small and mostly affected by respiratory infections,
 although some direct  effects of pollution were detected.  After multiple
 regression analysis, S02 concentrations explained the largest proportion of
 variance in peak  flow rates (PEFR) and airway  resistance (indicated  by
MMFR), with clearest associations  shown after  walking exercise  during
episodic periods of heavy  pollution.   These  results  are  limited because  of
the small study group.
     Small, but persistent declines in  children's  lung function (FEV^  Q)
were observed after a pollution episode in Steubenville, Ohio in which
S02 reached high 24-hour levels along with a somewhat  lower TSP level
(Dockery et al., 1981).  Similar effects were  noted  following an episode

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                                       B-ll

 dominated  by high TSP levels and moderately high S02.  The authors
 conclude that this study provides suggestive but inconclusive evidence
 regarding  short-term  (24-hour) changes in air pollution and FEVj^Q.
 long-term  significance of these changes has not been assessed.
      A number of long-term epidemiological studies of chronic effects
 have  found that populations living in areas characterized by high particulate
 matter and S02 tend to have a higher prevalence of respiratory illnesses
 and symptoms and lower lung function capability compared with other
 groups living in areas with lower pollution levels (see Table B-3, EPA,
 1982b).  Other qualitative studies discussed below have detected differences
 that  might possibly be explained by contrasting exposures to S02 rather
 than  other pollutants.  As in most epidemiological studies, however, the
 influence  of particles and other factors confound interpretation.
      Neri et al. (1975) compared adolescents and adults in a large city
 with  a similar group living near a large smelting operation (Sudbury,
 Ontario) that required frequent shutdowns because 24-hour pollution
 levels in town often reached "maximum permissible values" (_>_ 790 yg/m3
 [0.3  ppm] S02 or _> 400 ug/m3 suspended particulate matter).  After
 controlling for smoking and occupational  differences, residents of the
 smelter town had significantly lower lung function than the city dwellers.
 The criteria document concludes that very high periodic peak (_< 1 hr)
 S02 exposure levels likely accounted more for any pollutant effects than
 long-term exposures-to relatively low annual  average  levels of S02 or
 annual mean particulate levels (which did not vary by much between the
two areas) (CD,  p.  14-100).
      The possibility that the lung function  decrements as noted by Neri
et al. may reflect  the cumulative effects of  repeated peak exposures has

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                                       B-12
 been  examined  in  other Canadian cross-sectional studies.  Comparisons
 were  made  between children  (Becklake et al., 1978) and adults (Aubrey
 et  al.,  1979)  living near point sources and exposed to high SOg peaks
 with  similar groups in communities with little S02 pollution.  Annual
 particle levels (TSP) were moderately high in all  areas, with one of the peak
 S02 areas  having  frequent peaks of TSP as well.  No significant differences
 in  respiratory symptom prevalence were noted for either group nor in
 pulmonary  function among the adults.  However,  among the children in the
 high  pollution areas, small airway function (as measured by closing
 volume)  was impaired, and a trend towards reduced  lung function as the
 winter progressed was noted. The authors felt that these subtle effects
 might reflect the early stages of airway disease in the children exposed
 to high  S02 peaks with or without accompanying  high particulate matter peaks.
 Because  of the preliminary nature of the study, the results can only suggest
 minor effects that might be weakly associated with repeated exposures to
 S02.
      Van der Lende et al. (1973,  1975,  1981) followed a group of Dutch
 adults living in an industrialized town  along with a similar group of
 rural  residents for nine years.   The initial  cross-sectional  comparison
 revealed no difference in  lung function,  although  the prevalence of
 chronic cough and  phlegm,  and sputum production, was higher among the
urban  residents.   Repeated follow-up studies  were  done at  three  year
 intervals over a  period when the urban S02  levels  decreased considerably
from high (with frequent peaks)  to more  moderate levels, and  particles
 (British Smoke) remained at  relatively low  levels.   After  controls for
smoking arid occupational differences, the urban  residents  showed an

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                                       B-13
accelerated decline in lung function  over  that  observed  for  rural  residents.
Difficulties in assessing exposure to particles (calibration of  smoke
data) and SOg (representativeness  of  monitor)  limit  interpretations of
these results.

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APPENDIX C.  PULMONARY FUNCTION TESTS USED IN CONTROLLED HUMAN STUDIES
             OF SOg1
A.  Introduction
     Pulmonary function tests can provide objective information to
assist clinical judgment and help in the evaluation of respiratory
impairment caused by air pollutants such as S02.  The tests and terms
used to describe various aspects of respiratory function referred to in
this paper are defined in the glossary that follows this section.
     These tests principally measure respiratory mechanics, which includes
the combined effects of gravity, elastic recoil, and smooth muscle tone
upon airway caliber, lung volumes and airflow patterns.   Several  tests
have been developed in an attempt to differentiate among 1) kinds of
effects; for instance airway narrowing or obstruction as in asthma,
bronchitis, and emphysema, and restriction of the thorax, as in fibrosis
or skeletal and chest muscle disorders, and 2) region or site of action;
for instance the large airways (bronchi), small airways  (bronchioles),
and gas exchange regions.
General  references  for this  Appendix include:  Cotes  (1979),  Fishman
 (1976),  Macklem and Mead (1967),  Mead et  al.  (1967),  and  Wanner  (1980).

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                                       C-2


 B.   Glossary  of  Terms used to Describe Respiratory Mechanics and
     its  Tests

 Airway conductance  (Gaw):  The  reciprocal of airway resistance.

 Airway resistance  (Raw, pulmonary flow resistance):  Resistance to the
      flow  of gas in the airways (one component of the total respiratory
      resistance) measured by body plethysmography.  Average values for
      normal  healthy individuals rtnge from 0.6-2.4 cm H20/l/sec.  A
      normal  resting subject in whoiif bronchial obstruction is induced
      does  not usually experience symptoms until Raw is increased 3-fold
      or more and severe dyspnea may not result until Raw is increased 5-
      to 15-fold.  Raw and its derivatives (Gaw, SGaw, §Raw) are mainly
      affected by alterations in the resistance characteristics of the
      large airways.

 Alveolar oxygen  tension (PAQ2):  Partial pressure of oxygen in the alveolar
      airspace (reflects amount of oxygen in alveolar air).

 Arterial oxygen  tension (PAoa):  Partial pressure of oxygen in arterial
      blood (reflects amount of oxygen in arterial  blood).

 Bronchoconstriction:  Constriction of the airways,  may be caused by
      neural  reflexes or direct effect on smooth muscle.

 Bronchospasm:   See bronchoconstriction.

 Closing  capacity (CC):   The volume at which,  during expiration, the
      closure and trapping of gas in the alveolus (caused by increase in
      applied pressure and reduction in the diameter of the small  airways)
      first occurs;  CC = RV + CV.  The assumption is that with narrowing
      of the small  airways, closure will  occur at a higher lung volume.

 Closing  volume (CV):  Volume of the lungs above residual  volume where
      the closure and trapping of gas in the  alveolus  occur (detected by
      the change in expired nitrogen gas concentration);  CV = CC - RV.
      CV is higher with  narrowed small  airways, as  in  smokers.

 CC:   See closing capacity.

CV:   See closing volume.

Flow rate from 25-75% expired vital  capacity  (FEF25_75%):   Flow rate
     measured  from 25% to  75% of expired  vital  capacity.

Flow rate at 50% forced  vital  capacity  (FEF5Q%):  Flow  rate measured
     with 50%  expired vital  capacity remaining.  Same  as  MEFR.
     Primarily measures  intermediate to large  airway function.

Forced expiratory volume  (FEV):   Same as  vital  capacity.

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                                       C-3
Forced expiratory volume at 1.0 sec  (FEV^g)1  Fraction of vital capacity
      expired in 1.0 second.  Reduced in subjects with obstructive respiratory
      disease but not in those who have restricted expansion without
      obstruction.  Mainly affected  by alterations in the large airways.

Forced vital capacity (FVC):  Same as vital capacity.

Functional residual capacity  (FRC):  The volume of air remaining in the
      lungs at the end-expiratory position.  Measures small airway function.

FEV]>o:  See forced expiratory volume at 1.0 sec.

FEF25_75%:  See flow rate 25-75% expired vital capacity.

FEF50%:  See flow rate at 50% forced vital capacity.

FR:  See respiratory frequency.

FRC:  See functional residual capacity.

FVC:  See vital capacity.

Maximum expiratory flow from 40% forced vital capacity (MEF4Q%):
      Maximum rate of flow during forced expiration at 40% vital
      capacity.

Maximum expiratory flow from 50% forced vital capacity (MEF5Q%):
      Maximum rate of flow during forced expiration at 50% vital ca-
      pacity.  Same as FEF5Q%.  Primarily measures intermediate to
      large airway function.
Mid-maximal expiratory flow rate (MMFR, MMF,
      See maximum expiratory flow from 50% forced vital capacity.
      Same as FEF5p%.

MEF 40%:  See maximum expiratory flow from 40% forced vital capacity.

MEF 50%:  See maximum expiratory flow from 50% forced vital capacity.

MEFR 50%:  See maximum expiratory flow from 50% forced vital capacity.

MMFR:  See mid-maximal expiratory flow rate.

Nitrogen washout test:  Method to assess the uniformity of distribution of
      ventilation throughout the lungs; measures residual  volume, functional
      residual capacity, and closing volume.

PAQ2:  See alveolar oxygen tension.

PaQ2:  See arterial oxygen tension.

Residual volume (RV):  Volume of a gas that remains in the lung
      at the end of a complete expiration.

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                                       C-4


Raw:  See airway  resistance.

RV:   See residual  volume.

Rj:   See total  respiratory resistance.

Specific airway conductance  (SGaw):  Extent to which the airways
      conduct the  flow of gas normalized to the individual's thoracic
      gas volume:
ssaw
                  {jaw
                  TGV
Specific airway resistance (SRaw):  Resistance to flow in the air
      ways 'normali zed to the individual's thoracic gas volume: SRau =
      Raw x TGV.                                                 aw

SRaw:  See specific airway resistance

SGaw:  See specific airway conductance.

Thoracic gas volume (TGV):  Volume of gas in the thorax, whether in
      free communication with the airways or not.

Total respiratory resistance (Rj):  Total resistance of the respiratory
      system consists of three components, airway resistance, lung tissue
      resistance, and thoracic cage resistance.  Primarily measures large
      airway function.

TGV:  See thoracic gas volume.

Vital capacity (VC):   Maximum volume of gas that can be expelled
      from the lungs  by forceful  effort following a maximal inspiration.
      Reduction of VC may be due to loss of distensible lung tissue or
      some type of limitation of respiratory movement not related to
      disease of lung tissue.

Vmax50%:   Maximum flow calculated at 50% of expired vital capacity from
      a partial flow  volume curve begun from approximately 60% of inspired
      vital  capacity.  Primarily reflects changes in the caliber of the
      small  airways.

Vmax75%=   Maximum flow calculated at 75% of expired vital capacity from
      a partial flow  volume curve begun from approximately 60% of inspired
      vital  capacity.  Primarily  reflects changes in the caliber of the
      small  airways.

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APPENDIX D.  ANALYSIS OF ALTERNATIVE AVERAGING TIMES AND EXPOSURE
     This appendix summarizes important aspects of several  air quality,
modeling, and exposure analyses (Frank and Thrall, 1982; Burton et al.,
1982; Anderson, 1982) that were conducted in direct support of this
staff paper.  The information is used to support discussions of alternative
averaging times and population exposure in Sections VI and  VII.  The
major questions examined include:   1) the usefulness of a 24-hour standard
as a surrogate for a 1-hour standard; 2) the relative protection afforded
by current and alternative standards in the ranges of interest specf^fid
in Section VI; 3) the impact of eliminating the annual S02  standard; and
4) how many people are potentially exposed to 1-hour SOg values of 0.5 to
0.75 ppm, the range of interest used for the August 1982 draft of this
staff paper.  The reader is directed to the complete reports for a more
detailed discussion of the issues  addressed, methodology, and results.
Further work, particularly in specifying population exposures and examining
the lower bound of 1-hour S02 values recommended by CASAC (0.25 ppm) following
their review of the August draft,  is underway in support of decision-making
on the review of the SOg standards.
A.   Analysis of SOg Air Quality Data
     Frank and Thrall (1982) examined SOg monitoring data collected
during 1979 and 1980 representing  11 million hourly values  at approximately
900 monitoring sites.  Summary statistics for this data set are given in
Tables 4-1 and 4-2 in Section IV.   Sites were classified according to
three types:  population-oriented, source-oriented (excluding smelters),
and smelter-oriented.  Because of  the limited and variable  number of
sites per area (typically 1 or 2 for source-oriented sites), differences
in site location criteria and data completeness, and assumptions needed
in scaling data, generalizations based on these analyses should be
derived and used with caution.

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                                       D-2

 1.     24-hour Standard as a Surrogate for 1-Hour Average
       The  relationship among various measures of 1-hour and 24-hour standards
 is examined  in a series of tables and figures (Frank and Thrall, 1982).
 The  usefulness of a 24-hour standard as a surrogate for a 1-hour standard
 depends on the extent to which the 24-hour standard limits 1-hour values to
 acceptable levels without causing additional controls in areas where both
 24-hour and  1-hour air quality is already acceptable.  Table D-l shows
 that current control programs already limit the 2nd maximum 1-hour values
 in most site-years examined.  The distribution of 1-hour values versus 24-hour
 values shows that tightening of the 24-hour standard to 0.12 ppm would not
 change the 1-hour status of over 60% of the sites with second maximum 1-hour
 values in excess of 0.5 ppm.  Relaxing the 24-hour standard to over 0.16 ppm
 could permit a substantially larger number of sites with second maximum 1-hour
 values above 0.75 ppm.
      Figure D-l is a graphic display of the same data.   The figure indicates
that a 24-hour standard in the 0.12 to 0.14 range would  control  maximum 1-hour
 values at virtually all population-oriented sites.   At many smelter and other
source-oriented sites, the current 24-hour standard would be a useful
surrogate only if current  air quality were considered acceptable.   As  indicated
in Figure D-l and in Tables  7 and 8 of Frank and  Thrall  (1982),  current  air
quality at many of these sites  involves  multiple  hourly  exceedances  of  0.5
to 0.75 ppm S02-   Reducing the  24-hour standard to  0.12  ppm would  not  result
in improvements in most of the  sites  with  high 1-hour values,  but  would  call
for additional  controls at a number of sites  meeting the  current 24-hour
standard with no  second maximum 1-hour values  higher than  0.5  ppm.   Thus,

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                               D-3

TABLE D-l.  CURRENT STATUS OF SECOND HIGH 1-HOUR VALUES VERSUS  SECOND
            HIGHEST 24-HOUR VALUES IN TERMS OF SITE-YEARS (FRANK  AND
            THRALL, 1982).
2nd Highest 1-Hour
Values (ppm)
*
Ol
1/1
5
Population

Source

Ol
J
< 0.25 '
0.26-0.50
0.51-0.75
> 0.75
< 0.25
0.26-0.50
0.51-0.75
> 0.75
<_ 0.25
0.26-0.50
0.51-0.75
> 0.75
< 0.25
0.26-0.50
0.51-0.75
> 0.75
Number of
Site-Years
938
316
73
50
634
109
10
0
264
181
48
19
5
15
14
30
2nd Highest 24-Hour Values(ppm)
<0.12 0.13-.14 0. 15-. 16 .$0.16
938 000
305 533
54 11 4 4
19 7 3 21
634 000
107 2' 00
6 202
0 000
264 000
176 122
39 4 32
10 315
5 000
13 110
9 '5 00
9 4 2 15
* "All Sites" category includes data which could not be classified as
  population, source, or smelter.

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                              D-4
I/I
LU

ID
Q

O
    2.50-
                                  A = population-oriented sites

                                  B = source-oriented sites

                                     • smelter-oriented sites

                                     • "all sites"
                .06
.33
.42
                      SECOND  HIGHEST 24-HOUR VALUE

       Figure D-l.  Basic relationships  between  the  second  highest
       1-hour value per year  and the second highest  24-hour value
       (After Frank and Thrall,  1982).   The initial  staff ranges of
       interest for 1-hour standard (0.5 to 0.75 ppm)  and possible
       24-hour surrogates (0.12  to 0.16  ppm) are indicated  by  shading.
       Sites with data above  the diagonal line(s) would be  "controlled"
       by 1-hour standards, while those  below  the diagonals would be
       controlled by 24-hour  standards.   In the  hatched area,  the
       controlling standard would vary.   Based on the  data  in  this
       figure, the current 24-hour standard would keep 1-hour  values
       below 0.5 ppm in almost all of  the population oriented  sites,
       but would not prevent  many of the source  and  most of the smelter
       sites from having at least two  1-hour values  per year in excess
       of the indicated range.

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                                       D-5

a 24-hour standard that would markedly improve maximum 1-hour air  quality  at
most sites would be unnecessarily restrictive at sites with  acceptable  air
quality.
2.    Impact of Eliminating the Annual Standard
      Table D-2 shows the current status of annual  average S02 values versus
the second highest 24-hour values.  Few sites exceed the current annual
standard (0.03 ppm).  For source (including smelter) sites,  attaining
the 24-hour standard would result in attaining the  annual  standard
(Frank and Thrall, 1982).  For population-oriented  sites,  however, most
of the sites exceeding the current annual standard  already meet the 24-
hour standard; therefore, without an annual standard, further improvement
would not be expected.
      To further examine the consequences of eliminating an  annual standard,
Frank and Thrall (1982) examined the distribution of annual  averages
after: 1) adjusting levels downward to reflect attainment  of the 24-hour
standard, by itself or in conjunction with the current 3-hour standard
(0.5 ppm) and/or the midpoint of the range of alternative 1-hour standards
(0.5 ppm); and 2) allowing for limited growth up to the level of the 24-hour
standard.  Following these adjustments, fewer smelter sites  would  exceed
the annual standard, but "a substantially larger number of cases exceeding
the annual standard would occur, primarily among the population-oriented
locations" (Frank and Thrall, 1982). The 38 population-oriented sites
that would exceed t'he annual standard are identified in Table 18 of
Frank and Thrall (1982) and include a number of heavily populated  cities
and counties, including New York City, Philadelphia, Cook  County,  IL
(Chicago), and Jefferson, KY (Louisville).

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TABLE D-2.  CURRENT STATUS OF ANNUAL AVERAGES VERSUS SECOND-HIGHEST
    24-HOUR VALUES (ppm) BY SITE TYPE (FRANK AND THRALL,  1982)
Annual Average
ug/m3 (ppm)
< 60 (< 0.023)
61-80 (0.024-0.031)
81-100 (0.032-0.038)
> 100 (> 0.038)
Second Highest 24-Hour Value (ppm)
Population
Total < 0.14 > 0.14
711 710 1
34 34 0
7 6 1
1 10
Source
Total < 0.14 > 0.14
498 487 11
12 8 4
1 1 0
1 1 0
Smelter
Total < 0.14 > 0.14
44 39 5
844
8 3 5 )!
404

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                                       D-7
B.    Modeling Analysis
      Burton et al.  (1982) analyzed the relationships  among alternative
averaging times through air quality modeling of representative  large
point sources.  This analysis is.an important supplement  to air quality
data analysis because:   1) most emissions  limitations  for major S0£
sources are based on modeling, rather than monitoring  data; 2)  monitoring
sites around point  sources are generally too limited to capture maximum
short-term values;  and 3) models can give  estimates  of the spatial
extent of potential  exposures.
      The modeling  analysis simulated several hypothetical power plant
situations involving unscrubbed 1000 megawatt (MW) power  plants with  400
foot stacks.  Flat,  rolling, and complex terrain settings were  examined.
The CRSTER and COMPLEX I models were used  in modes that simulate the
temporal variability in S02 emissions.  Details of the analysis are
included in the report (Burton et al., 1982).  The preliminary  findings
are subject to uncertainties inherent in air quality modeling,  apply
strictly .only to the few cases examined, and are sensitive to assumptions
made about implementation approach and background levels.  Nevertheless,
they should be illustrative of relationships among averaging times for
large point sources.
      The major questions concern the extent to which  current S02 standards
limit peak 1-hour concentrations around major point  sources. Because
the annual standard  is rarely controlling  near large point sources
(Frank and Thrall,  1982), only the 24-hour and 3-hour  standards were  examined
in the modeling analyses.  Figures D-2a and b show the geographical extent
and number of expected exceedances of a 1-hour concentration of 0.5 ppm

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                                                               b)
                                                                                                                   a
                                                                                                                    i
                                                                                                                   oo
Figure D-2.  Location and Number of Expected Exceedances per Year of a 1-Hour Average Value of 0.5 ppm for

a 1000 MW Power Plant just complying with, a) the Current 24-Hour SOp Standard, and b) the Current 3-Hour

S02 Standard (Burton et al., 1982)

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                                       D-9

when the current standards are just  met.   Figure D-2a  indicates  that the
current 24-hour standard would permit yearly  second  hourly  maxima  in
excess of 0.5 ppm as far as 12 km (7.2 miles)  from the source.'  Over 20
exceedances of this concentration occur in areas within 2 to  5 km  of the
source.  Figure D-2b shows that the  3-hour standard  is substantially
more protective in this modeled case.  Second  maxima in excess of  0.5
ppm are confined to areas less than  5 km from  the source with no more
than 3-4 expected exceedances at any site. Figures  D-3a and  b show the
maximum expected 5 highest concentrations for  the same cases. The 24-
hour standard would permit 4 exceedances  of a  1-hour concentration of
0.75 ppm, while the 3-hour standard  would permit only  1. The second
maximum hourly concentration associated with  the 24-hour standard  would
exceed 1 ppm, with correspondingly higher peak (5-10 minutes) values possible.
      Based on this analysis, the current 24-hour standard  would not prevent
multiple exceedances of 1-hour values in  the  range of  0.25  to 0.75 ppm
at distances of up to 12 km from major point  sources.   The  current 3-hour
standard provides substantially better protection against such excursions
and could itself be a useful surrogate.
      The above analysis was for the flat-terrain case. Available data do
not suggest rolling terrain would involve substantially different
conclusions.  Results of complex terrain  modeling are  limited and  less
reliable.  As noted previously, the  results are also sensitive to
a number of modeling assumptions used.  In a  number  Of routine applications,
somewhat greater protection may be provided by the 24-hour  standard
than in this analysis.

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                                      D-10
a)
b)
                EKFECTEO       BXFECTEO        EIFECTED       EIFICTED       EIFECTED
                HIGHEST      SECOND HIGHEST    THUD HIGHEST    FOMTH HIGHEST   FIFTH HIGHEST
               HI      M-HOUR BVEKKCE
                                                             1-HOWt RVERBGE
                        3-HOUR IWERRGE
                EXFECTED        EKFECTED       CKFECTEO        EXFECTED       EIFECTED
                HIGHEST      SECOND HIGHEST    THIHO HIGHEST    FOURTH HIGHEST   FIFTH HIGHEST
                       24-HOUR flVERKE
                        3-HOUR RYEIIRCE
                                                             1-HOUR dVERRCE
       Figure  D-3.   Maximum  5 Concentrations for a  1000  MW  Power Plant  just
       complying with,  a) the Current 24-Hour S0? Standard  and  b) the Current
       3-Hour  S02 Standard  (Burton  et al.,  1932).

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                                       D-ll

C.    Exposure Analysis
      A complete analysis of exposures of sensitive populations  to  SOg
would involve extensive air quality simulations,  analyses  and  modeling
of activity patterns, and improved information on location and activities
of sensitive groups.  Available techniques for exposure analysis are
currently being applied to SOg, but no results are available.  To provide
some preliminary indication of exposure,  the initial  results of  the
modeling described above were used to estimate the number  of individuals
living in areas with potential for at least one hour per year  in excess
of 0.5 ppm (Anderson, 1982).
      As a first approximation, a screening algorithm was  used to identify
those power plants that under several scenarios,  might exceed  0.5 ppm
for 1-hour.  The census tract data was used to calculate the number of
individuals living within various radii  (up to 20 km) of the plants.
Based on the analysis of Figure D-2,  most of the  exceedances of  1-hour
values of interest will occur within  10 km of the source;  hence,  potentially
exposed populations will include those living within this  distance.
      Assuming "current" emission rates,  the algorithm indicated 77 power
plants that potentially might cause exceedances of 0.5 ppm.  This represents
a total  potential  exposure of 7 to 8  million people (one person  exposed
to two plants is counted twice) who live  within 10 km of these sources.
If asthmatics and atopies comprise the same proportion as  they do in the
U.S. population at large (about 5 to  10%),  then several  hundred  thousand
sensitive individuals live in locations where,  with current emissions they
might be exposed.   Because a number of sources  actually  emit lower  amounts
than needed to meet regulations,  exposures  would  increase  if each source
just met its  emission limits.  Assuming  all  plants just  met current S02

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                                  D-12

emission  limitations, between 7 and 21 million people (up to 10% of the
U.S. population) may live within 10 km of sources capable of causing
hourly exceedances of 0.5 ppm.  Thus, assuming asthmatics and atopies
are distributed in geographical patterns similar to the population at
large, up to 10% of the sensitive population may live 1n areas that
would be permitted to exceed 0.5 ppm at some location,  at least once per
year.
      The above estimates are crude and tend to overstate exposures
because of 1) potential  multiple counting,  2) conservative assumptions
in the screening algorithm,  3) at any given plant/time,  the area in
excess of 0.5 ppm will  be much smaller than the area  of  the 10 km radius
circle,  and 4) indoor/outdoor differences,  activity patterns  and the
like substantially reduce the numbers of exercising asthmatics that
actually encounter a  peak S02 value.

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APPENDIX E.   CASAC CLOSURE  LETTER

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           UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                       WASHINGTON, D.C.  20460


                         August 26, 1983
                                                         OFFICE OF
                                                      THE ADMINISTRATOR
Honorable William D. Ruckelshaus
Administrator
Environmental Protection Agency
Washington, D.C.  20460

Dear Mr. Ruckelshaus:

     The Clean Air Scientific Advisory Committee (CASAC) has
completed its second and final review of the revised draft Office
of Air Quality Planning and Standards (OAQPS) Staff Paper entitled
Review of the National Ambient Air Quality Standards for Sulfur
Oxides; Assessment of Scientific and Technical Information.

     The document is consistent in all important aspects with
the scientific evidence presented and interpreted in the combined
criteria document for sulfur oxides and particulate matter.  It
has organized the data relevant to the establishment of sulfur
dioxide primary and secondary ambient air quality standards in a
logical and compelling way, and the Committee believes that it
provides you with the kind and amount of technical guidance that
will be needed to make appropriate decisions about revisions to
the standards.

     During the course of the Committee's review of the Staff
Paper for Sulfur Oxides a number of significant scientific issues
related to the establishment of primary and secondary standards
were addressed.  A Teview of the existing data base for this
pollutant led the Committee to conclude that there are two scienti-
fically supportable options for revising the existing standards.
One option for which there is strong but not unanimous support
on CASAC includes the following: establishment of a new 1-hour
primary standard in the range between .25-.75 parts per million,
retention of a 24-hour primary standard, conversion of the
current .03 ppm annual primary standard to an annual secondary
standard at or below that level, and selection of a revised 3-hour
secondary standard between a range of .40-.50 ppm.  The other
option for which there is some support on the Committee is to
retain the existing primary and secondary standards, while
providing some additional public health protection by converting
the existing 3-hour secondary standard into a primary standard.
The choice between these options is a policy decision which is
not within the scope of the Committee's mission.  CASAC's wishes
to inform you that either of these options would be supported by
the available scientific evidence.

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                             -2-

     Other scientific issues and studies of interest-to the
review and possible revision of the primary and secondary
standards are reviewed in the attached report.  In addition,
I have attached a recent CASAC report on research needs for
the gases and particles program within the Agency.  It is
clear that there are major gaps in our understanding of
these pollutants and that the Agency should develop a more
balanced and more adequately funded research program.

     I hope the CASAC1s findings and recommendations prove
useful to you as you review and consider revisions to the
sulfur dioxide standards.  The Committee appreciates the
opportunity to advise you on this important issue, and it
will provide further review and comment to you during the
public comment period that follows the proposal of revised
standards in the Federal Register.
                              Sincerely,
                              Bernard D. Goldstein, Chairman
                              Clean Air Scientific Advisory
                                Committee
Attachment

cc:  Alvin Aim
     Charles Elkins
     Terry F. Yosie

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- f
            Findings, Recommendations and Comments
    of  the Clean Air Scientific Advisory Committee on  the
      OAQPS Revised Draft Staff Paper for Sulfur Oxides


     CASAC's evaluation of the scientific basis for a  review

and possible revision of the ambient air quality standards

for sulfur dioxide began with its recommendation in November

1978 that the Agency evaluate the joint interaction of sulfur

oxides  and particulate matter on human health and the

environment by the development of a joint criteria document

for these pollutants.  Following three public reviews of the

criteria document and its subsequent revision by Agency staff,

the Committee concluded in a letter to the Administrator

dated January 29, 1982 that the Agency's assessment of the

existing literature for these pollutants was scientifically

adequate.  This report addresses the OAQPS staff's interpretation

of the criteria document and the scientific rationale that is

develped to support their proposals for reviewing and revising the

SO2 standards.                 ~

The Scientific Basis for Primary SOj Standards

     1.   A major OAQPS conclusion of the criteria document

review process was that sulfur dioxide continued to pose a

serious health problem to important subgroups of the population

which warranted its continued separate control.   Thus,  OAQPS

does not recommend a joint SO2/particles primary standard,

believing that  current information on health effects and U.S.

exposures to these two pollutant categories warrants a

continuation of separate controls.

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                             -2-



     CASAC concludes that separate SC>2 and particles standards,



each set with appropriate consideration for potential  interactions,



does appear to protect public health.  Furthermore, the complexities



of  setting and implementing a joint SO2/particles standards



through monitoring and other requirements create numerous uncertain-



ties which the available scientific evidence is ill-equipped to



resolve.  CASAC concurs with the OAQPS position and its supporting



rationale and recommends that you retain the current approach of



setting separate primary and secondary standards for sulfur dioxide



and particulate matter.



     2.  The scientific basis for a 24-hour standard stems primarily



from epidemiological studies.  These studies (Lawther et al. 1970



[analysis of bronchitics]; Martin and Bradley, 1960, Mazumdar et



al., 1981, and Ware et al., 1981 [analysis of mortality]) do not



show evidence of clear thresholds, but they suggest that risk to



public health increases as concentration levels increase. The Air



Quality Criteria Document for Sulfur Oxides/Particulate Matter and



the SC>2 staff paper interpret these studies as suggesting that



increases in excess mortality occurred in the range of 500-1000



ug/m3 British Smoke and .19-.38 ppm SO2,  and that such effects



are most likely when both pollutants exceeded 750 ug/m3 (.29 ppm



SO2>.   Lawther"s study of reported symptoms among bronchitics



also suggests that this population group experiences significant



responses associated with 24-hour averages of .19 ppm SO2-   Based

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                             -3-



upon these studies and the need for a margin of safety the



staff paper developed a range of interest between .14 to .19



ppm in recommending a revised 24-hour primary SO2 standard.



     The upper end of the recommended range of .14 to .19 ppm



represents a level at which effects are identified in the



criteria document and for which there is little or no margin



of safety for exposed sensitive individuals.  You should be aware



that the ranges of interest developed in the staff paper for the



24-hour standard were based on epidemiological studies which



provided quantitative concentration/response data of  the



populations studied.  A  final decision on whether or  not to



revise  the  24-hour standard  should  also  incoporate  information



generated  through controlled  human,  animal  toxicology and  the



less quantitative epidemiology  studies discussed  in the  criteria



document  and  staff paper.   In view  of all  of  the  above,  CASAC



 recommends that you  consider "selecting  a value at the lower



end of  the range for the 24-hour  standard,  taking into  account



whether a separate  1-hour primary standard is also established.



      3.  CASAC's review of the scientific evidence related to



 the annual primary standard presents a dilemma because the



 Committee could find no real quanitative basis for retaining



 this standard.  This is a troublesome issue because there is



 the possibility that repeated S02 peaks of 1-hour and 24-hour



 exposures might lead to effects on human respiratory systems

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                             -4-



over the long-term.  Second, an annual primary standard



affords protection against health effects that can't be



measured well in short-term controlled human studies.  Third,



air quality analysis conducted by OAQPS staff suggests that



1-hour and 24-hour primary standards in the range stated in



the staff paper would not prevent SO2 concentrations from



exceeding the current annual primary standard in some heavily



populated areas of the country.  Fourth, as pointed out in



the discussion of  secondary standards, there  is a scientific



basis for a secondary standard at the level of the annual



current primary standard.  Following extended discussion the



Committee concluded that  some protection against chronic SC>2



exposures is needed, but  that the most persuasive scientific



basis for an annual standard is  found in the  effects on welfare.





     4.  The scientific basts for the development of a  1-hour



primary standard  rests largely on several major controlled



human clinical  studies conducted by three separate  laboratories



that were published  in the  peer  reviewed literature  in  1981



and  1982.  These  studies  documented measurable  changes  in



respiratory  function of exercising  asthmatics exposed  for  short



periods at or  below  concentration  levels of .50  parts  per



million  (ppm).  The  studies (Kirkpatrick et al.  1982;  Koenig



et al.  1982;  Linn et al.  1982;  and  Sheppard et  al.  1981)  raise

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                             -5-



the issue of how adequately the existing primary standards are



protecting public health and provide a scientific basis for a



1-hour primary standard that provides additional protection



against such reported short-term effects.



     The OAQPS staff, after reviewing this data, proposed



consideration of a 1-hour primary standard in the range



between .50 to .75 ppm.  The staff noted that the lower end of



the range represented the lowest level where potentially



significant responses in asthmatics have been observed with



oronasal breathing, and that the upper bound of the range



represented levels at which the risk of significant functional



and symptomatic responses in exposed asthmatics and other



sensitive groups appeared high.



     CASAC has evaluated the OAQPS staff position that resulted



in the establishment of the range of interest at .50-.75 ppm.



The staff suggest that there may be little or no margin of



safety at the upper bound of the range.  Air quality analyses



conducted by OAQPS also indicate that a 1-hour standard selected



from within the range would still permit exposures in excess



of one to two ppm during the peak five or ten minute intervals.



A related point is that establishment of a 24-hour standard



in the range of .14-.19 ppm would not necessarily protect



against shorter term peaks above the proposed 1-hour range



of .50-.75 ppm.  This information suggests that a 1-hour



primary standard selected between .50-.75 ppm range might

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                             -6-
not adequately protect sensitive populations with an adequate
margin of safety from the effects acknowledged in the staff
paper that would occur as a result of brief peak exposures
to concentrations greater than the .50-.75 ppm hourly average
that a 1-hour standard would permit.  Because five to ten
minute peaks can reach levels as much as two or more times
.the 1-hour average, CASAC recommends that the range be modified
to state  the lower bound at  .25 ppm.
     In reviewing the  issue of whether  to establish a 1-hour
primary standard between .25-.75 ppm several additional
factors should be considered.  These include 1)  it  is not
clear that the reported effects experienced at or below  .50
ppm are significant.   The functional changes and symptoms
reported  in  the  .50-.75 ppm  range  appear to be reversible.
You will  need to determine which effects you consider  to be
adverse;  2)  it  is probable that some asthmatics  are more
sensitive than  those who took part in  the  studies;  3)  given
current air  quality  conditions  there  is a  low probability of
exposure  to  exercising asthmatics  at peak  concentration  levels;
and  4)  as the staff  paper  suggests,  other  stimuli  interacting
with  SC>2, such  as  temperature  and  humidity, may  increase the
 risk  of an attack  to exercising  asthmatics more  than  either
of  these  factors  acting alone.

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                             -7-
The Scientific Basis for Secondary SO? Standards
     The kinds of effects reviewed by CASAC in relation to
the establishment of secondary ambient air quality standards
include those on vegetation, materials, and acidic deposition.
     1.  Current scientific information documents effects on
vegetation resulting from both short-term and long-term
exposures to SC>2 and/or SO2 in combination with other
pollutants.  One should keep in mind that there is no single
concentration at which all species of plants are injured,
just as there is not single point or threshold at which all
humans suffer significant effects from SO2-  What is at issue
in the development of secondary standards is the need to
protect sensitive vegetative species from effects such as
physiological and biochemical changes, foliar injury, and
reduced growth and yield.  The available studies of SC>2
effects on vegetation represent approximately one percent of
total plant species, but they include such important species
as soybeans, barley, and white pine, to name a few.
     An issue of increasing concern in the protection of
vegetation is that SC>2 is not present alone in the ambient
air except at a few isolated point sources.  It almost
invariably occurs in the presence of other pollutants,
primarily nitrogen oxides and ozone.  The scientific evidence
is conclusive that the combination of such pollutants is more
damaging to vegetation than the presence of SC>2 a.lone.

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                             -8-



     The staff paper recommends consideration of a 3-hour



standard at or below the current secondary standard



level of .50 ppm to protect vegetation.   Although there are



reports in the literature concerning plant injury at .10 to



.20 ppm averaged over several hours, there are great



uncertainties associated with the effects of the exposures



at these lower levels.  The existing data on the acute effects



of SO2 on vegetation suggest to CASAC that a concentration



limit selected within a range of .40 to .50 ppm for a 3-hour



period would provide adequate protection to sensitive



vegetative species.



     The review of longer term effects on plants was hampered



by a very limited data base, thus making it difficult to



distinguish whether such effects resulted from -chronic lower-



level exposures or a series of shorter-term peak exposures.



Available data do suggest, however, that changes in species



diversity and reduced growth in vascular plants are effects



that may occur over the long term.  In addition, non-vascular



plants, particularly lichens and mosses, are affected by SC>2



during prolonged periods of exposure.  On the basis of



scientific work conducted to date, CASAC concurs with the



OAQPS staff recommendation that an annual secondary standard



at or below .03 ppm (a level equivalent to the existing annual



primary SOj standard) would afford adequate protection  to



vascular plant vegetation.  The basis for concern over effects

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                             -9-

in non-vascular plants at lower levels needs to be strengthened.

CASAC also agrees with the staff proposal to address this

issue in the context of later action on fine particles and

acidic deposition.

     2.  The action of SC>2 alone or in combination with other

pollutants has been associated with a number of damages to

building materials, corrosion of ferrous and non-ferrous

structures, and impairment of other goods and materials.

     OAQPS staff have reviewed the evidence documenting

materials damage from SC>2.  These effects are responsible for

economically significant losses which have been adequately

summarized in both the criteria document and the staff paper.

Analyses of existing air quality data by OAQPS indicate that

continued protection against SO2~induced materials damage is
                                             -~y
needed, and toward that end, the staff paper recommends

consideration of a long-term "SO2 standard at or below the

level of the existing annual primary standard (.03 ppm).

CASAC concurs with the staff recommendation.

     3.  Throughout its review of both the Air Quality Criteria

Document for Sulfur Oxides/Particulate Matter and the Staff

Paper for Sulfur Oxides, CASAC has recognized the complexity

of the acidic deposition problem.  Since SO2 is only one of the

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                             -10-



precursor pollutants that lead to the formation of acidic



deposition, CASAC recommended in August 1980 that EPA prepare



a separate Critical Assessment Document that recognizes and



incorporates information on causes, effects and data bases



for all of the various pollutants relevant to acidic deposition.



This CASAC recommendation was accepted by two previous



Administrators, Douglas Costle and Anne Burford, and the



assessment document should be available for CASAC review in



the near future.  At that time the Committee will be in a



position to provide a more comprehensive and critical



assessment of the acidic deposition problem.



Re-affirmation of the Existing Primary and Secondary Standards



     Throughout its review of the staff paper, CASAC



recognizes that large uncertainties exist in Jthe data that



support.development of the options for setting the standards



discussed in the previous pages.  Given these uncertainties



CASAC discussed the extent to which the existing standards



provide adequate protection to the public health.  The



Committee recognizes the substantial  improvements in air



quality that have occurred since the  1971 promulgation of the



primary SC>2 standards.  In addition, more information on the



effects of the short-term SC>2 exposures should become available



in the peer reviewed literature  in the next few years.  Air



quality modeling analyses also suggest that attainment of the



proposed 24-hour and annual standards would not ensure complete

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                             -11-
attainment of the proposed 1-hour primary standard at all sites
within the ranges of interest stated.  The reverse also
appears to be true.
     CASAC's evaluation of the scientific evidence -associated
with existing averaging times in the staff paper leads the
Committee to conclude that continuation of the existing
primary and secondary standards also provides protection
aganist the effects identified in the criteria document and
staff paper from SC>2 at ground level.  If you choose to
follow this option some CASAC members suggest that additional
health protection can be obtained by converting the existing
3-hour secondary standard into a primary standard.  A principal
argument supporting the latter is that since the states are
already implementing a 3-hour secondary standard, conversion
                                             ---/
to a 3-hour primary standard would not be impractical.  In
summary, in view of the many'uncertainties that pertain to
the review of the SC>2 standards, retention of the existing set
of primary and secondary SO2 standards is an option that you
ought to seriously consider at the present time.
Conclusion
     CASAC recognizes that your  statutory responsibility to
set standards requires public health policy  judgments  in
addition to determinations of a  strictly scientific nature.
The submission of  this closure letter completes the Committee's

-------
                             -12-



scientific assessment of this pollutant and we see no need to



provide any additional formal comnTents on the standards prior to



their proposal in the Federal Register.  The public comment



period will then provide sufficient opportunity for the



Committee to provide any additional comment or review that



may be necessary.

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                                    REFERENCES

 Abe,  H.,  Y.  Ishii, and H. Kato  (1971).  Evaluation of atmospheric factors
       by  analyses of corrosion products and surface deposits on copper
       plates.  Rail. Tech. Res. Inst. 12:170-174.

 A.D.  Little  Inc.  (1968).  Research on Chemical Odors.  Part I.  Determination
       of  Odor Thresholds for 53 Commercial Chemicals.  The Manufacturing
       Chemists' Association, Washington, DC.

 Adepipe,  N.O., R.E. Barrett, and D.P. Ormrod  (1972).  Phototoxiclty and
       growth response of ornamental bedding plants to ozone and sulfur
       dioxide.  J. Am. Soc. Hortic. Sci. 97:341-345.

 Aharonson, E.F.  (1976).  Deposition and Retention of Inhaled Gases and
       Vapors. In;  Air Pollution and the Lung.  E.F. Aharonson, A. Sen-David,
       and M.A. Klingberg, eds., John Wiley and Sons, New York. pp. 13-24

 Alarie, Y. (1973).  Sensory irritation by airborne chemicals.   CRC Crit.
       Rev. Toxicol. 2:299-363.

 Alarie, Y., W.M. Busey, A.A. Krurrnn, and C.E. Ulrich (1973).  Long-term
       continuous exposure to sulfuric acid mist in cynomolgus  monkeys  and
       guinea pigs.  Arch. Environ. Health 27:16-24.

 Alarie, Y.C., A.A. Krumm, W.M. Busey, C.E. Ulrich, and R.J. Kantz, II. (1975).
       Long-term exposure to sulfur dioxide, sulfuric acid mist, fly ash,
       and their mixtures.  Results of studies in monkeys and guinea pigs.
       Arch. Environ.  Health 30:254-262.

 Alarie, Y., C.E. Ulrich, W.M. Busey, A.A. Krum, and H.N. MacFarland (1972).
       Long term continuous exposure to sulfur dioxide in cynomolgus
      monkeys.  Arch.  Environ. Health 24:115-128.

 Alarie, Y., C.E. Ulrich, W.M. Busey, H.E. Swann, Jr., and H.N. MacFarland
       (1970).  Long-term continuous exposure of guinea pigs to sulfur
       dioxide.  Arch.  Environ. Health 21:769-777.

 Amdur, M.O. (1973).   Animal  studies. In:   Proceedings of the Conference
       on Health Effects of Air Pollutants, Washington, D.C. October 3-5,
       1973.  A report  prepared for the Committee on Public Works,  United
       States  Senate.   Serial  No.  93-15.   U.S.  Government Printing  Office,
      Washington, D.C.  pp.  175-205.

Amdur, M.O. (1961).-  The effect of aerosols on the response to irritant
      gases.  _!TK   Inhaled Particles and  Vapors.   C.N.  Davies, ed., Pergamon
      Press,  Oxford,  England,   pp.  281-294.

Amdur, M.O. (1964).   The effect of high  flow-resistance  on the response
      of guinea  pigs  to irritants.   Am.  Ind.  Hyg.  Assoc.  J.  25:564-568.

Amdur, M.O. (1959).   The physiological  response of guinea  pigs to
      atmospheric pollutants.   Int.  J. Air Pollut. 1:170-183.

-------
 Amdur, M.O. (1974).  The long road from Donora.   1974 Cummings Memorial
       Lecture.  Am. Ind. Hyg. Assoc.  J. 35:589-597.

 Amdur, M.O., W.W. Melvin, Jr., and P. Drinker  (1953).   Effects of  Inhalation
       of sulfur dioxide by man.  Lancet 2:758-759.

 Amdur, M.O., and D.W.  Underhill  (1970).  Response of  guinea  pigs to  a
       combination of sulfur dioxide and open hearth dust.  J.  A1r  Pollut.
       Control  Assoc. 20:31-34.                           *>

 Amdur, M.O., and D. Underhill  (1968).   The effect of  various aerosols on
       the response of  guinea pigs  to  sulfur dioxide.   Arch.  Environ. Health
       16:460-468.

 Amdur, M.O., J.  Bayles, V.  Ugro, and  D.W. Underhill (1978a).   Comparative
       irritant potential  of sulfate salts.  Environ. Res. 16:1-8.

 Amdur, M.O.,  V.  Ugro,  and D.W.  Underfill 1  (1978b).  Respiratory  response of
       guinea  pigs to ozone  alone and  with sulfur dioxide.  Am.  Ind. Hyq
       Assoc.  39:958-961.

 Andersen, I.,  P.L.  Jensen,  S.E. Reed, J.W. Craig, D.F. Proctor, and
       G.K.  Adams  (1977).   Induced  rhinovirus infection under controlled
       exposure to sulfur  dioxide.   Arch. Environ. Health 32:120-126.

 Andersen, I.,  G.R.  Lundqvist, P.L.  Jensen, and D.F.  Proctor  (1974).  Human
       response to controlled levels of  sulfur dioxide.  Arch. Env.  Health


 Andersen, I.,  L.  Mohave,  and D.F. Proctor (1981).  The human response
       to  controlled  levels of sulfur dioxide and inert dust.   Scand  J
       Work  Environ.  Health 7:1-7.

 Anderson, G.E. (1982) Systems Applications,  Inc., San  Rafael , CA.  Personal
       communications with Henry Thomas  (July,  1982).

 Ashenden, T.W. (1979).   The effects of long-term exposures to SO?  and
       N02 pollution on the growth of Dactyl is glomerata L.  and  Poa
       pratensis L.  Environ. Pollut. 18:249-258.                	

 Ashenden, T.W., and T.A. Mansfield   (1977).   Influence  of wind speed on
      the sensitivity of ryegrass to S02. J. Exp. Bot. 28:729-735.

Aubrey, F., G.W.  Gibbs, and M.R. Becklake (1979).  Air pollution and
      health in three urban communities.  Arch.  Environ.  Health
      34:340-368.

Bates, D.V., and M. Hazucha (1973).  The short-term effects of  ozone  on
      the lung. _[n:  Proceedings of the Conference on  Health Effects of
      Air Pollutants, National  Academy of Sciences, Washington,  DC
      October 35, 1973.   Serial  No.  93-15, U.S. Senate  Committee on Public
      Works, Washington, DC, pp.  507-540.

-------
 Becklake,  M.R.,  J.  Soucie, G.W. Gibbs, and H. Ghezzo  (1978).  Respiratory
       health  status of children 1n three Quebec urban communities.  An
       Epidemiologic Study.  Bull. Europ. Physiopath. Resp.  14:205-221.

 Bedi ,  J.F., L.J.  Folinsbee, S.M. Horvath, and R.S. Ebenstein (1979).
       Human exposure to sulfur dioxide and ozone:  absence of a synergistlc
       effect.  Arch. Environ. Health 34:233-239.

 Bedi,  J.F., S.M.  Horvath, and L.J. Folinsbee (1982).  Human exposure to
       sulfur  dioxide and ozone in a high temperature-humidity environment.
       Am.  Ind. Hyg. Assoc. J. 43:26-30.

 Bell,  J.N.B., and W.S. Clough (1973).  Depression of yield in ryegrass
       exposed to  sulfur dioxide.  Nature 241:47-49.

 Bell,  K.A., W.S.  Linn, M. Hazucha, J.D. Hackney, and D.V. Bates (1977).
       Respiratory effects of exposure to ozone plus sulfur dioxide in
       Southern Californians and Eastern Canadians.  Am.  Ind. Hyg.  Assoc.  J.
       38:696-706.

 Bennett, J.H., A.C. Hill, A. Soleimani , and W.H. Edwards (1975).   Acute
       effects of  combinations of sulfur dioxide and nitrogen dioxide
       on plants.  Environ. Pollut. 9:127-132.

 Berry, C.R. (1974).  Age of pine seedlings with primary  needles affects
       sensitivity to ozone and sulfur dioxide.   Phytopathology  64:207-209.

 Berry, C.R. (1971).  Relative sensitivity of red, jack,  and white  pine
       seedlings to ozone and sulfur dioxide.  Phytopathology 61:231-232.

 Biller, W. F., and T.  B.  Feagans (1981).   Statistical  forms of  National
       Ambient Air Quality Standards.   Presented at the Envi ronmetrics
       1981 Conference (April  8-10), Alexandria, Va.

 Bird, C.E. (1977).  Corrosion behavior  of galvanized sheet  in relation to
       variation in coating thickness.   Matter Prot. and  Perform.   16:14-16.

 Boushey, H.A.  , M.J. Holtzman, J.R.  Sheller,  and J.A.  Nadel  (1980).
      Bronchial  hyperreactivity.   Am.  Rev.  Respir. Dis.  121:389-413.

 Brain, J.D. (1970).  The  uptake  of inhaled  gases by the  nose.   Ann.  Otol.
      Rhinol.  Laryngol  79:529-539.

 Burton, C.S.,  J.  Nordin,  T.  Stoeckenius  (1982).   On a  New Short-Term
      Standard for Sulfur  Dioxide:  The  Protection from  Calculated  Peak
      1-Hour  Concentrations  Provided by  the  Existing  3-  and  24-Hour
      NAAQS in the Vicinity  of a Hypothetical Power Plant.   Systems
      Applications, Inc.  San  Rafael, CA.

Burton, C.S.,  and A.D.  Thrall  (1982).  A  Brief  Review of Peak to One-hour
      Average  Ratios Observed in the Vicinity of Power Plants.  Systems
      Applications, Inc.,  San Rafael, CA.

-------
 Burton, 6.G. , M.  Corn, J.B.L.  Gee, C.  Vasallo, and A. P. Thomas  (1969).
       Response of healthy men  to  inhaled low concentrations of gas-aerosol
       mixtures.  Arch. Environ. Health 18:681-692.

 Bushtueva, K.A. (1962).   New Studies of the Effect of Sulfur Dioxide and
       of Sulfuric Acid Aerosol on Reflex Activity in Man.  In:  Limits of
       Allowable Concentrations of Atmospheric Pollutants.  Book 5, B.S. Levine,
       translator, U.S. Department of Commerce, Office of Technical Services,
       Washington, D.C. pp. 86-92.

 Campbell, 6.6., G.G.  Shurr,  D.E. Slawikowski, and J.W.  Spence (1974).
       Assessing air pollution damage to coatings.  J. Paint Technol .
       46:59-71.

 Cohen, A. A., S. Bromberg, R.W. Buechley, L.T.  Heiderescheit , and C.M. Shy
       (1972).   Asthma  and air pollution from a coal  fueled power plant
       Am.  Rev.  J.  Pub. Health 62:1181-1188.

 Cohen, H.J., R.T.  Drew, J.L. Johnson, and K.V. Rajagopalan (1973).
       Molecular basis  of biological  function of molybdenum.  The relationship
       between  sulfite  oxidase and the acute toxicity of bisulfite and SO?
       Proc.  Natl.  Acad. Sci . 70:3655-3659.

 Cole,  P.,  R. Forsyth,  and J.S.J.  Haight (1982).   Respiratory resistance of
       the  oral  airway.  Am. Rev.  Respir.  Dis.  125:363-365.

 Colley, J.R.T., J.W.B. Douglas, and  D.D.  Reid  (1973).   Respiratory disease
       in young  adults:  Influence of early  childhood lower respiratory
       tract  illness, social class, air  pollution, and smoking.   Br.  Med.  J.
       0 «
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  Service of  the Library of Congress.

Corn, M. , N. Kotsko, D. Stanton, W.  Bell,  and A. P.  Thomas  (1972).  Response
      of rats to inhaled mixture of  SO?  and SO?-NaCl  aerosol in  air.   Arch
      Environ. Health 24:248-256.

Costa, D.L., and M.O. Amdur  (1979).   Effect of  oil  mists on  the  irritancy
      of sulfur dioxide.   I.  Mineral  oils  and light  lubricating  oil.   Am.
      Ind.  Hyg. Assoc.  J.  40:680-685.

Cotes, J.E. (1979).   Lung  Function Assessment and Application in Medicine.
      Blackwell Scientific Publications, London,  England,   pp. 266-267.

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

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

-------
Deal, E. C. Jr., E.  R. McFadden, Jr., R.  H.  Ingram,  Jr.,  and  J. J. Jaeger
      (1979).  Hyperpnea and heat flux: initial  reaction  sequence in
      exercise-induced asthma.   J.  Appl.  Physiol:  Respirat. Environ.
      Exercise Physiol. 46:476-483.

Denison, W.E. (1973).   Life  in  tall  trees.   Sci. Am.  228-74.

DHEW [U.S. Department  of Health, Education,  and  Welfare]  (1970). 'Air
      Quality Criteria for Sulfur Oxides.  National  Air Pollution Control
      Association Publication #AP-50.

Dockery, D. W., N.R. Cook, B.G.  Ferris, Jr., F.E.  Speizer, J.D. Spengler,
      and J.H. Ware  (1981).   Change  in pulmonary function in  children
      associated with  air pollution  episodes.   Presented  at the 74th
      Annual  Meeting of the  Air Pollution Control  Association, Philadelphia,
      PA  (June 21-26,  1981). Paper  #81-11.1.

Dodge, R.R., and B.  Burrows  (1980).   The  prevalence  and incidence of asthma and
      asthma-like symptoms in a general population sample.  Am. Rev. Respir.
      Dis. 122:567-575.

Douglas, J.W.B., and R.E. Waller (1966).  Air pollution and respiratory
      infection in children. Br. J. Prev. Soc.  Med.  21:1-8.

Dreisinger, B.E., and  P.C. McGovern  (1970).   Monitoring Atmospheric
      Sulfur Dioxide and Correlating Its  Effects on  Crops and Forests
      in the Sudbury Area.  In:   Impact of Air Pollution  on Vegetation
      S.N. Linzon, ed., OntalTo Department of Energy  and  Resource
      Management, Toronto.

Dubrovskaya, F.I. (1957).  Hygienic  Evaluation of  Pollution of Atmospheric
      Air of a Large City with  Sulfur Dioxide Gas.   lr±:   Limits of
      Allowable Concentrations  of Atmospheric Pollutants. Book  3.
      B.S. Levine, translator,  U.S.  Department of  Commerce, Office of
      Technical  Services, Washington, D.C. pp. 37-51.

Ehrlich, R., J.C. Findlay, and  D.E.  Gardner  (1978).   Susceptibility to
      bacterial  pneumonia in animals exposed to  sulfates. Tox. Lett.
      1:325-330.

Eisen, H.N. (1976).   Immunology.  Harper  and Row,  Hagerstown, Md. pp. 410.

EPA [U.S. Environmental  Protection  Agency]  (1982a).   Air  Quality Criteria for
      Particulate Matter and Sulfur  Oxides.   Environmental Criteria and
      Assessment Office, Office of  Research  and  Development,  Research
      Triangle Park, N.C. EPA 600/8-82-029a-c  (December,  1982).

EPA [U.S. Environmental  Protection Agency]  (1973).   Effects of Sulfur
      Oxides in the  Atmosphere  on Vegetation;  Revised Chapter 5 for Air
      Quality Criteria for Sulfur Oxides.  Office  of  Research and
      Development, Research  Triangle Park, N.C.  EPA-R 3-73-030.

-------
 EPA [U.S.  Environmental  Protection Agency]  (1982a).  Review of the National
       Ambient A1r Quality  Standards for Particulate Matter:  Assessment of
       Scientific  and  Technical  Information  (OAQPS Staff Paper).  Office of
       Air  Quality Planning and  Standards.  Research Triangle Park, N.C.
       EPA-450/5-82-001.

 Evans, L.S.  and P.R.  Miller  (1975).  H1stolog1cal  comparison of single and
       additive 03 and SO2  injuries to elongating ponderosa pine needles.
       Am.  J. Bot.  62:416-421.

 Fairchild, G.A.,  J. Roan,  and J. McCarroll  (1972).  Atmospheric pollutants
       and  the pathogenesis of viral respiratory infection.  Arch. Environ.
       Health 25:174-182.

 Ferin, J., and L.J. Leach  (1973).  The effect of S02 on lung clearance of
       T102 particles  in rats.  J. Am. Ind. Hyg. Assoc.  3:260-263.

 Fink,  F.W.,  F.H. Buttner, and W.K. Boyd (1971).  Technical-Economic
       Evaluation of Air Pollution Corrosion Costs  on Metals in the U.S.
       APTD-0654.   U.S. Environmental  Protection Agency, Research Triangle
       Park,  N.C.

 Fischl, M. A., A.  Pitchenik, and L. B. Gardner (1981).   An index predicting
       relapse  and  need for hospitalizatlon in patients  with acute bronchial
       asthma.  N.  Engl.  J. Med.  305:783-789.

 Fishman, A.P.  (1976).   Chronic cor-pulmonale.  Am. Rev. Respir.  Dis.  114-
       775-794.

 Frank, N.H., and A. D. Thrall (1982).   Relationships Among S02 Averaging
       Times  and Ambient  Standards:   Monitoring and Data Analysis Division
       Report.  Office of Air Quality Planning and  Standards,  Research  Triangle
       Park,  N.C.

 Frank, N.H., B.E.  Blagun, and H. Slater (1981).  Diurnal  Patterns of  Sulfur
       Dioxide Presented  at the 74th Annual  Meeting of the  Air Pollution
       Control Association, Philadelphia,  Pennsylvania.   Paper #81-33.3.

 Frank, N.R.  (1964).  Studies  on  the effects  of acute exposure to sulfur
       dioxide in  human subjects.  Proc. R.  Soc.  Med. 57:1029-1033.

 Frank, N.R., M.O.  Amdur, and  J.L.  Whittenberg (1964).   A comparison
      of the acute effects of S02  administered alone or in combination  with
      Nad  particles on  the respiratory mechanics  of healthy  adults.
       Int.  J. Air  Water  Pollut.  8:125-1 33.

 Frank, N.R., M.O.  Amdur, J. Worcester,  and J.L.  Whittenberger  (1962).
      Effects of  acute controlled  exposure to S02  on respiratory  mechanics
      in healthy male  adults. J.  Appl. Physiol. 17:252-258.

Frank, N.R. and F.E.  Spei zer  (1965).   SOg effects  on the respiratory
      systems in dogs.  Changes  in  mechanical  behavior  at  different levels
      of the  respiratory system  during acute  exposure to the  gas.  Arch.
      Environ. Health  11:624-634.

-------
Frank, N.R., R.E. Yoder,  J.D.  Brain,  and  E.  Yokoyama  (1969).  S02  (35S labeled)
      absorption by the nose and mouth  under conditions of varying
      concentration and flow.   Arch.  Environ.  Health  18:315-322.

Frank, N.R., R.E. Yoder,  E.  Yokoyama, and F.E. Speizer  (1967).  The
      diffusion of   SO?  from tissue  fluids  into the  lungs following
      exposure of dogs to 35S02.'  Health  Phys. 13:31-38.

Franklin, W. (1981).  Asthma in the emergency  room:   Assessment and Treatment.
      N. Engl. J. Med. 305:826-827.

Fraser, D.A., M.C. Battigelli,  and H.M. Cole (1968).  Ciliary activity and
      pulmonary retention of inhaled  dust in rats exposed to sulfur dioxide.
      J. Air Pollut. Control Assoc. 18:821-823.

Giddens, W.E., and G.A. Fairchild (1972). Effects  of'sulfur dioxide on
      the nasal mucosa of mice.  Arch.  Environ. Health 25:166-173.

Gillespie, J.R. (1980).  Review of the  cardiovascular and pulmonary
      function studies on beagles exposed for  68 months to auto exhaust
      and other air pollutants.  In:  Long-term Effects of Air Pollutants
      in Canine Species.   J.F.  Stara, D.L. Dungworth, J.C. Orthoefer, and
      W.S. Tyler, eds. EPA Report #600/8-80-014, pp.  115-153.

Gillette, D.G. (1975). S02  and material  damage.  J.  Air Pollut. Control
      Assoc. 25:1238-1243.

Gokemeijer, J.D.M., K. DeVries, and N.G.M. Orie  (1973).  Response of the
      bronchial tree to chemical  stimuli. Rev.  Inst. Hyg. Mines (Hasselt)
      28:195-197.

Goldstein, B. (1983).  CASAC Review and Closure of  the OAQPS Staff Paper for
      Sulfur Oxides.  Closure  letter  to William 0.  Ruckelshaus (August, 1983).

Greenwald, I. (1954).  Effects  of inhalation of low concentrations of
      sulfur dioxide upon man  and other mammals.  AMA Arch. Ind. Hyg. Occup.
      Med. 10:455-475.

Gunnison, A.F., and E.D.  Palmes (1973).   Persistence  of plasma S-sulfonates
      following exposure  of  rabbits to  sulfite and  sulfur dioxide.  Toxicol.
      Appl. Pharmacol. 24:266-278.

Guttman, H. (1968).  Effects of atmospheric  factors on the corrosion of
      rolled zinc.  In:  Metal  Corrosion  in  the Atmosphere, a Symposium
      Presented at the Seventieth Annual  Meeting, American Society for
      Testing and Materials, Boston Massachusetts,  June 25-39, 1967.
      ASTM Special Technical Publication  no. 435, American Society for
      Testing and Materials, Philadelphia, PA. pp.  223-239.

Haynie, F.H. (1974).  The economics of  clean air.   Mater. Prot. Perf.
      13:33-38.

-------
 Haynie,  F.H.  (1980).  Theoretical air pollution and climate effects on
       materials  confirmed by zinc corrosion data,  in:  Durability of
       Building Materials and Components.  P.J. Sereda and G.G. Levitan,
       eds., ASTM Special Technical Publication 691, American Society for
       Testing and Materials, Philadelphia, PA, pp. 157-175.

 Haynie,  F.H., J.W. Spence, and J.B. Upham (1976).  Effects of Gaseous
       Pollutants  on Materials—A Chamber Study.  EPA-600/3-76-015, U.S.
       Environmental Protection Agency, Research Triangle Park, NC.

 Haynie,  F.H., and J.B. Upham (1974).  Correlation between corrosion
       behavior of steel and atmospheric pollution data.   In:  Corrosion
       1n Natural  Environments.  ASTM Special  Technical PubTlcation 558,
       American Society for Testing and Materials, Philadelphia, PA, pp.
       33-51.

 Haynie,  F.H., and J.B. Upham (1971).  Effects of atmospheric pollutants
       on the corrosion behavior of steels.   Mater. Prot.  Perform 10:18-21.

 Hawksworth, D.L.  and F. Rose (1970).  Qualitative scale  for estimating
       sulfur dioxide air pollution in England and Wales  using epiphytic
       lichens.  Nature (London) 227:145-148.

 Heagle, A.S., D.E. Body, and G.E. Neely (1974).  Injury  and yield responses
       of soybean to chronic doses of ozone  and sulfur dioxide in the field.
       Phytopathology 64:132-136.

 Heagle, A.S., and J.W. Johnston (1979).   Variable responses of soybeans
      to mixtures of ozone and  sulfur dioxide.   J. Air Pollut.  Control
      Assoc. 29:729-732.

 Heck, W.W., and J.A.-Dunning (1978).   Response  of oats to sulfur dioxide:
       Interactions of growth temperature with exposure temperature or
      humidity.   J.  Air Pollut. Control  Assoc.  28:241-246.  '

 Hill, A.C., S.  Hill,  C.  Lamb, and T.W.  Barrett  (1974).  Sensitivity  of
      native desert  vegetation  to SOg  and to  SOg  and  NO?  combined.   J.  Air
      Pollut.  Control  Assoc.  24:  153-157.

 Hirsch, J.A.,  E.W. Swenson,  and A.  Wanner  (1975).   Tracheal  mucous  transport
      in beagles  after long  term  exposure to  1  ppm sulfur dioxide.   Arch.
      Environ.  Health 30:249-253.

Holland, W.W.,  and D.D.  Reid  (1965).   The urban factor in chronic  bronchitis.
      Lancet 1:445-448.

Horvath, S.M.,  and L.J. Folinsbee  (1977).  Interactions of  Two Air Pollutants,
      Sulfur Dioxide  and Ozone, on  Lung  Functions.  Grant ARB-4-1266,
      California  Air  Resources  Board,  Sacremento,  CA.

-------
Irreverre, F., S.H. Mudd,  W.D.  Heizer,  and  L.  Laster  (1967).  Sulfite
      oxidase deficiency:   studies of a patient with  mental retardation,
      dislocated ocular lenses, and abnormal urinary  excretion of S-sulfo-
      L-cysteine, sulfite, and  thiosulfate. Biochem. Med. 1:187-217.

Islam, M.S., E. Vastag, and W.T. Ulmer  (1972).  Sulfur-dioxide induced
      bronchial hyperreactivity against acetylcholine.  Int. Arch. Arbeitsmed.
      29:221-232.

Jacobson, J.S. and L.J. Colavito (1976).  The  combined  effect of sulfur
      dioxide and ozone on bean and tobacco plants.   Environ. Exp. Bot.
      16:277-285.

Jaeger, M.J., D. Tribble,  and H.J. Wittig (1979).  Effect of 0.5 ppm sulfur
      dioxide on the respiratory function of normal and asthmatic subjects.
      Lung 156:119-127.

Johnson, T. (1982a).  PEDCo Environmental memorandum  (March 5,.1982), to
      John Bachmann titled "Equivalent  1-hour  and  24-hour S02 Standards."

Johnson, T. (1982b).  PEDCo Environmental memorandum  (September 10, 1982),
      to Tom Feagans and Henry  Thomas titled "Population Estimates of
      Asthmatics and Atopies."

Kagawa, J., and K. Tsuru (1979).  Respiratory  effect  of 2-hour exposure
      with intermittent exercise to ozone and  sulfur  dioxide alone and in
      combination in normal subjects.  Jap. J. Hyg. 34:690-696.

Karpovich, P.V. (1953). Physiology of  muscular activity.  W.B. Saunders
      Co., Philadelphia, p. 114.

Katz, G.V., and S. Laskin  (1976).  Pulmonary Macrophage Response to
      Irritant Gases.  In:  Air Pollution and  the  Lung. E.F. Aharonson,
      A. Ben-David, and M.A. Klingberg,  eds.,  John Wiley and Sons, New York,
      pp. 83-100.

Kawabori, I., W.E. Pierspn, L.L. Conquest,  and C.W. Bierman (1976).
      Incidence of exercise-induced asthma  in  children. J. Allergy
      Clin. Immunol. 58:447-455.

Keller, T. (1980).  The effect  of a continuous springtime fumigation with SOg
      and C02 uptake and structure of the annual ring in spruce.  Can. J. For.
      Res. 10:1-6.

Keller, T. (1978).  Wintertime  atmospheric  pollutants—do they effect the
      performance of deciduous  trees in  the ensuing growing season.  Environ.
      Pollut. 16:243-247.

Kiernan, K.E., J.R.T. Colley, J.W.B. Douglas,  and  D.D.  Reid (1976).
      Chronic cough in young adults in  relation to smoking habits, childhood
      environment and chest illness. Respiration  33:236-244.

Kikigawa, K., and K. lizuka (1972).  Inhibition of platelet aggregation
      by bisulfite-sulfite.  J. Pharm.  Sci. 61:1904-1907.

-------
                                         10
 Kirkpatrick, M.B., D.  Sheppard,  J.A. Nadel , and H.A. Boushey  (1982).
       Effect of oronasal  breathing  route on sulfur dioxide-Induced
       bronchoconstriction in exercising asthmatic subjects.  Am. Rev. Respir.
       Dis.  125:627-631.

 Kleinman, M.T., R.M. Bailey, Y.C. Chang, K.W. Clark, M.P. Jones, W.S. Linn,
       and J.D.  Hackney (1981).   Exposures of human volunteers to a controlled
       atmospheric  mixture of ozone, sulfur dioxide and sulfuric acid.  Am.
       Indust. Hyg.  Assoc.  J. 42:61-69.

 Koenig,  J.Q.  (1982).   University of Washington, Seattle, Washington.
       Personal  communication (letter) with John Bachmann (March 29, 1982).

 Koenig,  J.Q., W.E.  Pierson, and R. Frank (1980).  Acute effects of inhaled
       S02 plus  Nad droplet aerosol  on pulmonary function in asthmatic
       adolescents.  Environ. Res. 22:145-153.

 Koenig,  J.Q., W.E.  Pierson, M. Horike, and R.  Frank (1982a).  Bronchoconstrictor
       responses  to  sulfur  dioxide or sulfur dioxide plus sodium chloride
       droplets  in allergic, nonasthmatic adolescents.   J. Allergy Clin.  Immunol
       69:339-344.

 Koenig,  J.Q., W.E.  Pierson, M.  Horike, and R.  Frank (1982b).  Effects of
       inhaled sulfur dioxide ($02) on pulmonary function in healthy adolescents-
       exposure to SO? alone on S02 + sodium chloride  droplet aerosol  during
       rest and exercise.  Arch. Environ.  Health 37:5-9.

 Koenig,  J.Q., W.E.  Pierson, M.  Horike,  and R.  Frank (1981).   Effects  of
       SOg plus NaCl aerosol combined with  moderate exercise on pulmonary
       function in asthmatic adolescents.   Environ.  Res.  25:340-348.

 Kreisman, H., C.A. Mitchell, H.R. Hosein,  and  A. Bouhuys (1976).   Effect
       of  low concentrations of  sulfur dioxide  on respiratory function in
      man.  Lung 154:25-34.

 Lambert,  P.M., and D.D. Reid (1970).   Smoking,  air  pollution and  bronchitis
      in  Britain.  Lancet 1:853-857.

 Larsen, R.I. (1968).  A New Mathematical Model  of  Air Pollution Concentration
      Averaging  Time,  and Frequency.   (Presented at 61st  Annual Meeting
      of the Air Pollution Control Association, St. Paul, Minnesota).

 Larson, T.V., R. Frank, D.S.  Covert,  D. Holub, and  M.S.  Morgan  (1982).
      Measurements of  respiratory ammonia and the chemical neutralization
      of inhaled sulfuric acid  aerosol in anesthetized dogs.  Am. Rev.
      Resp.  Dis. (In Press).

Larson, T.V., N.R.  Horike, and  H.  Harrison  (1978).  Oxidation of sulfur
      dioxide by oxygen and ozone  in aqueous solution:  A kinetic study  with
      significance  to atmospheric  rate processes.  Atmos. Environ. 12:1597-1611.

-------
                                        11
Laskin, S., M. Kuschner, and R.T.  Drew (1970).   Studies in pulmonary
      carcinogenesis.  In:   Inhalation Carci nogenesis.  AEC Symposium
      Series 18.  M.G. Hanna, Jr., P.  Nettesheim, and J.R. Gilbert, eds.,
      U.S. Atomic Energy Commission, Oak  Ridge,  TN.  pp. 321-351.

Laskin, S., M. Kuschner, A.  Sellakumar, and  G.V. Katz  (1976).  Combined
      Carcinogen-irritant animal  inhalation  studies.  In:  Air Pollution
      and the Lung.  E.F. Aharonson, A. Ben-David, and M.A. Klingberg,
      eds. John Wiley and Sons, New York.  pp. 190-213.

Lawther, P.J.  (1958).  Climate, air pollution and chronic bronchitis.
      Proc. R. Soc. Med. 51:262-264.

Lawther, P.J., A.G.F. Brooks, P.W. Lord,  and R.E. Waller  (1974a).  Day-to-day
      changes in ventilatory function  in  relation to the environment.
      Part I.  Spirometric values.  Environ. Res. 7:24-40.

Lawther, P.J., A.G.F. Brooks, P.W. Lord,  and R.E. Waller  (1974b).  Day-to-day
      changes in ventilatory function  in  relation to the environment.
      Part II.  Peak expiratory flow values.  Environ. Res. 7:41-53.

Lawther, P.J., A.G.F. Brooks, P.W. Lord,  and R.E. Waller  (1974c).  Day-to-day
      changes in ventilatory function  in  relation to the environment.  Part
      III.  Frequent measurements  of peak  flow.  Environ. Res. 8:119-130.

Lawther, P.J., P.W. Lord, A.G.F.  Brooks,  and R.E. Waller  (1973).  Air
      pollution and pulmonary airway resistance:  A  pilot study.  Environ.
      Res. 6:424-435.

Lawther, P.J., A.J. MacFarlane, R.E. Waller, and A.G.F. Brooks  (1975).
      Pulmonary function and sulphur dioxide, some preliminary findings.
      Environ. Res. 10:355-367.

Lawther, P.J., R.E. Waller,  and M. Henderson  (1970).  Air pollution and
      exacerbations of bronchitis.  Thorax 25:525-539.

LeBlanc, F., and D.N. Rao (1975).   Effects of air pollutants on lichens
      and bryophytes.  In:  Responses of plants to Air Pollution.  J.B.
      Mudd and T.T. Kozlowski , eds., Academic Press, New York, NY, pp.
      237-272.

Lebowitz, M.D., E.J. Cassell , and  J.R.  McCarroll (1972).  Health and the
      urban environment.  XV.   Acute respiratory episodes as reactions by
      sensitive individuals  to air pollution and weather.  Environ. Res.
      5:135-141.

Lebowitz, M.n., and G.A. Fairchild (1973).   The  effects of sulfur dioxide
      on A2 influenza virus  on pneumonia and weight reduction in mice:  An
      analysis of stimulus  - response  relationship.  Chem. Biol. Interact.
      7:317-326.

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                                         12


 Lehmann, K.B. (1893).  Experimental!e Studien  uber  den  Einfluss technisch
       und hygienisch wlchtlger Gase und  Dampfe auf  den  Organismus.   VI.
       Schwefliger Saure.   [Experimental  studies on  the  effects on the  system
       of technically and  hygienically important gases and  fumes.  VI.  Sulfuric
       Acid.]  Arch. Hyg.  18:180-191.

 Leikauf, 6., D.B. Yeates, K.A.  Wales, D.  Spektor, R.E.  Albert, and
       H. Lippmann (1981).  Effects  of sulfuric acid aerosol on respiratory
       mechanics  and mucociliary particle  clearance in healthy nonsmoking
       adults. Am.  Ind. Hyg.  Ass. J.  42:273-282.

 Lewis, T.R., D.E. Campbell, and T.R.  Vaught, Jr.  (1969).   Effects on
       canine pulmonary function via induced NO-2 impairment, particulate
       interaction and subsequent SOX.  Arch. Environ. Health 18:596-601.

 Lewis, T.R., W.J. Moorman,  W.F.  Ludmann,  and K.I. Campbell   (1973).  Toxicity
       of long-term  exposure to  oxides of  sulfur.  Arch.  Environ.  Health
       26:16-21.

 Linn,  U.S.,  R.M.  Bailey,  D.A. Shamoo, T.G. Venet, L.H. Wightman and
       J.D. Hackney  (1982a).   Respiratory  responses of young adult  asthmatics
       to sulfur dioxide exposure near simulated ambient  exposure  conditions
       Environ. Res.   29:220-232.

 Linn,  W.S.,  D.A.  Shamoo,  C.E. Spier, L.M. Valencia, U.T. Anzar, T.G. Venet,
       and J.D. Hackney (1982b).  Respiratory effects of  0.75 ppm  sulfur
       dioxide in  exercising asthmatics: influence of upper-respiratory defenses
       Environ. Res.  (In Press).

 Linn,  W.S.,  M.P.   Jones, R.M. Bailey, M.T. Kleinman, C.E. Spier, R.D. Fischer
       and J.D. Hackney (1980).  Respiratory effects of mixed nitrogen
       dioxide and sulfur dioxide in human volunteers under  simulated
       ambient exposure conditions.   Environ.  Res.  22:431-438.

 Linzon,  S.N.  (1971).  Economic effects of sulphur dioxide on forest
       growth.  J. Air Pollut.  Control  Assoc.  21:81-86.

 Linzon,  S.N.  (1978).  Effects  of airborne sulfur pollutants on  plants.
      _In:  Sulfur in the  Environment:   Part II, Ecological  Impacts,  J.O
       Nriagu, ed., John  Wiley  and Sons, New York,  NY.  pp. 109-162.

 Lunn, J.E., J. Knowelden,  and  A.J.  Handyside  (1967).   Patterns of
       respiratory illness  in Sheffield infant schoolchildren.  Br. J. Prev
      Soc. Med. 21:7-16.

Lunn, J.E., J. Knowelden,  and  J.R.  Roe (1970).   Patterns of  respiratory
      illness in  Sheffield junior schoolchildren.  A follow-up study
      Br. J.  Prev. Soc. Med. 24:223-228.

Macklem, P.T., and J. Mead (1967).   Resistance  of central and peripheral
      airways measured by  a  retrograde catheter.  J. Appl.  Physiol. 22:395-401.

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                                         13


 Martin, A.E.  (1964).   Mortality  and morbidity  statistics and air pollution.
       Proc.  R.  Soc.  Med.  57:969-975.

 Martin, A.E., and W.H.  Bradley  (1960).   Mortality, fog and atmospheric
       pollution—An  investigation  during the winter of 1958-59.  Mon. Bull.
       Minist. Health  Lab.  Serv. .19:56-72.

 Mazumdar, S., H.  Schinmel , and I.  Higgins  (1981).  Daily Mortality, Smoke
       and S02 in  London,  England 1959-1972.  Proceedings of the Proposed
       SOX and Particulate  Standard Specialty Conference.  Air Pollution
       Control Association, Atlanta, Georgia, pp. 219-239.

 Mazumdar, S.  and  N. Sussman  (1981).  Relationships of air pollution to
       Health:   Results  from  the Pittsburgh study.  Proceedings of the 74th
       Annual  Meeting, Air  Pollution Control Association, Philadelphia, PA.
       (June 21-26, 1981).

 McJilton, C.E., R. Frank,  and R.J. Charlson (1976).  Influence of relative
       humidity on functional effects of an inhaled S02-aerosol  mixture.   Am.
       Rev. Respir. Dis. 113:163-169.

 McJilton, C., R. Frank, and  R. Charlson  (1973).  Role of relative humidity
       in  the  synergistic effect of a sulfur dioxide-aerosol  on the lunq.
       Science 182:503-504.

 McLaughlin, S.B., and N.T. Lee (1974).   Botanical studies in the vicinity
       of  Widows Creek Steam  Plant:   Review of  air pollution  effects studies,
       1952-1972 and results  of 1973 surveys.   Division of Environmental
       Planning, Tennessee Valley Authority, Mussel  Shoals,  Alabama.

 McLaughlin, S.B., D.S. Shriner, R.  K.  M'Conathy, and  L.K. Mann  (1979).   The
       effects of S02 dosage kinetics and exposure frequency  on  photosynthesis
       and transpiration of kidney beans  (Phaseolus  vulgaris  L.).  Environ.
       Exp. Bot.  19:179-191.	

 McLaughlin, S.B., and G.E. Taylor  (1981).  Relative humidity:  Important
      modifier of pollutant uptake  by  plants.   Science 211:167-169.

 Mead, J., J.H. Turner, P.T. Macklem, and J.B.  Little  (1967).   Significance
      of the relationship  between lung  recoil  and maximum expiratory flow.
      J. Appl. Physiol.  22:95-108.

Melville, 6.N. (1970).   Changes  in  specific airways conductance in  healthy
      volunteers following nasal  and oral inhalation of SO?.  West  Indian
      Med. J.  19:231-235.

MES [Meteorological  Evaluation  Services, Inc.]  (1982).  Comments on Draft
      OAQPS Staff  Paper  Entitled  Review of the  National Ambient Air Quality
      Standards  for  Sulfur Oxides:  Assessment  of Scientific and Technical
      Information.   Prepared for  American Electric  Power  Service Corporation,
      Canton,  Ohio.

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                                        14


 Miller,  J.E.,  D.G.  Sprugel , R.N. Mullen, H.J. Smith, and P.B. Xerikos
       (1980).   Open-air fumigation system for Investigating sulfur dioxide
       effects  on crops.  Phytopathology 70:1124-1128.

 Ministry of  Health  (1954).  Mortality and morbidity during the London
       Fog of December 1952.  London, Her Majesty's Stationary Office.

 Morehouse, L.E., and A.T. Miller (1948).  Physiology of exercise.  The C.V.
       Mosby  Co., St. Louis, pp. 246-259.

 Mudd,  S.H.,  F.  Irreverre, and L. Laster (1967).   Sulfite oxldase deficiency
       1n man:   demonstration of the enzymatic defect.  Science 156:1599-1602.

 Mueller, P.K.,  G.M. Hidy, K. Harren, T.F.  Lavery, and R.L. Baskett (1980).
       The occurrence of Atmospheric Aerosols in  the Northeastern United States,
      JJK  Aerosols Anthropogenic and Natural, Sources and Transport, T.J.
       Kneip  and P.O. Lioy, eds.  Ann. N.Y. Acad. Sci. 338:463-482.

 Nadel , J.A., and D.F. Tierney (1961).  Effect of a previous deep inspiration
       on  airway resistance 1n man.   J.  Appl. Physiol.  16:717-719.

 Nadel, J.A., H. Salem, B.  Tamplln,  and  Y.  Tokiwa (1965).   Mechanism of
      bronchoconstriction during inhalation  of sulfur dioxide.   J. Aopl.
      Physiol. 20:164-167.

 Nakamura,  K. (1964).  Response of pulmonary  airway resistance by interaction
      of  aerosols and gases in different physical  and chemical  nature,
      Nippon Eiseigaka Zasshi  19:38-50.

 NAS [National Academy of Sciences]  (1958).   Handbook  of respiration.   National
      Research Council.   W.B.  Saunders  Co.,  Philadelphia,  pp.  147-149.

 NAS [National Academy of Sciences]  (1978).   Sulfur Oxides.   National
      Academy of Sciences,  Washington,  D.C.

 Neely, G.E.  (1982).   Research  agronomist,  Corvallis Environmental  Research
      Laboratory (U.S.  Environmental  Protection  Agency, Corvallis, OR).
      Personal  Communication with Larry  Zaragoza (April 2,  1982).

 Neely, G.E., D.T. Tingey,  and  R.G.  Wilhour  (1977).   Effects of  ozone  and
      sulfur dioxide singly and  in  combination on  yield, quality and  N-
      fixation of alfalfa.   Proceedings  of the International  Conference
      on Photochemical Oxidant  Pollution and Its Control.   EPA-600/3-77-001b.

 Neri , L.C., J.S. Mandel , D.  Hewitt, and  D. Jurkowski  (1975).  Chronic
      obstructive pulmonary disease in two cities  of  contrasting  air
      quality.   Can. Med. Assoc.  J. 113:1043-1046.

Newhouse, M.T., M.  Dolovich, G.  Obminski , and  R.K.  Wolff  (1978).   Effect
      of TLV levels  of SOg  and H2$04  on  bronchial  clearance in exercising
      man.  Arch.  Environ.  Health 33:24-32.

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                                         15
  NIAID  (1979).  Asthma and other allergic diseases.  U.S. Department of
        Health, Education, and Welfare.  NIH Publication 79-387.   Washington,
        U * I* •

  Nieboer, E., D.H.S. Richardson, K.J. Puckett, and F.D. Tomassini  (1976).
        The phytotoxicity of sulfur dioxide in relation to measurable responses
        in lichens.  In:  Effects of Air Pollutants on Plants.   T.A.  Mansfield,
        ed. Cambridge University Press, New York, pp.  61-114.

  Niinimaa, V., P. Cole, S. Mintz, and R.J. Shephard (1981).  Oral  nasal
        distribution of respiratory airflow.   Resp. Physiol. 43:69-75.

  Nobel, P.S. (1974).  Introduction to Plant  Biophysical  Physiology.
       W.H. Freeman and Co., San Francisco,  CA.

 Noggle, J.C., and H.C. Jones (1979).   Accumulation of Atmospheric Sulfur
       by Plants  and Sulfur-Supplying Capacity of  Soils.   EPA-600/7-79-109.

 Oshima, R.J.  (1978).   The impact of  sulfur  dioxide on vegetation:  a sulfur
       dioxide-ozone response model.   Final  Report to  the  California Air
       Resources  Board  Agree.   No.  A6-162-30.

 Peacock,  P.R., and J.B.  Spence  (1967).   Incidence of  lung tumors in LX
       mice  exposed to  (1)  free  radicals;  (2)  S02.  Br. J. Cancer 21:606-
       618.

 Proctor,  D.F.  (1981).  Oronasal  breathing and studies of effects of air
       pollutants  on the  lungs  (letter).   Am.  Rev.  Respir. Dis. 123:242-243.

 Reichel,  6.  (1972).  The  Effect  of Sulfur Dioxide  on the Airway  Resistance
       of  Man.  Annual meeting of the German Society for Industrial  Medicine.

 Reid,  L.  (1970).   Evaluation of model systems for  study of airway
      epithelium  cilia, and mucus.  Arch. Intern. Med. 126:428-434.

 Reinert, R.A., and D.E. Weber  (1980).  Ozone and sulfur dioxide-induced
      changes in  soybean growth.  Phytopathology 70:914-916.

 Rosenberg, C.R.,  R.J. Hutnik, and D.D. David  (1979).   Forest Composition
      of varying  distances from a coal-burning power  plant.  Environ
      Pollut 14:307-317.

Rossier, P.H., A.A. Buhlmann, and K.  Wiesinger (1960).  Respiration-
      Physiologic Principles and their Clinical  Applications.  The C  V
      Mosby Co.,  St. Louis, p.  402.                 '               '  '

Saibene, p.. P.  Mognoni ,  C.L. Lafortuna,  and R.  Mostardi  (1978).  Oronasal
      breathing during  exercise.   Pfuegers Arch.  378:65-69.

Samet, J.M., Y. Bishop,  F.E. Speizer,  Y.  Bishop,  J.D.  Spengler, and B  G
      Ferris,  Jr.   (1981).   The  relationship between  air  pollution and  emergency
      ^J'oin5 in an industrial  community.  J.  Air  Pollut,  Control Assoc.
            —

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                                         16


 Schachter, E.N.  (1982).   Effects of sulfur dioxide on airway function
       (letter to the  editor).  Am. Rev.  Respir. Dis. 125:125.

 Schimmel,  H.  (1978).   Evidence for possible acute health effects of ambient
       air  pollution from  time series analysis:  methodological questions and
       some new results based on New York City daily mortality, 1963-1976.
       Bull  N.Y.  Acad.  54:1052-1108.

 Schimmel,  H., and T.J. Murawski (1976).  The relation of air pollution to
       mortality.  J.  Occup. Med. 18:316-333.

 Schryer, D.R., W.R. Cofer, III, and R.S. Rogowski  (1980).  Synergistic
       effects in trace gases—aerosol  interactions.   Scince 209:723.

 Scott, W.D.,  and P.V. Hobbs (1967).  The formation of sulfate in water
       drops.   J. Atmos. Sci. 24:54-57.

 Senior, R.M., and S.S. Lefrak (1980).   Status Asthmaticus. Chapter 49
      Jn:   Pulmonary Diseases and Disorders.  A. P.  Fishman, ed. McGraw-
       Hill  Book Co. pp. 593-599.

 Shalamberidze, O.P. (1967).  Reflex effects of mixtures  of sulfur and
       nitrogen dioxides.   Hyg.  Sanit.  32:10-15.

 Shapiro, R.  (1977).  Genetic effects of bisulfite  (sulfur dioxide).
       Mutat.  Res. 39:149-176.

 Sheppard, D.  (1982).   University of California at  San Francisco
       Medical Center.   Personal  Communication with John  Bachmann (April  15,
       1982).

 Sheppard, D.A., A. Saisho, J.A.  Nadel ,  and  H.A.  Boushey  (1981a).   Exercise
       increases sulfur dioxide  induced  bronchoconstriction  in  asthmatic
       subjects.  Am.  Rev.  Respir.  Dis.  123:486-491.

 Sheppard, D., J.A. Nadel,  and H.A.  Boushey  (1981b).   Inhibition  of sulfur
       dioxide-induced  bronchoconstriction by  disodium cromoglycate in
      asthmatic subjects.   Am.  Rev.  Respir.  Dis. 124:257-259.

 Sheppard, D., W.S. Wong, C.F. Uehara, J.A.  Nadel,  and H.A.  Boushey  (1980).
      Lower threshold  and  greater bronchomotor responsiveness of  asthmatic
      subjects to sulfur dioxide.   Am.  Rev.  Respir. Dis.  122:873-878.

 Shih, V.E., I.F.  Abrams, J.L. Johnson,  M. Carney,  R.  Mandells, R.M. Robb
      J.P.  Cloherty, and K.V. Rajagopalan  (1977).  Sulfite  oxidase
      deficiency.   Biochemical and  clinical investigations  of a  hereditary
      metabolic disorder in sulfur metabolism.   N. Eng. J.  Med. 297-1022-
      1028.

Shownan,  R.E.  (1975).   Lichens as indicators of  air quality around a
      coal-fired  power generating plant.  Bryologist  78:1-6.

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                                        17
Sim, V.M., and R.E. Rattle (1957).   Effect of possible  smog  irritants on
      human subjects.  J. Am. Med.  Assoc.  165:1908-1913.

Snell, R.E., and P.C. Luchsinger (1969).   Effects  of  sulfur  dioxide on
      expiratory flow rates and total  respitatory  resistance in  normal
      human subjects.  Arch. Environ.  Health  18:693-698.

Speizer, F.E., and N.R. Frank (1966a).  A  comparison  of changes  in pulmonary
      flow resistance in health volunteers acutely exposed to SO2 by mouth
      and by nose.  Br. J. Ind. Med. 23:75-79.

Speizer, F.E., and N.R. Frank (1966b).  The uptake and  release of S02
      by the human nose.  Arch. Environ. Health  12:725-728.

Spence, J.W., F.H. Haynie, and J.B. Upham  (1975).   Effects of gaseous
      pollutants on paints:  A chamber study. J.  Paint Technol. 47:57-63.

Spiegleman, J.R., G.D. Hanson, A. Lazarus, R.J.  Bennett,  M.  Lippmann, and
      R.D. Albert (1968).  Effect of acute sulfur  dioxide exposure on
      bronchial clearance in the donkey.   Arch.  Environ.  Health  17:321-326.

Sprugel, D.G., J.E. Miller, R.N. Muller, H.J. Smith,  and  P.B. Xerikos
      (1980).  Sulfur dioxide effects  on yield and seed quality  in field
      grown soybeans.  Phytopathology  70:1129-1133.

Stacy, R.W., M.M. Friedman, J. Green,  D.E. House,  L.  Raggio, L.J. Roger, and
      M. Hazucha (1981).  Effects of 0.75  ppm sulfur  dioxide on  pulmonary
      function parameters of normal human  subjects.   Arch. Environ. Health
      36:172-178.

Strandberg, L.G. (1964).  SOg absorption in the  respiratory  tract.
      Arch. Environ. Health 9:160-166.

Stankunas, A.R., D.F. Unites, and E.F. McCarthy  (1980).  Air Pollution
      Damage to Man-Made Materials:  Physical and  Economic Estimates.  TRC
      Environmental Consultants Inc. Wethersfield, Connecticut,  p. II-5.

Stankunas, A.R., D.F. Unites, and E.F. McCarthy  (1981).  Air pollution
      damage to manmade materials.   Presented at the  74th Annual Meeting,
      Air Pollution Control Association, Philadelphia,  Pennsylvania, Paper
      no. 81-65.3.

Thompson, J.R., and D.M. Pace (1962).   Effects of  SOg on  established cell
      lines cultivated in vitro. Can. J.  Biochem. Physiol.  40:207-217.

Thomas, M.D. (1951).  Gas damage to plants.  Ann.  Rev.  Plant Physiol.
      2:293-322.

Thomas, M.D., and R.H. Hendricks (1956).   Effect of air pollution on plants.
      In:  Air Pollution Handbook.   P.L. Magill, F.R. Holden, and C. Ackley,
      eds. McGraw-Hill, New York, pp.  1-44.

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                                        18


Thrall, A. D. (1982).  Using Logistic Regression to Estimate Short-Term
      Exceedance Probabilities from Annual Averages.  Memorandum to  N.H.  Frank,
      Monitoring and Data Analysis Division,  Office of Air Quality Planning
      and Standards, Research Triangle Park,  N.C.

Tingey, D.T., R.A. Reinert, J.A. Dunning,  and W.E.  Heck (1973a).  Foliar
      injury responses of 11 plant species to ozone/sulfur dioxide mixtures.
      Atmos. Environ. 7:201-208.
             •-.!-../•
Tingey, D.T., R.A. Reinert, C. Hickliff, and  W.W. Heck (1973b).   Chronic
      ozone or sulfur dioxide exposures or both  affect the early  vegetative
      growth of soybean.  Can. J. Plant Sci.  53:875-879.

Tingey, D.T., R.A. Reinert, J.A. Dunning,  and W.W.  Heck (1971a).  Vegetation
      injury from the interaction of nitrogen dioxide  and  sulfur  dioxide.
      Phytopathology 61:1506-1511.

Tingey, D.T., W.W. Heck, and R.A. Reinert  (1971b).   Effect of low
      concentrations of ozone and sulfur dioxide on foliage,  growth, and
      yield of radish.  J. Am. Soc. Hort.  Sci. 96:369-371.

Tomono, Y. (1961).  Effects of SO? on human pulmonary  functions.  Sangyo  Igaku
      3:77-85.

Toyama, T. (1964).  Air pollution and its  health effects in Japan.   Arch.
      Environ. Health 8:153-173.

Toyama, T. (1962).  Studies on aerosols.   Synergistic  response of the
      pulmonary airway resistance of inhaling sodium chloride aerosols
      and SOg in man.  Sangyo Igaku 4:82-92.

Upham, J.B. (1967).  Atmospheric corrosion studies  in  two  metropolitan
      areas.  J. Air Pollut. Control  Assoc. 17:398-402.

Van der Lende, R., C. Huygen, E.J. Jansen-Koster, S. Knijpstra, R. Peset,
      B.F. Visser, E.H.E.  Wolfs, and N.G.M. Orie (1975).   A temporary
      decrease in ventilatory function of  an  urban  population during an
      acute increase in air pollution.  Bull.  Physiopathol.  Respir.
      11:31-43.

Van der Lende, R., T.J. Kok, R.P. Reig, J.P.  Schouten,  N.G.M. Orie,  and
      P.H. Quanjer (1981).  The relationship  between air pollution and
      diminished lung function values.  Results  of  a longitudinal
      epidemiological study in the Netherlands.   Proceedings  of 74th
      Annual APCA Meeting, Philadelphia, PA.

Van der Lende, R., G.J. Temmeling, B.F. Visser,  K.  de  Vries,  J. Wever-Hess,
      and N.G.M. Orie (1973).  Epidemiological investigations  in  the
      Netherlands into the influence of smoking  and atmospheric pollution
      on respiratory symptoms and lung function  disturbances.  Pneumonologie
      149:119-126.

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                                        19


von Nieding, H.M. Wagner, 6., H. Krekeler, H. Lollgen, W. Fries,  and
      A. Beuthan (1979).   Controlled studies of human exposure to single and
      combined action of N02, 03 and SOg.  Int. Arch. Occup.  Environ.  Health
      43:195-210.

Wanner, A. (1980).  Interpretation of pulmonary function tests.  In:
      Diagnostic Techniques in Pulmonary Disease, M.A. JSackner (ed.).
      Marcel Dekker, Inc., New York,  pp. 353-426.

Ware, J., L.A. Thibodeau, F.E. Speizer, S. Colome, and E.G. Ferris,  Jr.
      (1981).  Assessment of the health effects of sulfur oxides  and
      particulate matter:  analysis of the exposure-response  relationship.
      Environ. Health Persp.  41:255-276.

Weir, F.W., and P.A. Bromberg (1973).  Effects of sulfur dioxide  on  human
      subjects exhibiting peripheral airway impairment.   Project  No.
      CAWC S-15, American Petroleum Institute, Washington, D.C.,  pp. 1-40.

Weir, F.W., and P.A. Bromberg (1972).  Further investigation  of the  effects of
      sulfur dioxide on human subjects.  Annual Report Project No. CAWC
      S-15, American Petroleum Institute, Washington, D.C., pp. 1-74.

Widdicombe, J.G. (1954).  Respiratory reflexes from the  trachea and  bronchi
      of the cat. J. Physiol. 123:55-70.

Wilson, E.O., and W.H. Bossert (1971).  A Primer of Population Biology.
      Sinauer Associates, Inc.,  Stanford, Connecticut, p. 47.

Winner, W.E., and J.D. Bewley (1978a).  Contrasts between bryophyte  and
      vascular plant synecological responses in an S02-stressed White
      Spruce association in Central Alberta.  Oecologia  33:311-325.

Winner, W.E., and J.D. Bewley (1978b).  Terrestrial mosses as bioindicators
      of S02 pollution stress.  Synecological analysis and the index of
      atmospheric purity.  Oecologia 35:221-230.

Winner, W.E., J.D. Bewley, H.R.  Krouse, and H.M. Brown (1978). Stable
      sulfur isotope analysis of SOg pollution impact on vegetation.
      Oecologia 36:351-361.

Wolff, R.K.,  M. Dolovich, C.M. Rossman, and M.T. Newhouse (1975a).
      Sulphur dioxide and tracheo-bronchial  clearance in man.  Arch. Environ.
      Health 30:521-527.

Wolff, R.K.,  M. Dolovich, G. Obminski, and M.T. Newhouse (1975b).  Effect
      of sulfur dioxide on tracheobronchial  clearance at rest and  during
      exercise.  JJK   Inhaled Particles IV.   W.H. Walton,  ed. Pergamon
      Press,  London,  pp. 321-332.

Yamada,  J. (1905).   Untersuchunger fiber die  quantative Absorption  der  Da'mpfe
      eingen  Saiiren durch Tier and Mensch.  [Investigations on the quantitative
      absorption of some acid fumes in animals and man.J PhD. Thesis,  Wiirzburg
      (See Lehrmann,  K.B., 1908, Arch. Hyg.  67:57-98.)

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                                        20


Yokoyama, E., R.E. Yoder, and N.R.  Frank (1971).   Distribution  of  35S  in
      the blood and its excretion in urine of dogs exposed to   SOo.   Arch.
      Environ. Health 22:389-395.                                 i

Zarkower, A. (1972).  Alterations in antibody response  induced  by  chronic
      inhalation of S02 and carbon.   Arch. Environ.  Health 25:45-50.
                          >**. ":
Zenz, C. (1975).  Occupational  Medicine:  principles and  practical
      applications.  Year Book  Publishers, Inc.,  Chicago, pp. 113-114.

Zimmerman, P.W., and W. Crocker (1934).   Toxicity of air  containing
      sulfur dioxide gas.  Contrib.  Boyce Thompson Instit. 6:455-470.

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                                   TECHNICAL REPORT DATA
                            (Please read Instructions on the reverse before completing)
 1. REPORT NO.
 EPA-450/5-82-007
                                                            3. RECIPIENT'S ACCESSION NO.
4. TITLE AND SUBTITLE
 Review of  the National Ambient Air Quality Standards
 for Sulfur Oxides:   Assessment of Scientific and
 Technical  Information              OAQPS Staff Paper
              5. REPORT DATE
              November  1982
              6. PERFORMING ORGANIZATION CODE
7. AUTHOR(S)
                                                            8. PERFORMING ORGANIZATION REPORT NO
9. PERFORMING ORGANIZATION NAME AND ADDRESS
 Office of  Air,  Noise and Radiation
 Office of  Air Quality Planning and  Standards
 U.S. Environmental  Protection Agency
 Research Triangle Park, North Carolina   27711
                                                            10. PROGRAM ELEMENT NO.
              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
16. ABSTRACT            :            ~~~~	~~—	"	~
      This  paper evaluates and interprets the available scientific and technical  infor-
 mation  that EPA staff believes  is most relevant to the review of primary (health)
 and secondary (welfare) National Ambient Air Quality Standards for sulfur oxides
 (SO ) and  presents staff recommendations on alternative approaches to reaffirming  or
 revising the standards.  The assessment is intended to bridge the gap between the
 scientific review in the EPA criteria document for particulate matter and sulfur
 oxides  and the judgments required of the Administrator in  setting ambient air
 quality standards for sulfur oxides.

      The major recommendations  of the staff paper include  the following:
      1) that the health and welfare data support the need  for sulfur dioxide
 standards;
      2) that the reaffirmation  of the existing suite of primary and secondary S02
 standards  (annual, 24-hour, 3-hour) remains a reasonable policy choice;
      3) that new data from controlled human exposure studies warrants consideration of
 a  short-term (1-hour) standard;
      4) that a short-term standard  (<_ 4-hours) to protect  vegetation should be
 retained.
                                KEY WORDS AND DOCUMENT ANALYSIS
                  DESCRIPTORS
                                              b. IDENTIFIERS/OPEN ENDED TERMS
                                                                         c.  COSATI Field/Group
 Sulfur Oxides
 Sulfur Dioxide
 Air  Pollution
 Particulate Matter
 Air Quality Standards
 I. DISTRIBUTION STATEMEN

  Release to Public
19. SECURITY CLASS (ThisReport)
 Unclassified
21 ^NO. OF PAGES
                                              20. SECURITY CLASS (Thispage!
EPA Form 2220-1 (Rev. 4-77)   PREVIOUS EDITION is OBSOLETE

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