PxEPA
              United States
              Environmental Protection
              Agency
                                          600884020A1
             Environmental Criteria and
             Assessment Office         July 1984
             Research Triangle Park NC 27711   External Review Draft
              Research and Development
     Quality
Criteria for
Ozone  and Other
Photochemical
Oxidants
Review
Draft
(Do Not
Cite or Quote)
              Volume  I of V
                            NOTICE

               This document is a preliminary draft. It has not been formally
               released by EPA and should not at this stage be construed to
               represent Agency policy. It is bei ng circulated for comment on its
               technical accuracy and policy implications.

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                                 EPA-600/8-84-020A
Draft                                      July 1984
Do Not Quote or Cite                External Review Draft
          Air  Quality Criteria
        for Ozone and Other
     Photochemical Oxidants

              Volume  I  of V
                       NOTICE

This document is a preliminary draft. It has not been formally released by EPA and should not at
this stage be construed to represent Agency policy. It is being circulated for comment on its
technical accuracy and policy implications.
          Environmental Criteria and Assessment Office
          Office of Health and Environmental Assessment
             Office of Research and Development
             U.S. Environmental Protection Agency
             Research Triangle Park, N.C. 27711
                                U.S. Environmental Protection Agency
                                Region V, Library
                                230 South Dearborn Street
                                Chicago, Illinois  60604   X*'

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                                   NOTICE

          Mention of trade names or commercial products does not constitute
          endorsement or recommendation for use.
S.  Qfiflronment ~I n--t—tion Agency

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                                   ABSTRACT


     Scientific information is presented and evaluated relative to the health
and welfare effects associated with exposure to ozone and other photochemical
oxidants.   Although it is not intended as a complete and detailed literature
review, the document covers pertinent literature through 1983 and early 1984.

     Data on health and welfare effects are emphasized, but additional infor-
mation is provided for understanding the nature of the oxidant pollution pro-
blem and for evaluating the reliability of effects data as well as their
relevance to potential exposures to ozone and other oxidants at concentrations
occurring in ambient air.  Separate chapters are presented on the following
exposure-related topics:   nature, source, measurement, and concentrations of
precursors to ozone and other photochemical oxidants; the formation of ozone
and other photochemical oxidants and their transport once formed; the proper-
ties, chemistry, and measurement of ozone and other photochemical oxidants;
and the concentrations of ozone and other photochemical oxidants that are
typically found in ambient air.

     The specific areas addressed by chapters on health and welfare effects
are the toxicological appraisal of effects of ozone and other oxidants; effects
observed in controlled human exposures; effects observed in field and epidemic-
logical studies; effects on vegetation seen in field and controlled exposures;
effects on natural and agroecosystems; and effects on nonbiological materials
observed in field and chamber studies.
                                      m
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                              CONTENTS


                                                                      Page

VOLUME I
  Chapter 1.    Summary and Conclusions 	      1-1

VOLUME II
  Chapter 2.    Introduction 	      2-1
  Chapter 3.    Precursors to Ozone and Other Photochemical
               Oxidants 	      3-1
  Chapter 4.    Chemical and Physical  Processes in the Formation
               and Occurrence of Ozone and Other Photochemical
               Oxidants 	      4-1
  Chapter 5.    Properties, Chemistry,  and Measurement of Ozone
               and Other Photochemical Oxidants 	      5-1
  Chapter 6.    Concentrations of Ozone and Other Photochemical
               Oxidants in Ambient Air 	      6-2

VOLUME III
  Chapter 7.    Effects of Ozone and Other Photochemical  Oxidants
               on Vegetati on 	      7-1
  Chapter 8.    Effects of Ozone and Other Photochemical  Oxidants
               on Natural and Agroecosystems 	      8-1
  Chapter 9.    Effects of Ozone and Other Photochemical  Oxidants
               on Nonbiological Materials 	      9-1

VOLUME IV
  Chapter 10.   Toxicological Effects  of Ozone and Other
               Photochemical Oxidants  	     10-1

VOLUME V
  Chapter 11.   Controlled Human Studies of the Effects of Ozone
               and Other Photochemical Oxidants 	     11-1
  Chapter 12.   Field and Epidemiological Studies of the Effects
               of Ozone and Other Photochemical Oxidants 	     12-1
  Chapter 13.   Evaluation of Integrated Health Effects Data for
               Ozone and Other Photochemical Oxidants 	     13-1
0190LG/B
                                       IV
May 1984

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                               TABLE OF CONTENTS
LIST OF TABLES 	    ix
LIST OF FIGURES 	    x
AUTHORS AND CONTRIBUTORS 	    xi i
LIST OF ABBREVIATIONS AND SYMBOLS 	    xv

1.  SUMMARY AND CONCLUSIONS 	    1-1
     1.1  INTRODUCTION 	    1-1
     1.2   PRECURSORS TO OZONE AND OTHER PHOTOCHEMICAL OXIDANTS 	    1-2
           1.2.1   Nature of Precursors 	    1-2
           1.2.2   Measurement of Precursors 	    1-3
           1.2.3   Sources and Emissions of Precursors 	    1-6
           1.2.4   Ambient Air Concentrations of Precursors 	    1-8
     1.3   CHEMICAL AND PHYSICAL PROCESSES IN THE FORMATION AND
           OCCURRENCE OF OZONE AND OTHER PHOTOCHEMICAL OXIDANTS 	    1-12
           1.3.1   Chemical Processes 	    1-12
           1.3.2   Physical Processes 	    1-14
     1.4   PROPERTIES, CHEMISTRY, AND MEASUREMENT OF OZONE AND
           OTHER PHOTOCHEMICAL OXIDANTS 	    1-15
           1.4.1   Properties 	    1-15
           1.4.2   Reactions of Ozone and Other Oxidants in Ambient
                   Air	    1-16
           1.4.3   Reactions of Ozone and Peroxyacetyl Nitrate in
                   Aqueous (Biological) Systems 	    1-17
           1.4.4   Sampling and Measurement of Ozone and Other
                   Photochemical Oxidants 	    1-18
                   1.4.4.1   Quality Assurance and Sampling 	    1-19
                   1.4.4.2   Measurement Methods for Total Oxidants
                             and Ozone 	    1-20
                   1.4.4.3   Calibration Methods	    1-23
                   1.4.4.4   Relationship of Total Oxidants and
                             Ozone Measurements 	    1-25
                   1.4.4.5   Methods for Sampling and Analysis of
                             Peroxyacetyl Nitrate and Its
                             Homol ogues 	    1-27
                   1.4.4.6   Methods for Sampling and Analysis of
                             Hydrogen Peroxi de 	    1-32
     1.5   CONCENTRATIONS OF OZONE AND OTHER PHOTOCHEMICAL
           OXIDANTS IN AMBIENT AIR 	    1-36
           1.5.1   Ozone Concentrations in Urban Areas 	    1-37
           1.5.2   Trends in Urban and Nationwide Ozone
                   Concentrations 	    1-40
           1.5.3   Ozone Concentrations in Nonurban Areas 	    1-42
           1.5.4   Patterns in Ozone Concentrations 	    1-43
           1.5.5   Concentrations and Patterns of Other
                   Photochemical Oxidants 	    1-45
                   1.5.5.1   Concentrations 	    1-45
                   1.5.5.2   Patterns	    1-47
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                               TABLE  OF  CONTENTS
                                  (continued)
           1.5.6   Relationship Between  Ozone and Other
                   Photochemical  Oxidants  	     1-48
     1.6   EFFECTS OF OZONE AND PEROXYACETYL NITRATE  ON VEGETATION  ..     1-51
           1.6.1   Effects  of Ozone on Vegetation 	     1-51
                   1.6.1.1    Introduction  	     1-51
                   1.6.1.2    Limiting Values of Plant Response  	     1-52
                   1.6.1.3    Methods for Determining  Ozone  Yield
                             Losses 	     1-55
                   1.6.1.4    Estimates of  Yield Loss	     1-56
                   1.6.1.5    Effects on  Crop Quality  	     1-64
                   1.6.1.6    Yield Loss  from Ambient  Exposures  	     1-64
                   1.6.1.7    Statistics  Used to Characterize Ozone
                             Exposures 	     1-64
                   1.6.1.8    Relation Between Yield Loss and Foliar
                             Injury	     1-66
                   1.6.1.9    Physiological  Basis of Yield
                             Reductions  	     1-66
                   1.6.1.10  Factors Affecting Plant  Response to
                             Ozone 	     1-67
                   1.6.1.11  Economic Assessment of Ozone Effects  ...     1-69
           1.6.2   Effects  of Peroxyacetyl  Nitrate on Vegetation 	     1-71
                   1.6.2.1    Introduction	     1-71
                   1.6.2.2    Factors Affecting Plant  Response to
                             PAN 	     1-71
                   1.6.2.3    Limiting Values of Plant Response  	     1-71
                   1.6.2.4    Effects of  PAN on Plant  Yield	     1-72
     1.7   EFFECTS OF OZONE AND OTHER PHOTOCHEMICAL OXIDANTS ON
           NATURAL ECOSYSTEMS 	     1-72
           1.7.1   Introduction 	     1-72
           1.7.2   Oxidant-Induced Effects on a Western Coniferous
                   Forest Ecosystem 	     1-74
           1.7.3   Effects  of Ozone on Other Ecosystems 	     1-77
           1.7.4   Effects  on Interrelated Ecosystems 	     1-80
                   1.7.4.1    Aquatic Ecosystems 	     1-80
                   1.7.4.2    Agricultural  Ecosystems  	     1-81
           1.7.5   Ecosystem Responses to  Stress 	     1-81
     1.8   EFFECTS OF OZONE AND OTHER PHOTOCHEMICAL OXIDANTS ON
           NONBIOLOGICAL MATERIALS 	     1-83
           1.8.1   Introduction 	     1-83
           1.8.2   Effects  and Damage Functions 	     1-84
                   1.8.2.1    Elastomers	     1-84
                   1.8.2.2    Textile Fibers and Dyes  	     1-85
                   1.8.2.3    Paints	     1-87
           1.8.3   Economic Assessment of  Effects of  Ozone  on
                   Materi al s 	     1-87
     1.9   INTRODUCTION TO  HEALTH EFFECTS  	     1-89
           1.9.1   Organization of Health  Effects Information 	     1-89
           1.9.2   Literature Coverage and Selection  	     1-92

                                         vi
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TOXICOL
OXIDANT
1.10.1
1.10.2
1.10.3
OGIC EFFECTS OF OZONE AND OTHER PHOTOCHEMICAL
s 	 	
Introduction 	
Respiratory Transport and Absorption of Ozone ....
Effects of Ozone on the Respiratory Tract 	
1.10.3.1 Morphological Effects 	
1.10.3.2 Pulmonary Function 	
1.10.3.3 Biochemical Effects of Ozone in the
Lung of Experimental Animal s 	
1.10.3.4 Effects of Ozone in Altering Host
Defense Against Microbes 	
1.10.3.5 Tolerance 	
                              TABLE OF  CONTENTS
                                  (continued)
     1.10
                                                                         1-93
                                                                         1-93
                                                                         1-94
                                                                         1-96
                                                                         1-96
                                                                         1-99

                                                                         1-105

                                                                         1-110
                                                                         1-115
           1.10.4  Extrapulmonary Effects  of  Ozone  	     1-118
                   1.10.4.1  Central  Nervous  System and Behavioral
                             Effects  	     1-118
                   1.10.4.2  Cardiovascular Effects 	     1-119
                   1.10.4.3  Hematological  and Serum Chemistry
                             Effects  	     1-119
                   1.10.4.4  Cytogenetic and  Teratogenetic
                             Effects  	     1-121
                   1.10.4.5  Other Extrapulmonary Effects	     1-122
           1.10.5  Effects  of Other Photochemical Oxidants  	     1-123
     1.11   EFFECTS OF OZONE AND  OTHER PHOTOCHEMICAL OXIDANTS  IN
           CONTROLLED EXPOSURES  	     1-127
           1.11.1  Pulmonary Function Effects in  Controlled Human
                   Studies:   Mechanical  Function  of the Lung  	     1-127
                   1.11.1.1  General  Population	     1-127
                   1.11.1.2  Subjects with Preexisting Disease 	     1-136
                   1.11.1.3  Intersubject  Variability	     1-137
                   1.11.1.4  Attenuation with Repeated Exposures ....     1-137
           1.11.2  Other Effects of Ozone  in  Controlled Human
                   Exposures 	     1-138
           1.11.3  Effects  of Peroxyacetyl  Nitrate  and Mixtures in
                   Control 1ed Human Exposures 	     1-139
     1.12   FIELD AND EPIDEMIOLOGICAL  STUDIES  OF THE EFFECTS OF
           OZONE AND OXIDANTS 	     1-139
           1.12.1  Introduction	     1-139
           1.12.2  Field and Epidemiological  Studies of Effects
                   of Effects of Acute Exposure 	     1-140
           1.12.3  Epidemiological studies of Effects of Chronic
                   Exposure 	     1-143
     1.13   SUMMARY OF THE EVALUATION  OF INTEGRATED  HEALTH EFFECTS
           DATA 	".	   1-144
           1.13.1  Health Effects in  the General  Human Population  	   1-144
           1.13.2  Health Effects in  Potentially  Susceptible
                   Individuals 	   1-148
           1.13.3  Extrapolation of Effects Observed in Animals
                   to Human Populations 	   1-149
                                      vn
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                               TABLE OF CONTENTS
                                  (continued)
           1.13.4  Health Effects of Other Photochemical  Oxidants
                   and Pol 1utant Mixtures 	   1-150
           1.13.5  Identification of Potentially At-Risk Populations
                   or Subpopulations 	   1-150
     1.14  REFERENCES 	   1-153
                                        viii
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                                LIST OF TABLES


Table                                                                   Page


1-1   Hydrocarbon (HC) composition typically measured in urban
      areas (from sample collected in Milwaukee, 1981) 	    1-10
1-2   Summary of ozone monitoring techniques 	    1-22
1-3   Ozone calibration techniques 	    1-24
1-4   Summary of parameters used in determination of PAN by
      GC-ECD 	    1-29
1-5   Infrared absorptivities of peroxyacetyl nitrate 	    1-30
1-6   Measurement methods for hydrogen peroxide 	    1-34
1-7   Second-highest 1-hr ozone concentrations in 1982 in
      Standard Metropolitan Statistical Areas with populations
      >1 million, given by census divisions and regions 	    1-38
1-8   Ozone concentrations for short-term exposures that
      produce 5 or 20 percent injury to vegetation grown under
      sensitive conditions 	    1-53
1-9   Seasonal 7-hour ozone concentrations (ppra) at which yield
      losses of 10 percent or 30 percent are predicted from
      exposure-response models 	    1-60
1-10  Ozone concentrations at which significant yield losses
      have been noted for a variety of plant species exposed to
      03 under various experimental conditions 	    1-62
1-11  Injury thresholds for 2-hour exposures to ozone 	    1-79
1-12  Morphological effects of ozone in experimental animals 	    1-101
1-13  Effects on pulmonary function of short-term exposures
      to ozone 	    1-104
1-14  Effects on pulmonary function of long-term exposures
      to ozone 	    1-107
1-15  Biochemical changes in experimental animals exposed to ozone ..    1-112
1-16  Effects of ozone on host defense mechanisms in experimental
      animals 	    1-117
1-17  Extrapulmonary effects of ozone in experimental animals 	    1-125
1-18  Summary table:  Results of controlled human exposures to
      ozone 	    1-128
1-19  Estimated values of oxygen consumption and minute ventilation
      associated with representative types of exercise 	    1-133
1-20  Summary table:  Acute effects of ozone and other photochemical
      oxidants in population studies 	    1-141
                                      ix
019GC1/B                                                              6/29/84

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                                LIST OF  FIGURES


                                                                        Page


1-1   National  trend in estimated emissions of volatile organic
      compounds,  1970 through 1982	    1-7
1-2   National  trend in estimated emissions of nitrogen
      oxides,  1970 through 1982 	    1-9
1-3   Collective  distributions of the three highest 1-hour
      ozone concentrations for 3 years (1979,  1980, and 1981)
      at valid sites (906 station-years) 	    1-41
1-4   Relationship between 03 concentration, exposure duration,
      and a reduction in plant growth or yield (see Table 7-18;
      also U.S. EPA, 1978) 	    1-54
1-5   Examples of effects of 03 exposure on yield of various
      plants.   03 concentration (ppm) is expressed as 7-hr
      seasonal  mean.  Soybean (A) data from Kress and Miller
      (1983);  peanut (B) data from Heagle et al.  (1983) and
      Heck et al. (1982); corn (C) and wheat (D)  data from
      Heagle and  Heck (1980) and Heck et al. (1982) 	    1-57
1-6   Relative 03-induced yield reduction of selected crops
      as predicted by the Weibull model  (Heck et  al., 1983) 	    1-58
1-7   Summation of abiotic and biotic agents involved in
      diseases of trees, given by types of diseases and
      functional  parts of the tree.   Decline diseases are
      caused by a combination of biotic and abiotic agents	    1-73
1-8   Conceptual  sequence of levels showing continuum of
      pi ant responses 	    1-82
1-9   Summary of morphological effects in experimental animals
      exposed to ozone 	    1-100
1-10  Summary of effects of short-term ozone exposures on pulmonary
      function i n experimental animals 	    1-103
1-11  Summary of effects of long-term ozone exposures on pulmonary
      function in experimental animals 	    1-106
1-12  Summary of biochemical changes in experimental animals
      exposed to ozone 	    1-111
1-13  Summary of effects of ozone on host defense mechanisms in
      experimental animals 	    1-116
1-14  Summary of extrapulmonary effects of ozone in experimental
      animal s  	    1-124
1-15  Group mean decrements in 1-sec forced expiratory volume
      during 2-hr ozone exposures with different levels of
      intermittent exercise:  light (VE < 25 L/min); moderate
      (VV = 26-43 L/min); heavy (Vp = 44r63 L/min); and very
      he&vy (tf  > 64 L/min)	    1-135
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Project Team:   Air Quality Criteria for Ozone and Other Photochemical Oxidants

Ms. Beverly E.  Til ton, Project Manager
  and Coordinator for Chapters 1 through 6
Environmental  Criteria and
  Assessment Office
MD-52
U.S. Environmental Protection Agency
Research Triangle Park, NC  27711

Dr. J. H. B. Garner
Coordinator for Chapters 8 and 9;
  Co-coordinator for Chapter 7
Environmental  Criteria and
  Assessment Office
MD-52
U.S. Environmental Protection Agency
Research Triangle Park, NC  27711

Mr. Thomas B.  McMullen
Assistant Coordinator for Chapters 3 and 4
Environmental  Criteria and
  Assessment Office
MD-52
U.S. Environmental Protection Agency
Research Triangle Park, NC  27711

Mr. James A. Raub
Coordinator for Chapters 10 through 13
Environmental Criteria and
  Assessment Office
MD-52
U.S. Environmental Protection Agency
Research Triangle Park, NC  27711

Dr. David T. Tingey
Coordinator for Chapter 7
Environmental Research Laboratory
U.S.  Environmental Protection Agency
200 SW 35th Street
Corvallis, OR  97330
                                       xi
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                           AUTHORS AND CONTRIBUTORS


Chapter 1.  Summary and Conclusions


Principal Authors

Dr. Donald E. Gardner
Northrop Services, Inc.
Environmental Sciences
P. 0. Box 12313
Research Triangle Park, NC  27709

Dr. J. H. B. Garner
Environmental Criteria and Assessment Office
MD-52
U.S. Environmental Protection Agency
Research Triangle Park, NC  27711

Dr. Judith A. Graham
Health Effects Research Laboratory
MD-82
U.S. Environmental Protection Agency
Research Triangle Park, NC  27711

Dr. Jimmie A. Hodgeson
Professor, Department of Chemistry
407 Choppin Hall
Louisiana State University
Baton Rouge, LA  70803

*Dr. Thomas J. Kulle
Department of Medicine
School of Medicine
29  South Green Street, GSB-414
University of Maryland
Baltimore, MD  21201

Mr. James A. Raub
Environmental Criteria and Assessment Office
MD-52
U.S.  Environmental Protection Agency
Research Triangle Park, NC  27711

Ms.  Beverly  E. Til ton
Environmental Criteria and Assessment Office
MD-52
U.S.  Environmental Protection Agency
Research Triangle Park, NC  27711

Dr.  David T. Tingey
Environmental Research Laboratory
200 SW  35th Street
Corvallis,  OR   97330

                                      xi i
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Contributing Authors

*Dr.  Robert Frank
Department of Environmental Health Sciences
Johns Hopkins School of Hygiene and Public Health
615 N.  Wolfe Street
Baltimore, MD  21205

*Dr.  Milan J. Hazucha
School  of Medicine
Center for Environmental Health and Medical Sciences
University of North Carolina
Chapel  Hill, NC  27514

Mr. Michael W.  Holdren
BatteHe, Columbus Laboratories
505 King Avenue
Columbus, OH  43201

Dr. Donald H. Horstman
Health Effects Research Laboratory
MD-58
U.S.  Environmental Protection Agency
Research Triangle Park, NC  27711

Mr. James M. Kawecki
TRC Environmental Consultants
701 West Broad Street
Suite 401
Falls Church, VA  22046

Dr. Jan G. Laarman
Department of Forestry
North Carolina State University
Raleigh, NC  27607

Dr. Michael D.  Lebowitz
Department of Internal Medicine
College of Medicine
University of Arizona
Tucson, AZ  85724

Mr. Thomas B. McMullen
Environmental Criteria and Assessment Office
MD-52
U.S.  Environmental Protection Agency
Research Triangle Park, NC  27711

Dr. Daniel B. Menzel
Laboratory of Environmental Toxicology and Pharmacology
Duke University Medical Center
P. 0. Box 3813
Durham, NC  27710
                                      xm
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Contributing Authors (continued)

Dr. Harold G. Richter
Office of Air Quality Planning and Standards
Monitoring and Data Analysis Division
MD-14
U.S. Environmental Protection Agency
Research Triangle Park, NC  27711

Dr. Halvor Westberg
Director, Laboratory for Atmospheric Research,
  and Professor, Civil and Environmental Engineering
Washington State University
Pullman, WA  99164-2730

Dr. Arthur M. Winer
Assistant Director
Statewide Air Pollution Research Center
University of California
Riverside, CA  92521
*These authors also reviewed portions of Chapter 1 at the  request  of the U.S.
Environmental Protection Agency.   The  evaluations  and conclusions  contained
herein, however,  are not necessarily those of the reviewers.
                                      xiv
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                             LIST OF ABBREVIATIONS
ACh
APR
AM
ANOVA
AGO
APHA

aq
ASL
aim
ATPS

avg
b.p.
BTPS

bz
C
°C
CA
CAMP
CARB
cc
CC
°dyn
CE
CHEM
CH4
CHESS
CL
CLst
cm
acetylcholine
air:fuel ratio
alveolar macrophage
analysis of variance
airway obstructive disease
American Public Health Association
approximately
aqueous
above sea level
atmosphere
ATPS condition (ambient temperature and pressure, saturated
with water vapor)
average
boiling point
BTPS conditions (body temperature, barometric pressure,
and saturated with water vapor)
benzene
carbon
degrees Celsius
chromotropic acid
Continuous Air Monitoring Program
California Air Resources Board
cubic centimeter
closing capacity
dynamic lung compliance
continuous exercise
gas phase chemiluminescence
methane
Community Health Environmental Surveillance System
lung compliance
static  lung compliance
centimeter
019DH/G
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                                                6/30/84

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                       LIST OF ABBREVIATIONS (continued)
CNS
CO
co2
COHb
COLD
concn
COPD
CV
DBH
DL
DLCO
DNPH
DOT
E
ECD
ECG, EKG
EEC
EKMA
E0
EPA
ERV
FEF
   max
FEF
FEF
   200-1200
FEF
   25-75%
FEF
   75%
central nervous system
carbon monoxide
carbon dioxide
carboxyhemogl obi n
chronic obstructive lung disease
concentration
chronic obstructive pulmonary disease
closing volume
tree diameter at breast height
diffusing capacity of the lungs
carbon monoxide diffusion capacity of the lungs
2,4-di nitrophenylhydrazi ne
Department of Transportation
elastance
electron-capture detector
electrocardi ogram
electroencephalogram
Empirical Kinetic Modeling Approach
normal electrode potential
U.S. Environmental Protection Agency
expiratory reserve volume
maximal forced expiratory flow achieved
during an FVC
forced expiratory flow
mean forced expiratory flow between 200 ml and 1200 ml of
the FVC [formerly called the maximum expiratory flow rate
(MEFR)]
mean forced expiratory flow during the middle half of the
FVC [formerly called the maximum mid-expiratory flow rate
(MMFR)]
instantaneous forced expiratory flow after 75% of the FVC
has been exhaled
019DH/G
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                                                 6/30/84

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                       LIST OF ABBREVIATIONS (continued)
FEV
FEV1
FEVt/FVC
FID
FIVC
fR
FRC
FRM
ft
FTIR
FVC
G
g
G-6-PD
Gaw
GC
g/mi
GPT
GS-CHEM
GSH
Hb
HC
HCN
HCOOH
Hct
HFET
Hg
HO-
H02
MONO
HONO,,
forced expiratory volume
forced expiratory volume in 1 sec
a ratio of timed forced expiratory volume (FEV.) to
forced vital capacity (FVC)
flame ionization detector
forced inspiratory vital capacity
respiratory frequency
functional residual capacity
Federal Reference Method
foot
Fourier-transform infrared
forced vital capacity
conductance
grams(s)
glucose-6-phosphate dehydrogenase
airway conductance
gas chromatography
grams per mile
gas-phase titration
gas-solid chemiluminescence
glutathione
hemoglobin
hydrocarbons
hydrogen cyanide
formic acid
hematocrit
Highway Fuel Economy Driving Schedule
mercury
hydroxy radical
hydroperoxy
nitrous acid
nitric acid
019DH/G
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                       LIST OF ABBREVIATIONS (continued)
HPLC
HPPA
hr
hr/day
HRP
H2°2
hv
1C
IE
in
IR
IRV
IVC
k
kg
kgm/min
KI
km
LDH
LD50
LM
L/min
In
L/s
1ST
M
m
MAST
    •
max Vp
max V0«
high-pressure liquid chromatograpy; also,
3-(p_-hydroxyphenyl)propionic acid
hour(s)
hours per day
Horseradish peroxidase
water
hydrogen peroxide
sulfuric acid
photon
inspiratory capacity
intermittent exercise
inch(es)
i nfrared
inspiratory reserve volume
inspiratory vital capacity
constant
kilogram
ki1ogram-meter/mi n
potassium iodide
kilometer
lactate deyhydrogenase
lethal dose (50 percent)
light microscopy
liters/min
natural logarithm (base e)
liters/sec
local standard time
molar
meter(s)
Kl-coulometric (Mast meter)
maximum ventilation
maximal aerobic capacity
019DH/G
                                      xvm
                                                 6/30/84

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                       LIST OF ABBREVIATIONS (continued)
mb
MBC
MBTH
MEFR
MEFV
MetHb
mg
mg/m
MGE
min
ml
mm
mM
MMAD
MMC
MMFR or MMEF
m.p.
mph
MS
MSL
MT
MTBE
MVV
NA
NAAQS
NADB
NAMS
NAPBN
NAS
NBS
NBKI
NECRMP
millibar(s)
maximum breathing capacity
3-methyl-2-benzothiazolinone hydrazone
maximum expiratory flow rate
maximum expiratory flow-volume curve
methemoglobin
mil 1igram(s)
milligrams per cubic meter
modified graphite electrode
minute(s)
mil 1iliter(s)
mil 1imeter(s)
mi 11imolar
mass median aerodynamic diameter
mean meridional circulation
maximum mid-expiratory flow rate
melting point
miles per hour
mass spectrometry
mean sea level
metric tons
methyl tertiary butyl ether
maximum voluntary ventilation
not available
National Ambient Air Quality Standard
National Aerometric Data Bank
National Aerometric Monitoring Stations
National Air Pollution Background Network
National Academy of Sciences
National Bureau of Standards
neutral buffered potassium iodide
Northeast Corridor Regional Modeling Project
019DH/G
                                      xix
                                                6/30/84

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                       LIST OF ABBREVIATIONS (continued)
NEDS
NEROS
NH
NF
nm
NMHC
NMOC
NO
N02
N03
N0x
AN2, dN
NR
NYCC
°2
V
°3
P(A-a)0
PABA
PAco2
PaCO£
PAN
PA°2
Pa02
PBZN
PEF
PEFV
PG
PH
National Emissions Data System
Northeast Regional Oxidant Study
ammonia
ammonium sulfate
ammonium nitrate
National Forest
nanometer
nonmethane hydrocarbons
nonmethane organic compounds
nitric oxide
nitrogen dioxide
nitrogen trioxide
nitrogen oxides
nitrogen washout
natural rubber
New York City Driving Schedule
oxygen
oxygen radical
ozone
alveolar-arterial oxygen pressure difference
para-aminobenzoic acid
alveolar partial pressure of carbon dioxide
arterial partial pressure of carbon dioxide
peroxyacetyl  nitrate
alveolar partial pressure of oxygen
arterial partial pressure of oxygen
peroxybenzoyl nitrate
peak expiratory  flow
partial expiratory  flow-volume  curve
prostaglandin
reciprocal  of H  ion concentration
arterial pH
 019DH/G
                                       xx
                                                 6/30/84

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                       LIST OF ABBREVIATIONS (continued)
 L
PMN
PNA
PPN
ppb
ppm
PPt
PSD
psig
Pst
PST
PUFA
R
RAPS
Raw
RBC
Rcoll
rh
RL
RQ, R
Rt
Rti
RTI
RV
S.D.
SAROAD
SBNT
SBR
SCAB
SCE
Se
transputmonary pressure
polymorphonuclear leukocyte
peroxynitric acid
peroxypropionyl nitrate
parts per billion
parts per million
parts per trillion
prevention of Significant Deterioration
pounds per square inch gauge
static transputmonary pressure
Pacific Standard Time
polyunsaturated fatty acid
resistance to flow
Regional Air Pollution Study
airway resistance
red blood cell
collateral resistance
relative humidity
total pulmonary resistance
respiratory quotient
total respiratory resistance
tissue resistance
Research Triangle Institute
residual volume
standard deviation
arterial oxygen saturation
Storage and Retrieval of Aerometric Data
single-breath nitrogen test
styrene-butadiene rubber
South Coast Air Basin
sister chromatid exchange
selenium
019DH/G
                                     xxi
                                                6/30/84

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                       LIST OF ABBREVIATIONS (continued)
sec
SEM
SGaw
SH
SLAMS
SMSA
SOD
so2
so4
SPF
SRaw
SRM
SSET
STA
STP
STPD

SURE
TEL
TEM
Tenax GC
TF
tg/yr
TGV
THC
TLC
TML
TNMHC
TV
TWC
UV
second(s)
scanning electron microscopy
specific airway conductance
sulfhydryls
State and Local Air Monitoring Stations
Standard Metropolitan Statistical Area
superoxide dismutase
sulfur dioxide
sulfate
specific pathogen-free
specific airway resistance
standard Reference Material
small-scale eddy transport
seasonal tropopause adjustment
standard temperature and pressure
STPD conditions (standard temperature and
pressure, dry)
Sulfate Regional Experiment Sites
tetraethyl lead
transmission electron microscopy
adsorbent used in NMOC analysis
tropopause-folding events
teragrams per year
thoracic gas volume
total hydrocarbons
total lung capacity
tetramethyl lead
total nonmethane hydrocarbons
tidal volume
three-way catalyst
ultraviolet photometry
microgram per  cubic meter
019DH/G
                                     xxn
                                                 6/30/84

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                       LIST OF  ABBREVIATIONS  (continued)
MM
U
UHAC
U.S.
UV
V
YQ
vc
vco
v
V
 D
>D
 D  anat
 max
vo
    , Q0
v/v
VHAC
VOC
vol %
w/w
WCOT
XAD-2
XO
micromolar
uranium
uranium hydroxamic acid chelates
United States
ultraviolet
vanadium
alveolar ventilation
ventilation/perfusion ratio
vital capacity
carbon dioxide production
physiological dead space
dead-space ventilation
anatomical dead space
minute ventilation; expired volume per minute
inspired volume per minute
lung volume
maximum expiratory flow
oxygen uptake
oxygen consumption
volume - volume
vanadium hydroxamic acid chelates
volatile organic  compounds
volume percent
weight - weight
wall-coated  open  tubular (column)
absorbent  used in NMOC analysis
xylenol orange
year(s)
wavelength
 019DH/G
                                      xxm
                                                 6/30/84

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                          1.   SUMMARY AND CONCLUSIONS

1.1  INTRODUCTION
     This document consolidates and  assesses  knowledge regarding the origin
and distribution of ozone and other photochemical oxidants and the effects of
these pollutants on humans,  experimental  animals, vegetation, terrestrial  eco-
systems, and nonbiological materials.  Because  the indirect contributions of
the photochemical oxidants to  visibility degradation, climatic changes, and
acidic deposition can not at present be  quantified, these atmospheric effects
and phenomena are  not  addressed in this document.  They have been fully ad-
dressed, however, in other, recent air quality criteria documents (U.S. Envi-
ronmental Protection Agency,  1982a,b).
     While a number of photochemical oxidants have been observed in or postu-
lated to occur  in  ambient air, only data on ozone, peroxyacyl nitrates, and
hydrogen peroxide are examined in this document.   Coverage has been limited to
these three  oxidants  on  the basis of available  information on effects and
ambient air  concentrations.  Of these oxidants,  only  ozone  and peroxyacetyl
nitrate have been studied at concentrations having relevance for potential ex-
posures of human populations  or of vegetation,  ecosystems,  or nonbiological
materials.   Although by  definition  a photochemical oxidant, nitrogen dioxide
is not  included  among  the oxidants discussed in this document.   A separate
criteria document is issued for oxides of nitrogen, as specified by the Clean
Air Act.   The  second criteria  document  prepared by the U.S. Environmental
Protection Agency (EPA)  on the  oxides of nitrogen was  published in 1982 (U.S.
Environmental Protection Agency, 1982a).
     This document presents a  review and evaluation  of literature published
through 1983, and  in  some cases, through early  1984.   The document is not
intended as a complete literature review, however; but is intended, rather, to
present current  data  of  probable consequence for  the derivation of national
ambient air quality standards  for protecting public health and welfare.
     In the  early  chapters  of this document, an overview is presented of the
nature, origins, and distribution in ambient air of those organic and inorganic
compounds that  serve as  precursors to ozone and  other photochemical oxidants.
The currently available measurement techniques for these precursors are briefly
evaluated, inasmuch  as the assessment of  the  occurrence of the precursors
depends upon their accurate measurement.  Similarly,  an overview is presented

019GC1/A                            1-1                           6/29/84

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of the chemical and  physical  processes  in the atmosphere by which precursors
give rise to  the  production  of ozone and other photochemical  oxidants.   In
subsequent chapters, the properties and generic reactions responsible for the
effects ascribed to  ozone  and other photochemical oxidants are presented as
background for understanding  the detailed information presented in the chapters
on health and welfare effects.  Likewise,  techniques  for the measurement of ozone,
total oxidants, and individual oxidant species other  than ozone are evaluated,
since the significance of aerometric and exposure data on these pollutants  is
dependent upon the accuracy and specificity of the analytical techniques used.
Typical concentrations of the respective oxidants  are presented to permit assess-
ment of potential  exposures of human populations and  other receptors.
     Remaining chapters of the document contain the actual air quality criteria;
that is, quantitative and qualitative information  that describes the nature of
the  health and  welfare  effects attributable to ozone and other photochemical
oxidants  and  the  concentrations  at which these pollutants  are thought to
produce the observed effects.
     The  legislative basis for the development and  issuance  of air quality
criteria and related information is found in Sections 108 and 109 of the Clean
Air Act as amended in 1977 (U.S. Congress, 1977).
1.2  PRECURSORS TO OZONE AND OTHER PHOTOCHEMICAL OXIDANTS
1.2.1  Nature of Precursors
     Photochemical oxidants  are  products  of atmospheric reactions  involving
volatile organic compounds (VOC), oxides of nitrogen (NO ), hydroxyl radicals,
                                                        P\
oxygen,  and sunlight.   They  are almost  exclusively  secondary pollutants,
formed in the atmosphere from their precursors by processes that are a complex
function of precursor emissions and meteorological factors.
     Although vapor-phase hydrocarbons (compounds of carbon and hydrogen only)
are the predominant organic compounds in the ambient air that serve as precur-
sors  to  photochemical   oxidants,  other  volatile organic compounds  are  also
photochemically  reactive  in  those atmospheric  processes that  give rise  to  the
oxidants.   In particular, halogenated organics (e.g., haloalkenes)  that parti-
cipate in photochemical reactions are present  in ambient air, although at  lower
concentrations than the hydrocarbons.  They are apparently oxidized through the
same  initial step  involved in the oxidation of the hydrocarbons;  that is,  attack


019GC1/A                            1-2                            6/29/84

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by hydroxyl  radicals  (HO-)-   Alkenes, haloalkenes, and  aliphatic aldehydes
are,  as classes, among  the most reactive organic compounds found in ambient
air.   Alkenic hydrocarbons and halocarbons are unique  among VOC in ambient air
in that they  are  susceptible both to attack by HO-  and to ozonolysis (oxida-
tion by  ozone)  (Niki et  al., 1983).   Methane,  halomethanes, and certain
haloethenes are of negligible reactivity  in ambient air and have  been classed
as unreactive by the U.S.  Environmental  Protection Agency (1980).
     The oxides of  nitrogen  that are important  as  precursors to ozone and
other photochemical  oxidants are nitrogen dioxide (N0?) and nitric oxide (NO).
Nitrogen dioxide is  itself an oxidant that produces  deleterious effects, which
are the subject of a separate criteria document (U.S.  Environmental  Protection
Agency, 1982a).   Nitrogen dioxide is an important precursor to ozone and other
photochemical oxidants  (1) because  its photolysis in ambient  air  leads  to the
formation of  oxygen atoms that  combine with molecular oxygen  to  form ozone;
and  (2) because  it  reacts with  acetylperoxy  radicals  to form peroxyacetyl
nitrate (PAN), a relatively potent phytotoxicant (Taylor, 1969; Qshima et al.,
1974) and lachrymator (Heuss and Glasson, 1968).   Although ubiquitous, nitrous
oxide (NpO) is unimportant in the production of oxidants in ambient air because
it is  virtually inert  in the troposphere.  (In  the stratosphere, where the
wavelength distribution is different, N^O is photolyzed.)
     Since methane is considered only negligibly  reactive  in  ambient air, the
volatile organic compounds of importance as oxidant precursors  are usually
referred to as nonmethane hydrocarbons (NMHC) or, more properly,  as nonmethane
organic compounds  (NMOC).

1.2.2  Measurement of Precursors
     Numerous analytical  methods  have  been employed to  determine nonmethane
organic compounds (NMOC)  in  ambient air.  To present  an overview of the most
pertinent  information,  measurement methods for  the organic species may be
arranged in  three major classifications:   nonmethane hydrocarbons,  aldehydes,
and other oxygenated compounds.
     Nonmethane hydrocarbons  have  been  determined primarily  by methods that
employ a flame ionization detector (FID) as the sensing element.   Early methods
for  the  measurement of  total  nonmethane hydrocarbons did  not provide for
speciation of the complex mixture  of organics  in  ambient  air.  These methods,
still in use for analysis of total nonmethane organic  compounds,  are essentially
organic carbon analyzers, since the response of the FID detector  is essentially
019GC1/A                            1-3                           6/29/84

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proportional to the  number  of  carbon atoms present in  the  organic molecule
(Sevcik, 1975).   Carbon atoms bound,  however,  to oxygen, nitrogen,  or halogens
give reduced relative responses (Dietz,  1967).   This detector has been utilized
both as a  stand-alone  continuous  detection system (non-speciation) and also
with gas chromatographic  techniques  that provide for speciation of the many
organics present in ambient air.   A number of studies  of non-speciation analy-
zers have  indicated  an overall poor performance of the  commercial  instruments
when calibration or  ambient  mixtures containing NMOC concentrations less than
1 ppm C were analyzed (e.g., Reckner, 1974; McElroy and Thompson, 1975; Sexton
et al. , 1981).  The major problems associated with the non-speciation analyzers
have been  summarized in  a recent technical assistance  document  published  by
the  U.S. Environmental  Protection Agency (1981).   The document also presents
ways to reduce some of the existing problems.
     Because of the above deficiencies,  other approaches to the measurement of
nonmethane  hydrocarbons  are currently  under  development.    The  use of gas
chromatography  coupled  to an  FID system circumvents many  of the problems
associated  with continuous  non-speciation analyzers.   This  method,  however,
requires sample preconcentration because the organic components are present at
part-per-billion (ppb) levels or lower in ambient air.  The two main preconcen-
tration  techniques in present use are  cryogenic  collection and the  use of
solid adsorbents  (McBride and McClenny, 1980; Jayanty  et al., 1982; Westberg
et  al.,  1980;  Ogle et al. ,  1982).  The preferred preconcentration method  for
obtaining  speciated  data is  cryogenic collection.   Speciation methods involv-
ing  cryogenic  preconcentration have  also been  compared with continuous  non-
speciation  analyzers (e.g.,  Richter, 1983).  Results indicate poor correlation
between methods at ambient concentrations below 1 part-per-million carbon  (ppm
C).
     Aldehydes, which are both primary  and  secondary pollutants in  ambient
air, are  detected by total  NMOC  and  NMHC speciation methods but  can  not  be
quantitatively  determined by those methods.  Primary measurement  techniques
for  aldehydes  include  the  chromotropic  acid  (CA) method  for formaldehyde
(Altshuller and McPherson,  1963; Johnson  et al.,  1981), the 3-methyl-2-benz-
othiazolone (MBTH) technique for  total  aldehydes  (e.g., Sawicki  et al.,  1961),
Fourier-transform  infrared  (FTIR) spectroscopy (e.g.,  Hanst  et al. , 1982;
Tuazon  et  al., 1978, 1980,  1981b), and  high-performance liquid chromatography
employing  2,4-dinitrophenyl-hydrazine derivatization (HPLC-DNPH) for aldehyde

019GC1/A                            1-4                           6/29/84

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that release light energy  that  is proportional  to the NO concentration.   Al-
though the NO chemiluminescence  is interference-free,  other nitrogen compounds
do interfere when directed through the N0? converter.   The magnitude of these
interferences is dependent  upon the  type of converter  used  (Winer et al. ,
1974; Joshi and Bufalini, 1976).  Other NO and NO- measuring methods have also
been summarized in Chapter 3.   None of the other techniques is widely used to
monitor air quality.

1.2.3  Sources and Emissions of Precursors
     The photochemical production of  ozone, the principal component of "smog,"
depends both on the presence of precursors, volatile  organic compounds (VOCs)
and nitrogen oxides (NO ), that are emitted by manmade and by natural sources,
                       J\
and on  suitable conditions of sunlight,  temperature,  and other meteorological
factors.  Because of the intervening  requirement for meteorological conditions
conducive  to the  photochemical  generation of ozone, emission inventories are
not as  direct  predictors of ambient  concentrations in  the case  of secondary
pollutants such as ozone and other oxidants as they are  for primary pollutants.
     Emissions of manmade  VOCs  (excluding several relatively unreactive com-
pounds such as methane)  in the  United States have been estimated at 18.2 tg/yr
for  1982.   Trends  in  manmade VOC  emissions  for  1970 through 1982 are shown in
Figure  1-1 (U.S.  Environmental  Protection Agency,  1983).   The annual  emission
rate  for  manmade  VOCs has decreased some 28 percent  during this period.  The
main sources nationwide  are industrial processes, which  emit a wide variety  of
VOCs such  as chemical  solvents; and transportation, which includes  the emission
of VOCs in  gasoline vapor as well as in  gasoline combustion products.  Estimates
of  biogenic emissions of organic compounds  in  the United States  are highly
inferential  but  data suggest that the  yearly rate is  the same  order of  magni-
tude  as manmade  emissions.  Biogenic  emissions are temperature-dependent and
those  of  isoprene are  light-dependent, as well.   In addition, isoprene emissions
are  produced mainly by deciduous  trees and  therefore  should be lower in winter
than when  the  trees have leaves.  These  factors result  in diurnal  and seasonal
variations in  emission rates.
      Emissions of manmade  NO   in  the United States  were estimated at 20.2 tg/yr
                             /\
for  1982.   Annual emissions  of  manmade NO  were some  12 percent  higher  in 1982
                                          /\
than in 1970,  but the rate leveled off in the  late 1970s and exhibited  a small
decline from  about  1980 through 1982.   The increase over the  period  1970

 019GC1/A                            1-6                            6/29/84

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   30
   20
(/)
z
o
o
o
   10
                                                   i—r
          TRANSPORTATION
IND. PROC., STAT. SOURCE
        SOUD WASTE


        NON-IND~SOLVENTS~
                  MISC.

                 I	I
                                       i—r
    1970  1971  1972   1973  1974  1975  1976  1977   1978   1979   1980   1981


                                    YEAR



     Figure 1-1. National trend in estimated emissions of volatile organic com-

     pounds, 1970 through 1982.



     Source:  U.S. Environmental Protection Agency (1983).
                                  1-7

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through 1982 had two main causes:   (1)  increased fuel  combustion in stationary
sources such as  power  plants;  and (2)  increased fuel  combustion  in highway
motor vehicles,  as the result of the increase in vehicle miles driven.  Total
vehicle miles driven increased  by 42 percent over the 13 years in question.
Trends in manmade NO  emissions over 1970 through 1982 are shown in Figure 1-2
(U.S. Environmental  Protection Agency,  1983).   Estimated biogenic NO  emissions
are based on uncertain  extrapolations from very limited studies, but appear to
be about an order of magnitude less than manmade emissions.

1.2.4  Ambient Air Concentrations of Precursors
1.2.4.1  Hydrocarbons in Urban Areas.  Most of the available ambient  air  data
on the  concentrations  of nonmethane hydrocarbons (NMHC)  in urban  areas have
been obtained during the 6:00 to 9:00 a.m. period.   Since hydrocarbon emissions
are at their peak during that period of the day, and since atmospheric disper-
sion  is  limited  that early in the morning, NMHC concentrations measured then
generally reflect maximum diurnal levels.  Representative data for urban areas
show mean NMHC concentrations between 0.4 and 0.9 ppm.
     The hydrocarbon composition  of  urban atmospheres  is  dominated by species
in the C? to CIQ molecular-weight range.  The paraffinic hydrocarbons (alkanes)
are  most prominent,  followed by aromatics and  alkenes.   Based  on  speciation
data  obtained  in a  number of urban areas, alkanes generally constitute 50 to
60 percent of the hydrocarbon burden in ambient air, aromatics 20  to  30 percent,
with alkenes and acetylene making up the  remaining 5 to 15 percent  (Sexton and
Westberg, 1984).
     Table  1-1 shows  a  typical example  of  the hydrocarbon composition  in
ambient air  in urban areas (Westberg and  Lamb, 1982).
1.2.4.2  Hydrocarbons  in Rural Areas.  Rural nonmethane hydrocarbon concentra-
tions  are  usually one  to two orders of magnitude lower than those  measured in
urban  areas  (Ferman, 1981; Sexton and  Westberg, 1984).   In samples from sites
carefully  selected  to  guarantee their  rural character, total NMHC concentra-
tions  ranged from 0.006  to 0.150  ppm C  (e.g., Cronn,  1982;  Seila,  1981; Holdren
et al.,  1979).   Concentrations  of  individual species  seldom exceeded  0.010  ppm
C.   The bulk of species present  in  rural  areas  are alkanes; ethane,  propane,
n-butane,  ijo-pentane,  and n-pentane are most abundant.   Ethylene and propene
are  sometimes present  at <0.001 ppm C,  and  toluene  is usually present  at
~0.001 ppm  C.   Monoterpene  concentrations are usually about <0.020  ppm C.

019GC1/A                            1-8                           6/29/84

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   20
05  1C
«••  15
Z

g

w
CO
UJ


 X
    10
          TRANSPORTATION
         FUEL COMBUSTION
        IND. PROC., SOLID WASTE, MISC.  V
       	I	j	I	I	I
    1970  1971   1972   1973   1974   1975    1976   1977   1978   1979   1980   1981



                                     YEAR




     Figure  1-2. National trend in estimated emissions of nitrogen oxides, 1970

     through 1982.



     Source:  U.S. Environmental Protection Agency (1983).
                                   1-9

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    TABLE 1-1.   HYDROCARBON (HC) COMPOSITION TYPICALLY MEASURED IN URBAN AREAS
                    (FROM SAMPLE COLLECTED IN MILWAUKEE, 1981)
HC concn. ,
  ppb C
                  Hydrocarbon
                         HC concn.,
                          ppb C
      Hydrocarbon
     ,5
      5
14.0
25.5
16.0
18.5
 9.
28.
65.0
 2.0
 3.5
 3.5

49.0
24.0
 2.0

 0.5

 2.0
 4.5
13.0

10.0

11.0
    6.5
    4.5
    9.5
    2.0
Ethane                      4.5
Ethylene                    5.5
Acetylene                   8.0
Propane                     5.0
Propene                     8.0
j/-Butane                    3.0
n-Butane                    1.5
1-butene                    1.5
i^-Butene                   33.5
t-2-Butene
c-2-Butene                  2.5
^-Pentane                   2.5
ri-Pentane                   2.5
1-Pentene
t-2-Pentene                 6.5
c-2-Pentene                18.5
Cyclopentene
Cyclopentane                6.5
2,3-Dimethylbutane          4.0
2-Methylpentane
c-4-Methyl-2-pentene        3.0
3-Methylpentane             5.0
1-Hexene                    3.0
n-Hexane                   22.0
t-2-Hexene                  3.0
c-2-Hexene                 17.0
Methylcyclopentane          7.0
2,4-Dimethylpentane
Benzene
Cyclohexane
2-Methylhexane
2,3-Di methylpentane
3-Methylhexane
2,2,3-Tri methylpentane
ri-Heptane
Methyl eyelohexane
2,4-Dimethylhexane
2,3,4-Trimethylpentane
Toluene
2,3-Dimethylhexane
2-Methylheptane
3-Ethylhexane
n-Octane
Ethylcyclohexane
Ethyl benzene
g, m-Xylene
Styrene
o-Xylene
n-Nonane
v-Propylbenzene
rt-Propyl benzene
p_-Ethyl toluene
m-Ethyltoluene
o-Ethyl toluene
1,3,5-Tri methyl benzene
1,2,4-Trimethyl benzene
1,2,3-Trimethyl benzene
Methylstyrene
1,3-Di ethyl benzene
1,4-Di ethyl benzene
Total identified
  hydrocarbons

I Olefin
                  HC concn.,
                    PPb c

                     46
                            Total unidentified
                              hydrocarbons
                                                   HC  concn.,
                                                     ppb  C
                                                                      87
Z Aromatic

2 Paraffin
Acetylene

134

301
16
497
27

60
3

Total NMHC
summing i
species


by
ndividual





584


Source:  Westberg, H.; Lamb, B. (1982)
019GC1/A
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During the summer months, isoprene concentrations as high as 0.150 ppm C  have
been measured (Ferman, 1981).  The maximum concentrations of isoprene usually
encountered,  however, are in the range of 0.030 to 0.040 ppm C.
1.2.4.3  Aldehydes  in Urban Areas.   Aldehydes  observed in urban  atmospheres
include formaldehydes, acetaldehyde,  chloral,  propanal,  n-butanal, and benz-
aldehyde.   Formaldehyde  concentrations are the best characterized of these
aldehydes because  the chromotropic  acid methodology  for  formaldehyde  was
established in the  early 1960s.   With the exception of  early  data from Los
Angeles (1961),  reported concentrations of formaldehyde in urban areas fall in
the 0.01 to  0.03  ppm range, with maximum  concentrations  ranging up to 0.09
ppm.
     Comparing these  concentrations  with  concentrations  of NMHC  in urban
areas,  it  is apparent  that formaldehyde probably constitutes less  than 3
percent of the total  NMOC in most urban areas.  Acetaldehyde  concentrations
are generally lower than formaldehyde in a given urban area.   Concentrations
of  total aldehydes  in urban atmospheres can vary from a few ppb  up  to about
0.2 ppm  (200 ppb).   In polluted  atmospheres, acrolein, propanal,  butanal,  and
benzaldehyde have each been measured at concentrations <0.015 ppm.
1.2.4.4  Aldehydes  jn Rural Areas.   Very few total aldehyde measurements  have
been made  in  rural  areas.  Breeding et  al. (1973) reported values for total
aldehydes of 0.001  to 0.002 ppm  in rural Illinois and  Missouri.   Formaldehyde
levels  in  remote  atmospheres apparently  range  from 0.1 to 10 ppb,  with global
background formaldehyde  concentrations varying from 0.3 to 0.5  ppb  (Duce et
al., 1983).
1.2.4.5  Nitrogen Oxides  in Urban Areas.   Concentrations of NO , like hydrocar-
         ~~~                                                    J\
bon concentrations, tend  to peak in urban areas during the early morning, when
atmospheric dispersion  is limited and automobile traffic is dense.  Most NO
is  emitted as  nitric oxide (NO), but  the  NO  is rapidly converted to N0? by
ozone  and  peroxy radicals produced  in atmospheric  photochemical reactions.
The relative concentrations  of  NO versus NO- fluctuate day-to-day, depending
on  diurnal  and day-to-day  fluctuations  in ozone  levels  and photochemical
activity.
     Urban NO  concentrations during the 6:00 to 9:00 a.m.  period in 10 cities
             J\
ranged  from  0.05  to 0.15 ppm in studies done in the last 5 to 7 years (e.g.,
Westberg and  Lamb,  1983;  Richter, 1983;  Eaton  et al. ,  1979).   Concurrent NMHC
measurements for  these  10 cities showed  that NMHC/NO   ratios ranged  from 5 to
16.
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1.2.4.6   Nitrogen Oxides  in  Rural Areas.   Concentrations  of NO   in  clean
remote environments  are usually <0.5 ppb  (Logan,  1983).   In exceptionally
clean air, NO  concentrations as low as  0.015 ppb have been recorded (Bellinger
             X
et al., 1982).   Concentrations  of  NO  at nonurban sites in the north-central
                                     f\
northeastern United  States appear to be higher than NO  concentrations  in  the
                                                      xv
west by a factor of 10 (Mueller and Hidy, 1983). From the limited amount  of
data available,  NO   concentrations in unpopulated  rural  areas  in the  west
                  s\
average £  1  ppb; but in nonurban northeastern areas average  NO  can exceed 10
ppb.
1.3  CHEMICAL AND PHYSICAL PROCESSES IN THE FORMATION AND OCCURRENCE OF OZONE
     AND OTHER PHOTOCHEMICAL OXIDANTS
     The photochemistry of the polluted atmosphere is exceedingly complex, but
an understanding of  the  basic phenomena is not difficult to acquire.  Three
processes occur:  the  emission  into the atmosphere  of  precursors  to ozone,
from predominantly manmade  sources;  photochemical  reactions that  take place
during  the  dispersion and transport of these  precursors;  and chemical and
physical scavenging  that  reduces  the concentrations of ozone  (03)  and other
oxidants, and their  precursors,  along  the trajectory.   Because transport and
dispersion  of  the  precursors together determine  the ambient concentrations
ozone may finally reach, an understanding of certain meteorological phenomena,
in addition to photochemical reactions, is also necessary.

1.3.1   Chemical Processes
     In the troposphere, 0_ is formed indirectly through the action of sunlight
on nitrogen  dioxide  (N0?).   In the absence of competing reactions, a steady-
state or equilibrium concentration of 0_ is soon established between the 0_,
NO,,, and NO (nitric  oxide).   The  injection of organic  compounds  (primarily
hydrocarbons) into the atmosphere  upsets  the equilibrium and allows the ozone
to accumulate at much  higher than  steady-state concentrations.  Recent work on
the  photochemistry  of smog  has demonstrated  fairly conclusively that the
hydroxyl radical, HO-, is the key  species in causing organic compounds to play
a major role in smog reactions.
     The length  of  the induction  period before the  accumulation of 03 begins
depends heavily on the initial concentration of HO radicals.  There  is evidence
that nitrous acid (HONO), which is a good source of  HO  radicals, occurs in the
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atmosphere,  but at very low concentrations.   The most important source of HO*,
appears, rather, to be aldehydes, which are constituents of automobile exhaust,
as well as decomposition products of most atmospheric photochemical  reactions
involving hydrocarbons.
     The occurrence of  organic  compounds and sunlight does not mean that the
photochemical  reactions  will  continue  indefinitely.   Terminating reactions
gradually remove  N0?  from  the reaction mixtures, such that the photochemical
cycles would slowly come  to an end unless  fresh NO and N0?  emissions were
injected into  the atmosphere.   Besides  ozone,  other oxidants that  contain
nitrogen, such  as  peroxyacetyl  nitrate  (PAN), nitric acid  (HNO,), and peroxy-
nitric acid  (HNO.), as well as organic  nitrates  and inorganic nitrates,  are
some of the terminating compounds.
     The maximum  concentration that 0~ can  reach  in  polluted atmospheres
appears to depend on  the hydrocarbon-nitrogen oxides ratio.  At  a  low ratio
(1:1 to  2:1),  insufficient HO-  radicals are  available  from the  hydrocarbon
species to effect the conversion of NO  to  N0?,  a necessary first step.   At
high ratios (greater than 12:1 to 15:1), conversion of NO to N0? occurs rapidly,
but  the  terminating  reactions  remove  N0? from  the  reaction  cycles and CL
cannot build up to high concentrations.  Only at intermediate ratios (4:1 to
10:1) are conditions  favorable  to the  formation  of  appreciable concentrations
of 03.
     Recent studies on the  fundamental  photochemistry of organic compounds have
been reasonably successful.  The reactions of paraffinic compounds (alkanes) are
fairly well  understood, as  are  those of olefinic compounds  (alkenes).  Photo-
chemical reactions  of the  aromatic  compounds, however,  are  poorly understood.
     Natural hydrocarbons  (i.e.,  those  organic  compounds emitted  from vegeta-
tion), as well   as hydrocarbons from manmade sources, can react photochemically
with  nitrogen  oxides  to yield 0,, although natural hydrocarbons are reported
to be mainly scavengers of  0, rather than producers of 0,.
     Besides direct adverse effects on human health and on vegetation, CL con-
tributes to  visibility degradation and to acidic deposition.  Through  its
photolysis by  sunlight, with  subsequent generation  of HO radicals,  ozone par-
ticipates only  indirectly,  but not insignificantly, in the formation of both
sulfate  and  nitrate aerosols, which cause reduced visibility.  These sulfate
and  nitrate species,  on further reaction, result  in acidic deposition.
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1.3,2  Physical  Processes
     Meteorological  processes are quite important in determining the extent to
which 03 precursors can  accumulate,  and thereby the concentration of 03 that
can result.   Atmospheric mixing depends principally on the amount of turbulent
mixing, wind speed and direction, or all three.   Geography can have a significant
impact, also, particularly at land-sea interfaces.
     The degree of turbulent mixing can be characterized by atmospheric stabi-
lity.  Pollutants do  not spread rapidly in stable  layers,  nor do they mix
upwards rapidly  through  stable layers to higher altitudes.   Rather,  stable
layers are  usually characterized by temperature inversions, in which the tem-
perature increases with increasing altitude.   Since pollutants emitted below or
into an inversion layer  will not readily mix across the inversion  layer, they
may persist for a considerable time and distance until the inversion is broken,
usually by surface heating resulting from sunlight.
     The extent  to which surface heating can cause mixing heights  to increase
(and to cause dilution of 0- and its precursors) is highly dependent on geo-
graphy.  Along both the Pacific Coast and the Northeast Coast, as well  as near
the Great Lakes,  low-level  inversions (i.e., the mixing height is not great)
frequently persist through  the afternoon,  making these areas  prone to  local
and regional air pollution episodes.
     Wind speed  and direction  determine the extent  to which pollutants  can  be
increased by passing   over  successive sources,  or can  be  diluted by being
rapidly removed  from  the source  area.   The plumes of  precursors  and  resulting
0-  from large metropolitan  areas have been  shown to  persist  for hundreds  of
miles.  Three  kinds  of  transport  of ozone and other  pollutants have been
described,  in terms of transport distance.   In  urban-scale  transport,  maximum
concentrations of  0,  are produced about 20  miles  or so (and  about  2  to 3
hours) downwind from  the major pollutant source areas.  In mesoscale transport,
0«  has  been observed  up  to  200 miles  downwind from  the  sources of its  precur-
sors.  Synoptic-scale transport  is associated with  large-scale,  high-pressure
air masses that may extend over and persist for many hundreds of miles.
     The significance  of sunlight in photochemistry is related to  its  intensity
and  its spectral distribution, both of which have direct effects on the speci-
fic  chemical reaction  steps that initiate and sustain oxidant  formation.  Days
on  which  significant  ozone-oxidant  concentrations  occur are usually days with
warm,  above-normal temperatures.  These are also characteristic  of high pressure

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systems with inversions and low winds.   The photolysis of aldehydes is affected
by the spectral distribution of light,  since it is strongly dependent on wave-
length in the near ultraviolet region.
     Ozone formed in the stratosphere can be brought downwards to the earth's
surface by events called  "tropopause  folds."   These events are most commonly
observed in the mid-latitudes during spring and early summer.   Relatively high
concentrations of 0- can  occur for short periods  of  time,  minutes to a few
hours, over local areas.
1.4  PROPERTIES, CHEMISTRY,  AND  MEASUREMENT OF OZONE AND OTHER PHOTOCHEMICAL
     OXIDANTS
1.4.1  Properties
     Ozone, peroxyacetyl nitrate, and hydrogen peroxide, along with other photo-
chemical oxidants occurring  at  very low concentrations  in  ambient air,  are
characterized chiefly by  their  ability to remove electrons from or to share
electrons with other molecules or ions (i.e., oxidation).  The capability of a
chemical species for  oxidizing  or reducing other chemical  species is termed
"redox potential" (positive or negative standard potential) and is  expressed in
volts.   Ozone has a standard potential of +2.07 volts  in aqueous systems (for
the redox pair,  0-/H?0).  Hydrogen peroxide has a standard potential  of +1.776
in the redox pair,  H^Op/H^O.   No standard potential  for peroxyacetyl  nitrate in
neutral or buffered aqueous systems, such as those that occur in biological sys-
tems, appears in the literature.   In acidic solution (pH 5 to 6), PAN hydrolyzes
fairly rapidly;  in alkaline solution it decomposes with the production of nitrite
ion and molecular oxygen.
     The toxic effects of oxidants are attributable to their oxidizing ability.
Their oxidizing  properties also  form the basis of the measurement techniques
for all three of these pollutants.  The calibration of ozone and PAN measurements,
however, is achieved via their spectra in the ultraviolet and infrared, respec-
tively.  The calibration of measurement methods for H?02 is achieved with iodo-
metric techniques that depend on the oxidizing properties of H^Op-
     An important property of PAN, especially in the laboratory, is its thermal
instability.  Its explosiveness dictates its synthesis for calibration purposes
by experienced personnel only.  All three pollutants must be generated ijn situ
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for the calibration of measurement techniques.   For ozone and H?0?,  generation
of calibration gases is reasonably straightforward.

1.4.2  Reactions of Ozone and Other Oxidants in Ambient Air
     The atmospheric reactions of ozone and of other photochemical  oxidants such
as peroxyacetyl nitrate (PAN) and hydrogen peroxide (H?02) are complex and diverse,
but are becoming increasingly well-characterized.   The reactions of these species
result in products  and processes that may have significant environmental and
health- and welfare-related implications, including effects on biological systems,
nonbiological materials, and such phenomena as visibility degradation and acidi-
fication of cloud and rain water.  Ozone may play a role in the oxidation of SO,,
to H2$04, both indirectly in the gas phase (via formation of OH radicals and
Criegee biradicals) and directly in aqueous droplets.  Evidence is also accumu-
lating that hydrogen peroxide, like ozone, is involved in both gas-phase photo-
chemistry and  aqueous-phase  oxidations.   For example,  studies  of the  rates  of
oxidation of S02 by H202 in solution suggest that this reaction is sufficiently
fast  that  it could be the major aqueous-phase route for the oxidation of S02
under certain  atmospheric conditions.  In addition, the importance of oxidants
such  as  PAN  in various aspects  of  atmospheric  chemistry,  such as  long-range
transport of NO  and multi-day air pollution episodes, is now being recognized.
               /\
     Ozone can react with organic compounds in the troposphere.  It is important
to recognize,  however, that organics undergo competing reactions with OH radicals
in the daytime (Atkinson et al., 1979; Atkinson and  Lloyd, 1984) and, in certain
cases, with  NO- radicals during  the night (Japar and Niki, 1975; Carter  et  al.,
1981; Atkinson et al. , 1984a,b,c,d), as well as photolysis.  Only for organics
whose ozone  reaction  rate constants are greater than ~10    cm  molecule    sec
can  consumption by  ozone be considered to be atmospherically important (Atkinson
and  Carter,  1984).
      Ozone reacts  rapidly with the  acyclic mono-, di-, and tri-alkenes and  with
                                                                       _"| Q
cyclic  alkenes.   The rate constants for  these  reactions  range  from ~10     to
~10~14  cm3 molecule"1  sec'1 (Atkinson and Carter,  1984), corresponding to
atmospheric  lifetimes ranging from a few minutes for the more reactive cyclic
alkenes,  such as the monoterpenes, to several  days.   In polluted atmospheres,
a significant portion of the consumption of  the more reactive  alkenes  will
occur via  reaction  with  ozone, rather  than with OH  radicals,  especially  in  the
afternoons during  photochemical  oxidant  episodes.   Reactions  between  ozone  and

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alkenes can result  in  aerosol  formation (National Academy of Sciences, 1977;
Schuetzle and Rasmussen, 1978), with alkenes of higher carbon numbers the chief
contributors.
     Because of their respective rate constants, neither alkanes (Atkinson and
Carter, 1984)  nor alkynes (Atkinson  and Aschmann, 1984) are  expected  to  react
with ozone  in  the atmosphere,  since  competing  reactions with OH  radicals  have
higher rate constants.
     The aromatics  react  with ozone, but quite  slowly  (Pate et al. ,  1976;
Atkinson et al. ,  1982),  such that their reactions with ozone are expected to
be unimportant in the atmosphere.   Cresols are more reactive toward ozone than
the aromatic hydrocarbons (Atkinson et al.,  1982), but their reactions with OH
radicals (Atkinson  et  al.,  1978,  1982) or N03 radicals (Carter et al., 1981;
Atkinson et al., 1984a) predominate.
     For oxygen-containing organic compounds, especially those without carbon-
carbon double  bonds, reactions with  ozone are  slow.   For  carbonyls and ethers
(other than ketene) that contain  unsaturated  carbon-carbon  bonds,  however,
much faster reactions are observed (Atkinson et al.,  1981).
     The kinetics of the  reactions of ozone with a variety  of nitrites,  ni-
triles, nitramines, nitrosamines,  and hydrazines have been  studied (Atkinson
and Carter, 1984), but only for the hydrazines are these reactions sufficiently
rapid  to be of atmospheric  importance.  Chamber  studies  have  shown   that N-
nitrosodimethylamine can  result from the  reaction of  ozone with  simple hydra-
zines  (Tuazon  et  al. ,  1981).   Whether this  product would ever be formed by
reaction with  ozone in the atmosphere obviously depends upon the presence, and
level, of the  precursor hydrazines in ambient air.
     Certain reactions of ozone other than its reactions with organic compounds
are important  in  the  atmosphere.   Ozone reacts  rapidly with NO  to form  N0?,
and subsequently  with  N0? to produce the nitrate (NO.,) radical and an oxygen
molecule.   Photolysis  of  ozone can be a significant pathway  for  the formation
of OH  radicals, particularly in polluted atmospheres when  ozone concentrations
are at their peak.

1.4.3  Reactions of Ozone and  Peroxyacetyl Nitrate in Aqueous (Biological)
       Systems
     Both ozone and PAN can react directly and rapidly with  many organic mole-
cules, including  many  types occurring in biological  systems.  Additionally,
active species such as singlet oxygen, hydroxyl radicals, and superoxide are

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produced either as products of primary reactions or from the decomposition of
ozone or PAN in water; these species also have the potential for causing bio-
logical  damage.
     The reactions of ozone with biologically important functional  groups have
been described in the literature, although such information remains relatively
sparse and is based on j_n vitro work that is not always pertinent to reactions
that occur under  the  conditions of iji vivo  exposure.   Among the functional
groups with which ozone reacts relatively rapidly are the carbon-carbon double
bonds (alkenic group)  found in biologically important compounds such as some
of the essential  fatty acids and polyunsaturated fatty acids (PUFA) of the kind
found in the lipids of cell membranes.   Amines are, in general, close to alkenes
in their reactivity toward  ozone,  although  amino groups existing as  the  amide
or salt are  less  susceptible to  ozone than  unprotected  amino groups.   Sulfur-
containing compounds, such as methionine, can also undergo electrophilic attack
by ozone,  resulting  in the formation of both sulfoxides and sulfones.  Under
some conditions (e.g., pH > 9), ozone is rapidly converted to hydroxyl radicals,
which are  less selective  than  ozone in reactions with organic  molecules.  The
conversion of ozone  to superoxide (O-O and  hydroperoxy  radicals  (HQ^*) has
also been reported.
     Aromatic compounds  are much less reactive  toward ozone  than alkenic com-
pounds  in  aqueous systems.   In compounds  containing  both  aromatic  and alkenic
groups, such as the indole  ring of tryptophan, the initial ozone attack occurs
exclusively  at the alkenic part of the molecule.  Aldehydes react with ozone
with  and without the involvement  of oxygen.  Either way, acyl hydrotrioxides
are formed that subsequently decompose to peroxides and carboxylic acids.  Sim-
ple ketones  react slowly  or not  at all with ozone.
      Reactions between ozone and specific molecules of  importance  in  biological
systems have been described in Chapter 10.
      Knowledge of the  solution chemistry of PAN is limited.  It is known, how-
ever, that PAN  can react with alkenes, with  sulfur-containing compounds, and
with  aldehydes.   The half-life of  PAN in water  (pH 7.2) is only about 4.4 min-
utes.   Thus, some of the  toxicological effects  ascribed to PAN should possibly
be attributed to  its decomposition products  instead.

1.4.4  Sampling  and Measurement  of Ozone  and  Other Photochemical Oxidants
      The  analysis of ozone and  other,  related atmospheric oxidants includes
requirements for representative sampling,  specific  and sensitive  measurement
methodologies, methods for the generation of  standard  samples,  absolute  methods
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for the calibration  of  these standards, and procedures  by  which to provide
quality assurance for the whole measurement process.   In the summary presented
below, recommended procedures are given for all  of these analytical steps.   Sam-
pling and quality assurance are discussed in general  terms for all of the oxidants.
Methods of analysis, sampling, and generation and calibration are discussed speci-
fically for ozone, peroxyacetyl nitrate (PAN) and its homologues, and hydrogen
peroxide.   Because  of the  large  existing data base that  employed  measurements
for  "total  oxidants,"  non-specific iodometric techniques are discussed and
compared to current specific CL measurements.
1.4.4.1   Quality Assurance and Sampling.   A  quality assurance  program is
employed by the U.S. Environmental Protection Agency for assessing the accuracy
and precision of monitoring data and for maintaining and improving the quality
of ambient air  data.  Procedures and operational  details have been prescribed
in each of the following areas: selection of analytical  methods and instrumen-
tation  (i.e.,  reference and equivalent methods);  method specifications for
gaseous standards;  methods  for  primary and secondary (transfer  standards)
calibration; instrumental zero and span check requirements,  including frequency
of cohorts,  multiple-point  calibration procedures,  prevention and remedial
maintenance  requirements;  procedures  for  air pollution  episode monitoring;
methods for  recording  and  validating  data;  and  information  on  documentary
quality control (U.S. Environmental Protection Agency, 1977a).
     A  crucial  link in  the measurement  cycle involves sampling strategies  and
techniques.  Sampling strategies,  which involve  the  design  and operation of a
sampling network, must be consistent with the specific purpose of the measure-
ments.  Ambient  air monitoring data are collected for a variety of purposes,
each  of which  may have  different requirements that affect sampling strategy.
For  example,  a  sampling  strategy for health effects research studies may
require a  number of monitoring stations carefully situated to assess human
exposure for a  given urban population over a finite  period  of time.   In addi-
tion,  since  ozone,  PAN,  and HLCL  are all secondary pollutants formed  after an
initial induction period,  stations for monitoring peak concentrations should
be located downwind of the  urban center of precursor emissions.
     The  reactivity and instability of CL  and other photochemical oxidants
dictate special  sampling  techniques.   Samples of air containing 0, cannot be
collected and  stored and  must  be  analyzed  dynamically.   Analysis  for  PAN must
likewise be performed as soon as possible after collection.    Hydrogen peroxide

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collected in aqueous media is fairly stable,  but samples are subject to inter-
fering reactions from ozone  trapped in solution.   Sampling probes should be
constructed of Teflon or  some similarly inert material, and inlet residence
times should be as short as possible.   Other design criteria for 03 monitoring
stations have been  given  (Standing Air Monitoring Work Group,  1977; National
Academy of  Sciences,  1977).   The most important of these are that inlets of
the sampling probe  should be positioned 3 to 15 m (10 to 49 ft) above ground
and at  least 4 m  (13  ft)  from large trees and 120 m (349 ft) from heavy auto-
mobile traffic.
1.4.4.2  Measurement Methods for Total Oxidants and Ozone.   Techniques for the
continuous  monitoring of  total  oxidants and 0- in ambient air are summarized
in Table 5-13.   The earliest methods used for routinely monitoring oxidants in
the atmosphere were based on  iodometry.  When atmospheric oxidants are absorbed
in potassium iodide (KI)  reagent, the iodine produced,
                          03 + 3I~ + H20 = I3~ + 02 + 20H~              (1-1)
is  measured by ultraviolet  absorption in  colorimetric instruments and by
amperometric means  in electrochemical  instruments.  The term "total  oxidants"
is  of historical  significance only and should  not be construed to  mean  that
such  measurements  yield a sum of  the  concentrations  of the oxidants  in the
atmosphere.  The  various oxidants in the  atmosphere react  to yield iodine  at
different  rates  and with different stoichiometries.  Only  ozone reacts imme-
diately to  give a  quantitative yield of iodine.  Hydrogen peroxide,  for example,
produces  iodine  at a slow  rate  and because  of  its  low  concentration compared
to  ozone would be  expected  to have  little effect upon a total oxidants measure-
ment.   As  discussed below,  the  total  oxidants  measurement correlates fairly
well  with  the  specific  measurement of  ozone,  except during  periods  when  signi-
 ficant N02 and SO™ interferences  are present.   The major  problem  with the
 total oxidants measurement  was the  effect of these interferences.   Total
 oxidants instruments have now been replaced by specific ozone monitors in all
 aerometric networks  and  in  most  research  laboratories.   Biases  among  and
 between "total oxidants" and ozone methods are still  important,  however,  for
 evaluating existing data on  health and welfare "effects levels" where concen-
 trations were  measured  by "total oxidants"  methods.
      The reference method promulgated by EPA for compliance monitoring is the
 chemiluminescence  technique  based on the  gas-phase  ozone-ethylene reaction
 (U.S.  Environmental  Protection  Agency, 1971b).  The  technique  is specific  for

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ozone, the response (luminescence intensity) is a linear function of concentra-
tion, detection limits of 0.001 to 0.005 ppm are readily obtained, and response
times of  30 seconds  or  less are readily obtained.   Prescribed  methods  of
testing and prescribed performance  specifications  that a commercial analyzer
must meet  in order to be designated as  a  reference method or an equivalent
method have  been published  by EPA (U.S. Environmental  Protection Agency,
1975).  An analyzer may be designated as a  reference method if it  is based on
the same principle as the reference method and meets performance specifications.
Commercial analyzers  that have  been  designated as  reference  methods were
listed in  Chapter  5  (Table 5-7).  An acceptable equivalent method must meet
the prescribed performance specifications and  also  show  a consistent  relation
with the  reference method.   Commercial  analyzers that  have been  designated as
equivalent methods were also listed in Chapter 5 (Table 5-7).
     The  designated  equivalent methods  are based  on  either  the gas-solid
chemiluminescence procedure  or the  ultraviolet absorption procedures  (Table
1-2).  The first designated equivalent method was based on ultraviolet absorp-
tion of the mercury 254 nm emission line.  The absorption coefficient of ozone
is accurately known at this wavelength with an accepted value of 134 M   cm  .
Detection limits of 0.005 ppm are readily obtained by modern digital capabili-
ties  for  making  precise  measurements  of weak  absorbancies at  moderate path-
lengths.   Compensation for potential  interferences  that  also absorb at 254 nm
is made by comparing an  averaged transmission  signal  of ozone in air to the
transmission signal  through  an otherwise identical air sample from which the
ozone  has been  preferentially  scrubbed.   Advantages of this  UV  absorption
technique are  that a reagent gas is  not required  and control of  sample air
flow is not critical.  In addition, the measurement is in principle an absolute
one,  in that the ozone concentration  can be computed from the  measured trans-
mission signal  since  the  absorption coefficient and pathlength are accurately
known.
     In the gas-solid chemiluminescence analyzer,  the reaction between ozone
and  Rhodamine-B  adsorbed  on  activated  silica produces chemiluminescence, the
intensity  of  which  is  directly proportional  to ozone concentration.  The
sensitivity  is  greater than  the gas-phase  chemiluminescence  method and a
controlled  reagent  gas flow  is not  required.   The  sensitivity  of the  reaction
surface decays  gradually  with time, but the analyzer  contains internal means
to compensate for the decay.

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 I
ro
ro

Principle
Continuous
col or 1 metric
Continuous
electrochemical
Chemi luminescence
Chemi luminescence
Ultraviolet
photometry

Reagent
10(20)X KI
buffered at
pH = 6.8
2% KI
buffered at
pH = 6.8
Ethyl ene ,
gas-phase
Rhodamine-B
None
TABLE 1-2.
Response
Total
oxldants
Total
oxidants
03-spec1f1c
Os-spec1f1c
03-spec1fic
SUMMARY OF OZONE MONITORING TECHNIQUES
Minimum
detection limit
0.010 ppm
0.010 ppm
0.005 ppm
0.001 ppm
0.005 ppm
Response
time, 90% FSa
3 to 5 minutes
1 minute
< 30 seconds
< 1 minute
30 seconds
Major
1 nterf erences
N02(+20%, 10XRI)
S02(-100%)
N02(+6%)
S02(-100X)
Noneb
None
Species that
absorb at 254 nm
References
Llttman and Benollel (1953)
Toklwa et al. (1972)
Brewer and Mllford (1960)
Mast and Saunders (1962)
Toklwa et al. (1972)
Nederbragt et al. (1965)
Stevens and Hodgeson (1973)
Regener (1960, 1964)
Hodgeson et al. (1970)
Bowman and Horak (1972)
      aFS = full response.

       A signal enhancement of 3 to 12% has been reported for measurement of 03 1n humid versus dry air (California Air Resources Board, 1976).

       No significant interferences have been reported 1n routine ambient air monitoring.   If abnormally high concentrations of species that
       absorb at 254 nm (e.g., aromatic hydrocarbons and mercury vapor)  are present, some positive response may be expected.  If high aerosol
       concentrations are sampled, Inlet filters must be used to avoid a positive response.

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1.4.4.3  Calibration Methods.   All  the  analyzers  discussed above  must be
periodically calibrated with ozonized air streams, in which the ozone concen-
tration has been determined by  some absolute technique.  This includes  the UV
absorption analyzer, which, when  used for continuous ambient monitoring, may
experience ozone losses in the inlet system because of contamination.
     An ozone calibration  system  for  a primary laboratory calibration system
consists of a clean air source, an ozone generator,  and a sampling manifold.
The ozone generator most often used is a photolytic source employing a mercury
pen-ray lamp that  irradiates a  quartz tube through which clean air  flows at  a
controlled rate  (Hodgeson et  al.,  1972).  The ozone  concentration may be
varied by means  of a mechanical sleeve over the lamp envelope or by changing
the lamp voltage or current.  Once the  output  of the generator has  been cali-
brated by a primary reference method, it may be used to calibrate 0, transfer
standards, which are portable  generators, instruments, or other devices used
to calibrate analyzers  in the field.    Reference calibration procedures that
have been used for total oxidants and ozone-specific analyzers in this country
are summarized in Table 1-3.
     The original  reference  calibration procedure promulgated by EPA was the
1 percent neutral  buffered potassium  iodide  (NBKI) method  (U.S.  Environmental
Protection Agency,  1971).   This technique was employed in most of the United
States, with the  exception of California, which  routinely used  a 2 percent
NBKI procedure  that was quite  similar to the EPA  method except for  the  use of
humidified air through  the ozone source  (California Air Resources Board, 1976).
The Los  Angeles  Air Pollution Control  District (LAAPCD) used a 1 percent un-
buffered KI procedure and measured the  iodine  produced by  a titration technique
rather than  the  photometric technique used  in  the  California  and EPA  methods.
A number of studies  conducted between 1974 and 1978 revealed several deficien-
cies with  KI methods,  the most notable  of which were poor  precision or  inter-
laboratory comparability  and a positive bias of NBKI  measurements relative to
simultaneous absolute  UV absorption measurements.  The positive  bias  was also
observed  with  respect  to  gas-phase titration  (GPT)  of ozone with  standard
nitric oxide  (NO)  samples.   The positive bias  observed is  peculiar to the use
of phosphate buffer in the NBKI techniques.  The  bias was  not observed  in the
unbuffered LAAPCD  method  (which nevertheless suffered  from poor  precision),  nor
in the 1 percent EPA KI method  without  phosphate buffer (Hodgeson et al., 1977),
nor in a KI procedure that  used boric acid as  buffer  (Flamm, 1977).  A  summary

019GC1/A                            1-23                               6/29/84

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                                                        TABLE  1-3.  OZONE  CALIBRATION  TECHNIQUES
 I
ro
Method
IX NBKI
2X NBKI
IX Unbuffered
KI
UV photometry
Gas-phase
titration (GPT)
IX BAKI
Reagent
IX KI,
phosphate buffer
pH = 6.8
2X KI
phosphate buffer
pH = 6.8
IX KI
pH = 7
None
No standard
reference gas
IX KI,
boric acid buffer
pH » 5
Primary standard8
Reagent grade
arsenious oxide


03 absorptivity at
Hg 254 nm emission
line
No SRM (50 ppm in N2)
from NBS
Standard KI03f
solutions
Method used,
organization,
and dates
EPA
1971-1976
CARB
until 1975
LAAPCD
until 1975
All
1979-present
EPA, States
1973-present
EPA
1975-1979
Purpose
Primary reference
procedure
Primary reference
procedure
Primary reference
procedure
Primary reference
procedure
Alternative reference
procedure (1973-1979)
Transfer standard (1979-present)
Alternative reference
procedure
Bias,
[oa]t/[o3]uv
1.12 ± 0.05b
1.20 ± 0.05b
0.96C

1.030 ± 0.015*
1.00 i 0.05
      aln the case of the  iodometric methods, the primary standard is the reagent used to prepare or  standardize  iodine  solutions.
       The  uncertainty  limits represent  the range of values obtained in several independent studies.
      C0nly one  study available  (Demore  et al., 1976).
      dUV photometry used  as reference method by CARB since 1975.  This technique used as an  interim, alternative reference procedure by
       EPA  from  1976 to 1979.
      eTMs is the value reported  in the latest definitive study (Fried and Hodgeson, 1982).  Previous studies  reported  biases  ranging  from
       0 to 10 percent  (Burton et  al., 1976; Paur and McElroy, 1979).
       This procedure also recommended a standard I3~ solution absorptivity to be used instead of the preparation of  standard iodine solutions.

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of results of these prior studies was presented in the previous criteria docu-
ment (U.S. Environmental  Protection  Agency,  1978a) and in a review by Burton
et al.  (1976).   Correction  factors for converting NBKI calibration data to a
UV photometry basis were given in Chapter 5.
     Subsequently, EPA evaluated four alternative reference calibration proce-
dures based on UV photometry, GPT with excess NO, GPT with excess ozone and the
boric acid buffered KI  technique  (BAKI).  The  results  of  these studies  (Rehme
et al.,  1981)  showed  that UV photometry was superior in accuracy, precision,
and simplicity of  use;  and in 1979  regulations  were amended to specify UV
photometry as the reference calibration procedure (U.S. Environmental Protection
Agency, 1979a,b,c,d).   Laboratory photometers used as reference systems for ab-
solute 0» measurements have been described by Demore and Patapoff (1976), Bass et
al. (1977), and Paur and Bass (1983).
     These laboratory photometers contain long path cells (1 to 5 m) and employ
sophisticated digital  techniques for making effective double beam measurements
of small  absorbancies  and low ozone concentrations.   A  primary  standard UV
photometer, such as those above, is one that meets the requirements and specifi-
cations  given  in the  revised  ozone calibration procedures  (U.S.  Environmental
Protection Agency, 1979d).   Since  these  are  currently  available  in  only a  few
laboratories, EPA has allowed the use of transfer standards, which are devices
or methods that can be calibrated against a primary standard and transferred to
another  location for calibration of 0, analyzers.  Examples of transfer stand-
ards that have been used are commercial 0, photometers, calibrated generators,
and GPT  apparatus.  Guidelines on transfer standards have been published by EPA
(McElroy, 1979).
1.4.4.4   Relationship of Total Oxidants  and  Ozone Measurements.   The temporal
and quantitative  relationship between simultaneous total  oxidants  and  ozone
measurements has  been examined in this chapter because of the existence of a
data base obtained by "total oxidants" measurements.  Such a comparison is com-
plicated  by the  relative scarcity of data, the presence of both positive (N0?)
and negative (S0?) interferences in total oxidants measurements, and the change
in the basis of calibration.  In particular, the presence of N0? and S0? inter-
ferences  prevents the establishment of a definite quantitative relationship be-
tween ozone and oxidants data.  Nevertheless,  some interesting conclusions can
be drawn and are summarized below.
019GC1/A                            1-25                               6/29/84

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     An expected relationship between total  oxidants  and specific 0., measurements
can be predicted based  upon  the known response of oxidant instrumentation to
oxidizing and reducing  species  in  the atmosphere.  The predicted relation in
this document assumes that N0?  is  the only  significant positive interference
and that SCL is the predominant  negative interference.   Because of the potential
presence of oxidizing (NO^) and reducing (S0~) interferences,  it  is difficult
or impractical to  intercompare  measurements during evening and early morning
hours when  ozone concentrations  are  at a minimum.  The relationship  is best
compared at the midday  to early afternoon  diurnal maximum of  ozone when  NCL
concentrations are approaching  a minimum;  the S0» concentration at this time
will depend on  local  emissions.   A comparison of maximum hourly  averages  is
appropriate since  the primary and secondary ambient air quality  standards  are
based on this value.   If legitimate corrections or compensations have been made
for SO £ and NOp interferences, the  corrected total oxidants concentrations should
always be higher than simultaneous  CL concentrations  by an amount dependent on
type and concentrations  of other oxidants present.   The major other oxidants
known to exist  in  the atmosphere are  PAN and  hLCL.  Maximum concentrations of
these oxidants  occur  near the ozone diurnal  maximum (Chapter  6)  with values
that are only a fraction of the CL  maximum  (section 6.6 and 6.7).  In addition,
both of these are classified as slow oxidants in that they release iodine  at a
slow rate in aqueous solution.  Therefore,  if a contribution from these species
is discernible at all in the total  corrected oxidants reading, it should be only
a  small  fraction  of  the ozone contribution.  For most of the aerometric data
base, particularly outside the  state of California,  no attempts were made to
correct total oxidants concentrations for NCL and S02 because  such corrections
were  impractical  or  impossible.   For uncorrected total oxidants data, the
counterbalancing effects of S02 and N02 interferences make it  even more diffi-
cult to discern contributions from oxidants other than ozone.  The uncorrected
total oxidants data should then be either higher than or lower than correspond-
ing  ozone  data, depending  on the relative concentrations  of SO,, and NO^.
     The simultaneous comparisons that have been made in large part confirm the
predictions above.   Studies  concluded in  the  early to  mid-1970s were reviewed
in the previous criteria document (U.S. Environmental Protection  Agency,  1978a).
Averaged data showed  fairly good qualitative  and quantitative  agreement between
diurnal  variations of total oxidants  and ozone.  Uncorrected data showed  distinct
 019GC1/A                            1-26                                6/29/84

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morning and evening peaks resulting from N0? interference.   Data taken from indi-
vidual days of respective studies showed considerably more variation,  with total
oxidants measurements both higher and lower than ozone measurements.
     The most recent comparison in the literature involved simultaneous ozone and
total oxidant measurements in the Los Angeles basin by the California Air Resources
Board (1978) in 1974, 1976, and 1978.  The maximum hourly data pairs were corre-
lated (Chock et al., 1982) and yielded the following regression equation for 1978,
in which a large number (927) of data pairs were available:

                         Oxidant (ppm) = 0.870 03 + 0.005
                         (Correlation coefficient = 0.92)             (1-2)

The oxidant data were uncorrected for N02 and S0~ interferences, and,  again, on
individual days maximum oxidant averages were both higher than  and lower than
ozone averages.
     In summary, specific ozone measurements agree fairly well with total oxi-
dants corrected for N0« and S0? interferences, and in such corrected total oxi-
dants measurements ozone is the dominant contributor to total oxidants.  Indeed,
it is difficult to discern the presence of other oxidants in most total oxidant
data.  There can,  however,  be major temporal discrepancies between ozone and
oxidants data, which  are  primarily a result of oxidizing and reducing inter-
ferences with  KI  measurements.   As a result  of  these interferences,  on any
given day the total oxidant values may be higher than or lower than simultaneous
ozone data.  The  measurement  of ozone is a  more  reliable  indicator than  total
oxidant measurements of oxidant air quality.
1.4.4.5  Methods for the Sampling and Analysis of Peroxyacetyl Nitrate and Its
         Homologues.  Only two analytical techniques  have been  used to obtain
significant data  on  ambient peroxyacetyl nitrate  (PAN)  concentrations.   These
are  gas chromatography with electron capture  detection  (GC-ECD)  and long-path
Fourier transform  infrared (FTIR)  spectrometry.   Atmospheric  data on  PAN con-
centrations have been obtained predominantly by GC-ECD because of its relative
simplicity and  superior sensitivity.  These techniques  have  been described  in
this chapter along with  attendant methods of sampling.   Since PAN is thermo-
dynamically unstable, standards must be generated and analyzed by some absolute
technique for  the  purpose  of calibrating the GC-ECD.   Thus,  PAN generation
techniques and  absolute methods  for analyzing these  samples  have  also been
summarized.
019GC1/A                            1-27                               6/29/84

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     By far the most widely used technique for the quantitative determination
of ppb concentrations of  PAN  and its homologues is GC-ECD (Stephens, 1969).
With carbowax or SE30 as a stationary phase,  PAN,  peroxypropionyl  nitrate (PPN),
peroxybenzoyl  nitrate (PBzN),  and other homologues (e.g., peroxybutyrl nitrate)
are readily separated from components such as air,  water, and other atmospheric
compounds, as well  as  ethyl  nitrate, methyl  nitrate, and other contaminants
that are  present  in synthetic mixtures.   Electron-capture detection provides
sensitivities in  the ppb  and  sub-ppb ranges.   Table 1-4  shows parameters  used
by several investigators  to  determine  trace  levels of PAN by GC-ECD.  Sample
injection into the  GC is  accomplished by means of a gas-sampling valve with  a
gas-sampling loop of a  few milliliters1 volume.  Sample  injection may be  per-
formed manually or automatically.  Typically, manual  air samples are collected
in 50-200 ml  ungreased glass syringes and purged through the gas-sampling valve.
Samples collected from  the  atmosphere  should be analyzed as soon as possible
because PAN and its homologues  undergo thermal decomposition  in the  gas phase
and at the surface of containers.
     The  recent work of Singh and Sal as (1983a, 1983b) on the measurement of PAN
in the free (unpolluted) troposphere (see Chapter 6) is illustrative of current
capabilities for  measuring  low concentrations.   A minimum detection limit of
0.010 ppb was  obtained.   The literature contains conflicting reports on  the
effects of variable relative  humidity  on PAN measurements  by GC-ECD.  Some
investigators have  reported a reduced response to PAN calibration samples when
dry diluent gas  is  used,  whereas others  have  not observed  this effect.   The
reduced response  has been attributed to losses of PAN to surfaces within the
inlet system and the GC.  Presumably, water vapor may deactivate surfaces.   For
the present,  if  a moisture effect  is  suspected  in a PAN analysis,  the bulk
of this evidence  suggests that  humidification of PAN calibration samples  (to a
range approximating the humidity of the samples being analyzed) would be  advisa-
ble.
     Conventional long-path infrared spectroscopy and Fourier-transform infrared
spectroscopy (FTIR) have  been used to detect and measure atmospheric PAN.  Sen-
sitivity  is  enhanced by the  use of FTIR.  The most  frequently  used IR  bands
have been assigned  and the  absorptivities shown  in Table 1-5 permit the quan-
titative  analysis of PAN  without calibration standards.  The  absorptivity of the
990 cm    band of  PBzN has been  reported by Stephens  (1969).   Some  recent  simul-
taneous measurements of PAN and other atmospheric pollutants  such  as Q^>  HNu3»

019GC1/A                             1-28                                6/29/84

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                                     TABLE 1-4.   SUMMARY OF PARAMETERS USED IN DETERMINATION OF PAN BY GC-ECD
Reference
Heuss and Glasson,
1968

Grosjean, 1983

Darley et al. ,
1963
Stephens and Price,
1973



Lonneman et al . ,
1976
Holdren and Spicer,
1984
Peake and Sandhu,
1982
Singh and Sal as,
1983b
Grosjean et al . ,
1984
Nielson et al. ,
1982
Column
dimensions
and material
4 ft x 1/8 in
Glass

6 ft x 1/8 in
Teflon
3 ft x 1/9 in
Glass
1.5 ft. x 1/8 in
Teflon



3 to 4 ft x 1/8 in
Glass
5 ft x 1/8 in
Teflon
3.3 ft x 1/8 in
Glass
1.2 ft x 1/8 in
Teflon
1.7 ft x 1/8 in
Teflon
3.9 ft x 1/12 in
Glass
Stationary
phase
SE30
(3.8%)

10% Carbowax 400

5% Carbowax 400

5% Carbowax E 400




10% Carbowax 600

60/80 Mesh
Carbowax 600
5% Carbowax 600

10% Carbowax 600

10% Carbowax 400

5% Carbowax 400

Column
Solid temperature,
support °C
80-100 25
Mesh
Diatoporte S
60/80 Mesh 30
Chromosorb P
100-200 Mesh 35
Chromosorb W
Chroraosorb 25
G 80/100
mesh treated
with dimethyl
dichlorosilane
Gas Chrom Z 25

Gas Chrom Z 35

Chromosorb W 33

80/100 Mesh 33
Supelcoport
60/80 Mesh 30
Chromosorb G
Chromosorb 25
W - AW - DCMS
Flow Elution
rate, Carrier time, Concentration
ml/min gas min range
N.A.a N.A.a N.A.a


40 N2 N.A.a

25 N2 2.17

60 N2 1.75




70 95% Ar 2.7
5% CH4
70 90% Ar 3.00
10% CH4
50 N2 N.A.a

30 95% AR N.A.3
5% CH4
40 N2 5.0

40 N2 6.0

ppb
range

ppb
range
3 to 5
ppb
37
ppb



0.1 to 100 ppb

ppb

0.2 to 20
ppb
0.02-0.10
ppb
2-400
ppb
11 ppb

a
 'N.A.  - not available in reference.

-------
                            TABLE 1-5.   INFRARED ABSORPTIVITIES OF PEROXYACETYL NITRATE
CO
o
Absorptivity, ppm-1
Frequency
cm-1
1842
1741
1302
1162. 5
930
791.5
Mode
v(c=o)
vas(N02)
vs(N02)
v(c-o)
v(o-o)
6(N02)
Liquid PAN
(Bruckmann and
Wlllner, 1983)
12.4
32.6
13.6
15.8
N.A.a
13.4
PAN 1n air
(Stephens,
1969)
10.0
23.6
11.2
14.3
N.A.a
10.1
Frequency
cm-1
1830
1728
1294
1153
930
787
m-1 x 104
PAN In air
(Stephens and
Price, 1973)
10.0
23.6
11.4
13.9
1.8
10.3

PAN 1n octane
(Holdren and
Spicer, 1984)
9.44
26.5
9.44
9.66
N.A.a
10.1
         Not available 1n reference.

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HCOOH, and HCHO have been made by long-path FTIR spectrometry during smog epi-
sodes in the Los Angeles Basin.   Tuazon et al .  (1978) describes an FTIR system
operable at pathlengths  up  to 2 km for ambient measurements of PAN and other
trace constituents.  This system employed  an eight-mirror multiple  reflection
cell with a 22.5-m base path.  Detection of PAN was by bands at 793 and 1162 cm  .
The 793 cm   band is characteristic of peroxynitrates, while the 1162 cm   band
is reportedly attributable to PAN only (Hanst et al .  , 1982).  Tuazon et al .  (1981)
reported a detection limit for PAN of 3 ppb at a 900-meter pathlength.
     Hanst et  al .  (1982) made measurements with a 1260-m folded optical path
system  during  a 2-day  smog  episode  in  Los  Angeles  in 1980.   An  upper  limit  of
1 ppb of peroxybenzoyl nitrate (PbzN) was placed, based on observations in the
vicinity of the PBzN  band at 990 cm  ;  the maximum PAN  concentration  observed
was 15  ppb.
     Sampling may constitute one of the major problems in the analysis of trace
reactive species, such as PAN, by long-path FTIR spectrometry.  The large inter-
nal  surface area of the  White cells may serve  to promote  the decomposition  or
irreversible adsorption  of reactive trace  species.    High volume sampling rates
and  inert  internal surface  materials  are  used  to minimize these effects.
     Because of  the thermal  instability of  dilute  PAN samples and the explosive
nature  of  purified PAN,  calibration samples are not commercially available.
Each  laboratory involved in  making such measurements must  prepare  its  own
standards.  Calibration  samples  are usually prepared by various means at con-
centrations in  the  ppm range, and they must be analyzed by  some absolute tech-
nique.
      Earlier methods  used  to synthesize PAN have  been  summarized by  Stephens
(1969).  The photolysis  of alky! nitrites  in oxygen  was the  most  commonly used
procedure  and  may  still  be used by  some  investigators.  As  described  by  Stephens
et  al .  (1965),  the  liquefied  crude  mixture obtained  at  the  outlet of  the photol-
ysis  chamber  is purified by preparation-scale  GC.   [CAUTION:  Both the liquid
crude  mixture  and the purified  PAN samples are violently explosive and should
be  handled behind  explosion  shields  using  plastic  full-face  protection,  gloves,
and a leather  coat at all  times.]   The pure PAN is  usually diluted to about
1000  ppm  in nitrogen  cylinders at 100  psig and stored at  reduced  temperatures,
      Gay  et al .  (1976) have  used  the  photolysis  of  C12: aldehyde: N02  mixtures
 in  air or oxygen for the preparation of PAN and a number of its homologues at

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high yields.  This procedure  has  been utilized in a portable  PAN generator
that can be used for the calibration of GC-ECD instruments in the field (Grosjean,
1983; Grosjean et al.,  1984).
     The other technique for PAN preparation in current use involves the nitra-
tion of peracetic acid.   Several investigators have recently reported on a con-
densed-phase synthesis  of PAN with peracetic acid  that  produces high yields of
a pure product  free of other alkyl nitrates (Hendry and Kenley, 1977;  Kravetz
et al., 1980; Nielsen et al., 1982; Holdren and Spicer, 1984).  Most of these
procedures call  for the addition of peracetic acid (40  percent in acetic acid)
to a hydrocarbon solvent (pentane, heptane,  octane) maintained at 0°C in a dry-
ice acetone bath, followed by acidification  with sulfuric acid and slow addition
of sodium  nitrate.  After the nitration is complete, the  hydrocarbon fraction
containing  PAN  concentrations of 2 to  4  mg/ml  can be stored  at  -20°C for
periods longer than a year (Holdren and Spicer, 1984).
     The most direct method for absolute analysis of these PAN samples is by
infrared absorption, using absorptivities given in Table 1-5.  Conventional IR
instruments and  10-cm  gas  cells can analyze  gas  standards  of  concentrations
>35  ppm.   Liquid microcells can be used  for  the  analysis of  PAN  in octane
solutions.
     The alkaline hydrolysis of PAN to acetate ion and nitrite ion in quantita-
tive yield  (Nicksic et al., 1967) provides a means independent of infrared for
the  quantitative analysis  of PAN.  Following hydrolysis,  nitrite ion  may be
quantitatively analyzed by the Saltzman colorimetric procedure (Stephens, 1969).
The  favored procedures now use ion chromatography to analyze for nitrite  (Nielsen
et al., 1982) or acetate (Grosjean, 1983, 1984) ions.  Another calibration pro-
cedure has  been  proposed that is  based on the thermal decomposition of PAN in the
presence of excess NO (Lonneman et al., 1982).  The peroxyradical, CH3C(0)02, and
its  decomposition products  rapidly oxidize NO to  N02 with a  stoichiometry that
has  been  experimentally measured.  By the use of  NO  standard mixtures  and the
measurement by  chemiluminescence  of the NO consumed, the  absolute  PAN  concentra-
tion can  be determined.
1.4.4.6  Methods for Sampling and Analysis of Hydrogen Peroxide.   Hydrogen perox-
ide  (H?0?), like ozone  and  PAN, is  formed as  a product of the  photooxidation  of
hydrocarbons  and reaches maximum concentrations during daylight hours.  There
are  some  early  reports of  H?0? concentrations as high as 180  ppb  at an ozone
maximum of 650  ppb, but it  now  appears  more  likely that maximum  H202 concentra-
tions  are in the range  of  10 to  50 ppb and  are only a small  fraction  (<  10%)
019GC1/A                            1-32                                6/29/84

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of the corresponding ozone maximum.   Applied and potentially useful  techniques
for the measurement of ambient H»0p  are summarized in Table 1-6.
     With the exception  of  Fourier-transform infrared (FTIR) studies,  all  of
the techniques that have been used for atmospheric H^CL measurements have em-
ployed aqueous traps  for sampling.   Recent studies have indicated that this
approach leads to  interference  from  ozone, which will always  be  present at
higher concentrations.  Absorbed 0-  has been observed to  promote both the for-
mation and destruction  of  H?CL  in aqueous media  (Zika and Saltzman, 1982).
Therefore, an obvious  research  need  in HpO- measurements is a clear delinea-
tion of  the  nature of any 0» interferences  and the development of means for
their prevention.
     Of  the  procedures  given  in Table 1-6,  only  the  titanium colorimetric,
enzyme-catalyzed,   and FTIR  methods  have  been used for atmospheric sampling.
The other procedures  do not appear  promising for ambient  air  analysis.  The
titanium sulfate-8-quinolinol  reagent has been used in several earlier studies
on atmospheric H202 (Bufalini  et al., 1972; Gay et al.,  1972a; Gay et al., 1972b;
Kok et al.,  1978a).   Hydrogen peroxide in  air is  scrubbed  in  a coarse-fritted
bubbler containing aqueous titanium sulfate-ammonium sulfate-sulfuric acid solu-
tion.   After sampling, the solution is extracted with an aliquot of 8-quinolinol
in chloroform.  The absorbance at 450 nm of the titanium (IV)-H202-9-quinolinol
complex  in chloroform is determined.   A positive interference  is expected from
any compound that can liberate H»0» via acid hydrolysis (Pobiner, 1961), e.g.,
t-butylhydroperoxide.   Of  the major  atmospheric pollutants investigated  (S02,
03, NOp,  NO,  and  hydrocarbons), only S0? at high concentrations gave a small
(0.7 percent) negative interference (Gay et al., 1972b).
     In  the  titanium  tetrachloride  method, samples are collected in a midget
impinger containing an aqueous TiCl.-HCl  solution.  A stable TiCl^-h^O,, complex
is formed immediately, and after the solution is diluted to a  known volume, the
absorbance of the  complex at 410 nm is determined.  The principal difficulty
with this method is the formation of fine particles, presumably TiO^, which scat-
ter visible radiation and create an apparent absorption.    In an intercomparison
of hL02  measurement methods, Kok et al. (1978a) reported rather poor agreement
between  the  two  titanium reagents and between  these and  chemiluminescence.
     A promising method for the measurement of hydrogen peroxide in the atmos-
phere at very low  concentrations is based on the chemiluminescence obtained from
the Cu(II)-catalyzed oxidation of luminol  (5-amino-2,3 dihydro-1,4-phthalazine-
dione) by H202 (Armstrong and Humphreys, 1965).  The product of the reaction with
019GC1/A                           1-33                               6/29/84

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                                                  TABLE 1-6.   MEASUREMENT METHODS FOR HYDROGEN PEROXIDE
Method
Titanium
colorimetry
Chemi 1 umi nescence
Enzyme- catalyzed
Enzyme-catalyzed
Enzyme- cata 1 yzed
Fourier- transform
infrared absorption
Electrochemical
H202-olefin
reactions
Mixed-ligand
complex reagents
Reagent(s)
(1) Titanium Sulfate
-8-Quinolinol
(2) Titanium Tetrachloride
Luminol, Cu(II)
basic solution
Scopoletin, horseradish-
peroxidase (HRP)
Leuco crystal violet,
HRP
3-(p-hydroxyphenyl )
propionic acid
None
Aqueous solutions
l,2-di-(4-pyridyl)
ethyl ene
Vanadium and
uranium hydroxamic
acid chelates
Limits of
detection
(1) 1.6 x 10-6 M
(2) ca 10-6 M
0.001 to 1 ppm
1.5 x 10-11 M
10-8 M
10-6 to 10-4 Mf
0.005 ppm (est.)
5 x 10-6 to 1 M
10-6 to 5 x 10-4 M
10-6 M
Interferences
Positive
Alkyl hydro-
peroxides
PANd
NA
NA
NA
NA9
NA
03
NA
Negative
S02C?
S026
NA
NA
NA
None
NA
NA
NA
Applications Primary reference
Atmospheric (1) Gay et al. (1972a, 1972b)
(2) Pilz and Johann (1974);
Kok et al. (1978a)
Atmospheric, Armstrong and Humphreys (1965);
rainwater Kok et al. (1978a,1978b)
Atmospheric, Andreae (1955); Perschke
rainwater and Broda (1961); Zika and
Saltzman (1982)
Mottola et al. (1970)
Zaitsu and Ohkura (1980)
Atmospheric*1 Hanst et al. (1982)
— Pisarevskii and Polozova (1980)
	 Hauser and Kolar (1968)
Csanyi (1981);
Meloan et al. (1961)
 Except where noted, detection limits are in moles/1 iter(M)  in aqueous solution.
 03 may be both a positive and negative interference  in all  these procedures using aqueous sampling.   See Text.   NA = not available.
°The S02 interferences is reported to be small  at high S02 concentrations (Gay et al.,  1972b).   Studies of potential positive and
 negative interferences are incomplete for these methods.
 The reported PAN interference is small (Kok et al.,  1978b).
p
 'The report of an S02 interference is undocumented.
  fThe  lower  limit could presumably be reduced by the use of larger samples.
  9With sufficient resolution, there should be no interferences.  IR absorption by atmospheric water vapor is the major analytical
   limitation.
  VjOz bands have not  been  observed in any long-path FTIR studies.  The estimated lower limit of detection in these studies  is
   approximately  0.005  ppm.

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H.CL is 3-amino-phthalic  acid,  a nitrogen molecule, and a photon of light at
450 nm.   A small positive interference was reported for PAN (Kok et al., 1978b).
If 03 absorption leads to the formation of H-O^ as reported (Zika and Saltzman,
1982; Heikes et al. ,  1982),  then 0»  is a major  interference.  There have also
been undocumented reports of a negative interference from SCL.
     Perhaps the most promising chemical  approach for the measurement of trace
concentrations of  H^CL  employs  the catalytic acitivity of the enzyme, horse-
radish peroxidase (HRP), on the oxidation of organic substrates by H^O,,.  This
general  method involves three components:  a substrate that is oxidizable, HRP,
and \\yQy.  Three  substrates that have been used are scopoletin (6-methoxy-7-
hydroxy-1,2-benzopyrone), 3-(p-hydroxyphenyl)propionic  acid  (HPPA), and  leuco
crystal  violet (LCV).  The scopoletin reagent has recently been used in atmos-
pheric analysis.  The disappearance of scopoletin fluorescence, upon oxidation
of scopoletin  by  HJ^?'  1S monitorecl  anc' the  fluorescence  intensity  is used  to
obtain the concentration  of H909 from a calibration curve.   The most  signifi-
                                                                  -11
cant advantage of the scopoletin method is the sensitivity (ca. 16    M).  The
chief disadvantage  of the method is that  the  concentration  of H?CL must be
within a narrow concentration range in order to obtain an accurately measurable
decrease  in  fluorescence.  This limits the  usefulness of the technique in
determining unknown H^Op concentrations over several orders of magnitude.  With
the leuco  crystal  violet  (LCV)  substrate,  intensely colored  crystal violet  is
formed from the reaction of hLCL with LCV, catalyzed by HRP.   The absorbance is
measured at 596 nm, where the molar absorption coefficient of crystal  violet is
10  M    cm  ,  a very high  value and an  inherent advantage  of this method.
Finally, Zaitsu and Ohkura  (1980) have tested a number of 4-hydroxy phenyl  com-
pounds and found that 3-(p-hydroxyphenyl) propionic acid (HPPA) provided a  sen-
sitive and rapid  means for determining H?0?.  A product is formed that fluo-
resces at 404 nm, and the intensity of this fluorescence is monitored as a  func-
tion of HpOp concentration.  The detection limit was reported to be 10    mole
HpOp with  a  test solution of only 0.1 ml volume used.  The molar sensitivity
could presumably be improved by the use of large sample volumes.
     The enzymatic methods appear to be the most promising colorimetric methods
of H^Op  and  have considerably greater sensitivity than the methods employing
titanium  reagents.   However,  studies of potential atmospheric interferences
have apparently not been conducted for any of these three substrates.
019GC1/A                            1-35                               6/29/84

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     Hydrogen peroxide can be monitored directly in  the gas phase by FTIR absorp-
tion at 1250 cm   , where the absorption coefficient is 8.4 cm   atm   at I cm
resolution (Hanst et al.,  1981).   One FTIR measurement of the possible presence
of 0.070 ppm HpO- was reported during an  intense smog episode in Pasadena,
California (Hanst  et  al. ,  1975).   Unfortunately, minimum detection limits at
1 km pathlength  are  degraded to 0.040 ppm because of  neighboring absorption
bands of H20 and CH4 (Hanst et al., 1981).
     As with 0~, H907 calibration standards are not  commercially available and
              O   tL £
are usually prepared  at the  time of  use.  The most convenient method  for pre-
paring aqueous  samples containing  micromolar concentrations  of H,,02 1S s^mP^
the serial dilution  of commerical  grade 30 percent H£02 (Fisher Analytical
Reagent).   Techniques for the convenient generation  of gas-phase standards are
not available.   A technique  often used for generating ppm concentrations  of
H?0p in air involves the  injection of microliter quantities of 30 percent H,^
solution into a metered stream of air that flows into a Teflon bag.  Aqueous and
gas-phase samples  are then standardized by conventional  iodometric  procedures
(Allen et al., 1952; Cohen et al., 1967).
     Hydrogen peroxide liberates  iodine from an iodide solution  quite slowly,
but in the presence of a molybdate catalyst the reaction is rapid.  The iodine
liberated can  be determined  by titration with  standard thiosulfate at higher
concentrations or  by photometric measurement of the tri-iodide ion at low con-
centrations.  The  molar absorption coefficient  of the  tri-iodide  ion  at 350 nm
has  been  determined to be 2.44 x  10  (Armstrong and  Humphreys,  1965).  The
stoichiometry  is apparently  1 mole of iodine released per mole of H202-   How-
ever,  definitive studies of  the stoichiometry have not been  performed for  H202
as  they have for the  iodometric determination of 03-
 1.5   CONCENTRATIONS OF OZONE AND OTHER  PHOTOCHEMICAL OXIDANTS  IN AMBIENT  AIR
      In  the context of this  document,  the  concentrations of ozone and other
 photochemical  oxidants  found  in  ambient  air  are  important for:

      1.    Assessing potential exposure  of individuals;  communities;  the general
           population and  those  subpopulations  in communities that may be
           especially susceptible to  adverse  effects  from these  oxidants;
           natural  ecosystems, managed ecosystems such as crops; and  nonbiologi-
           cal  materials such  as  polymers and paints.
 019XX/A                             1-36                               6/29/84

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     2.    Assessing whether  levels  of  ozone  and other photochemical  oxidants
          in  ambient  air  are within or near  the range of  concentrations  shown
          to  produce  adverse effects in health and welfare  effects  studies.
     3.    Determining whether levels of ozone and other photochemical  oxidants
          are as  high indoors as  in the ambient air, for  the  purpose of  asses-
          sing actual, as opposed to potential, exposures of  individuals in
          the general  population  or susceptible subpopulations.
     4.    Assessing whether  non-ozone  photochemical oxidants  occur  in ambient
          air at  levels within or near the range of concentrations  shown to
          produce potentially adverse  effects in health and welfare effects
          studies.
     5.    Assessing whether  concentrations of ozone plus  the  other  photochemical
          oxidants together  occur at levels  sufficient to produce adverse
          effects in  the  general  or susceptible subpopulations,  or  in vegetation
          and ecosystems.
     6.    Evaluating  the  relationship(s) between ozone and  the other photochemi-
          cal oxidants, in order  to determine whether ozone can function as  a
          control surrogate  in the  event that these other,  non-ozone photochem-
          ical oxidants are  found to produce adverse effects  on public health
          and welfare.
1.5.1  Ozone Concentrations in Urban Areas
     The current ozone standard is expressed in terms of a 1-hour value not to
be exceeded on more than 1 day per year.  Thus, the second-highest value is a
concentration of significance, since it determines compliance with the standard
and is, thereby, an indicator of exposures having potential health and welfare
significance.
     In Chapter  6, the second-highest 1-hour  ozone  concentrations  reported
in each of 4 years have been given for the 80 most populous Standard Metropoli-
tan Statistical Areas  (SMSAs)  of the United States,  i.e., those with popula-
tions > 0.5 million.   In  Table 1-7, 1982 ozone concentrations for the subset
of SMSAs with populations >_ 1 million are given by geographic area,  demarcated
according to United States  Census divisions and  regions  (U.S. Department of
Commerce, 1982).   The  second-highest  concentrations measured  in  1982  in those
38 SMSAs  having populations  of at  least  I million ranged  from 0.09 ppm in the
Ft. Lauderdale, Florida, and Seattle, Washington, areas to 0.32 ppm in the Los
Angeles and  Riverside, California, areas.  The  second-highest  1-hour ozone
concentrations for 32  of  the 38 SMSAs in Table 1-7 equal or exceed 0.12 ppm.
The data  clearly  show,  as well,   that the highest 1-hour  ozone concentrations
in the  United  States  occur in the northeast (New England and Middle Atlantic

019XX/A                             1-37                               6/29/84

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       TABLE 1-7.   SECOND-HIGHEST  1-HR OZONE  CONCENTRATIONS  IN  1982  IN
           STANDARD METROPOLITAN STATISTICAL  AREAS WITH  POPULATIONS
              >  I MILLION,  GIVEN BY  CENSUS  DIVISIONS  AND REGIONS3
Division
and region
SMSA
population,
SMSA millions
Second-highest
1982 03
concn. , ppm
NORTHEAST

  New England
Boston, MA
  Middle Atlantic  Buffalo,  NY
                   Nassau-Suffolk,  NY
                   Newark,  NJ
                   New York, NY/NJ
                   Philadelphia,  PA/NJ
                   Pittsburgh, PA
SOUTH
  South Atlantic
Atlanta, GA
Baltimore, MD
Ft. Lauderdale-Hollywood, FL
Miami, FL
Tampa-St. Petersburg, FL
Washington, DC/MD/VA
  >2

1 to <2
  >2
1 to <2
  >2
  >2
  >2
  >2
  >2
1 to <2
1 to <2
1 to <2
  >2
0.16

0.11
0.13
0.17
0.17
0.18
0.14
0.14
0.14
0.09
0.14
0.11
0.15
SOUTH

  West South
   Central
Dallas-Ft. Worth, TX
Houston, TX
New Orleans, LA
San Antonio, TX
  >2
  >2
1 to <2
1 to <2
0.17
0.21
0.17
0.14
 NORTH CENTRAL

   East  North
    Central
 Chicago,  IL
 Detroit,  MI
 Cleveland, OH
 Cincinnati,  OH/KY/IN
 Milwaukee, WI
 Indianapolis,  IN
 Columbus, OH
  >2
  >2
 1 to  <2
 1 to  <2
 1 to  <2
 1 to  <2
 1 to  <2
 0.12
 0.16
 0.12
 0.13
 0.13
 0.12
 0.13
   West North
    Central
 St.  Louis,  MO/IL
 Minneapolis-St.  Paul
 Kansas City,  MO/KS
                                          MN/WI
   >2
   >2
 1 to <2
 0.15
 0.10
 0.10
 019XX/A
                  1-38
                                                                        6/29/84

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   TABLE 1-7 (cont'd).   SECOND-HIGHEST 1-HR OZONE CONCENTRATIONS IN 1982 IN
      STANDARD METROPOLITAN STATISTICAL AREAS WITH POPULATIONS > 1 MILLION
                    GIVEN BY CENSUS DIVISIONS AND REGIONS3
Division
and region SMSA
WEST
Mountain Denver-Boulder, CO
Phoenix, AZ
Pacific Los Angeles-Long Beach, CA
San Francisco-Oakland, CA
Anaheim- Santa Ana-
Garden Grove, CA
San Diego, CA
Seattle-Everett, WA
Riverside- San Bernardino-
Ontario, CA
San Jose, CA
Portland, OR/WA
Sacramento, CA
'.MSA Sw,und-hlyh*il
population, 1982 03
millions concn. , ppm

1 to <2
1 to <2
>2
>2

1 to <2
1 to <2
1 to <2
I to <2

1 to <2
I to <2
1 to <2

0.14
0.12
0.32
0.14

0.18
0.21
0.09
0.32

0.14
0.12
0.16
 Standard Metropolitan Statistical Areas and geographic divisions and regions
 as defined by Statistical Abstract of the United States (U.S. Department of
 Commerce, 1982).
Source:   U.S. Environmental Protection Agency, SAROAD data file for 1982.

States),  in  the Gulf  Coast area (West South Central states), and on the west
coast (Pacific  states).   Second-highest 1-hour  concentrations  in the SMSAs
within each of these three areas averaged 0.15, 0.17, and 0.19 ppm, respectively,
for 1982.  It should be emphasized that these three areas of the United States
are subject to those meteorological and climatological factors that are conducive
to local oxidant formation, or transport, or both.  It should also be emphasized
that 11 of the 16 SMSAs in the country with populations >_ 2 million are located in
these areas.
     Sources  of  oxidant precursors are  strongly correlated with population
(Chapter  3).  In accord with this  relationship, three  population  groups within
the 80 largest SMSAs had the following median values for their collective second-
highest 1-hour ozone concentrations in both 1981 and 1982:  populations >^ 2 million,
0.15 ppm 0.,; populations of 1 to 2 million, 0.13 ppm 0,.; and populations of 0.5
          C5                                           «3
to 1 million, 0.12 ppm 0.,.
019XX/A                             1-39                               6/29/84

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     Among all stations  reporting  valid  ozone data (>_ 75 percent of possible
hourly values per year)  in 1979,  1980, and 1981 (collectively, 906 station-
years) in the United States, the median second-highest 1-hour ozone value was
0.12 ppm, and  5  percent of  these  stations reported  second-highest 1-hour
values > 0.28 ppm (Figure 1-3).
     A pattern of concern  in assessing human physiological and vegetational
responses to  ozone  is  the occurrence  of  repeated  or prolonged periods, or
both, when the ozone concentrations equal  or exceed levels near those known to
elicit responses.   In  addition,  the number of days  of  respite between such
multiple-day periods of high ozone is of possible consequence.   Data presented
in Chapter 6  show  that the probabilities  of  prolonged  exposures to (conse-
cutive days)  or  respites from (consecutive days) specified concentrations are
location-specific.   In  Pasadena, CA, a high-ozone  area,  there  is  a  42 percent
probability (based on 1979 through 1981 aerometric data) that an ozone concen-
tration  of 0.18  ppm, once  reached,  is  likely  to persist  for 3  days  or longer.
Other, lower-ozone  areas show lower  probabilities  of  such multiday  high  ozone
concentrations.  These and other data presented demonstrate the occurrence, at
least in some urban areas, of multiple-day exposures to relatively high concen-
trations of ozone.

1.5.2.  Trends in Urban and Nationwide Ozone Concentrations
     Discussion  in  Chapter 5 pointed  out  and substantiated  that aerometric
data obtained  by potassium iodide methods in  earlier years  are  essentially
concentrations of ozone rather  than "total oxidants."  Comparison of concen-
trations  of  "total  oxidants"  in  major  urban  areas  for 1974 and 1975 (U.S.  En-
vironmental  Protection Agency,  1978)  with ozone  data for those  same  urban
areas  for 1979  through 1982 (U.S. Environmental  Protection Agency,  SAROAD
file)  shows  that the more  recent ozone concentrations are in  the same general
range  for many  cities,  have declined in  some, and  are somewhat higher in
others.
     Trends  in  nationwide  ozone concentrations, gauged  by annual averages  at
two  subsets  of stations reporting  data from  1974  through 1981,  show  declines
of 15  to 20 percent.   These  trend  data represent urban  areas almost exclusively.
Interpretation of  this trend is complicated  by  four potentially significant
influences:   (1) a change in calibration procedure (1979);  (2) improved data-
quality  audits (1979);  (3) possible  shifts in  underlying meteorological  patterns;

019XX/A                              1-40                                6/29/84

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2
g
      99.99

    0.45
    0.40
    0.35
    0.30
    0.25
              99 9 99 8
 99  98   95    90    80  70 60 50 40  30   20    10    5    21  0.5 0.2 0 1 0.05  0.01
o
2   0.20
O
o
LU

O   0.15

O
    0.10
    0.05
      HIGHEST

 	2nd HIGHEST


	3rd HIGHEST
                                        I      II         I   \/\
       0.01  0.050.1 0.2  05  1   2    5   10    20   30  40  50  60  70  80    90   95    98  99    99.899.9    99.99


                 STATIONS WITH PEAK 1 hour CONCENTRATIONS < SELECTED VALUE, percent



        Figure 1-3. Collective distributions of the three highest 1-hour ozone concentrations for 3

        years (1979, 1980, and 1981) at valid sites (906 station-years).

-------
and (4) changes  in  precursor emission rates.   When adjustments for the first
two factors are made, a portion of the decrease is real.   The exact portion of
the decline that is attributable to the calibration change can not be determined
without minute  examination  of aerometric data records from  each  monitoring
station, since some monitoring stations began  using the UV calibration procedure
as early as  1975,  some changed to UV calibration in 1979 (but not all in the
same month  of 1979), and some used  the  interim  BAKI calibration procedure
permitted by  EPA for up to 18 months after promulgation of the UV calibration
procedure (Hunt and Curran,  1982;  also Chapter 5).

1.5.3.   Ozone Concentrations in Nonurban Areas
     Nonurban areas  are  not  routinely  monitored for ozone concentrations.
Consequently, the aerometric data  base for nonurban areas is  considerably less
substantial than for urban  areas.   Data on maximum 1-hour concentrations and
arithmetic mean 1-hour concentrations reveal that maximum (peak)  1-hour concen-
trations at  nonurban sites  classified  as rural  (SURE study,  Martinez and
Singh,  1979;  NAPBN studies,  Evans et al., 1982) may exceed the concentrations
observed at nonurban sites  classified as suburban (SURE study, Martinez and
Singh,  1979). For  example,  maximum 1-hour ozone concentrations measured in
1980 at Kisatchie National  Forest (NF),  Louisiana; Custer NF, Montana;  and
Green Mt.  NF, Vermont,  were  0.105, 0.070, and  0.115 ppm,  respectively.  Arith-
metic mean concentrations for  1980  were 0.028, 0.037, and 0.032  ppm at the
respective sites.  For four  nonurban (rural) sites in the SURE study, maximum
1-hour ozone  concentrations  were  0.106, 0.107,  0.117, and 0.153; and mean
1-hour concentrations  ranged  from 0.021  to 0.035 ppm.  At the five nonurban
(suburban) sites of  the SURE study, maximum concentrations were 0.077, 0.099,
0.099,  0.080, and 0.118 ppm, respectively.  The mean 1-hour concentrations at
those sites  were 0.023,  0.030, 0.025, 0.020,  and  0.025  ppm, respectively.
     Comparison of  these  data with data  for  nonurban and remote locations
during the 1973-1976 period  show  that mean concentrations at  these various
nonurban locations  are not  dissimilar.   Ranges  of  concentrations  and the
maximum 1-hour concentrations  at  the NAPBN and SURE sites show the probable
influence, however,  of ozone transported from urban areas.  In one documented
case, for  example, a 1-hour  peak  ozone concentration of 0.125 ppm at  an  NAPBN
site in Mark  Twain  National  Forest, Missouri, was measured during passage of
019XX/A                             1-42                               6/29/84

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an air mass whose trajectory was calculated to have included Detroit, Cincinnati,
and Louisville in the preceding hours (Evans et al.,  1982).
     These data corroborate the conclusion given in the 1978 criteria document
(U.S.  Environmental  Protection Agency,  1978)  regarding urban-nonurban and
urban-suburban gradients;  i.e.,  nonurban areas may sustain higher ozone con-
centrations than  those found in urban  areas.   Reasons for this phenomenon
include induction and transport times, as well as the possible additive effects
of plumes from suburban or smaller areas as air masses pass over them downwind
from  urban  areas.   Generally,  however,  lower  ozone  concentrations  occur  in
nonurban areas, as the data in Chapter 6 indicate.

1.5.4.  Patterns in Ozone Concentrations
     Since the photochemical reactions of precursors  that result in ozone  for-
mation are  driven  by sunlight,  as well  as  emissions,  the  patterns of ozone
occurrence  in  ambient  air  depend on daily and  seasonal variations in sunlight
intensity.  The typical diurnal pattern  of  ozone in ambient air has a minimum
ozone level around sunrise (near zero in most urban areas),  increasing through
the morning to a peak  concentration in early afternoon, and decreasing toward
minimal  levels again in the evening.  Obviously, meteorology is a controlling
factor;  if  strong winds disperse the precursors or heavy clouds intercept the
sunlight, high ozone levels will not develop.  Another important variation in
the basic diurnal  pattern  appears  in some  localities as a secondary peak in
addition to the early  afternoon peak.  This secondary peak may occur any time
from midafternoon to the middle of the night and is  attributed to ozone trans-
ported from an upwind area where high ozone levels  have occurred earlier in  the
day.  As  documented  in Chapter 6, secondary peak concentrations may be higher
than concentrations resulting from the photochemical  reactions of locally  emit-
ted precursors (Martinez and Singh,  1979).   At one  nonurban site in Massachusetts,
for example, primary peak concentrations of about 0.11, 0.14,  and 0.14 occurred
at noon,  from noon to about 4:00 p.m., and at noon, respectively,  on 3 succes-
sive days of high ozone levels (Martinez and Singh, 1979).   Secondary peaks  at
the same  site  for those same 3 days were about 0.150, 0.157, and 0.130 ppm at
about 6:00  p.m., 8:00  p.m.,  and 8:00 p.m.,  respectively (Martinez and Singh,
1979).
019XX/A                             1-43                               6/29/84

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     Because weather  patterns,  ambient temperatures, and the  intensity and
wavelengths of sunlight all play important roles in oxidant formation,  strong
seasonal as well  as diurnal patterns exist.   The highest ozone levels occur in
the summer  and fall  (second and third quarters), when  sunlight reaching the
lower  troposphere  is most  intense  and stagnant  meteorological  conditions
augment the potential  for ozone formation and  accumulation.  Average summer
afternoon levels can be from 150 to 250 percent of the average winter afternoon
levels.  Minor variations in the smog season occur with location,  however.   In
addition,  it  is  possible  for the maximum and  second-highest 1-hour ozone
concentrations to  occur outside the  two  quarters  of highest average ozone
concentrations (cf.  data for Tucson,  Arizona,  and  data for the  California
sites  given in Chapter 6).  Exceptions to seasonal patterns are important consi-
derations with regard to the protection of crops from ozone damage, especially
since  respective crops have different growing seasons in terms of length, time
of year, and areas of the country in which they are grown.
     As data for different averaging times clearly demonstrate, averaging smooths
out and submerges the occurrence of peak concentrations.  This is an obvious and
familiar  statistical  phenomenon.   It is pointed out, however, because  it has
direct relevance to  the protection of public health and welfare.  Averaging times
must correspond to or be  related in a consistent manner to the pattern  of expo-
sure that  elicits untoward  responses.
     Certain spatial  variations in ozone concentrations occur that  are  general-
ly  of  little consequence  in exposure  assessment.  For example, ozone concentra-
tions  increase with increasing altitude  (e.g., Viezee  and Singh,  1981).  The
gradients  are  of no  known  consequence  for  inhabited elevations.   They could
potentially be of  some  consequence  for high-altitude  flights  unless compensated
 for by adequate  ventilation/filtration systems.   Likewise, ozone  concentrations
 exhibit hemispheric  asymmetry (Logan  et al.,  1981),  with  concentrations highest
 in  the northern hemisphere.  Aerometric data sufficiently describe concentra-
 tions  in the  latitudes  of the United States such that the fact of asymmetry
 has no practical  consequences.
      Spatial  variations on a smaller scale assume more importance  relative to
 exposure assessment.   Indoor-outdoor gradients in ozone  concentrations are
 known to occur even in structures ventilated  by fresh  air  rather than air
 conditioning  (e.g.,  Sabersky et al., 1973; Thompson  et  al., 1973).   Ozone
 019XX/A                             1-44                               6/29/84

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reacts with surfaces  inside  buildings,  so that decay occurs fairly rapidly.
Ratios of  indoor-to-outdoor  (I/O) ozone concentrations  are  quite  variable,
however,  since the  presence  or absence of air conditioning,  air infiltration
or exchange  rates,  interior  air  circulation  rates,  and the  composition of
interior surfaces all affect  indoor ozone concentrations.  Ratios (I/O) in the
literature thus  vary  from  80 ± 10 percent (Sabersky et al.,  1973)  in an air-
conditioned office building (but with 100 percent outside air intake) to 10 to
25 percent in air-conditioned residences (Berk et al.,  1981).
     On a  larger scale,  within-city variations in  ozone concentrations can
occur, despite the commonly accepted maxim that ozone is a regional pollutant.
Data in Chapter 6 show, for example, relatively homogeneous ozone concentrations
in New Haven,  Connecticut (U.S. Environmental  Protection Agency, SAROAD files),
which is a moderately large city downwind of a reasonably well-mixed urban plume
(Cleveland et al.,  1976).   In a large metropolis such as New  York City, however,
appreciable gradients  in ozone concentration  can exist  from one side  of the
city to the other (Smith,  1981).  Such gradients must be taken into considera-
tion in exposure assessments.

1.5.5  Concentrations and Patterns of Other Photochemical Oxidants
1.5.5.1  Concentrations.   No  aerometric data are routinely obtained by Federal,
state, or  local  air pollution agencies for any photochemical oxidants  other
than nitrogen dioxide and ozone.  The concentrations presented in Chapter 6 for
non-ozone  oxidants  were  all  obtained in special  field  investigations.   The
limitations in the number of  locations and areas of the country represented in
the information  presented  simply  reflect the relative paucity of data in the
published literature.
     The four  non-ozone photochemical  oxidants for which  concentration data
have been presented are formic acid, peroxyacetyl  nitrate (PAN), peroxypropionyl
nitrate (PPN),  and hydrogen  peroxide.   Peroxybenzoyi nitrate has  not been
clearly identified in ambient air in the United States.
     Recent data  indicate  the presence  in  urban  atmospheres of only  trace
amounts of formic acid (5 15  ppb,  measured by FTIR).  Estimates in  the earlier
literature (1950s) of 600 to  700 ppb of formic acid in smoggy atmospheres were
erroneous  because  of faulty  measurement methodology (Hanst et al.,  1982).
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     The measurement methods (IR and GC-ECD) for PAN and PPN are specific and
highly sensitive, and have  been  in use in air pollution research for nearly
two decades.  Thus, the  more  recent literature on the concentrations of PAN
and PPN confirm  and extend, but do not contradict,  earlier findings reported
in the  two previous criteria  documents for ozone and  other  photochemical
oxidants (U.S.  Department of Health, Education, and  Welfare, 1970;  U.S.  Environ-
mental Protection Agency, 1978).
     Concentrations of PAN  have been reported  in the air pollution  literature
from about 1960 through the present.  The highest concentrations reported over
this extended period were  those found in the  1960s in the  Los Angeles area:
70 ppb  (1960), 214 ppb  (1965);  and 68 ppb (1968) (Renzetti and Bryan, 1961;
Mayrsohn and Brooks, 1965;  Lonneman et al.,  1976; respectively).
     The highest concentrations of PAN measured and  reported in the past 5 years
were 42 ppb at  Riverside,  California,  in 1980 (Temple and Taylor,  1983), and
47 ppb  at  Claremont, California,  also in 1980  (Grosjean,  1981).   These are
clearly the maximum concentrations  of  PAN reported for California  and for the
entire  country  in  this period.  Other  recently measured PAN concentrations  in
the Los Angeles Basin were  in the range of 10 to 20 ppb.  Average concentrations
of PAN  in  the  Los Angeles  Basin  in the  past  5 years  ranged from 4 to 13 ppb
(Tuazon et al., 1981a; Grosjean, 1981; respectively).   Only one published report
covering PAN concentrations outside California in the past 5  years is that  of
Lewis et al. (1983) for  New Brunswick, New Jersey.  The average PAN concentra-
tion was 0.5 ppb and the maximum was 11 ppb during a study  done there from  Septem-
ber  1978  through May 1980.   Studies outside  California from  the early  1970s
through 1978 showed average PAN concentrations  ranging from 0.4 ppb in Houston,
Texas,  in  1976 (Westberg et al., 1978) to 6.3  ppb in St. Louis, Missouri, in 1973
(Lonneman  et al.,  1976).  Maximum  PAN  concentrations outside  California  for the
same period ranged from  10  ppb  in  Dayton, Ohio,  in 1974 (Spicer et al. ,  1976)  to
25 ppb  in  St.  Louis (Lonneman  et al.,  1976).
      Reports of  PPN concentrations appear  in  the  literature from  about 1963
through the present.   The  highest PPN concentration reported in early studies
was  6 ppb  in Riverside, California  (Darley  et al.,  1963).  The next highest
reported PPN concentration  was 5 ppb  at  St.  Louis, Missouri,  in 1973  (Lonneman
et al.,  1976).   Among more  recent  data,  maximum PPN concentrations at respective
sites  ranged from  0.07  ppb  in  Pittsburgh, Pennsylvania, in 1981 (Singh  et  al.,
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1982) to 3.1 ppb at Staten  Island, New York  (Singh et a!.,  1982).   California
concentrations fell within this range.   Average PPN concentrations at the respec-
tive sites for the more recent data ranged from 0.05 ppb at Denver and Pittsburgh
to 0.7 ppb at Los Angeles in 1979 (Singh et al., 1981).
     Altshuller (1983) has  succinctly  summarized the nonurban concentrations
of PAN and PPN by pointing out that they overlap the lower end of the range of
urban concentrations at  sites  outside  California.   At  remote  locations,  PAN
and PPN concentrations are  lower than even the  lowest of the urban  concentra-
tions (by a factor of 3 to 4).
     In urban areas, hydrogen peroxide  (H,,02) concentrations have been reported
to range from < 0.5 ppb in Boulder, Colorado (Heikes et al., 1982) to < 180 ppb
in Riverside, California (Bufalini  et al., 1972).  In nonurban areas, reported
concentrations ranged  from 0.2 ppb near  Boulder,  Colorado, in 1978  (Kelly
et al., 1979) to < 7 ppb 54 km southeast of Tucson, Arizona (Farmer and Dawson,
1982).   These  nonurban  data were obtained by  the  luminol  chemiluminescence
technique  (see  Chapter 5).   The urban  data were obtained  by  a variety of
methods, including the  luminol  chemiluminescence,  the titanium (IV)  sulfate
8-quinolinol, and other wet chemical  methods (see Chapter 5).
     The higher  concentrations of  H^O,, reported in  the literature must  be
regarded as  especially  problematic,  since FTIR measurements of ambient air
have not demonstrated  unequivocally  the  presence of H?0?  even in the high-
oxidant atmosphere of  the  Los  Angeles  area.  The  limit of detection for a
1-km-pathlength FTIR system is around 0.04 ppm (Chapter 5); FTIR is capable of
measuring concentrations of H^O^ if it  is  present above the limit of detection.

1.5.5.2  Patterns.  The  patterns of  formic acid (HCOOH),  PAN,  PPN, and HLO-
may be  summarized  fairly succinctly.   They bear qualitative but not quantita-
tive resemblance to the patterns already summarized for ozone  concentrations.
Qualitatively, diurnal patterns are similar, with peak  concentrations of  each
of these occurring  in  close proximity  to the  time  of the ozone peak.  The
correspondence in  time of  day  is not exact, but is  close.  As the work  of
Tuazon et al. (1981) at Claremont, California, demonstrates, ozone  concentra-
tions return to baseline levels faster than the concentrations  of PAN, HCOOH,
or H202 (PPN was not measured).  The diurnal patterns of PAN were reported in
earlier criteria documents.   Newer  data merely confirm those patterns.
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     Seasonally,  winter concentrations (third and fourth quarters) of PAN are
lower than  summer  concentrations (second and third  quarters).   The winter
concentrations of  PAN  are proportionally higher, however,  than the winter
concentrations of ozone;  i.e.,  PAN-to-ozone  ratios are higher in winter.   Data
are not readily available on the seasonal  patterns of the other non-ozone oxi-
dants.
     Indoor-outdoor data on  PAN  are  limited to one report (Thompson et al.,
1973),  which  confirms  the  pattern  to be expected from the known chemistry of
PAN; that is, it persists longer indoors than ozone.   Data are lacking for the
other non-ozone oxidants.

1.5.6  Relationship Between Ozone and Other  Photochemical Oxidants
     The relationship  between  ozone  concentrations  and the concentrations of
PAN, PPN, H202,  and  HCOOH  is important only if these non-ozone oxidants are
shown to produce adverse  health or welfare  effects,  singly,  in combination
with each other, or  in various combinations with ozone.   If only ozone is
shown to produce adverse  health or welfare  effects,  then only ozone needs to
be controlled.   If any or  all  these other four oxidants is  shown to produce
adverse health or  welfare  effects,  then it, or  they,  will  also have to be
controlled.    Since ozone and all  four of the other  oxidants arise from reac-
tions among  the  same organic and inorganic precursors, an obvious question  is
whether the control of ozone will also result in the control of the other four
oxidants.
     Chapters 7  through  9  of this report document what  is known about the
welfare effects  of PAN (see  Sections 1.6 through 1.8).   No data are available
regarding the possible welfare effects of HCOOH, H202,  or PPN.   Chapters 10
through 13  document  what  is known about the  health  effects of PAN and H202
(see Sections 1.10 through  1.13).   Formic  acid is not  covered because of
extremely limited  aerometric data and  no health  effects  data pertinent to the
trace quantities of formic acid measured in  the ambient air.  No health effects
data are available  for PPN.   One report that PBzN is a potent lachrymator is
not  discussed in the health effects chapters since no reliable data indicate
its  presence  in  ambient  air, even in high-oxidant areas.  The health effects
data reported in Chapter 10 on H202 show that  all levels  tested  to date  are
orders of magnitude above even the highest concentrations reported for ambient
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air; and, as noted above, the highest concentrations reported for ambient air
are not  strongly documented.  Thus, the brief discussion below focuses on the
relationship between ozone and PAN concentrations in ambient air.
     The most straightforward evidence of the lack of a quantitative, monotonic
relationship between ozone  and  the other photochemical oxidants  is the range
of  PAN-to-0_ and, indirectly, of PAN-to-PPN ratios presented in the  review of
Altshuller (1983) and  summarized  in Chapter 6.   Ratios of PAN concentrations
to ozone concentrations, as derived by Altshuller (1983),  show that PAN-to-peak
03  ratios vary  from  1  to 12 across the  country (PAN at time of  CL  peak);
ratios for average  PAN to average 0_  concentrations vary from 2  to 20 across
the country.  The correspondence  between PAN and ozone concentrations is not
exact but is  similar for most locations at which  both pollutants have been
measured concurrently.    Disparities between  locations  point up the lack of  a
consistent quantitative relationship.   Likewise, disparities between the ratio
of  the average  concentrations  of  the two pollutants and  the ratio of their
concentrations when  ozone  is at its maximum level also point up the  lack of a
monotonically quantitative relationship.
     Certain other information presented in this chapter bears out the lack  of
a monotonic  relationship between ozone and PAN.  Not only are ozone-PAN rela-
tionships not  consistent between  different  urban areas, but they  are not
consistent in urban  versus  nonurban areas, in summer versus winter,  in indoor
versus outdoor  environments,  or  even, as the ratio  data  show,  in location,
timing,  or  magnitude of diurnal peak concentrations within the  same city.
Data  obtained  in Houston  by Jorgen et al.  (1978) show variations  in peak
concentrations of PAN measured concurrently at three separate monitoring sites
in  the same city.  Temple and Taylor (1983) have shown that PAN concentrations
are a greater percentage of ozone concentrations in winter than in the remainder
of  the year in California.  Lonneman et al.  (1976) demonstrated that PAN-to-03
ratios are considerably  lower in nonurban than in urban areas.   Thompson et  al.
(1973) showed that  PAN persists longer than ozone  indoors.   (This is to be
expected from its lower  reactivity with surfaces and its enhanced stability  at
cooler-than-ambient  temperatures such as  found  in air-conditioned buildings.)
Tuazon et al. (1981b) demonstrated that PAN persists in ambient air longer than
ozone, its persistence paralleling that of nitric acid, at least in the locality
studied  (Claremont,  CA).  Reactivity data presented in the 1978 criteria document
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for ozone and other photochemical oxidants indicated that all precursors that
give rise to PAN also give rise to ozone.   The data also showed,  however,  that
not all precursors giving  rise to ozone also give rise to PAN.   Not all  that
give rise to  both  are equally reactive toward both,  however;  and therefore
some precursors preferentially give rise,  on the  basis of units of product per
unit of reactant,  to  more of one product than the other  (U.S. Environmental
Protection Agency,  1978).
     Altshuller (1983) prepared for the U.S.  Environmental Protection Agency a
comprehensive  review  and  analysis  of  concentrations  and relationships for
ozone and other smog components, including PAN.  The smog components he reviewed
relative to ozone  included aldehydes,  aerosols,  and  nitric  acid,  as well  as
the non-ozone  oxidants  covered in this chapter.    It  must be emphasized that
Altshuller examined  the  issue of whether ozone  could serve  as an abatement
surrogate for  all  photochemical  products, not just oxidants and not just the
subset of photochemical oxidants  of concern  in this document.  His conclusion
was that "the ambient air measurements indicate that ozone may serve direction-
ally,  but cannot be  expected to serve quantitatively, as a  surrogate for the
other products"  (Altshuller, 1983).  He found  a greater correspondence between
aldehydes and their  organic precursors than between  aldehydes and ozone.  He
found  also that  the correspondence  between ozone and  PAN  concentrations (as well
as  PPN, H?02,  and  HCOOH)  is  greater by far than the ozone-aldehyde relationship.
     In summary, the  significance for public  health or welfare of  the imposition
of  an  additional oxidant  burden from non-ozone oxidant  rests on the answers to
three  basic questions:

     1.   Do  PAN,  PPN,  H202,  or HCOOH,  singly or in combination,  elicit adverse
          or  potentially  aaverse  responses?
     2.   Do  any or  all of these  non-ozone  oxidants act additively or  synergistically
          in  combination  with ozone to  elicit adverse or potentially  adverse
          responses?  Do  any or all act antagonistically with  ozone?
     3.   Do  the time course and  magnitude  of the concentrations  of these non-ozone
          oxidants parallel  the time course and  magnitude of ozone concentrations
           in  the ambient  air?

      Given  the information on health and welfare effects presented in subsequent
 chapters, coupled with the aerometric data presented  in Chapter 6, the relation-
 ship between ozone and PAN concentrations is the specific relationship of most
 concern in this document.
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1.6  EFFECTS OF OZONE AND PEROXYACETYL NITRATE ON VEGETATION
1.6.1  EFFECTS OF OZONE ON VEGETATION
1.6.1.1  Introduction.   Foliar injury to vegetation is one of the earliest and
most obvious manifestations of ozone injury to vegetation.   The effects of ozone
are not limited, however, to visible injury.   Although plant foliage is the pri-
mary site of injury, secondary effects from ozone can occur.  They include re-
duced plant growth of both roots and foliage, decreased yield, changes in crop
quality, and  alterations in susceptibility to biotic  and  abiotic stresses.
     Ozone exerts a  phytotoxic effect only if a  sufficient  amount reaches the
sensitive cellular  sites within  the leaf.   Ozone diffuses  from  the ambient
air into the leaf through the stomata, which can exert some control  on ozone up-
take, to the active sites within the leaf.   Ozone injury will not occur (1) if
the rate of ozone uptake is low enough that the plant can detoxify or metabolize
ozone or its metabolites; or (2) if the plant is able to repair or compensate for
the effects of ozone (Tingey and Taylor, 1982).   This is analogous to the response
of plants to sulfur dioxide (S02) (Thomas et al., 1950).  Cellular disturbances
that are not  repaired or compensated for are ultimately expressed as visible
injury to the leaf or as secondary effects that can be expressed as reduced root
growth, reduced yield of fruits or seeds, or both.
     Plant growth and yield are the end products of a series of biochemical and
physiological  processes  related to  uptake,  assimilation,  biosynthesis, and
translocation.  Sunlight drives those processes that convert carbon dioxide into
the organic compounds (photosynthesis) necessary for plant growth and development.
The mineral nutrients and water necessary for plant growth are extracted by the
plant from the soil.  Plant organs then convert these raw materials into a wide
array of compounds required for plant growth and yield.  A disruption or reduc-
tion in the rates of uptake, assimilation, or subsequent biochemical reactions
will be reflected in reduced plant growth and yield.  Ozone would be expected to
reduce plant growth  or yield:  (1) if it directly affected the plant process that
was limiting plant growth; or (2) if it affected another step sufficiently such
that this process became the step limiting plant growth (Tingey, 1977).  Conversely,
ozone will  not limit plant growth if the process affected  is not or does not
become rate-limiting.  This implies that not all the effects of ozone on plants
are reflected  in growth  or yield reductions.  This also suggests that there are
combinations  of  ozone concentration and exposure duration  that the plant can
experience  that  will not result in  visible injury or reduced plant  growth and

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yield.   Indeed, numerous studies have demonstrated combinations of concentration
and time that did not cause a significant detectable effect on plant growth or
yield.
     Ozone induces a diverse range of effects on plants and plant communities.
These  effects  are usually  classified  as either  injury or damage.   Injury
encompasses all plant reactions such as reversible changes in plant metabolism
(e.g.,   altered photosynthesis), leaf  necrosis,  altered plant  quality,  or
reduced  growth that  do  not impair  yield  or intended  use of  the  plant
(Guderian, 1977).  In contrast, damage or yield loss includes all effects that
reduce  the  intended  use  or  the  value of  the  plant,  such as  a  reduction in  the
quantity  or  in aesthetic value; or any impairment in the intended use of the
plant.    For  example,  visible foliar injury to ornamental  plants, detrimental
responses  in native species, and  reductions  in fruit and  grain  production
are all considered as damage or yield loss.  Although it is not always classi-
fied as damage, the occurrence of foliar injury is an indication that phytotoxic
concentrations of ozone are present.  In areas displaying foliar injury,  addi-
tional   studies should be conducted to assess the risk of ozone to vegetation and
to  determine  if  the intended use or value of the plants is being impaired.
1.6.1.2   Limiting Values of Plant Response.  Several approaches have been used
to  estimate the ozone concentrations and exposure durations that  induce foliar
injury.   Most  of these studies  have used short-term exposures (less than 1 day)
and have  measured visible injury as the  response variable.  In one approach to
estimating the concentrations and durations that would induce specific amounts
of  visible  injury,  plants  were exposed to  a range of  ozone concentrations  and
exposure  durations and the  resulting data were evaluated by regression analysis
(Heck  and Tingey, 1971).  Data  for  several  species were summarized to illustrate
the range of concentrations  required to  induce  foliar  injury  (5 and 20 percent)
on  sensitive,  intermediate,  and less sensitive  species (Table 1-8).
     An alternative  approach for estimating  the ozone  concentrations and exposure
durations that induce foliar injury is to  use limiting-value  analysis (Jacobson,
1977).   The  limiting-value  method was  developed from  a review of  the literature
and represents the  lowest concentration  and  exposure  duration reported to  cause
visible injury on various  plant species.  The analysis was based on more than
100 studies  of agricultural  crops  and  18 studies  of tree  species.  The analysis
yielded the following range of concentrations and exposure durations that are
 likely to induce foliar injury (U.S.  Environmental Protection  Agency, 1978).

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 TABLE 1-8.   OZONE CONCENTRATIONS FOR SHORT-TERM EXPOSURES THAT PRODUCE 5 OR 20
        PERCENT INJURY TO VEGETATION GROWN UNDER SENSITIVE CONDITIONS3
Exposure
time, hr
0.5
1.0
2.0
4.0
8.0
Sensitive plants
0.35 to 0.50
(0.45 to 0.60)
0.15 to 0.25
(0.20 to 0.35)
0.09 to 0.15
(0.12 to 0.25)
0.04 to 0.09
(0.10 to 0.15)
0.02 to 0.04
Intermediate plants
0.55 to 0.70
(0.65 to 0.85)
0.25 to 0.40
(0.35 to 0.55)
0.15 to 0.25
(0.25 to 0.35)
0.10 to 0.15
(0.15 to 0.30)
0.07 to 0.12
Less
sensitive plants
SO. 70 (0.85)
£0.40 (0.55)
£0.30 (0.40)
£0.25 (0.35)
£0.20 (0.30)
 The concentrations in parenthesis are for the 20% injury level.   Table from
 U.S.  Environmental Protection Agency (1978).
1.    Agricultural crops:
     0.20 to 0.41 ppm for 0.5 hr
     0.10 to 0.25 ppm for 1.0 hr
     0.04 to 0.09 ppm for 4.0 hr

2.    Trees and shrubs:
     0.20 to 0.51 ppm for 1.0 hr
     0.10 to 0.25 ppm for 2.0 hr
     0.06 to 0.17 ppm for 4.0 hr
It should be emphasized that both approaches estimate concentrations and exposure
durations that might induce visible injury but that they cannot be used to pre-
dict impacts on crop yield or intended use.  It should also be emphasized that
both approaches are still considered valid.
     The concept of  limiting values has also been used to estimate the ozone
concentrations and  exposure durations which could  potentially reduce plant
growth and yield (U.S.  Environmental  Protection Agency, 1978).  The data were
analyzed and  plotted  in a manner similar  to the  appraoch  of  Jacobson  (1977)
(Figure 1-4).   In Figure 1-4 the line bounds mean ozone concentrations and ex-
posure durations below which effects on plant growth and yield were not detected.
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   1.0
OL
a
O
LU
O

I
Z
O
N
O
   0.1
  0.01
                           1      I   I   I   I  1111
                                     21D  11Q
           \   44 • 19O18 *45  *46       •48-52
                                             10
             XO24   '	*" Q31   7QQ20
              \      J514  30   59
                                 • •42430Q9
*  1213    41    ,
\     26       '
  \  1C*  CD29
   \      39
    \
                                             33
                                               34-
                                           53
           EXPOSURE, hr/day
             A < 1.99
             D   2 TO 3.99
             O   4 TO 5.99
             • 3* 6
           IMOS. = REF. NOS. ON TABLE 11-4
           I I II  I         I      I    I   I  I  I  I  II
                                                     57
8  10
           20        40    60   80  100
           EXPOSURE PERIOD, days
                                                           200
                                                                    400
      Figure 1-4. Relationship between O3 concentration, exposure dura-
      tion, and a reduction in plant growth or yield (see Table 7-18; also
      U.S. EPA, 1978).
      Source: U.S. Environmental Protection Agency (1978).
                                  1-54

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This graphical  analysis  used data from both greenhouse and field studies and
indicates that  the  lower limit for reduced plant performance is a mean ozone
concentration of 0.05 ppm for several hours per day for exposure periods greater
than 16 days.  The 03 response threshold increases to about 0.10 ppm at 10 days
and to about 0.30 ppm at 6 days.
1.6.1.3   Methods for Determining Ozone Yield Losses.   Diverse  experimental
procedures have  been  used  to study the effects of ozone on plants, including
studies under highly controlled conditions, exposures in open-top chambers, and
field exposures  without  chambers.  In  general, the more controlled conditions
are most  appropriate  for investigating specific responses and  for providing
the scientific basis for interpreting and extrapolating results.  These systems
are powerful tools  by which  to gain  increased  understanding of  the biological
effects of air pollutants.   To assess the impact of ozone on plant yield, however,
it is desirable to minimize deviations from the typical environment in which the
plant is  grown.   For  field crops, this  implies  that  the studies should be
conducted in the field,  but for crops that are typically grown in glass houses,
the studies should be conducted under glass-house conditions.
     To improve  estimates  of yield loss in the field, the National Crop Loss
Assessment Network (NCLAN)  was initiated by EPA in 1980 to estimate the magni-
tude of crop losses caused by 03  (Heck et al., 1982).  The primary objectives
of NCLAN were:

     1.    To define the relationships between yields of major agricultural
          crops and 0- exposure as required  to support the needs  of eco-
          nomic assessments  and  the  development of National  Ambient Air
          Quality Standards;
     2.    To assess  national economic consequences  resulting from the
          exposure of major agricultural crops to 0-; and
     3.    To advance the understanding of the  cause and effect  relation-
          ships  that  determine crop responses  to  pollutant  exposures.

     The NCLAN experimental  sites were selected on the basis  of (1) differing
climatic conditions, (2) distribution  of crop species, and (3) the existence
of established  research  groups  studying air  pollution  effects on plants.
Cultural conditions at these  sites approximate typical agronomic practices and
open-top field exposure chambers  are used to minimize perturbations of the plant
environment during the exposure.   The investigators involved have attempted to

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use realistic 03 concentrations and sufficient replication to permit the develop-
ment of exposure-response models.   The data have been analyzed using regression
approaches.   The exposures are characterized by a 7-hr (9:00 a.m.  to 4:00 p.m.)
seasonal mean 03 concentration.  This is the time period during which 0, is added
to the exposure chambers.
1.6.1.4  Estimates of Yield Loss.   Studies, frequently using open-top exposure
chambers, have been  conducted to  estimate the effects of 03 on the yield of
various crop species.  These  studies can be grouped  into two types, depending
on the  experimental  design  and statistical methods used to analyze the data:
(1) studies  in which predictive  equations relating  03  exposure to plant
response were developed;  and (2) studies in which discrete treatment levels were
compared to a control.   The advantage of the regression approach is that exposure-
response models can  be  used to interpolate results between treatment levels.
Both types of experimental design, however, provide useful  data for determining
the effects of 03 on plants.
     In the NCLAN studies, ozone was added to either charcoal-filtered or ambient
air to create the range  of 03 concentrations that is required when the regression
approach is used to estimate Og-induced yield loss.   In summarizing the data,  03~
induced yield loss was derived from comparing performance of 0_-exposed plants
to that of plants in charcoal-filtered air.  Various regression techniques have
been used to derive exposure-response functions.   The use of regression approaches
permits the estimation of the effects of 03 on plant yield over the range of con-
centrations, not  just at  the  treatment means, as is  the case with analysis of
variance methods.   Examples of graphs of exposure-response equations and the data
used to derive them show the fit of the various models to the experimental data
(Figure 1-5).
     Linear regression equations have been used to estimate yield loss but for
some species and  cultivars  there  appear to be systematic deviations from the
                                                                          2
data even though  the equations had high coefficients  of determination  (r  ).
The use  of  plateau-linear or polynomial equations appeared  to fit the data
better.  More recently,  a Weibull  model has been used that yields a curvilinear
response line providing a reasonable fit to the data.  This model has also been
used to  develop yield response equations,  combining  the responses  for  several
cultivars of a species (Figure 1-6).   Statistical analysis  indicates that  for
most crops the model fits the combined data, as well as the data for the indivi-
dual cultivars.   Yield  losses  for some major crop  species were estimated
using  the combined  models.   It appears that 03 affects the yield of corn and
wheat  much  less  than it does  the  yields  of cotton, soybeans, and  peanuts.
019XX/A                             1-56                               6/29/84

-------
 CO

lj>
    3000
    2500
    2000
    1500
    1000
                          1         \
                         CORSOY SOYBEAN
      (A)
      Y = 3099.3 -15135.0 ±03  R2 = .975

      I        I        I         I
         0.00     0.05     0.10     0.15

               O3 CONCENTRATION, ppm
                                      0.20
                                               160
                                            ^ 120
                                            JS
                                            .0.
                                            "
                                                80
                                         Q
                                         O
                                         a.
                                                40
                                                                        PEANUT (NC-6)
                                                                        RALEIGH, 1980
                                                          (B)
                                                  1. Y = 173-1046 + 03  R2 = .96
                                                  2. Y = 142.3 IF 03^.037
                                                    Y= 184.6-1160 ± 03 IF 03 >.037 R2 = .99

                                                        I         I         I
0.00      0.05     0.10      0.15

        O3 CONCENTRATION, ppm
                                                                                 0.20
X
O
UJ

a
Hi
Ul
v>
     260
     240
     220
200
     180
160
  OJ
                          I          I
                           CORN (COKER 16)
                           RALEIGH, 1976
             Y = 222.91 + 331.11 ± 03-3511.99 ± 032
             Y = 247.8 - 260 ± 03 R2 = .65
                 J_
                      I
I
00     0.05      0.10      0.15

       O3 CONCENTRATION, ppm
                                          0.20
                                                 _CD
                                                 _a
                                                 "Si
                                            Q
                                            u
                                            m
                                            CO
                                                               WINTER WHEAT (HOLLY)
                                                               RALEIGH, 1977
                                               - (D)
                                                  1. Y = 4.5333 + 19.31 ± 03-215.1 ± 032
                                                  2. Y = 5.7 16 + 03 R2 = .82
                                                  3. Y = 4.9 IF 03 < .087
                                                    Y = 8.2 - 38 ± 03 IF 03 > .087 R2 = .99
                                                         I
                             I
 0.00     0.05     0.10     0.15    0.20

        O3 CONCENTRATION, ppm
       Figure 1-5. Examples of effects of O3 exposure on yield of various plants. O3
       concentration (ppm) is expressed as 7-hr seasonal mean. Soybean (A) data from
       Kress and Miller (1983); peanut (B) data from Heagle et al., (1983) and Heck et
       a!., (1982); corn (C) and wheat (D) data from Heagle and Heck (1980) and  Heck et
       al., (1982).
                                           1-57

-------
   1.0
01
g  0.8
(0
LU
oc
111

>  0.6
g

QC
O  0.4
Q.
O
OC
Q.
   0.2
   0.0
	WHEAT
     	  SOYBEANS


     	  PEANUTS
     0.0
 0.02       0.04        0.06       0.08


           O3 CONCENTRATION, ppm
                                                          0.10
       Figure 1-6. Relative O3-induced yield reduction of selected crops
       as predicted by the Weibull model (Heck et al., 1983).
                                 1-58

-------
     The yield response models  can  be used to estimate the 0, concentrations
that induce losses (e.g.,  10 and 30  percent losses) in various plant species and
cultivars (Table 1-9).   In general,  when several  models were fit to the data they
tended to predict similar concentrations that induced yield losses.  In the case
of corn, turnip, and winter wheat, however, the linear model tended to underesti-
mate the 0- concentrations that would cause 10 or 30 percent yield reductions.
The similarity among the estimated concentrations for a given cultivar suggests
that the predicted  values  are influenced to a greater extent by the original
data than  by  the  model  used to  describe the data.  A brief  review  of the data
(Table 1-9) indicates that for several species, mean yield reductions of 10 per-
cent were predicted when the 7-hr seasonal mean 0~ concentration exceeded 0.04
to 0.05 ppm.
     In  addition  to the studies  in  which regression approaches were  used,
various  other approaches  have  been  used to investigate the  effects  of 0~
treatments  that  were different  from the  control,  rather than to develop
exposure-response equations.   In general,  these data were  analyzed using
analysis of variance.   Table  1-10 summarizes concentrations of  0.,  reported  to
produce  a  loss  of 10 percent  in  the  yield of a number  of crops.  To summarize
the data from studies that used discrete treatments, the lowest 0_ concentration
that significantly reduced yield was determined from the analyses of the authors
(Table 1-10).   The lowest concentration reported to reduce yield was frequently
the lowest concentration used in the study; hence, it was not always possible to
estimate a  no-effect  exposure level.  In  general,  the data indicate that 0_
concentrations of 0.10  ppm (frequently the lowest  concentration used  in the
studies) for  a  few  hours per day for several  days  to  weeks generally  caused
significant yield reductions.   Although it appears from this analysis that a
higher 0- concentration was required to cause an effect than estimated from the
regression studies, it should be noted that the concentrations derived from the
regression studies were based on a 10 percent yield loss, while in studies using
analysis of variance (Table 1-10) the 0.10 ppm concentration frequently induced
mean yield losses of 10 to 50 percent.
     The data from the previous criteria document (U.S. Environmental Protection
Agency,  1978) were used to develop limiting values that suggested that 0_ concen-
trations of 0.04  to 0.06 ppm for 4  hours  or more were likely to injure plant
foliage.  The growth data summarized  in that document  indicated that plant growth
and yield  can be  reduced  at 0-  concentrations  of 0.05  to  0.08  ppm  for  several

019XX/A                              1-59                               6/29/84

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                                            TABLE 1-9.  SEASONAL 7-hour OZONE CONCENTRATIONS  (ppra) AT WHICH YIELD
                                         LOSSES OF 10 PERCENT OR 30 PERCENT ARE PREDICTED FROM EXPOSURE-RESPONSE MODELS
 i
en
o

Plants
Grains/Seeds
Soybean
(Corsoy)
(Corsoy)
(Davis)
(Davis)
(Essex)
(Hodgson-F)*
(Hodgson-P)*
(Williams)
Peanut - 1979+
Peanut - 1980
Peanut - 1980

Peanut - 1980
Kidney bean
Kidney bean
Field Corn
(Coker 16)
(Coker 16)

(Coker)
(PAG 397)
(Pioneer 3780)
Winter wheat
(Blueboy II)
(Blueboy II)

(Blueboy II)
(Coker 47-27)
(Coker 47-27)

(Coker 47-27)
(Holly)
(Holly)

(Holly)
(Holly)


Model


Kg/ha = 3099.3 - 15135 x 03
g/plant = 15.6 exp [-(03/0.129)1'70]
seed wt/« = 534.5 - 3988. 6x03-H0960xO§
g/plant = 31.1 exp [-(03. 0.129)0'91]
g/plant = 18.7 exp [-(03/0.309)0'76]
g/plant = 15.2 exp [-(03/0.207)0' so]
g/plant = 15.5 exp [-(Og/O.lSS)1'57]
g/plant = 19.4 exp [-03/0. 243)°' 94]
pod wt/plant = 112 - 563 x 03
pod wt/plant = 173 - 1046 x 03
pod wt/plant = 142.3 if 03 £ 0.037;
if 03 > 0.037 PW/P = 184.6 - 1160 x 03
g/plant - 148 exp [-(03/0.186)3'20]
seed wt/plant = 17.44 - 35.51 x 0,
g/plant = 16.5 exp [-(03/0.287)1-"]

g/plant 247.8 - 260 x 03
g/plant = 222.91-t-331.ll x 03-
3511.99 x 0§
g/plant = 240 exp [-(03/0.221)4'46]
g/plant = 166 exp [-(03/0.160)4'28]
g/plant = 149 exp [-(03/0.155)3' J1]

g/plant = 6.6 - 18 x 03
g/plant = 5.908 + 3.958 x 03 -
137.7 x 0§
g/plant = 5.88 exp [-(03/0.175)3'22]
g/plant = 5.8 - 21 x 03
g/plant = 5.765 - 18.79 x 03 -
20.00 x 0§
g/plant 5.19 exp - [-(03/0. 171)2'06]
g/plant = 5.7 - 16 x 03
g/plant = 4.533 + 19.31 x 03-
215.1 x 0§
g/plant = 4.95 exp [-(03/0. 1564'95]
g/plant = 4.9 if x S 0.087
if 03 > 0.087 g/p =8.2 -38 03
Control 03
Concentration


0.022
0.022
0.025
0.025
0.014
0.017
0.017
0.014
0.026
0.025
0.025

0.025
0.025
0.025

0.02
0.02

0.02
0.15
0.15

0.03
0.03

0.03
0.03
0.03

0.03
0.03
0.03

0.03
0.03

Yield
10%


0.040
0.043
0.038
0.038
0.037
0.039
0.043
0.038
0.043
0.039
0.049

0.046
0.072
0.086

0.113
0.132

0.133
0.095
0.075

0.063
0.0187

0.088
0.055
0.055

0.064
0.063
0.095

0.099
0.100

Loss
30%


0.077
0.076
0.070
0.071
0.109
0.096
0.084
0.098
0.078
0.067
0.073

0.073
0.165
0.164

0.300
-

0.175
0.126
0.111

0.131
0.129

0.127
0.104
0.103

0.107
0.128
0.129

0.127
0.126


Reference


Kress and Miller, 1983
Heck et al., 1983
Heagle et al . , 1983
Heck et al. 1983
Heck et al. 1983
Heck et al. 1983
Heck et al. 1983
Heck et al. 1983
Heagle et al. , 1983
Heagle et al . , 1983
Heck et al . , 1982

Heck et al . , 1983
Kohut and Lawrence, 1983
Heck et al., 1983

Heck et al. , 1982
Heagle & Heck, 1980

Heck et al . , 1983
Heck et al., 1983
Heck et al . , 1983

Heck et al . , 1982
Healge and Heck, 1980

Heck et al . , 1983
Heck et al. , 1982
Heagle and Heck, 1980

Heck et al., 1983
Heck et al., 1982
Heck et al., 1982

Heck et al . , 1983
Heck et al., 1982


-------
                                           TABLE 1-9.   SEASONAL 7-hour OZONE CONCENTRATIONS (ppra) AT WHICH YIELD
                                   LOSSES OF 10 PERCENT OR 30 PERCENT PREDICTED FROM EXPOSURE-RESPONSE MODELS (continued)
cr,
Plants
(Oasis)
(Oasis)

(Oasis)
Cotton
Root Crops
Turnip
(Just Right)
(Just Right)

(Just Right)
(Purple Top
White Globe)
(Purple Top
White Globe)
(Purple Top
White Globe)
(Shogoin)^
(Shogoin)
(Tokyo Cross)
(Tokyo Cross)

(Tokyo Cross)
Foliage Crops
Lettuce
Lettuce
Spinach
(America)
(Winter
Bloomsdale)
(Winter
Bloomsdale)
(Hybrid 7)
(Hybrid 7)
(Viroflay)
(Viroflay)
Model
g/plant = 4.9 - 12 x 03
g/plant = 4.475 + 3.320 x 03 -
93.49 x 0§
g/plant = 4.88 exp [-(03/0. 186)3'20]
g/plant = 41.5 exp [-(03/0. 197)1' 12]


edible rt wt/plant = 12.9 - 94 x 03
edible rt wt/plant = 10.7 if 03 SO. 038
if 03 > 0.038 = 15.5 - 127 x 03
g/plant = 10.89 exp [-(03/0.090)3'05]
edible rt wt/plant = 7.2 - 49 x 03

edible rt wt/plant = 6.0 if 03 SO. 034
if > 0.034 ERW/P =8.1 -60 x 03
g/plant = 6.22 exp [-(03/0.095)2' S1]

edible rt wt/plant = 5.3 - 36 x 03
g/plant = 4.68 exp (-(03/0.096)2- 12]
edible rt wt/plant = 18.1 - 116 x 03
edible rt wt/plant = 14.8 if 03 S 0.054
if 03 > 0.054 ERW/P = 27.0 - 226 x 03
g/plant = 15.25 exp [-(03/-.094)3'94]

fresh hd wt/plant = 1065.7 - 5978 x 03
g/plant = 1245 exp [-(03/0.098)1- 22]
g/plant =22.7 - 106 03
if 03 > 0.087 g/p =8.2 -38 03
g/plant = 23.3 - 121 x 03

g/plant = 20.8 exp [-(03/0.127)2-°7]

g/plant = 42.1 - 193 x 03
g/plant = 36.6 exp [-(03/0. 139)2' 68]
g/plant = 46.1 - 238 x 03
g/plant = 41.1 exp [-(O-j/0.129)1' "]
Control 03
Concentration
0.03
0.03

0.03
0.018


0.014
0.014

0.014
0.014

0.014

0.014

0.014
0.014
0.014
0.014

0.014

0.043
0.043
0.024

0.024

0.024

0.024
0.024
0.024
0.024
Yield
10*
0.068
0.088

0.093
0.041


0.026
0.046

0.043
0.027

0.045

0.040

0.027
0.036
0.028
0.061

0.053

0.057
0.053
0.043

0.041

0.049

0.043
0.060
0.041
0.048
Loss
30%
0.143
0.138

0.135
0.092


0.051
0.063

0.064
0.054

0.065

0.064

0.054
0.060
0.057
0.074

0.072

0.084
0.075
0.081

0.075

0.080

0.082
0.095
0.075
0.080
Reference
Heck et al.
Heagle and

Heck et al.
Heck et al.


Heck et al.
Heck et al.

Heck et al.
Heck et al .

Heck et al.

Heck et al.

Heck et al.
Heck et al.
Heck et al.
Heck et al.

Heck et al.

Heck et al.
Heck et al .
Heck et al.

Heck et al.

Heck et al.

Heck et al .
Heck et al.
Heck et al.
Heck et al.
, 1982
Heck, 1980

, 1983
, 1983


, 1982
, 1982

, 1983
, 1982

, 1982

, 1983

, 1982
, 1983
, 1982
, 1982

, 1983

, 1982
, 1983
, 1982

, 1982

, 1983

, 1982
, 1983
, 1982
, 1983
                *The Hodgson data were obtained from two designs in 1981; a full harvest (F) and a partial plot harvest (P),
                 where some plants were removed prior to harvest.

                *This model did not fit the data well and tended to underestimate the 03 concentrations which cause yield losses.

-------
                               TABLE 1-10.  OZONE CONCENTRATIONS AT WHICH SIGNIFICANT YIELD LOSSES HAVE BEEN NOTED FOR A VARIETY OF
                                               PLANT SPECIES EXPOSED TO 03 UNDER VARIOUS EXPERIMENTAL CONDITIONS
 i
01
IX)
              Plant species
Alfalfa
Alfalfa
Pasture grass
Ladino clover
Soybean
Sweet corn
Sweet corn
Wheat
Radish
Beet
Potato
Pepper
Cotton
Carnation
Coleus
Begonia
                       Exposure duration
                                 Yield reduction,
                                   % of control
                          03 concentration,
                                 ppm
         Reference
7 hr/d, 70 d
2 hr/d, 21 d
4 hr/d, 5d/wk, 5 wk
6 hr/d, 5 d
6 hr/d, 133 d
6 hr/d, 64 d
3 hr/d, 3 d/wk, 8 wk
4 hr/d, 7 d
3 hr
2 hr/d, 38 d
3 hr/d, every 2 wk, 120 d
3 hr/d, 3 d/wk, 11 wk
3 hr/d, 2 d/wk, 13 wk
24 hr/d, 12 d
2 hr
4 hr/d, once every 6 d for
a total of 4 times
51, top dry wt                0.10
16, top dry wt                0.10
20, top dry wt                0.09
20, shoot dry wt              0.10
55, seed wt/plant             0.10
45, seed wt/plant             0.10
13, ear fresh wt              0.20
30, seed yield                0.20
33, root dry wt               0.25
40, storage root dry wt       0.20
25, tuber wt                  0.20
19, fruit dry wt              0.12
62, fiber dry wt              0.25
74, no of flower buds         0.05-0.09
20, flower no.                 0.20
55, flower wt                 0.25
Neely et al., 1977
Hoffman et al., 1975
Horsman et al., 1980
Blum et al., 1982
Heagle et al., 1974
Heagle et al., 1972
Oshima, 1973
Shannon and Mulchi, 1974
Actedipe and Ormrod, 1974
Ogata and Maas, 1973
Pel 1 et al., 1980
Bennett et al., 1979
Oshima et al., 1979
Feder and Campbel1, 1968
Adedipe et al.,  1972
Reinert and Nelson, 1979
              Ponderosa pine
                   6 hr/d, 126 d
                              21,  stem dry wt
                                                                                             0.10
                                               Wilhour and Neely, 1977

-------
TABLE 1-10.   OZONE  CONCENTRATIONS AT WHICH SIGNIFICANT YIELD LOSSES HAVE BEEN NOTED FOR A VARIETY OF
          PLANT SPECIES  EXPOSED TO 03 UNDER VARIOUS EXPERIMENTAL CONDITIONS (continued)





1
en
CO








Plant species
Western white
pine
Loblolly pine
Pitch pine
Poplar
Hybrid poplar
Hybrid poplar
Red maple
American
sycamore
Sweetgum
White ash
Green ash
Willow oak
Sugar maple
Exposure duration
6

6
6
12
12
8
8
6

6
6
6
6
6
hr/d,

hr/d,
hr/d,
hr/d
hr/d
hr/d,
hr/d,
hr/d,

hr/d,
hr/d,
hr/d,
hr/d,
hr/d,
126 d

28 d
28 d
, 5 mo
, 102 d
5 d/wk, 6 wk
6 wk
28 d

28 d
28 d
28 d
28 d
28 d
Yield reduction,
% of control
9,

18,
13,
stem dry wt

height
height

growth
growth
+1333, leaf abscission
58,
50,
37,
9,

29,
17,
24,
19,
12,
height
shoot
height
height

height
total
height
height
height
growth
dry wt
growth
growth

growth
dry weight
growth
growth
growth
03 concentration,
ppm Reference
0.

0.
0.
0.
0.
0.
0.
0.

0.
0.
0.
0.
0.
10

05
10
041
15
15
25
05

10
15
10
15
15
Wilhour and Neely

Wilhour and Neely
Wilhour and Neely
Wilhour and Neely
Patton, 1981
Patton, 1981
, 1977

, 1977
, 1977
, 1977

Dochinger and Townsend, 1979
Kress and Skelly,

Kress and Skelly,
Kress and Skelly,
Kress and Skelly,
Kress and Skelly,
Kress and Skelly,
1982

1982
1982
1982
1982
1982

-------
hours per day.  These  concentrations  are similar to the concentrations (0.04
to 0.07 ppm)  shown  in  this document to  reduce  plant yield in field studies
(using various approaches) and in ambient air studies.
1.6.1.5  Effects on Crop Quality.   Although  only a  few studies  have been
reported,  0,.  can also  reduce  crop quality in addition to reducing the total
yield of the  crop.   Quality is a general term that  includes many features of
the crop such as  nutritional  composition, appearance, taste, and ability  to
withstand storage and shipment.  Examples of 0~-induced alterations in quality
are decreased oil  in  soybean  seeds (Howell  and Rose, 1980; Kress and Miller,
1983); decreased p-carotene, vitamin C, and carbohydrates in alfalfa (Thompson
et al., 1976; Neely et a!., 1977);  and increased  reducing sugars  in potatoes,
which are associated with undesirable darkening when potatoes are used to make
potato chips  (Pell  et al., 1980).
1.6.1.6  Yield Loss from Ambient Exposures.   Of the  studies  done  to determine
the impact  of ambient  air oxidants (primarily 0_) on plant  yield, most  have
compared the  yield  differences between plants grown in ambient air and those
grown in charcoal-filtered air.  Early research documented that ambient oxidants
reduced the yield  and  quality of citrus, grape,  tobacco, cotton,  and potato
(U.S. Environmental  Protection Agency,  1978).  More recent  studies have sub-
stantiated  the effects  of ambient oxidants on  plant yield.   Ozone has been
shown to  induce  significant yield reductions in tomato and  bean (Maclean  and
Schneider,  1976),  soybean (Howell  et  al.,  1979), two sweet  corn  cultivars
(Thompson et  al.,  1976),  and  in  native  plants  (forbes,  grasses,  and  sedges)
(Duchelle et  al., 1983).   In a study conducted over  several  years, bean yields
varied  from a 5  percent increase to  a 22 percent decrease  in response to 03
concentrations in  excess  of 0.06 ppm (Heggestad  et  al., 1980).  Studies con-
ducted  on  eastern  white  pine  in the southern Appalachian mountains have shown
that  exposure to 0, in ambient air has reduced the  radial  growth of sensitive
                   «j
individual  trees  30 to 50 percent annually over the last 15 to 20 years (Mann
et  al., 1980; Benoit  et al. , 1982).  Field  studies in the  San  Bernardino
National  Forest  have shown that  during  the  last  30  years exposure to ambient
air 0-.  reduced height  growth  of  ponderosa pine  by 25 percent, radial  growth by
37  percent,  and the  total wood volume  produced  by 84 percent (Miller  and
Elderman, 1977).
1.6.1.7  Statistics Used to Characterize Ozone Exposures.    The  characteriza-
tion  and  representation of plant  exposures  to 0_ has been, and continues to
be,  a major problem.   Research has  not yet  clearly  identified which  components
019XX/A                             1-64                               6/29/84

-------
of the pollutant exposure cause the plant response.   Most studies have charac-
terized the exposure  by  the use of mean 0, concentrations, although various
averaging times have  been  used.   Some studies have  also  used cumulative 0-
dose.   The difficulty of selecting an appropriate statistic by which to charac-
terize plant exposure has been summarized by Heagle  and Heck  (1980).  Ambient
and experimental  03 exposures have been presented  in published studies as
seasonal, monthly,  weekly,  or daily means; peak  hourly means; number of  hours
above a  selected  concentration; or the number of hours above  selected concen-
tration intervals.  None of these statistics have adequately characterized the
relationship among  0_ concentration,  exposure  duration,  interval  between
                     «3
exposures, and  plant  response.   The use of a mean concentration implies that
all concentrations  of 0- are equally  effective in causing  plant  responses and
minimizes the contributions of  the peak concentrations to the response.  The
mean  treats  low-level long-term  exposures  the  same as  high-concentration
short-term exposures.   Most of the reported exposure statistics are not directly
correlated with each  other  and it is difficult to relate them to ambient air
measurements of 0~, which  are usually reported  as  1-hr  means.   Also it is
difficult to transform  one  exposure statistic to another without reanalyzing
the original air monitoring data.
     Studies with beans  and tobacco (Heck et a!.,  1966)  showed that a dose
(concentration  x  time)  over a short period induced more injury than the same
dose  distributed  over a longer period.  Tobacco studies  showed that the 0_
concentration was approximately twice as important  as exposure duration in
causing foliar injury (Tonneijck, 1984).   In beans,  foliar injury was shown to
                                                       -2
occurred  when  the internal  0- flux  exceeded  5500  ug m   in 1  hr  (Bennett,
1979).  A single 3-hr exposure, however, at approximately half the concentration
(0.27 compared  with 0.49 ppm)  required a 64 percent greater internal flux of
0~ to produce  the same amount of  foliar injury  as  the 1-hr  exposure.   The
greater  importance  of concentration compared to exposure  duration has been
reported  by  numerous authors  (e.g.,  Heck and Tingey,  1971;  Henderson and
Reinert,  1979; Reinert and  Nelson, 1979).
      Not  only  are  concentration  and time important,  but  also the dynamic
nature of the  0-  exposure; i.e.,  is  the exposure  at a constant or variable
concentration?  Musselman  et al.  (1983)  recently showed  that  constant concen-
trations  of  0-  caused the  same  kinds  of  effects  in  plants  as  variable concen-
trations  at equivalent doses; but, the variable concentration exposures  caused
a  greater effect  than the  constant exposures.   Studies with  radishes exposed
019XX/A                             1-65                                6/29/84

-------
to ambient air ozone  showed  that significant yield reductions occurred when
the daily maximum 0-  concentration  exceeded 0.06 ppm at least 10 percent of
the days or more  (Ashmore,  1984).   In soybeans, reduced yield (weight/seed)
was most closely correlated with the number of 0~ peaks in excess of 0.10 ppm
                                                •3
(Pratt, 1982).   Studies with SO- have also shown that plants  exposed to variable
concentrations exhibited  a  greater  plant response than those  exposed to a
constant concentration (Mclaughlin et al., 1979; Male et a!.,  1983).
1.6.1.8  Relation Between Yield Loss and Foliar Injury.   Because plant growth
and production depends on photosynthetically functional  leaves, various studies
have been conducted to  determine the association between foliar  injury  and
yield for species in which the foliage is not part of the  yield.   Some research
has demonstrated significant yield loss with little or no  foliar injury (e.g.,
Tingey et al., 1971;  Tingey  and Reinert, 1975; Kress and  Skelly,  1982; Feder
and Campbell,  1968;  Adedipe et al.,  1972).  Other studies  showed that signifi-
cant foliar injury  did  not  always cause  a  yield  loss (Heagle et al., 1974;
Oshima et al., 1975).   The relative  sensitivities of two potato cultivars were
reversed when judged  by foliar injury versus yield reductions (Pell  et al.,
1980).   In field corn, foliar injury occurred at a lower 0~  concentration than
yield  reductions; but as  the 0-  concentration  increased, yield was reduced  to
a  greater extent than foliar injury was  increased  (Heagle et al., 1979a).   In
wheat, foliar injury  was  not a good predictor of 0--induced yield reductions
(Heagle et al.,  1979b).
1.6.1.9  Physiological  Basis of  Yield  Reductions.   As discussed  earlier  in
this summary, plant  growth  is the summation of a series  of biochemical  and
physiological  processes  related to  uptake,  assimilation, biosynthesis,  and
trans!ocation.  Am  impairment  in these processes may lead to  reduced plant
yeild  if the process  is limiting.
     For growth to occur, plants must assimilate carbon dioxide and convert it
into organic substances; thus, an inhibition in carbon assimilation (photosyn-
thesis) may be reflected in altered plant growth or yield.  In several species
03  (at 0.05 ppm and  higher)  inhibited photosynthesis,  as measured by gas-
exchange (e.g., U.S.  Environmental Protection Agency, 1978;  Coyne and Bingham,
1978;  Black et  al.,  1982).   Biochemical  studies showed that 03 (0.12 ppm for
2  hr)  inhibited  an  enzyme that  catalyzes the  assimilation of  carbon  dioxide
(Pell  and Pearson, 1983).
     In  addition to  decreasing  the  total  amount of carbon  dioxide that  is
assimilated, ozone alters the pattern  by  which  the reduced amount of  assimilate
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is partitioned throughout the  plant.   There is generally less photosynthate
translocated to the roots and to the reproductive organs (e.g.,  Tingey et al. ,
1971; Jacobson, 1982; Oshima et al., 1978, 1979; Bennett et al., 1979).  This
reduces root size and vigor as well  as marketable yield.
     Reproductive capacity (flowering and seed set) is  reduced by 0~  in orna-
mental plants, soybean,  corn,  wheat,  and some other plants (Adedipe  et al.,
1972a, Feder and Campbell, 1968; Heagle et al., 1972,  1974;  Shannon and Mulchi,
1974).  These data suggest that 0~ impairs the fertilization process in plants.
This  suggestion  has been confirmed in tobacco and corn studies  using low
concentrations (0.05 to 0.06 ppm) of 03 (Feder, 1968;  Mumford, 1972).
     Ozone both in  field and chamber studies stimulates premature senescence
and  leaf  drop  (Menser and Street, 1962; Heagle et al.,  1974;  Heggestad, 1973;
Pell  et al.,  1980;  Hofstra  et al., 1978).   In part,  the O^induced  yield
reductions have been  attributed to  premature senescence.   The premature leaf
drop  and  senescence decrease  the amount of photosynthate that a  leaf can
contribute to  plant  growth  and yield and also the time during which the leaf
contributes.
1.6.1.10  Factors Affecting Plant Response to Ozone.   Numerous factors influence
the  type  and  magnitude  of plant response to 0«.   Most studies of the factors
influencing plant  response  have been  limited  to  effects  on  foliar injury,
although some studies have measured  yield and a few have examined the physiolo-
gical basis for  such influences.   The factors studied  include environmental
factors,  biological  factors,  and interactions with other  air  pollutants.
1.6.1.10.1  Environmental conditions.   Environmental  conditions  before  and
during plant exposure are more influential in determining the magnitude of the
plant response than  post-exposure conditions.  The influence  of environmental
factors has  been studied primarily under controlled  conditions  but  field
observations have substantiated the results.   Most studies have evaluated  the
influence of  only  a single  environmental factor and,  in most, foliar injury
was  the plant  response  measured.   Some generalizations of  the  influence of
environmental  factors can be made.

     1.   Light conditions that are conducive  to stomatal opening appear
          to  enhance  03  injury (U.S.  Environmental  Protection  Agency,
          1978).   Light  is required to induce stomatal opening permitting
          the plant to absorb pollutants.
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     2.    No  consistent  pattern relating plant response  to  temperature
          has  been observed  (U.S. Environmental Protection Agency, 1978),
          although plants do not appear to be sensitive at extremely  high
          or  low  temperatures.

     3.    Plant injury tends to  increase with increasing  relative  humidity
          (U.S.  Environmental  Protection  Agency,  1978).   The  relative
          humidity  affect appears to  be  related to stomatal aperture,
          which  tends to  increase  with increasing  relative humidity.
          Mclaughlin  and Taylor (1980) demonstrated that plants  absorb
          significantly  more 0.. at high humidity  than at low humidity.
          It  is  generally  accepted  that plants in  the eastern United
          States  are injured by lower concentrations  of  0~ than  their
          counterparts  in California  .  This difference  has been  attri-
          buted to differences  in humidity (U.S. Environmental  Protection
          Agency, 1978).

     4.    As  soil moisture decreases, plant water stress increases and
          there  is  a reduction in plant sensitivity to 0^ (U.S. Environ-
          mental  Protection  Agency,  1978).  The  reduced CL  sensitivity  is
          apparently  related to stomatal closure,  which reduces CU uptake
          (U.S.   Environmental   Protection  Agency;  Olszyk and  Tiboits,
          1981;   Tingey  et al. ,  1982).  Water  stress does not  confer a
          permanent  tolerance  to 0-; once the water stress  is alleviated
          the plants regain their sensitivity  to CL (Tingey  et  al. ,
          1982).

1.6.1.10.2  Interaction  with plant diseases.  Ozone  affects  the development of

disease in plant populations.   Most  laboratory  evidence  suggests  that 03  (at

ambient concentrations  or greater for 4  or more hours)  inhibits  infection by

pathogens and  subsequent disease  development (Laurence, 1981; Heagle  1982;

U.S. Environmental  Protection Agency, 1978).   Increases, however, in diseases

from "stress  pathogens"  have  been  noted.   For example,  plants exposed to  03

were more readily  injured  by  Botrytis  spp.  than plants not exposed to 03

(Manning et al.,  1970a,b; Wukasch and Hofstra 1977a,b; Biseassar,  1982).   Both

field and laboratory studies  have  confirmed that the roots and cut stumps of

0--injured ponderosa and  Jeffrey  pines are more  readily colonized by  a root
 •J
rot  (Heterobasidion annosum).   The degree of infection was correlated  with the

foliar  injury  (James et al., 1980a; Miller et al.,  1982).   Studies in  the  San

Bernardino National  Forest  showed  that Og-injured  trees were  predisposed  to

attack  by bark beetles  and that fewer bark beetles were required to kill  an

03-injured tree  (Miller et al.  , 1982).
1.6.1.10.3   Interaction of ozone  with other  air pollutants.   The report   of

Menser  and  Heggestad (1966) provided the  initial impetus  for studying the

interaction  of 0,  with  SO-.  They showed that Bel W-3 tobacco plants  exposed
                 «3         <-
to  0,  (0.03 ppm) or S0? (0.24 to 0.28 ppm) were uninjured but  that substantial
     O                 £•
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foliar injury resulted when  the plants were exposed to both gases simultane-
ously.   Subsequent  studies (both greenhouse and  field)  have confirmed and
extended the observation that combinations of 0, and SO,, frequently cause more
                                               O       C,
visible injury than expected  based  on the  injury from the  individual gases.
This injury enhancement  (synergism)  is most common at low  concentrations of
each gas and also when the amount of foliar injury induced by each gas,  indivi-
dually, is  small.  At higher concentrations, or when extensive injury occurs,
the effects of the individual  gases  tends to be less than additive (antagonis-
tic).   The  effects of  pollutant combinations has also been investigated in
relation to other plant  effects besides foliar injury,  and these have  been
discussed in  several  reviews  and numerous individual reports (e.g., Reinert
et a!., 1975; Ormrod, 1982; Jacobson and Colavito, 1976; Heagle and Johnston,
1979;  Olszyk and Tibbitts, 1981).
     There have been fewer studies of the effects of 0, and S0»  on plant yield
than on  visible  injury  (Flagler and Younger, 1982a;  Foster et  al. ,  1983;
Heggestad and Bennett, 1981;  Heagle et al., 1983a).  In  field  studies,  the
addition of SCL  to  03 generally did not influence the 0- response unless the
concentrations and exposure frequencies  were greater than  those  of S0? that
typically occur in the ambient air of the United States.
     The applicability of the yield  results from pollutant combination studies
to ambient  conditions  is  not  known.  An analysis of  ambient air monitoring
data indicated that at sites  where the two pollutants were co-monitored, 10  or
fewer periods of co-occurrence  occurred during the growing  season (Lefohn and
Tingey, 1984).   Co-occurrence was defined as the simultaneous occurrence of
hourly-average concentrations of 0.05  ppm or greater for both pollutants.  At
this time,  it appears  that most of the  studies  of  the effects  on pollutant
cominations (03  and SO-)  on plant yield have used a higher  frequency of expo-
sure duration and pollutant  co-occurrence  than  occurs  in the ambient air.
     Only a few  studies have investigated the effects of 0-  with  other pollu-
tants and no clear trend is available.   Preliminary studies using three-pollu-
tant mixtures (0~, S0»,  N0»)  showed that the addition of S02 and NCL (at low
concentrations) caused a greater growth reduction than 03 alone.
1.6.1.11  Economic Assessment of Ozone Effects  Ozone  has  been  identified as
the most  important air pollutant in terms of spatial distribution and impacts
on agricultural yields.   Given  the  importance of United States agricultural
products to both domestic and world  consumption of food and fiber, significant
reduction in their supply would have substantial economic consequences.
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Various methods have been  used  to assess the economic impact of 0^, many of
which have been simplistic.   Reliable  assessment procedures should use theo-
retically justified economic  methodologies  that consider the effects to both
the producer and consumer.   These methods usually address price changes result-
ing from  adjustments in  production and the role of producer input and output
substitution strategies.   The resulting  estimates more accurately assess the
true economic impact than other procedures.
     Numerous studies  have attempted  to assess the dollar  losses  to crop
production that result from exposures  to ozone  in ambient air.  The  quality
of these  various  estimates  is variable.   For example,  the economic loss data
cited in the previous criteria document (U.S. Environmental  Protection Agency,
1978) used simplistic traditional approaches that were not well-based theoreti-
cally.  Therefore, the previous estimates should be viewed with caution.  Most
of the  economic assessments of  agricultural losses  since the last criteria
document (U.S.  Environmental Protection Agency, 1978) have focused on regional
losses.  Crop loss  estimates  for southern California  ranged from 45  million
(Adams  et a!.,  1982)  to approximately 100  million  dollars  (Leung  et a!.,
1982).  These studies  used different assessment methodologies and considered
the effects  of  ozone  on  different crops.   The  economic  impact of ozone  on
corn, wheat, and  soybeans  for the "Corn  Belt"  was estimated at 688 million
dollars (Adams  and  McCarl,  1984), while  for Illinois  alone the losses were
estimated at 55 to 200 million dollars (Mjelde et al., 1984).
     Only a  few studies  have  attempted to assess the national economic conse-
quences of  ambient  ozone.   Nationwide economic  losses have  been estimated to
be between approximately 2  billion (SRI,  1981; Adams and Crocker, 1982b)  and  3
billion dollars (Shriner et al.,  1982).   These estimates include more  complete
dose-response information  for an increasing number  of major commodities and
better  air  quality  data  than previous national  estimates (U.S. Environmental
Protection Agency,  1978).   These estimates  should be  considered preliminary,
however,  since  two  of the  three  studies used simple traditional  approaches.
      In summary,  the current  dollar  estimates of crop  damage are useful  primari-
ly as  indicators  of the  magnitudes of  impact.  A full  accounting of  the economic
mechanisms underlying agricultural production  is required to provide  definitive
estimates of the  extent  of  agricultural  losses.   Such  accounting should include
both  annual  and perennial  crops  (agronomic  and  horticultural) and  the associated
dynamic  adjustments  of agricultural  production.   It must consider the effects

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on intermediate consumers, such as livestock growers and food processors, and
final consumers, both domestic and foreign.  The effect of 0,, on ornamentals,
both physically and economically,  has also never been addressed.

1-6-2  Effects of Peroxyacetyl Nitrate on Vegetation
1.6.2.1  Introduction.  Peroxyacetyl  nitrate (PAN)  is an extremely phytotoxic
air  pollutant  that  is  produced by photochemical reactions  similar  to those
that produce  ozone.   The  sequence of events within  the plant leading to the
effects of  PAN is  conceptually similar to that described for 0.,, except that
the pollutants apparently have different reactive sites within the cells.   The
symptoms of photochemical  oxidant injury that were originally described (prior
to 1960) have  subsequently been shown to be identical with the symptoms produced
by PAN.  Following  the  identification of PAN  as a  phytotoxic air pollutant,
PAN  injury  (foliar  symptoms)  has  been observed throughout California and in
several other  states and foreign countries.
1.6.2.2   Factors Affecting Plant  Response to PAN.    Herbaceous   plants  are
sensitive to PAN and cultivar differences in sensitivity have been observed in
field and  controlled  studies.   Trees and other woody  species,  however, are
apparently  resistant  to visible  foliar  injury (Taylor,  1969; Davis, 1975,
1977).
     There  is an absolute requirement for  light  before,  during, and after
exposure or visible PAN injury will  not  develop (Taylor et  a!.,  1961).  Field
observations  have  shown that crops  growing  under  moisture  stress developed
little  or  no injury during photochemical oxidant episodes while, adjacent to
them, recently irrigated crops were  severely injured (Taylor, 1974).
     Only  a few studies have  investigated the effects of PAN and 0_ mixtures
on plants.   When plants were  exposed to  both gases  at  their  respective  injury
thresholds,  no interaction between the gases was  found (Tonneijck,  1984).   At
higher  concentrations,  the effects  were less  than  additive.  Studies  with
petunia confirmed  that  0, tended to  reduce  PAN injury (Nouchi et al. ,  1984).
1.6.2.3   Limiting  Values  of  Plant Response.   The  limiting-value method has
been used   to  estimate  the lowest PAN concentration and exposure duration
reported to cause  visible injury on  various plant species  (Jacobson,  1977).
The  analysis yielded  the  following range of concentrations  and  exposure dura-
tions  likely to induce  foliar  injury:  (1) 200 ppb  for 0.5 hr; (2) 100  ppb for
1.0  hr; and (3) 35  ppb  for 4.0 hr.

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     More recent studies,  however,  suggest that these  values  need to be lowered
by 30 to 40 percent to reduce the likelihood of foliar injury (Tonneijck,  1984).
For example, foliar  injury  developed  on petunia plants exposed at 5 ppb PAN
for 7  hours (Fukuda  and  Terakado, 1974).  Under field  conditions,  injury
symptoms may  develop on  sensitive  species when  PAN  concentrations reach
approximately 15 ppb for 4 hours (Taylor,  1969).
1.6.2.4  Effects of PAN on Plant Yield.   Only  limited  studies  have been con-
ducted to  determine  the  effects of PAN  on plant growth and yield.   In green-
house studies,  radish, oat, tomato, pinto bean, beet, and barley were exposed
to PAN concentrations of up to 40 ppb  for 4 hours per  day,  twice per week,  from
germination to crop maturity (Taylor et  al., 1983).   No significant effects on
yield were detected.   This  is  supportive of  field observations,  in which
foliar injury occurred on these species  from ambient PAN exposures but no evi-
dence was  seen  of  reduced yield in these  crops.   In  contrast, lettuce and
Swiss chard exposed to PAN concentrations of up to 40  ppb for 4 hours per day,
twice a  week,  from germination to crop  maturity showed yield losses up to 13
percent  (lettuce)  and 23  percent (Swiss chard) without visible foliar injury
symptoms (Taylor et  al. ,  1983).  The  results indicate that PAN at concentra-
tions below the injury threshold can cause  significant yield losses  in  sensi-
tive cultivars of leafy vegetable crops.  In addition  to reduced yield without
visible  injury,  photochemical  oxidant  events  have  caused  foliar injury on
leafy vegetables (Middleton  et al., 1950).  After  severe  PAN  damage, entire
crops may  be unmarketable  or else extensive hand work may  be required to
remove the injured leaves before the crop may be marketed.
     A comparison  of PAN  concentrations likely to cause either visible  injury
or reduced yield with the measured ambient concentrations (Chapter 6) indicates
that it  is unlikely that PAN effects will occur to plants in the United States
except in  some  areas  of California and  in possibly a few other localized areas.
1.7   EFFECTS  OF  OZONE AND OTHER PHOTOCHEMICAL OXIDANTS ON NATURAL ECOSYSTEMS
1.7.1  Introduction
     Temperate forest ecosystems within the United States currently are exper-
iencing  declines.   Tree responses,  unless they are  the  result of a  specific
biotic disease  or an acute pollutant exposure, are cumulative and frequently
the  culmination  of a number of chronic stresses (Figure 1-7).  Among chronic
stresses to which  trees are exposed is air pollution.
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       r~
 ABIOTIC AGENTS
   OF DISEASE
AIR POLLUTION
HIGH
 TEMPERATURES
FREEZING
 TEMPERATURES
PESTICIDES
DROUGHT
SALT
POOR SOIL
 AERATION
MINERAL
 DEFICIENCY
SOIL
 POLLUTION
MECHANICAL
 DAMAGE
           DECLINE DISEASES
          OF COMPLEX ORIGIN
 FUNCTIONAL PARTS
     OF A TREE
                         REDUCED
                         GROWTH <
                          SHOOT
                          BLIGHT
PHOTOSYNTHESIS
 TRANSPIRATION
    SHOOTS:^
CHLOROSIS OF
   FOLIAGE
^-HEIGHT GROWTH
                     FOLIAGE DISEASES
                       VASCULAR WILTS

                       &
                       SAP ROT
                BRANCHES AND STEM:
                  TRANSLOCATSON
                  STRUCTURE
                  STORAGE
                  SECONDARY GROWTH
                                            CANKER GALL
                   TRANSLOCATION
                   STRUCTURE
                   STORAGE
                                                            ROOTLET^
                                                            NECROSIS
     MYCORRHIZAE (FUNGUS ROOTS)
 BIOTIC AGENTS
   OF DISEASE
FUNGI
BACTERIA
MYCOPLASMAS
RICKETTSIA
SPIROPLASMA
VIRUSES
INSECTS
MITES
NEMATODES
HIGHER PLANTS
                           WATER AND MINERAL
                           ABSORPTION
                           PROTECTION
                           ROOT PATHOGENS
 Figure 1-7. Summation of abiotic and biotic agents involved in diseases of trees, given by
 types of diseases and functional parts of the tree. Decline diseases are caused by a com-
 bination of biotic and abiotic agents.

 Source:  Manion (1981).
                                      1-73

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     The mixed-conifer forests of the San Gabriel and San Bernardino mountain
ranges east of  Los  Angeles  have  been exposed to oxidant air pollution since
the early  1950s (Miller, 1973).  Ozone  was  first identified as the  agent
responsible for the slow decline and death of ponderosa pine (Pinus ponderosa
Laws) trees  in these forests  (Miller  et al., 1963).  Later, Jeffrey pine
(Pinus jeffreyi Grev. &  Balf.)  was  also found to be injured by 03 exposure.
Oxidant injury  of eastern white pine (Pinus strobus L.) has been observed for
many years in  the  eastern  United States.  It was  first  reported as  needle
blight in  the  early 1900s but in 1963 was shown to be the result of acute and
chronic ozone  exposure (Berry  and  Ripperton,  1963).   More recently,  oxidant
injury of  eastern white pine in the Blue Ridge Mountains of Virginia  has been
reported by Hayes  and  Skelly (1977) and on the  Cumberland  Plateau of east
Tennessee  by Mann  et  al.  (1980).   In addition,  ozone injury in  natural plant
communities has been reported by Treshow and Stewart (1973)  and  by Duchelle et
al. (1983).

1.7.2  Oxidant-induced Effects on a Western Coniferous Forest Ecosystem
     One of the most thoroughly studied ecosystems in the United States is the
mixed coniferous forest  ecosystem in the San  Bernardino Mountains  of  southern
California.  The San  Bernardino  Forest is located at the eastern  end of the
80-mile-long South  Coast Air Basin, where a severe air pollution problem has
been  created  by the  last  three decades of extensive  urban and industrial
development (Miller  and  Elderman,  1977).  Oxidants carried by the marine air
flow probably  entered the forest in the early 1940s or soon after when vegeta-
tion  injury was first recognized near the coast.  Sensitive plant species in
the National Forest, such as ponderosa pine, began showing unmistakable injury
in  the  early  1950s (Miller and Elderman, 1977), but the source of the injury
was  not identified as  QS until  1962 (Miller et  al.,  1963).   Extensive visible
injury  and concern about the possible adverse effects of chronic 03  exposure
on  an important forest ecosystem led to  an interdisciplinary study.   From  1973
to  1978,  a study was conducted to  determine the response of the organisms  and
biological processes of  the conifer forest to chronic oxidant exposures and to
interpret  responses within the ecosystem context  (Miller et  al., 1982).
      The  ecosystem processes analyzed were:  (1)  carbon  flow (the  movement of
carbon  dioxide into the plant;  its incorporation into  green plant organic
matter;  and then  its partitioning  among consumers,  litter, decomposers,  and
the soil;  and  its  return to the atmosphere);  (2) the movement of water in the
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soil-piant-atmosphere continuum; (3) mineral  nutrient  flow through the green
plant  litter  and soil-water  compartments;  and (4) the  shift  in diversity
patterns in time  and space as represented by changes  in composition of tree
species in stands, age, structure,  and density.
     All of the ecosystem processes mentioned above were shown by the study to
be affected directly or  indirectly.  Foliar  injury of  sensitive  ponderosa and
Jeffrey pine was observed when 03 concentrations ranged from 0.05 to 0.06 ppm.
During the period of study, average 24-hr 03 concentrations during the months
May through September ranged from a background of  0.03 to 0.04 ppm to a maximum
of 0.10 to 0.12 ppm.
     Less sensitive  trees,  in decreasing order of sensitivity, were white fir
(Abies concolor  Lindl.),  black  oak (Quercus kelloggii Newb.), incense cedar
( Libocedrus  decurrens  Torr.),  and  sugar pine (Pinus  lambertiana Doug!.).
Associated with  foliar  injury were  a decrease in  photosynthesis, a reduction
in tree growth  (both height and diameter), and a reduction in seed production
in ponderosa  and Jeffrey pine.   Foliar  injury, premature  needle fall, and
senescence decreased the amount  of foliage capable of conducting  photosynthesis
and a  reduction in  carbohydrates  decreased the capacity  of  the remaining
foliage.   Carbon  flow  in the form of  carbohydrates  diminished as stressed
trees  retained  smaller amounts of  assimilated carbon  after  transpiration
losses.  The amounts of  mineral  nutrients in the  living  foliage of injured
ponderosa pines were lower than in needles on healthy trees.  The store of
carbon and  mineral  nutrients  accumulated in the  thick needle layers under
stands of 0~-injured trees and  their movement back  into  the  trees was cur-
tailed.  Nutrient availability was influenced by a reduction in  the number of
species and the population  density of the fungi that normally colonize living
needles and  later  participate in decomposition, because the  usual  increase
that occurs with age was prevented by premature needle senescence and abscis-
sion (Miller et al. ,  1982).  Stressed trees  showed a decrease  in  the number of
mycorrhzial  rootlets and their  replacement  by small  saprophytic  fungi  in the
small   rootlets  of  stressed trees (Parmeter et al.,  1962).  Mycorrhizae  are
very sensitive to the photosynthetic capacity of the host and to the capacity
of the host to  translocate carbon compounds to the roots (Hacskaylo, 1973).
     A comparison of the radial  growth of ponderosa pine during years (1910 to
1940) of low pollution  (<0.03  ppm)  with years (1941 to 1971)  of high pollution
(0.03 to 0.12 ppm) indicate that 0.,  exposure reduced the average  annual  radial
growth by approximately  40 percent,  height  by 25  percent,  and wood volume by
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84 percent in trees less than 30 years of age.   The marketable volume of trees
30 years of age was  reduced by 83 percent in the  areas  with the highest 0~
concentrations.
     Stressed pines also  became  more  susceptible to root rot (Heterobasidion
annosum) and pine beetle (Dendroctonus brevicomis), as the result of weakening
of the  host  by  photochemical  oxidants.   Photochemical oxidant injury of pon-
derosa pines  results  in reduced oleoresin yield,  rate of flow and exudation
pressure, moisture of phloem and sapwood, and phloem  thickness.  All of  these
are believed  to  be important in the defense of the tree against bark beetles
(Stark and Cobb, 1969).   Studies also indicate that a disease-insect relation-
ship exists between  root-infecting  fungi  and bark beetles.   Approximately 80
percent of the ponderosa pines infested with bark beetles had been infected by
root-disease  fungi prior  to beetle  infestation (Stark and Cobb,  1969).   Ver-
ticicladiella wagenerii was the major fungus attacking the roots.  The fungus
moves from tree  to tree via the roots.  Heterobasidion  annosum was  likewise
found to  have infected  conifer roots prior to beetle attack.  Heterobasidion
usually does  not become a serious problem in California forests,  however, until
disturbances by humans,  such as logging, have occurred (Stark and Cobb,  1969).
Mortality rate  of  the trees reached 2  to  3  percent in some years.   Injured
ponderosa and Jeffrey pines older than  130 years produced significantly  fewer
cones per tree than  uninjured  trees  of the same  age (Luck, 1980).   Heavy
litter  accumulation occurred in  stands  with  the most  severe  needle  injury and
defoliation.   Pine seed establishment was hindered by litter depth, but the
growth  of oxidant-tolerant understory  species  was encouraged.   Buildup of
litter  and the  presence of  easily ignited  foliage  on  smaller trees  could lead
to destructive fires.    Removal by 0- and by fires of the pine-dominated forest
and the reduction of competition among remaining trees leads to a dominance in
these forests of  self-perpetuating,  fire-adapted,  0~-tolerant shrub and oak
species mixtures that provide fewer commodity and amenity values than the former
pine  forest  and that inhibit  reestablishment  of pines and  other conifers.
     Any  mature  natural community  transfers 10 to  20 percent of the energy
fixed by plants to herbivores (Woodwell, 1974).  Consumer organisms constitute
an extremely  diverse  group,  and  only  a  limited  amount of information on  their
response to pollutants  is available (Newman, 1979).  The influence of oxidants
on these  organisms is assumed to be  mainly  through the food webs.   At  this
time, studies have not  indicated a  direct impact of 0_  on the organisms  them-
selves.   The  breakdown, however, of  the processes  of energy  flow and nutrient
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cycling resulting from  the  disruption of photosynthesis, reproduction, or a
structural change among  the producers within ecosystems can affect consumers
by removing their shelter and food source.

1.7.3  Effects of Ozone on Other Ecosystems
     The  responses that  have been observed in the San Bernardino Forest eco-
system from 0~-associated stress  have also been observed in other ecosystems
within the United States that have been exposed to the same or lower ranges of
0, concentrations.
     Studies made along  the Blue  Ridge Parkway and on the Cumberland Plateau
of east  Tennessee  support  the  view  that exposure to CL  reduces  growth in
sensitive trees  (Benoit  et  al., 1982).   Eastern white pine of reproducing age
located in experimental  plots  situated along the Blue Ridge Parkway from the
Shenandoah National Park in the north to the southernmost end of the Parkway
in Virginia were studied to determine  the radial  increment during the 1955 to
1978 period.   Growth of trees classified as sensitive was 25 percent less;  and
in trees classified as intermediate in sensitivity, growth was 15 percent less
than in tolerant trees.  Mean radial  increments for all trees during the last
10 years of the study were smaller than for the previous 24 years.   Comparison
of growth during 1974 to 1978 with radial growth during 1955 to 1959 indicated
a decrease in growth of 26,  37,  and 51 percent for tolerant, intermediate,  and
sensitive trees.  During the period  of the study, concentrations of 0.05 to
0.07 ppm  of 03  were  recorded on a recurring  basis,  with episodic peaks of
0.12 ppm  or higher occurring (Benoit  et  al.,  1982).  Steady decline in  annual
ring increments of  sensitive white pine was  also  observed on the Cumberland
Plateau during  the years 1962 to 1979  (Mclaughlin  et al., 1982).  A reduction
of 70 percent in average annual growth and 90 percent in average bole growth
was observed in sensitive white pine when compared to both tolerant trees and
trees of intermediate sensitivity.   Annual  occurrences of 0, at hourly concen-
                                                           «3
trations  of 0.08 ppm  or  greater were associated with the growth reductions.
Reduction in growth of  sensitive  white pine on the Blue Ridge Parkway and on
the Cumberland  Plateau,  as  in  the case  of the San Bernardino Mountains, was
correlated with the predisposing symptoms of chronic decline,  which includes the
following sequence  of events and conditions:   (1)  premature senescence and loss
of older needles at the end  of the growing season; (2) reduced storage capacity
of carbohydrates in the fall and resupply capacity in the spring to support new
needle growth;  (3)  increased reliance of new needles on self-support during growth;
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(4) shorter new needles,  resulting in lower gross photosynthetic productivity;
(5) higher retention of current photosynthate by foliage resulting in reduced
availability of photosynthate for external usage (including repair of chroni-
cally stressed tissues of  older  needles); and (6) premature casting of older
needles (Mclaughlin et al., 1982).   Degeneration of feeder roots and mycorrhi-
zae usually precedes  the  onset  of above-ground symptoms (Manion, 1981).   De-
creases in nutrient and water uptake may also occur.  These changes produce
weakened trees.  Weakened  trees  are,  in turn, predisposed to attack by root-
rot fungi  such as Heterobasidion  annosum, Verticicladella  wagenerii,  and
V. procera,  to defoliation by insects,  and to attack by  the  pine  beetle,
Dendroctonus breviconn's.
     Injury by  03 to native  herbaceous  vegetation  growing in the Virginia
mountains was also observed (Duchelle et al.,  1983).   Ambient 0_ concentrations
were shown to  reduce  growth and productivity  of graminoid  and  forb vegetation
in the Shenandoah National Park.   For each year of the study, biomass production
was greatest for  vegetation grown in filtered-air chambers.  The total 3-year
cumulative dry weight  for the filtered chambers was  significantly (P <0.05)
different from non-filtered and  open-air plots.   Common milkweed (Ascelepias
syrica L.) and  common blackberry (Rubus allegheniensis Porter) were the only
two native species to develop visible injury.  Milkweed has been previously
shown to be quite sensitive to 03 (Duchelle and Skelly, 1981).   Ozone episodes
occurred several  times each year during  the period of the  study.  Peak hourly
concentrations ranged  from 0.08  to 0.12 ppm;  however, monthly hourly average
concentrations ranged  from 0.03  to 0.06 ppm.   The effects of  0, in  altering
the  natural  vegetation of the Virginia  mountains was not  assessed.   Lower
biomass production could  result  in selection for  vegetation  better able to
cope with  the  03 stress.   As in California,  0_  is transported from distant
sources to the Virginia mountains.  In the Blue Ridge and Appalachian Mountains,
these sources include the  industrial midwest,  eastern Virginia, and the Washing-
ton, D.C., area.
     In  Utah,  Treshow and Stewart  (1973)  conducted  one of the  few  studies
concerned  with the impact of air  pollution  on  natural  plant communities.
Grassland, oak,  aspen,  and conifer communities  in  the Salt Lake Valley and
Wasatch  Mountains were studied.   Some dominant species considered  keys  to
community integrity were found to be sensitive.  Bromus tectorum L.   (cheatgrass),
the  most prevalent species  in the grassland  community,  was also the most
sensitive  to  0».   Other  grasses  and forbs were not as sensitive (Table 1-11);
               O
however,  in  those grasses with  visible  injury,  carbohydrate production was
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                                                          TABLE  1-11.   INJURY THRESHOLDS FOR 2-HOUR EXPOSURES TO OZONE
                             Species
                                             Injury threshold,
                                              ppm 03 for 2 hr
          Species
Injury threshold,
 ppm 03 for 2 hr
 i
~~j
vo
Grassland-oak community species:

  Trees and shrubs:
    Acer grandidentatum Nutt.                   over 0.40
    Acer negundo L.                             over 0.25
    Arteresia tridentata Nutt.                       0.40
    Mahonia repens G. Don                       over 0.40
    Potentilla frutlcosa L.                          0.30
    Quercus gambelii Nutt.                           0.25
    Toxicodendron radicans (L.) Kuntze          over 0.30

  Perennial forbs:
    Achillea millefolium L.                     over 0.30
    Ambrosia psilostachya DC.                   over 0.40
    Calochortus nuttallii Torr.                 over 0.40
    Cirsium arvense (L. ) Scop.                       0.40
    Coniurn maculaturn L.                          over 0.25
    Hedysarum boreale Nutt.                          0.15
    Helianthus anuus L.                          over 0.30
    Medocago sativa L.                                0.25
    Rumex crispus L.                                 0.25
    Urtica gracilis Ait.                              0.30
    Vicia americana Muhl.                        over 0.40

  Grasses:
    Bromus brizaeformis  Fish. & Mey.                  0.30
    Bromus tectorum L.                                0.15
    Poa pratensis L.                                 0.25

Aspen and conifer community species:
              Trees and shrubs:
                Abies concolor (Gord. & Glend.) Lindl.           0.25
                Amelanchier alnifolia Nutt.                      0.20
                Pachystima myrsinites (Pursh) Raf.          over 0.30
                Populus tremuloides Michx.                       0.15
Perennial forbs:
  Alii urn acuminatum Hook                            0.25
  Angelica pinnata S.  Wats.                   under 0.25
  Aster engelmanni (Eat.) A.  Gray                   0.15
  Carex siccata Dewey                               0.30
  Cichorium intybus L.                              0.25
  Cirsium arvense (L. ) Scop.                   under 0.40
  Epilobium angustifolium L.                         0.30
  Epilobium watsoni Barbey                          0.30
  Eriogonum heraclioides Nutt.                       0.30
  Fragaria ovalis (Lehm.) Rydb.                      0.30
  Gentiana amarella L.                         over 0.15
  Geranium fremontii Torr.                     under 0.40
  Geranium richardsonii Fisch.  & Traut.             0.15
  Juncus sp.                                    over 0.25
  Lathyrus lanzwertii  Kell.                    over 0.25
  Lathyrus pauciflorus Fern.                         0.25
  Mertensia arizonica Greene                        0.30
  Mimulus guttatus DC.                         over 0.25
  Mimulus moschatus Dougl.                     under 0.40
  Mitel la stenopetala Piper                    over 0.30
  Osmorhiza occidental is Torr.                       0.25
  Phacelia heterophylla Pursh                 under 0.25
  Polemonium foliosissiraum A. Gray                  0.30
  Rudbeckia occidental is Nutt.                       0.30
  Saxifraga arguta D.  Don                     under 0.30
  Senecio serra Hook.                                0.15
  Taraxacum officinale Wiggers                  over 0.25
  Thalictrum fendleri  Engelm.                  over 0.25
  Veronica anagallis-aquatica L.                     0.25
  Vicia americana Muni.                         over 0.25
  Viola adunca Sm.                              over 0.30
                                                                          Annual forbs:
                                                                            Chenopodium fremontii Wats.                 under 0.25
                                                                            Callomia linean's Nutt.                     under 0.25
                 Ribes  hudsonianum  Richards.                       0.30
                 Rosa woodsii  Lindl.                          over  0.30
                 Sambucus  melanocarpa A. Gray                 over  0.25
                 Symphoricarpos  vaccinioiders Rydb.                0.30

               Perennial forbs:
                 Actaeu arguta Nutt.                               0.25
                 Agastache urticifolia  (Benth.) Kuntze             0.20
            Source:  Treshow and Stewart (1973).
                                                                            Descurainia californica  (Gray) 0.E. Schulz         0.25
                                                                            Galium bifolium Wats.                         over  0.30
                                                                            Gayophytum racemosura T.  & G.                       0.30
                                                                            Polygonum douglasii Greene                    over  0.25

                                                                          Grasses:
                                                                            Agropyron caninum (L.) Beauv.                 over  0.25
                                                                            Bromus carinatus Hook. & Arn.                under  0.25

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significantly reduced.  Aspen (Populus tremuloides Michx) was the most sensi-
tive member  of  the  aspen  community.   In both cases single 2-hr exposures to
0.15 ppm of  03  caused severe injury.  Removal of the dominant species (cheat-
grass)  from  plant  communities  could result in a  shift to another species.
Decline in or  removal  of  aspen could affect the growth of white fir because
seedlings require the  shade  provided by aspen for optimal  juvenile  growth.
Loss of aspen  populations could influence forest succession  by  restricting
white fir development,  causing  a  shift from a forest to a grassland or forb
vegetation community  (Treshow and  Stewart,  1973).   In a companion study con-
ducted in chambers  in the  greenhouse, 0, exposures of 0.15 to 0.3 ppm for 2 hr
per day reduced root and  top growth, and fewer seeds were produced (Harwood
and Treshow,  1975).
     It is apparent  that  in  natural  communities exposed to 0_, the tolerant
                                                             O
species would soon  become the  dominants.   The authors concluded  that 0, must
                                                                       O
be considered a significant environmental  parameter  that influences the composi-
tion, diversity, and stability  of  natural  plant communities.
     The foregoing  studies indicate that the impact  of 0, changes the composi-
                                                        O
tion and succession  patterns of plant communities.  The more mature stages of
ecosystems use  nutrients  and energy more  efficiently.   Mature systems are
tight;   disturbances  cause leakage.   The leakage may  be large enough under
certain circumstances to  in  time  reduce the potential  of the site to support
life (Woodwell,  1974).  Changes that cause reductions in biotic structure are
destabilizing and retrogressive.  The  entire  array  of plants  is  changed  by
disturbance from one in which large-bodied,  long-lived species occur to one in
which small-bodied,  short-lived, rapidly reproducing plants predominate (Woodwell,
1974).   This pattern  is exemplified  by the San Bernardino  National  Forest,
where the mixed conifer forest  is being replaced by  low-growing shrubs and
annual   herbs.   It is also occurring in the eastern United States, where the
degradation  of  the  Appalachian forests  from North  Carolina to Maine  is
currently taking place as  the red  spruce (Picea rubens Sarg. ) and other large,
long-lived species  are  being removed by at-present  unknown  forces (Johnson
and Siccama,  1983).   Also  associated with the loss of stable ecosystems is the
maintenance of  normal water and climatic conditions, protection from wind and
erosion, and protection from noise pollution (Guderian, 1977).

1.7.4  Interrelated Ecosystems
1.7.4.1  Aquatic Ecosystems.   It  is  extremely important to consider that an
adverse impact on a forest or agricultural  ecosystem may in turn adversely affect
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adjacent aquatic systems.   A variety of linkages for energy and nutrient exchange
exist.   Disruptions induced by air pollution stress on terrestrial ecosystems
often trigger dysfunctions in neighboring aquatic ecosystems,  such as streams,
lakes,  and reservoirs.   Sediments resulting from erosion can change the physical
character of stream channels,  causing changes in bottom deposits, erosion of
channel banks,  obstruction of flow, and  increased flooding.  They can  fill in
natural ponds  and reservoirs.   Finer sediments can  reduce water quality,
affecting public and industrial  water supplies and recreational areas.   Turbid-
ity caused by  increased erosion  can also  reduce  the penetration of light  into
natural waters.   This, in turn, can  reduce  plant photosynthesis and  lower
supplies  of  dissolved  oxygen, leading to  changes in  the natural  flora and
fauna  (Bormann  and  Smith,  1980).  Significant forest alterations, therefore,
may have a regional impact on nutrient cycling, soil stabilization, sedimenta-
tion,  and eutrophication  of  adjacent or nearby aquatic systems.   Interfacing
areas,   such  as wetlands and bogs, may  be especially vulnerable to  impact.
1.7.4.2  Agricultural  Ecosystems.  Natural and agricultural ecosystems possess
the same  basic functional components,  require  energy  flow  and  mineral  cycling
for maintenance,  and are  subject to the dominating influences of climate and
substrate.   Natural ecosystems vary  in  diversity from simple systems with few
species to complex  systems with  many  species.   Their  populations  also  vary in
genetic composition, age, and species diversity.  They are  self-regulating and
self-perpetuating.  Agroecosystems, on  the other hand,  are highly manipulated
monocultures of similar genetic  and age composition and are unable to maintain
themselves without the addition  of nutrients, energy, and human effort; oppor-
tunistic  native and imported species may  invade the  sites.  The manipulation
of  monocultures is designed  to  concentrate  ecosystem productivity  into a
particular species to maximize its yield  (e.g., corn, wheat, soybeans) for the
benefit of humans (Cox and Atkins, 1979).  If any of the species, varieties,
or  cultivars is very  sensitive  to C-  ,  its market value is destroyed.  When
                                    O
this occurs,  efforts are made to find a  resistant cultivar, as with tobacco,
or  to  grow  a  crop  less  sensitive to 0-  stress.  Cost alone  would prevent
replacement  of  the variety of species in  a natural ecosystem.

1.7.5  Ecosystem  Responses to Stress
     Ecosystems,  because  of  their complexity,  respond  to  stress  in  a  manner
different from  individuals (Figure 1-8).   Ecosystems  respond to stress through
the response of the organisms that compose them.  Three main levels of interac-
tion are  involved:  between the  individual and  its environment, the population
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     BIOCHEMICAL LEVEL
                                                   CELLULAR LEVEL
                                                                                                    WHOLE PLANT LEVEL POPULATION LEVEL

                                                                                                             CHRONIC OR ACUTE EXPOSURES
                                                                                                                                    COMMUNITY LEVEL
 I
oo
                                   BREAKDOWN OF
                                   METABOLIC PATH

                                     »     t
                                     CHANGES IN
                                 CELLULAR CONSTITUENTS
 REDUCED VIGOR.
 ADAPTABILITY.
 GROWTH, YIELD.
PRODUCT QUALITY
                              Figure 1-8.Conceptual sequence of levels showing continuum of plant responses.
                              Source: Adapted from Heck (1973).

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Apparently no research has been done on the potential effects on materials of
the peroxyacyl nitrates  or  of hydrogen peroxide.  In spite  of  the research
focus on  ozone,  however,  the amount of damage from ozone to actual in-house
materials remains poorly characterized.
     The materials known to be most susceptible to ozone attack are elastomers,
textile fibers and dyes,  and certain types of paints.   Ideally,  the nature and
amount of ozone damage to the materials can be approximated by physical damage
functions in combination with ambient air concentrations.   The economic impact
from ozone-related damage can then be estimated  by using accelerated replace-
ment and  repair  costs  or increased avoidance costs.  None of these areas is
sufficiently defined in the literature, however,  to assess the amount and cost
of oxidant-related damage.

1.8.2  Effects and Damage Functions
1.8.2.1   Elastomers.  Virtually all the available literature on photochemical
oxidant research  focuses on  ozone and its effects on economically  abundant or
important materials.  The  effects  of ozone on elastomers are the  best docu-
mented.   Natural  rubber  and  synthetic  polymers  such as polymers of styrene,
butadiene, and  isoprene, make  up  most of the elastomer  production  in the
United States.   These chemicals are used  for  formulating automotive tires and
for protective electrical  coverings.   The mechanism of ozone degradation on
elastomers shares similarities  and  differences  with simple oxidation from
atmospheric  oxygen.   Ozone  damage is  mainly  a surface phenomenon, whereas
damage from  simple  oxidation occurs  internally.   Ozone cracks occur at right
angles to the  direction  of stress (Mueller and  Stickney, 1970).   Over time,
the elastomer becomes hard and brittle, losing its physical integrity.   In the
absence of ozone and other photochemical  oxidants, oxidation  from  atmospheric
oxygen still  occurs,  but at a much  slower  rate  and apparently by different
mechanisms.
     High humidity  and  mechanical  stress greatly affect the formation, depth
of cracking,  and, in  automotive tires, the adhesion  between plies (Davies,
1979; Wenghoefer, 1974).  Ozone affects natural  rubber and other elastomers in
a dose-related fashion.
     Dose is defined in materials research as the product of concentration and
duration  of exposure.   The importance of ozone dose was demonstrated by Bradley
and Haagen-Smit  (1951), who  used a specially  formulated ozone-sensitive natural
rubber (NR).  Samples exposed to ozone at a concentration of 20,000 ppm cracked
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almost  instantaneously,  and those exposed  to lower concentrations  took  a
proportionately longer time to crack.  At concentrations of 0.02 to 0.46 ppm,
and under 100-percent  strain,  the cracking rate was proportional  to the time
of exposure,  from  3  to 65 min.   Cracking occurred at a rate of 0.02 to 0.03
ppm-hr over the entire range of concentrations.
     Similar  findings  were  reported by Edwards and Storey (1959), who exposed
two styrene-butadiene  rubber  (SBR)  elastomers to ozone at a concentration of
0.25 ppm for  19  to 51 hr under 100-percent strain.   With ozone doses of 4.75
ppm-hr to 12.75  ppm-hr,  a proportional  rate  in cracking depth was observed,
averaging 2.34 pm/hr for cold SBR and 4.01 pm/hr for hot SBR.   When antiozonants
were added to the  compounds, the  reduction  in cracking depth rate was propor-
tional  to the amount added.   Haynie et al. (1976) exposed samples of a tire
sidewall to ozone  at concentrations  of 0.08  and  0.5  ppm for 250 to 1000 hr
under 10 and  20  percent-strain.   Under 20-percent strain, the mean cracking
rate for 0.08 ppm  was 1.94 um/hr.  From these and other data,  they estimated
that at the ozone  standard of the time (0.08 ppm, 1-hr average), and at the
annual  NO  standard  of 0.05 ppm,  it would take 2.5 years for a crack to pene-
trate cord depth.
     In addition to stress, factors affecting the cracking rate include atmos-
pheric pressure, humidity,  sunlight, and other atmospheric pollutants.  Veith
and Evans (1980) found a 16-percent difference in cracking rates reported from
laboratories  located at various geographic elevations.
     Ozone has  been found to  affect the  adhesion of plies (rubber-layered
strips) in tire  manufacturing.   Exposure  to ozone concentrations of 0.05  to
0.15 ppm for  a few hours  significantly decreased  adhesion in an NR/SBR  blend,
causing a 30-percent decrease at the highest ozone level.  This adhesion prob-
lem worsened  at higher  relative  humidities.   When  fast-blooming waxes and
antiozonants  or  other  antioxidants  were added, only a combination of protec-
tive measures allowed  good adhesion and afforded protection from attack by
ozone and sunlight.   Wenghoefer  (1974)  showed that ozone  (up  to 0.15 ppm),
especially in combination with high relative  humidity (up to 90 percent),
caused greater adhesion  losses than heat and NO- did,  with or without high
relative humidity.
1.8.2.2  Textile Fibers  and Dyes.   The  effects of  ozone on dyes have  been
known for nearly three decades.   In 1955,  Salvin and Walker exposed certain
red and blue anthraquinone dyes to 0.1 ppm ozone and noted fading, which until
that time had been thought to be caused by N0_.  Subsequent work by Schmitt
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(1960, 1962) confirmed the fading action of ozone and the importance of rela-
tive humidity in the absorption and reaction of ozone in vulnerable dyes.   The
acceleration in fading of  certain  dyes by high  relative  humidity was noted
later by  Beloin (1972,  1973) at an  ozone  concentration of 0.05  ppm  and  a
relative humidity of 90  percent.  Kamath et al.  (1982) also found that a slight
rise in relative  humidity  (85 to 90 percent)  caused a 20-percent dye loss in
nylon fibers.
     Both the type  of dye  and the material in  which it is  incorporated are
important factors in the  resistance  a fabric has to ozone.   Haynie et al.
(1976) and Upham  et al.  (1976) found no effects from ozone  concentrations of
0.1 to 0.5 ppm  for  250  to 1000  hr  under high and low relative humidity (90
versus 50 percent)  on royal  blue rayon-acetate, red  rayon-acetate,  or plum
cotton.   On the other hand, Haylock and Rush (1976,  1978) showed  that  anthra-
quinone dyes on nylon fibers were sensitive to fading from ozone  at a  concen-
tration of 0.2 ppm  at 70 percent relative humidity and 40°C for 16 hr.  More-
over, the same  degree of  fading occurred in only 4 hr at 90  percent relative
humidity.   At higher concentrations, there was a parallel increase in  fading.
Along with Huevel et al.  (1978) and Salvin (1969),  Haylock  and Rush (1976,
1978) noted the importance of surface area in  relation to the degree of fading.
In explaining this  relationship,  Kamath et al.  (1982) found  that ozone pene-
trated into the fiber itself and caused most of the  fading through subsequent
diffusion to the surface.
     Field studies  by Nipe (1981) and  laboratory work by Kamath et al. (1982)
showed a positive association  between  ozone levels  and dye  fading of nylon
materials at an ozone concentration of 0.2 ppm and at various  relative humid-
ities.  In summary,  dye  fading is a complex function of ozone  concentration,
relative humidity,  and the presence of other gaseous pollutants.  At present,
the available research  is  insufficient for quantifying the amount of damage to
fibrous materials attributable to ozone alone.   Anthraquinone dyes incorporated
into cotton and nylon fibers appear to be the most sensitive to ozone  damage.
     The degradation of  fibers from exposure to ozone is poorly characterized.
In general, most  synthetic  fibers  such as modacrylic and polyester are rela-
tively resistant;  and cotton, nylon,  and acrylic fibers show variable sensiti-
vities to the gas.   Ozone  reduces the breaking strength of these fibers,  and
the degree of  reduction  depends on the  amount  of moisture present.   Under
laboratory conditions,  Bogaty et al.  (1952) found a 20 percent loss in breaking
strength in cotton textiles under high-moisture conditions after exposure to a
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0.06 ppm concentration of ozone for 50 days.   They equated these conditions to
a 500- to 600-day exposure under natural conditions.   Kerr et al.  (1969) found
a net loss of 9 percent in breaking strength of moist cotton fibers exposed to
ozone at a concentration of 1.0 ppm for 60 days.   The limited research in this
area  indicates that ozone  in ambient air may have a minimal effect on textile
fibers, but additional research is needed to verify this conclusion.
1.8.2.3  Paints.  The  effects  of ozone on paint are small in comparison with
those of other factors (Campbell et al., 1974).  Past studies have shown that,
of various paints,  only vinyl  and acrylic coil coatings are affected (Haynie
et al., 1976), and that this impact has a negligible effect on the useful life
of the material coated.  Preliminary results of current studies have indicated
a statistically  significant  effect of ozone and  relative  humidity  on latex
house paint,  but final  results are needed before  conclusions  can be drawn.
     Pigments in artists' paints have also been tested under controlled condi-
tions for  3  months  at an average exposure level  of 0.4 ppm of  ozone.  While
fading occurred  in  anthraquinone-based pigments,  no quantitative information
on dose-response relationships is available.

1.8.3  Economic Assessment of Effects of Ozone or Oxidants on Materials
     Damage to nonbiological materials from ozone is usually expressed in terms
of one  or  both of the  following  two  general  classes of costs  to producers
and  consumers:   (1)  ozone accelerated replacement and  repair costs,  as  when
the  service  life and/or aesthetics of a material  are impaired; and (2) in-
creased avoidance costs,  as when certain industries  (e.g., manufacturers  of
tires, plastics, paints, dyes, and fabrics) are obligated to incur expenditures
for  antiozonant  research and development, substitute  processes  and materials,
additives  and formulations, product packaging, advertising, etc.,  in  order to
offset sales  losses that would otherwise occur.
      In theory,  the  approach selected should depend on the observed behavior
of the  producers and consumers of the materials in question, and the type of
damage  to  which  they  are reacting.   In practice,  the  existing empirical  esti-
mates  of  ozone  damage  to materials  are far from  reliable for  the reasons
presented  in  the following paragraphs:
      First,  in  some  studies,  coverage is limited  to  one or two  classes of
materials, and to restricted geographical regions.  Other  studies are entirely
too  aggregative, suffering deficiencies because of (1) broad and vague notions
of materials  exposure and ozone concentrations; (2)  little or  no data on  the
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spatial and temporal  distributions  of  the exposed materials; (3) unverified
guesses regarding the  incidence  and level of cost increases  and  production
adjustments incurred by ozone-affected  industries;  and (4)  inadequate attention
to economic trade-offs  among  different industries  and different regions,  and
between producers versus consumers.
     Second, the engineering  and  economic estimates  are not well related to
the scientific  literature  in  this area,  and tend to  be far too  simplistic to
meet the concerns of the scientist.  Third, most of the cost assessments were
conducted  in  the early 1970s.  Few  recent  studies exist.   Moreover, these
earlier studies cite extensively from each other and  there  are few independent
analyses that do not merely rework old  data.
     As a consequence of the third item above,  many of the  ozone-related costs
reported in the  early  1970s for research and development, product substitu-
tion,  etc., are no longer appropriate.   Some of these were  presumably once-only
costs   that  are no longer charged against current  production.   Because the
literature is  dated,  there  may also be some current  research and development
and substitution attempts  that are  not reflected at  all in the  studies cited
in Chapter 9.   In  addition, studies are  outdated because  the supply-demand
relationships  that prevailed when the  studies were conducted may  no  longer be
valid.   In  sum, the cost estimates  largely  reflect  technologies, ozone or
oxidant concentrations, and economic conditions that prevailed  some 10 to 20
years  ago.
     Finally,  most of  the so-called  economic studies of ozone damage to mate-
rials  have been conducted using an engineering approach.  That approach focuses
on the  classification  and  quantification of the various kinds  of costs in-
curred  by  the  producers and users of the  ozone-sensitive materials.  Economic
theory would argue, however, that this  is merely the  first step  in the assess-
ment process, and that supply-demand relationships are then needed in order to
proceed with the calculation of social  net benefits (i.e.,  changes in producer
and consumer surpluses).   In  practice, however,  it appears that almost  all  of
the damage assessments conducted to date stop short of obtaining an econometric
measure of economic  surplus.   As such, the  studies  reported  in Chapter 9  of
this document must be interpreted accordingly.
     Despite the shortcomings of the quantitative economic assessments that are
available, the data  indicate  that,  among  the various  materials  studied, those
most likely  to affect the  economy  as  the result of  ozone exposure  include
elastomers and textile fibers  and dyes.   Among  these,  natural rubber used  for
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tires is probably  the  most important economically for the following reasons:
(1) significant ambient  air  exposure and long use life; (2) significant unit
cost; and (3)  large  quantities  and widespread distribution.  McCarthy et al.
(1983) calculated  the  cost of antiozonants in automobile and truck tires for
protection against ozone.  While limitations in this study preclude the reliable
estimation of damage costs, the figures ($163 million in 1984 dollars) indicate
the  magnitude  of  potential  damage  from exposure to ozone  in  ambient air.
Research has shown  that  house paint and certain textile  fibers and dyes are
also  damaged by ozone; but the absence  of reliable damage functions makes
accurate economic  assessments  impossible.   Thus,  while damage to these mate-
rials is undoubtedly occurring,  the actual damage  costs  cannot be estimated
confidently.

1.9  INTRODUCTION  TO HEALTH EFFECTS
     The purpose of  the  health  effects of  chapters  of this document is to
describe the known biomedical effects of ambient levels of 0- and other photo-
chemical oxidants.   Reports  of animal, clinical, and epidemiological  research
are available  for  this purpose.   They are reviewed in the following sections
of this chapter.   The  primary goal  of the  review process  is to describe and
assess concentration-response relationships,  particularly for concentrations
at or near those found in ambient air, for both humans and laboratory animals.
Such information is integral  to the standard-setting process.
1.9.1  Organization of Health Effects Information
     Reasons for the inclusion in this criteria document of Chapters 10 through
13 may  not  be  self-evident to those who have never been involved in the pre-
paration or review of criteria documents.  Thus, the basic reasons are briefly
noted below:

     1.    Chapter 10:  Toxicologic Effects of Ozone and Other Photochemical
          Oxidants.  Jji  vitro  studies on isolated  cells  and  tissues  and i_n
          vivo studies on laboratory animals permit the measurement of effects
          under circumstances that  are not permissible in clinical research.
          Such studies  in  animals are useful  for  identifying  mechanisms of
          effects; for determining concentration-response relationships over a
          wide range; for studying responses that require invasive procedures,
          such as  tissue sampling and surgery; and for sorting out and testing
          hypotheses as  a  prelude to  clinical  investigations and  as an  aid  in
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         the design of epidemiologies! studies.  This information can be used
         to  understand possible  linkages  between acute and chronic effects;
         and correlations  of  biochemical,  functional and structural changes
         with  growth,  development and aging of  the  lung as the result  of
         exposure  to  ozone.   The chief weakness of  animals  studies  lies in
         the  difficulties and  associated uncertainties  of extrapolating
         results to humans.

    2.   Chapter 11:  Controlled Human Studies  - Studies on humans  provide
         information about sensitive populations, dose-response relationships
         and  responses  to a  limited number of repeated exposures.   Such
         studies are  necessarily restricted  to ethically and legally accept-
         able  pollutant  concentrations and  exposure regimes,  as  well  as
         restricted to techniques for measurement of effects that are similarly
         constrained. The  emphasis  in human studies found in the literature
         is, therefore, on pulmonary function, with  less on clearance, resist-
         ance  to  infection and even less on cytological effects.  The chief
         weaknesses  of controlled  human  exposure studies are:  (a)  small
         sample size;  (b)  the necessary absence of  chronic  exposure  studies;
         (c) limitations on the  range of pollutant concentrations and type  of
         subjects  studied;  and (d)  use of  synthetic, simplified atmospheres,
         usually at unvarying concentrations,  and usually without the changes
         in  temperature,  humidity,  and pressure that occur  in ambient condi-
         tions.  The  latter (d)  also constitutes a  strength of such studies,
         however,  since  it permits  determination of concentration-response
         functions relative  to a specific  pollutant and specific end points.

    3.   Chapter 12:   Field and  Epidemiological  Studies  of the  Effects of
         Ozone and Other  Photochemical Oxidants  -  Epidemiological   studies
         attempt  to associate various characteristics  of human health  and
         function  with ambient air concentrations of photochemical  oxidants.
         Epidemiology  involves  the study of real-world  human  populations  in
         their normal  setting; of human responses to short-term and  long-term
         oxidant  exposure; and of sensitive subgroups within the population.
         Investigations within the  normal  setting are not,  of course,  without
         their drawbacks.   The information gathered on exposure-effect  rela-
         tions and results may be confounded by the presence of factors such
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          as variations in the time spent out of doors,  variations in activity
          levels,  cigarette smoking, poor hygiene, coexisting pollutants, and
          socioeconomic status.  Nevertheless, associations (or lack of them)
          can be drawn between health indicators and oxidant exposure.  These
          associations may complement or  extend the  findings  of clinical  and
          toxicological research.

     4.    Chapter 13:   Evaluation of Integrated Health Effects Data for Ozone
          and Other Photochemical  Oxidants -  The extensive body of data on the
          effects of ozone on the respiratory system  was reported and discussed
          in particular detail in Chapters 10, 11,  and 12.   Chapter 13 provides
          a vehicle for evaluating this  collective body of data for its signi-
          ficance to  public  health and  for   assessing  the  certainties and
          uncertainties associated  with  the   data.   Since  the purpose of a
          criteria document is to  provide a  scientific basis  for the deriva-
          tion and  promulgation  of standards,  this  chapter also addresses
          specific issues and questions  that  are important in  standard-setting.
          Paramount among  the issues  considered in  standard-setting  is  the
          identification of the population or subpopulation to be protected by
          the regulation, that is,  one that is at particular risk from exposure
          to ozone and  other  photochemical oxidants.  The  identification of
          such a population or subpopulation  presupposes the identification of
          one or more  effects that are  in and of themselves adverse, or that
          are indicators of other effects that are adverse but that not measur-
          able in man because of ethical  constraints.

     Three  issues  are  not broached at all in the  health effects chapters,
inasmuch as they are regulatory issues that by law rest with the Administrator
and by precedent are addressed for the Administrator  by the Agency's Office of
Air Quality  Planning and  Standards.   These issues are:   (1) determination of
what constitues an "adverse effect;"  (2)  assessment  of  risk;  and  (3) determi-
nation of  a  margin of  safety.  While  scientific data contribute significantly
to decisions regarding them,  the resolution of these  issues cannot be achieved
solely on the basis of experimentally acquired scientific information.   Conse-
quently, these issues are among the more problematic  or difficult concepts and
issues involved in protecting the public from the untoward effects of exposure
to air pollutants.
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1.9.2  Literature Coverage and Selection
     The number of scientific reports  on  the  biomedical  effects  of  photochemi-
cal oxidants has grown substantially in recent years.  To  provide a comprehen-
sive yet manageable review to satisfy  the objectives  of  the  criteria document,
the most  pertinent  references must be identified for in-depth  examination.
Guidelines were developed to facilitate this  process.
     The material selected for review and comment in the text generally comes
from the more recent literature,  with  emphasis on studies  conducted at or near
pollutant concentrations  found in ambient air.    Older  literature  that was
cited in  the previous criteria document  for  ozone  and  other photochemical
oxidants (U.S. Environmental  Protection  Agency,  1978) has often been summar-
ized and presented briefly.  An attempt has been made, however, to discuss at
greater length in the text older studies (1) judged  significant  because of
their usefulness  in deriving the 1979 standards;  (2) open to reinterpreted on
because of newer data; or (3) potentially useful  in  deriving subsequent stand-
ards.   The  newer  information  on  oxidants now available  may in some instances
make possible  a better understanding of the earlier studies, such  that a more
detailed and  comprehensive  picture  of health effects is emerging  on  several
issues.   An  attempt has  been made to discuss key literature in the text and
present it  in  tables  as well.  Reports of  lesser  importance  to the  purposes of
this document may appear in tables only.
     Generally, only published material  that has undergone scientific peer re-
view is included.   In the interest of admitting  new and  important information,
however, the  health effects  chapters  may also include  some other  materials
that is thought to meet the standards of scientific reporting.
     Studies cited  in the chapters on toxicologic (Chapter 10) and clinical
research  (Chapter 11) are  generally  confined to those employing  ozone at
concentrations of I ppm or less.   This concentration cutoff was chosen because
ozone concentrations  in  ambient  air rarely exceed 0.4  ppm  (averaged over 1
hour) and  then in  only  a few urban  areas  on rare  occasions (Chapter  6).
Typically,  1-hr maximum  ozone levels are well below 0.2 ppm.  Application of
the concentration cutoff  of I ppm eliminates discussions of  studies  on mor-
tality  and  sublethal  effects.  Higher concentrations are cited, however, when
(1) they have  been used to extend the range of concentration-response relation-
ships,  as  in multiple-concentration studies;  (2) they elucidate mechanisms of
effect; or  (3) their  use has resulted in  the discovery of previously  unreported
effects.
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     In selecting studies for consideration, each paper was reviewed in detail.
Technical considerations for inclusion of a specific study included, but were
not restricted to, an analysis of the exposure method;  specificity or appropri-
ateness of the  analytical  method used to monitor the oxidant concentration;
information on oxidant monitoring practices such as location, calibration, and
sampling time;  characteristics of the subjects;  techniques used for  obtaining
cohorts; and  the  appropriateness of  the technique used  to measure the  effect.
Interpretation of the results included consideration of the following factors:
the end  results  of the statistical  analysis;  the degree to which the results
are plausible in  the  context of  other extant  data; the  appropriateness of the
hypothesis developed; and the agreement between the hypothesis and the results
reported.  No additional  statistical analyses beyond those  reported by the
authors have  been undertaken.  Unless otherwise  stated, all  statements in the
text, positive or negative, are statistically significant at p < 0.05 or less.
1.10  TOXICOLOGIC EFFECTS OF OZONE AND OTHER PHOTOCHEMICAL OXIDANTS
1.10.1  Introduction
     The biological  effects  of  ozone  have been  studied  extensively  in  animals
and  a  wide array of toxic effects has been ascribed  to ozone inhalation.
Although much  has  been accomplished to improve the existing data, refine the
concentration-response relationships,  and better interpret the mechanisms of
ozone effects,  many  of the present data were not accumulated for the purpose
of making  quantitative comparisons across  animal studies or deriving concen-
tration-response functions.   In many  cases,  only qualitative comparisons can
be made.  To maximize  the extent that animal  toxicological data can be used to
estimate the  human  health risk of exposure to ozone, the qualitative as well
as quantitative  similarities between  the toxicity of ozone to animals and to
man  must be considered.   Significant  advances  have been made  in  understanding
the  toxicity  of ozone through  appropriate animal models.  This summary high-
lights  the results  of selected studies that will provide  data  useful for
predicting and assessing, in a  scientifically  sound manner,  possible human
responses to ozone.
     Summary  figures and  tables  are  presented  in  the following sections.
Studies were  selected for inclusion in these figures and tables on the basis
of specific criteria presented  below:

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     1.    Studies  have  been cited only  if the  reported effects are clearly due
          to  CL  exposure.  Studies  involving mixtures of 0-, and other pollutants
          or  tnose involving exercise, diet deficiencies,  or  other  possible
          modifiers  of  response to  0^  have  not been  included.
     2.    Cited  studies report the effects of 0- exposure  over a broad  range
          of  animal  species  and  strains and  for  varying lengths of time.
          Specific details on animal  species,  exposure duration,  and observed
          effects  can be  obtained from  the  tables in Chapter 10.
     3.    Each  closed  symbol  on the figures  represents  one or more  studies
          conducted  at  that particular concentration.   Specific responses can
          be  found in the accompanying  tables.
     4.    Only  pulmonary  function  effects  were divided by short-term  (<14
          days)  and  long-term (>14  days)  exposures to  follow the  discussion  in
          the text.

1.10.2  Respiratory  Transport and Absorption  of  Ozone
     The respiratory system  is the  route  of entry for  ozone and other oxidizing
air  pollutants, just  as  it  is  for air itself.   Throughout inhalation  and
exhalation, ozone  undergoes  transfer from the  gas phase  to  the airway surfaces
and  parenchyma.    Not all of the gas is taken  up, however; a variable fraction
is expelled with  exhalation.   Following  contact with the respiratory tract,
ozone or its  transformation  products can  react with  both extra- and  intracellu-
lar  elements.
     The amount of  ozone  acting at a given site in  the lung is related to the
airway  luminal   concentration at that level.   Thus,  ozone does not immediately
interact with cellular components  of  the  respiratory tract.   Instead, it first
comes into contact  with  the mucous or  surfactant layer lining the airway.   It
should  be  noted here that ozone is quite reactive chemically.   Reactions with
components of this layer result in an  increase in total  absorption of ozone in
the  upper  airways and  reduces  the  amount of ozone reaching sensitive tissues.
The  site  at  which uptake and subsequent interaction occur and the local dose
(quantity  of ozone  absorbed  per unit area),  along with cellular sensitivity,
will determine the type and extent of the injury.   For this reason,  a thorough
knowledge  of the  complex process  of gas transport  and  absorption within the
respiratory  tract is  crucial  to understanding the effects of ozone and other
oxidants  in humans.
     Measurements of the regional  uptake of  ozone and other oxidants that are
reactive  and metabolized by body tissue and  fluids are just beginning.  Com-
parative  uptake studies  between man and animals have not yet appeared in the
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literature.   Studies with aerosols, however, have shown similarities in deposi-
tion in both the total respiratory tract and in the pulmonary region in guinea
pig, rabbit,  rat,  and man.   Nevertheless, some  interspecies differences,
especially in regional deposition and uptake,  may be expected.  Such differences
may be  imposed  by  modes  of breathing.  For example, rodents  breathe only  by
nose, while  humans may breathe nasally, oronasally, or orally, depending on a
variety of factors.  Differences may also result from differences among species
in anatomic and morphometric structures.  For example,  respiratory bronchioles
are absent or primordial  in rats, but are well developed in primates.   Similarly,
the capacity  for  responding to a specific  dose may vary between animals and
humans because of dissimilarities in detoxification systems, pharmacokinetics,
metabolic rates, genetic  makeup,  or other factors.  Such differences must be
accounted for when  extrapolating the results of  animal studies to  the  human
population.
     The animal studies that have been conducted are beginning to indicate the
quantity  and site  of ozone uptake  in  the  respiratory  tract.  For  example,
experiments  conducted  to determine  the  nasopharyngeal  removal  of  ozone in
animals have demonstrated (1) that the fraction of ozone taken up is inversely
related to  the  flow rate and ozone concentration, (2)  that uptake  is greater
for nose  than  for  mouth  breathing,  and  (3)  that trachea! and  exposure chamber
concentrations are positively  correlated  (Yokoyama and Frank, 1972; Moorman
et al., 1973; Miller  et  al., 1979).  The limited  data available indicate that
at  concentrations  of  ozone  ranging from 0.1  to 2.0 ppm, removal of ozone  in
the nasopharyngeal  region would  be  expected to be  approximately 50  percent of
the inhaled ozone.
     Morphological   studies  have provided substantiating data that  ozone  is
absorbed  along  the entire  respiratory  tract, penetrating  further  into  the
peripheral  nonciliated  airways and  the respiratory bronchioles as inhaled
ozone  concentration  increases  from  0.2 ppm to 0.8 ppm  (Dungworth  et al.  ,
1975).   From  animal  studies,  it has been  predicted that in  man, rabbit, and
guinea pig  the  pattern of ozone  deposition  is similar, with  one specific area
of the lung, the junction of the conducting airways and the gas-exchange region,
receiving the  maximal dose  (Miller  et  al.,  1978).  This prediction  correlates
well with reported histopathological data of Dungworth et al. (1975) and Stephens
et al.  (1974).
     To date,  there  has  been only  one  study  (Yokoyama and  Frank, 1972) that
attempted to  measure  ozone  uptake  in the lower respiratory  tract.   These data
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indicate that in dogs, 80  to 87  percent of the inhaled ozone was  taken up by
the  lower  respiratory  tract.  It  should  be noted that this  estimates the
uptake as applied to the total lung and does not describe the uptake of ozone
by individual airways or  airway generations.
     Three models appear to  have merit for estimating  ozone uptake in the
respiratory  tract  (Aharonson et al., 1974;  McJilton et al. , 1972;  Miller
et al.,  1978).
     The model  of Aharonson et al.  (1974) is useful  in analyzing nasopharygeal
uptake data.   Applied to  ozone data,  the model  indicates that the  average mass
transfer coefficient is the nasopharygeal  region increases  with  increasing air
flow.
     The McJilton model  (McJilton  et al.,  1972) and the Miller  model (Miller
et al.,  1978) for  lower  respiratory  tract ozone uptake are  similar  in their
treatment of ozone  in  the  airways, taking  into  account convection, diffusion,
wall  losses, and ventilatory patterns;  and  in their  use of morphological  data
for  defining the dimensions  of  the  airways and their  liquid lining.   The
Miller  model  is more  realistic, however,  because  it accounts for chemical
reactions of ozone  with constituents  of the mucous-serous  layer.  Tissue  dose
is  predicted by the Miller  model  to be relatively  low in  the  trachea,  to
increase to  a maximum  between the junction of the conducting airways and the
gas-exchange region, and then to decrease  distally.   Comparison of the Miller
results with morphological  data indicates qualitative agreement in the pulmonary
region.   Comparison  in the tracheobronchial region  indicates,  however,  that
further research  is needed to define the  relevant toxic chemical  and physical
mechanisms.
      Ozone dosimetry modeling  is in  its formative stages, and at present  there
are  few experimental  results that are  useful for judging the validity of the
modeling efforts.  With experimental  confirmation, models can become practical
tools for  understanding  respiratory  tract transport  and absorption  of ozone
and  for understanding  ozone  dosimetry in respective  species.

1.10.3  Effects of  Ozone on  the Respiratory Tract
1.10.3.1   Morphological  Effects.   Morphological studies  of  the  effects  of
ozone have  indicated that  the pattern  and  distribution of tissue lesions are
similar in the  respective  species  studied.  They depend, however, upon (1)  the
location  of  the sensitive  cells and (2) the location  of the  junction  between
the conducting  airways and the gas-exchange region  of the  lung, both of which
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are species-specific.  Damage to all parts of the respiratory tract can occur
in animals, depending  on  the ozone concentration.  At  low  concentrations  of
ozone (< 1960 (jg/m  ; 1 ppm),  damage is principally confined to the junction
between the alveoli  and  the conducting airways.  Dogs, monkeys, and man have
respiratory and  nonrespiratory bronchioles, while respiratory bronchioles  are
either absent or poorly developed in mice, rats, and guinea pigs.   The location
of the ozone  lesion thus  differs according to  the  species  examined (Plopper
et al., 1979; Castleman et  al.,  1977,  1980; Dungworth  et a!.,  1975a;  Eustis
et al., 1981).  In both types of lungs, the effects of ozone have been found at
concentrations as low  as  392 |jg/m  (0.2 ppm) and for exposure times as short
as 2 hr (Stephens et al.,  1974a).
     In the upper and  lower conducting airways, ciliated cells appear to  be
the most sensitive cell type; they are damaged by exposures to ozone at concen-
trations as low  as  392 to 1568 ug/m   (0.2 to  0.8 ppm) for 8 or 24 hr for 7
days in rats (Schwartz et al., 1976), bonnet monkeys (Castleman et al., 1977),
Rhesus monkeys  (Dungworth et al. ,  1975b; Mellick et al.,  1977),  and  mice
(Ibrahim et al.,  1980).   When Moore and  Schwartz  (1981) and Boorman et al.
(1980) extended these exposures  to 180 days at the same concentrations, similar
changes in  these ciliated cells were observed.   Uniform damage was not always
noted;  most often shortened and  less dense cilia occurring in random patches
were reported.   Electron  microscopy revealed severe cytoplasmic changes and
condensed nuclei.   Damage  is  present in both trachea and bronchi  (Eustis  et
al., 1981;  Mellick  et  al.,  1977;  Castleman et al.,  1977).   The damaged cilia
are replaced by nonciliated clara cells that become hyperplasic (Evans et al.,
1976a;  Lum et al., 1978).
                                                3
     In mice, ozone  levels  of 980 and  1568 |jg/m (0.5 and 0.8 ppm) elicited a
pronounced  hyperplasia of these  nonciliated  cells that persisted for 10 days
after cessation  of  the exposure  (Zitnik et al., 1978; Ibrahim et al.,  1980).
In a number of  species,  ozone damage  is  clearly evident at the centriacinar
region, which includes the terminal  bronchiole region, portions of the respira-
tory bronchioles, and  possibly  the  alveolar ducts, depending on the species
(Stephens et al., 1973, 1974a,b;  Schwartz et al., 1976; Mellick et al., 1977).
     Type 1 epithelial cells are significantly affected (Stephens et al.,
1974a;  Evans et al., 1976a;  Castleman et al., 1980;  Eustis et al. ,  1981; Barry
                                                                            3
et al., 1983; Boorman  et  al. , 1980).  In monkeys, for example, at 1764 |jg/m
(0.9 ppm),  death  of type  1 cells reaches a maximum at 12 hr after continuous
exposure (Castleman  et al. ,  1980).   With the destruction of these cells, there
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is a  hyperplasia  of  type 2 alveolar epithelial cells,  which  re-covers the
denuded basal lamina (Stephens  et  al.,  1974a,b; Sherwin et al.,  1983;  Eustis
et al.,  1981).   Type 2  cells  are  relatively resistant to  ozone  exposure.
     Following and during  continued exposures,  these  type 2 cells begin  to
proliferate, which is a  hallmark of  ozone injury regardless of species.  In
rats,  DNA synthesis in type 2 cells was reported as early as 4 hr after expo-
                       3
sure  to  0-  to 392 pg/m  (0.2 ppm) (Stephens  et al.,  1974a) and  reached  a
          J                                                         3
maximum at  2  days  following  continuous  exposure to 686  or 980  ng/m  (0.35 or
0.5 ppm)  (Evans et al.,  1976a,b),  or 1568 ug/m  (0.8 ppm)  (Boorman  et al.,
1980).  Although type 2 cells proliferated in the  ozone-exposed lung, complete
maturation  of type 2 cells to type 1 cells did not occur, even as late as 180
days  of exposure  (Moore and Schwartz, 1981).  In the normal progression, type
2 cells would have matured into type  1 cells.   Continued ozone  exposure inhibits
both ciliagenesis and type 2  cell maturation.
      Inflammation occurs  in  all  species examined so far.   The inflammatory
                                                              3
response  is  seen  as  early as 4 hr after exposure to 1568 ug/m  (0.8 ppm) in
monkeys (Castleman et al., 1980).  In rats and monkeys, inflammation persists
with continued exposure,  although at  reduced levels.   The inflammatory exudate
includes  both fibrin  and various leukocytes  in the initial  phase.   In the
later phase the  inflammatory  cells  are predominantly macrophages (Castleman et
al.,  1980;  Brummer et  al. , 1977;  Boorman et  al.,  1980; Moore  and Schwartz,
1981).  Quantitative estimates  of  the degree of  inflammation  are,  however,
lacking at  present.  The  contribution of the inflammatory  response  to sub-
sequent long-term features of  ozone  toxicity has  not  been studied in detail,
even  though techniques are available.  A number of studies  have reported  that
                    3
exposure  to 980 ug/m   (0.5 ppm) and above thickens the  interalveolar septa  of
centriacinar alveoli (Schwartz  et  al. ,  1976; Castleman et al., 1980; Boorman
et al., 1980).  Thickness could be  caused by interstitial fibrosis.
      Although some delay  has been  observed between an  exposure to ozone  and
the maximum manifestation of morphological changes, the shortest time required
for ozone exposure to  result in significant morphological  changes  is 2 hr,  at
392 or  980  ug/m3  (0.2  or  0.5 ppm)  in  rats (Stephens et  al., 1973,  1974a,b)  or
4.7 or 6.6  hr  of exposure  by  endotracheal  tube  in cats  to 510,  980, or
1960  ug/m3  (0.26, 0.5, or 1 ppm) (Boatman et al.,  1974).  Most of these morpho-
logical  studies  were specifically  designed,  however,   to look at long-term
(i.e.,  days,  months,  years)  exposures rather than  acute  effects.   The data
from  acute  studies  are in agreement with molecular theories that ozone acts
0190GC/A                            1-98                               6/28/84

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rapidly to  oxidize some critical  tissue component.   Little  difference in
severity was noted  by  Schwartz et al.  (1976) between exposure to 8 hr/day or
24 hr/day when the exposure was continued for 7 days.   Quantitative studies of
different exposure  regimens  are lacking but are  technically  feasible.   The
sequence in which  the  anatomic  sites are affected appears to be  a  function of
concentration rather than of exposure duration.  Increasing the concentrations
of ozone not only  results  in more severe lesions, but  also extends the  lesion
to higher generations of the respiratory structure.
     Morphological studies of  vitamin  E-deficient or  supplemented rats have
been undertaken  to correlate  the  biochemical   findings  with  morphological
alterations (Plopper et  al.,  1979;  Stephens et al., 1983; Chow et al., 1981;
Schwartz et al.,  1976;  Sato  et al . , 1976a,b,  1978, 1980).  Despite the pre-
sence of vitamin  E in  the diets of these animals, however,  the morphological
lesion resulting from ozone exposure was unchanged.
     When comparisons  are  made at analogous anatomical  sites,  the morphol-
ogical  effects of  ozone  on the lungs of a  number of species  of animals are
seen to be  remarkably  similar.   Despite the inherent  differences  in anatomy
between most experimental animals and man,  the junction between the conducting
airways and the gas exchange region is the  site affected most  by ozone.
     Studies on  the  morphologic effects of  ozone exposures of experimental
animals are summarized  in  Figure 1-9 and Table 1-12 (see Section  1.10.1  for
criteria used to summarize the studies).
1.10.3.. 2  Pul monary Funct i on .   One  of the  limitations of animal  studies  is
that many pulmonary  function tests  comparable to those conducted after acute
exposure of human subjects are difficult to interpret.   Methods exist,  however,
for obtaining similar measurements of many  variables pertinent to understanding
the effects of ozone on the respiratory tract,  particularly after longer exposure
periods.   A number of  newer  studies  reported here reflects recent  advances  in
studying pulmonary function in small  animals.
     Changes in  lung function  following ozone exposure  have been  studied in
mice, rats, guinea pigs, rabbits, cats, dogs,  sheep, and monkeys.  Short-term
                                                        3
exposure for 2 hr  to  concentrations  of 431  to  980  vg/m   (0.22 to 0.5  ppm)
produces rapid, shallow  breathing  and increased pulmonary  resistance during
exposure (Murphy et al.,  1964;  Yokoyama,  1969; Watanabe et al., 1973; Amdur
et al., 1978).   The onset of these effects is rapid and the abnormal breathing
pattern usually disappears  within  30 min  after cessation of exposure.   Other
changes in lung function measured following short-term ozone exposures lasting
0190GC/A                            1-99                               6/28/84

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                                 summarized here.

-------
      TABLE 1-12.   MORPHOLOGICAL EFFECTS  OF  OZONE  IN  EXPERIMENTAL  ANIMALS
  Effect/response
03 concentration, ppm
                       References
Abnormal cilia 0.2, 0.35, 0.5, 0.8
0.2
0.2, 0.35
0.2, 0.5, 0.8
0.8
0.26, 0.5, 1.0
0.3
0.5, 0.8
0.5, 0.8
0.54, 0.88
0.7
0.8
0.8
0.8
0.85
Dungworth et al. (1975b)
Plopper et al . (1979)
Castleman et al . (1977)
Schwartz et al. (1976)
Boorman et al . (1980)
Boatman et al . (1974)
Sato et al. (1976a)
Eustis et al. (1981)
Mellick et al . (1975, 1977)
Stephens et al . (1974a)
Evans et al. (1976a)
Ibrahim et al . (1980)
Lum et al. (1978)
Plopper et al. (1978)
Stephens et al . (1978)
Increased number of
  alveolar macrophages
  (AM)
Increased evidence of
  collagen,  fibrosis
Increased lung weight,
  edema
 0.2
 0.2, 0.35.
 0.2, 0.35
 0.2, 0.5, 0.8
 0.25
 0.5
 0.5, 0.88
 0.5
 0.54, 0.88
 0.8
 1.0
 1.0
 0.5, 0.88
 0.5, 0.8
 0.2
 0.2

 0.5, 0.8
 0.54, 0.88
 1.0
 1.0

 0.5, 1.0
 0.54, 0.88
 1.0
 0.4
 0.35
0.5, 0.8
Plopper et al.  (1979)
Dungworth et al.  (1975b)
Castleman et al.  (1977)
Boorman et al.  (1977, 1980)
Barry et al. (1983)
Zitnik et al. (1978)
Stephens et al.  (1974a)
Last et al. (1979)
Freeman et al.  (1974)
Castleman et al.  (1980)
Freeman et al.  (1973)
Cavender et al.  (1977)
Brummer et al.  (1977)
Eustis et al. (1981)
Dungworth (1976)
Stephens et al,  (1976)

Last et al. (1979)
Freeman et al.  (1974)
Stokinger et al.  (1957)
Freeman et al.  (1973)

Fukase et al. (1978)
Freeman et al.  (1974)
Cavender et al.  (1977)
P'an et al. (1972)
Castleman et al.  (1977)
0190GC/A
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                                   6/28/84

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      TABLE 1-12.   MORPHOLOGICAL EFFECTS OF OZONE IN EXPERIMENTAL ANIMALS
                                  (continued)
Effect/response
Decreased weight
gain
Altered type 1 and
2 cells













03 concentration, ppm
0.2, 0.5, 0.8
0.5, 1.0
0.25
0.26, 0.5, 1.0
0.3
0.35, 0.5, 0.7, 1.0
0.5
0.5
0.5, 0.8
0.54, 0.88
0.5, 0.8
0.5, 1.0
0.54, 0.88
0.7, 0.8

0.8
0.85
References
Schwartz et. al . (1976)
Fukase et al. (1978)
Barry et al. (1983)
Boatman et al. (1974)
Sherwin et al. (1983)
Evans et al . (1976b)
Stephens et al. (1974b)
Zitnik et al. (1978)
Eustis et al. (1981)
Stephens et al . (1974a)
Mellick et al. (1975, 1977)
Cavender et al. (1977)
Freeman et al . (1974)
Castleman et al. (1973,
(1980)
Plopper et al . (1978)
Stephens et al. (1978)
3 hr to 14 days are usually greatest 1 day following exposure and disappear by
7 to 14 days following exposure.  These effects are associated with premature
closure of the  small,  peripheral airways and include increased residual  volume,
closing volume, and closing capacity (Inoue et al.,  1979).
     The effects of short-term  exposures  to ozone on pulmonary function and
airway reactivity  in  experimental  animals are summarized in Figure 1-10 and
Table 1-13 (see Section 1.10.1 for criteria for selecting studies summarized).
     Long-term  exposure of 4  to 6 weeks  to ozone concentrations of 392 to
490 ug/m  (0.2  to 0.25 ppm) increases lung distensibility at high lung volumes
in young rats  (Bartlett et al., 1974; Raub et al., 1983a).  Similar increases
                                                                            3
in lung distensibility were  found in older rats exposed to 784 to 1568 ug/m
(0.4 to 0.8 ppm) for  up  to 180  days (Moore and Schwartz, 1981; Costa et al. ,
1983; Martin et al. ,  1983).  Three to twelve months of exposure  to 0_ concen-
                             3
trations of 1176 to 1568 ug/m  (0.6 to 0.8 ppm) increased pulmonary resistance
and caused impaired stability of the small peripheral  airways in both rats
and monkeys (Costa et al.,  1983;  Wegner,  1982).  The effects in monkeys were
not completely reversed by 3 months following exposure; lung  distensibility
had also decreased in the postexposure period, suggesting the development of
lung fibrosis.
0190GC/A                            1-102                              6/28/84

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                       Figure 1-10. Summary  of  effects of  short-term  ozone  exposures on pulmonary
                                    function in  experimental  animals.   See Table 1-13 for reference
                                    citations for studies summarized here.

-------
                  TABLE 1-13.   EFFECTS ON PULMONARY FUNCTION
                       OF SHORT-TERM EXPOSURES TO OZONE
  Effect/response
03 concentration, ppm
     References
Increased breathing
  frequency
Decreased tidal  volume

Decreased lung
  compliance
Increased residual
  volume (RV),
  closing capacity
  (CC), and closing
  volume (CV)

Decreased diffusion
  capacity

Increased pulmonary
  resistance
Increased airway
  reactivity
   0.22, 0.41, 0.8
   0.34, 0.68, 1.0
   0.5

   0.34, 0.68, 1.0

   0.4, 0.8
   0.26, 0.5, 1.0
   1.0

   0.24 - 1.0
   0.26, 0.5, 1.0
   0.26, 0.5, 1.0
   1.0
   0.5
   1.0

   0.5
   0.7
   1.0
Amdur et al. (1978)
Murphy et al. (1964)
Yokoyama (1969)

Murphy et al. (1964)

Amdur et al. (1978)
Watanabe et  al. (1973)
Yokoyama (1969)

Inoue et al. (1979)
Watanabe et al. (1973)
Watanabe et al. (1973)
Gertner et al. (1983a, b)
Yokoyama (1969)
Yokoyama (1974)

Abraham et al. (1980)
Lee et al. (1977)
Holtzman et al. (1983)
 0190GC/A
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     The effects of  long-term  exposures  to ozone on pulmonary  function  and
airway reactivity in experimental  animals  are summarized in Figure 1-11 and
Table 1-14 (see Section 1.10.1  for criteria for summary).
     Studies of  airway reactivity following ozone exposure  in  experimental
animals show that ozone increases the reactivity of the lung to  mechanical  and
chemical stimulation partly by increased sensory neural activity travelling in
the vagus nerve and partly by a local action of ozone on the tissues.  Aerosolized
ovalbumin can reach immunologic receptors in the lungs  of mice preexposed to 980
            3
or 1568 M9/ra   (0-5  or  0.8 ppm) continuously for 3 to 5 days (Osebold et al.,
1980), resulting in an increased incidence of anaphylaxis.   Increased sensiti-
vity to  histamine or cholinomimetic drugs by  aerosol  or injection has been
noted in  several  species.   Easton and Murphy  (1967) showed  that the lethal
dose of  histamine  in guinea pigs was reduced  in  those  animals  preexposed  to
                                          3
concentrations as low  as  980 or 1960 ug/m  (0.5 or 1 ppm) of ozone for 2 hr.
The pulmonary  resistance  due to  subcutaneous  injection  of histamine increased
                                    3
in guinea pigs  exposed to 1568 ug/m  (0.8 ppm) of ozone for 1 hr (Gordon and
                                                            3
Amdur, 1980).  Similarly,  dogs exposed to 1372 and 1960 ug/m  (0.7 and 1.0 ppm)
of ozone for 2 hr had greater changes in pulmonary resistance following histamine
aerosol  inhalation  (Lee et  al.,  1977; Holtzman et al.,  1983a).   Sheep  exposed
            3
to 980  ug/m  (0.5 ppm) of  ozone for 2  hr  experienced increased pulmonary
resistance  for  the cholinomimetic  drug, carbachol  (Abraham et  al. , 1980).
     The time course of ozone-induced airway hyperreactivity suggests a possi-
ble association with inflammation  (Holtzman et al.,  1983a,b;  Sielczak.  et al.,
1983;  Fabbri  et al.,  1984),  but responses are variable and  not very well
understood.   Additional studies that demonstrate  increased collateral resistance
following 30-min  local  exposure of ozone or histamine  in sublobar bronchi of
dogs (Gertner et al., 1983a,b,c) suggest that  other mechanisms,   along with am-
plification of reflex pathways, may contribute to changes in airway reactivity.
1.10.3.3    Biochemical  Effects of  Ozone  in  the Lung  of Experimental Animals.
The lung is metabolically active, and several  key steps in metabolism have been
studied after 0-, exposure.  Since the procedures  for such studies are invasive,
this research  has  been conducted only in animals.  Effects, to  be summarized
below,  have been observed  on antioxidant  metabolism,  oxygen consumption,
proteins, lipids, and xenobiotic metabolism.
     The lung contains several compounds (e.g., vitamin E, sulfhydryls, gluta-
thione)  and enzymes (e.g.,  glutathione peroxidase, glutathione reductase,
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                                                       \f

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                  TABLE 1-14.   EFFECTS ON PULMONARY FUNCTION
                        OF LONG-TERM EXPOSURES TO OZONE
  Effect/response       03 concentration,  ppm
                            References
Increased lung volume
Increased pulmonary
  resistance
Decreased lung
  compliance
Decreased inspiratory
  flow
Decreased forced
  expiratory volume
  (FEV-.) and flow
  (FEF)
0.08, 0.12, 0.25
0.2
0.8
0.4
0.2, 0.8
0.64
0.5, 0.8
0.64
0.12, 0.25
0.64
0.8
Raub et al. (1983)
Bartlett et al. (1974)
Costa et al. (1983)
Martin et al.  (1983)
Costa et al. (1983)
Wegner (1982)
Eustis et al.  (1981)
Wegner (1982)
Raub et al. (1983)
Wegner (1982)
Costa et al. (1983)
glucose-6-phosphate dehydrogenase, and superoxide dismutase) that function as
antioxidants, thereby  defending  the  lung against oxidant  toxicity  from the
oxygen in air,  from  oxidants  produced during metabolic  processes,  and from
oxidizing air pollutants  such  as ozone.   Obviously, this  protection is only
partial  for  ozone  since exposure to ozone  causes  numerous effects on  lung
structure, function, and  biochemistry.   Acute exposure to high ozone  levels
(2920 pg/m ,  2 ppm) typically decreases antioxidant metabolism, whereas repeated
exposures to  lower  levels (<  1568 ug/m ,  0.8 ppm) increases this metabolism
(DeLucia et al., 1975).   In  rats maintained on normal  diets,  this response
has been observed  after  a week of continuous or  intermittent exposure to
392 ug/m3 (0.2 ppm) 03  (Mustafa,  1975; Mustafa and Lee,  1976;  Plopper  et al.,
1979).   Similar responses are  seen in monkeys and mice,  but at higher  concen-
trations  (980 ug/m  , 0.5  ppm;  Fukase et al., 1978; Mustafa and  Lee,  1976).
     The effects of ozone on  oxygen consumption have been studied since oxygen
consumption  is  a  fundamental  parameter  of cellular metabolism, reflecting
energy production  by cells.  As with antioxidant metabolism, acute exposure to
high  ozone  levels  (> 3920 ug/m  ;  >  2  ppm)  decreases metabolism (and  thus,
                    ~              ~                                3
oxygen consumption); repeated exposure to lower levels (> 1568 (jg/m , 0.8 ppm)
0190GC/A
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increases oxygen  consumption  (Mustafa et al. ,  1973; Schwartz  et  al.,  1976;
Mustafa and Lee,  1976).   Effects  in rats on normal diets have been observed
                                                                3
after  a  short-term  exposure  to ozone levels as  low a*s 392 ug/m  (0.2 ppm)
(Schwartz et al.,  1976; Mustafa et al.,  1973; Mustafa and Lee,  1976).   Monkeys
are affected at a  higher level  of ozone  (980 ug/m ,  0.5 ppm).
     Similar patterns  of  response  for both antioxidant metabolism and oxygen
consumption are observed  after exposure to ozone.   A 7-day exposure to ozone
produces linear concentration-related increases  in  activities  of glutathione
peroxidase, glutathione  reductase,  glucose-6-phosphate  dehydrogenase, and
succinate oxidase (Mustafa and Lee,  1976; Chow et al., 1974; Schwartz  et al.,
1976; Mustafa et al., 1973).   Rats on a vitamin E-deficient diet experience an
increase in  enzyme  activities at  196 pg/m  (0.1 ppm)  ozone as compared to
392 ug/m  (0.2 ppm)  in animals on normal diets  (Chow et al., 1981; Mustafa and
Lee, 1976; Mustafa, 1975).  Research  on  these enzymes  has shown that there  is
no  significant  difference in  effects from continuous  versus  intermittent
exposure; this, along with concentration-response data, suggests that the con-
centration of ozone is more important than duration of exposure in causing these
effects  (Chow et  al.,  1974;  Schwartz et al.,  1976; Mustafa and  Lee,  1976).
     Duration of exposure still plays a role,  however.   During exposures up to
1  or 4 weeks, antioxidant metabolism and 0? consumption  generally do not
change  on  the first day of exposure; by about day 4  a  plateau  is  reached
(Mustafa and  Lee, 1976;  DeLucia et al., 1975).  Recovery from these effects
occurs  by  6 days  post-exposure (Chow et al., 1976),  This  apparent tolerance
is  not long-lasting.   If rats are re-exposed after recovery is observed, the
increase in enzyme activities  is equivalent to that observed in animals exposed
for  the  first time (Chow et al., 1976).   The influence of age on responsiveness
is  also similar for antioxidant metabolism and  oxygen consumption (Elsayed
et  al.,  1982a;  Tyson  et  al.,  1982; Lunan et al., 1977).   Suckling neonates  (5
to  20  days  old) generally exhibited  a  decrease  in  enzyme  activities;  as  the
animals  grew  older  (up to about 180 days  old),  enzyme activities generally
increased with  age.   Species  differences may exist in this response (Mustafa
and Lee, 1976; Mustafa et al.,  1982;  Chow et al. , 1975; DeLucia et al., 1975).
Studies  in  which  monkeys have been compared to  rats did  not include,  however,
a  description of appropriate  statistical considerations applied (if  any).
Thus,  no definitive conclusions about  responsiveness  of  monkeys  versus rats
can be made.
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     The mechanism responsible for the increase in antioxidant metabolism and
oxygen consumption is not known.   The response is  typically attributed,  however,
to concurrent morphological changes, principally the loss of type 1 cells and
an increase in type 2 cells,  which are rich in the enzymes measured.
     Monooxygenases constitute  another class of  enzymes  investigated after
ozone exposure.   These enzymes  function  in the metabolism of both endogenous
(e.g., biogenic amines, hormones) and exogenous (xenobiotic) substances.  The
substrates acted upon  are  either activated or detoxified,  depending  on the
substrate and  the enzyme.   Acute  exposure to 1470 to  1960 |jg/m   (0.75 to
1 ppm) ozone decreased cytochrome  P-450  levels and enzyme activities related
to both cytochrome P-450 and  P-448.   The  health  impact of these  changes is
uncertain since only a few elements of a  complex metabolic system  were measured.
     The activity of lactate  dehydrogenase is increased in lungs of vitamin E-
deficient rats receiving a short-term exposure to 196  (jg/m (0.1 ppm)  ozone
(Chow et a!., 1981).   Higher  levels caused a similar response in rats, but not
in monkeys, on normal diets (Chow et al.,  1974, 1977).   This enzyme is frequent-
ly used as a marker of cellular damage because it is released upon cytotoxicity.
It is not  known,  however,  whether the increase in  this enzyme is a  direct
reflection of  cytotoxicity or whether it is an  indicator  of  an  increased
number of type 2 cells and macrophages in the lungs.
     An increase  in  a  few  of the measured  activities of lysosomal  enzymes has
                                                      3
been shown in the lungs of rats exposed to > 1372 ug/m  (0.7 ppm)  ozone (Oillard
et al.,  1972; Castleman  et al.,  1973a; Chow et al., 1974).  This  response is
most  likely  the  result of an  increase in inflammatory cells  in  the lungs
rather  than  an induction  of  enzymes, since  lysosomal  enzymes  in alveolar
macrophages decrease after jji vivo or j_n  vitro exposure to ozone (Hurst et al. ,
1970; Hurst and Coffin, 1971).
     As discussed  previously,  long-term exposure to  high 0-, concentrations
causes mild  lung  fibrosis  (i.e., local increase  of collagen in centriacinar
interalveolar septa).   This  morphological  change has been  correlated  with
biochemical  changes  in the activity  of prolyl  hydroxylase (an enzyme  that
catalyzes the production of  hydroxyproline) and in hydroxyproline content (a
component of collagen  that is  present in  excess  in  fibrosis)  (Last et al.,
1979; Bhatnagar et al.,  1983).   An increase  in collagen  synthesis  has been
observed, with 980 ug/m  (0.5 ppm) 0- being the minimally effective concentra-
tion tested  (Hussain et al., 1976a,b;  Last et al., 1979).   During a prolonged
exposure, prolyl  hydroxylase activity increases by day 7 and returns to control
0190GC/A                            1-109                              6/28/84

-------
levels by  60  days  of exposure.   When a  short-term  exposure  ceases,  prolyl
hydroxylase activity returns to  normal  by about 10 days post-exposure,  but
hydroxyproline levels remain elevated 28 days  post-exposure.   Thus,  the product
of the increased synthesis,  collagen, remains  relatively stable.
     Although  the ability of 0- to initiate peroxidation of unsaturated fatty
acids i_n vitro  is  well  established,  few i_n vivo studies of lung lipids have
been conducted.  Generally, ozone decreases unsaturated fatty acid content of
the lungs (Roehm et al.,  1972)  and decreases  incorporation  of fatty  acids into
lecithin (a saturated fatty acid) (Kyei-Aboagye et al., 1973).  These  altera-
tions, however, apparently do not alter  the surface-tension-lowering properties
of lung  lipids  that  are  important to breathing (Gardner et al., 1971; Huber
et al.,  1971).
     One of the earliest demonstrated effects of ozone  was  that very high
concentrations  caused mortality  as  a  result of pulmonary edema.   As  more
sensitive techniques were developed,  lower levels  (510 ug/m , 0.25  ppm) were
observed to  increase the protein  content of the  lung (Hu et al.,  1982).
Since some of the  excess protein could  be attributed  to serum proteins, the
interpretation was that  edema  had occurred.   This  effect was more pronounced
several   hours after exposure ceased.   At  higher concentrations,  a  loss of
carrier-mediated transport from the air side of the lung to the blood side was
observed (Williams et al., 1980).  These changes imply an effect on  the barrier
function of the lung, which regulates fluxes of various substances with poten-
tial physiological activities across the alveolar walls.
     The biochemical effects observed in experimental animals exposed to ozone
are  summarized in  Figure  1-12 and Table 1-15  (see Section  1.10.1  for criteria
used  in  developing this summary).
1.10.3.4  Effects of Ozone  in Altering Host Defense Against Microbes.  Reports
over  the years have presented substantial  evidence that exposure to  ozone
significantly increases  the ability  of  an  inhaled  infectious  microorganism to
colonize and  to proliferate within the  lung, resulting in significant  increases
in  mortality.   This  response is  dose-related  and is significant at  concentra-
tions of ozone as  low as 0.08 to 0.1 ppm (Coffin et al., 1968; Ehrlich et  al.,
1977; Miller  et al., 1978;  Aranyi et al., 1983).   The biological basis for
this  response appears  to be that ozone or one of  its reactive products can
impair  the normal  bactericidal pulmonary defenses, which results  in prolonging
the  life of the infectious  agent, permitting  its multiplication,  and ultimately,

0190GC/A                            1-110                              6/28/84

-------
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Figure 1-12.  Summary  of biochemical  changes in  experimental  animals  exposed to ozone.  See Table
    1-15 for reference  citations  for  studies summarized  here.

-------
            TABLE  1-15.   BIOCHEMICAL CHANGES  IN  EXPERIMENTAL ANIMALS
                               EXPOSED TO OZONE
  Effect/response
03 concentration, ppm
                       References
Increased 02
  consumption
Increased lysosomal
  activities
Increased lung
  hydroxyproline and
  prolylhydroxylase
  activity

Altered collagen and
  elastin levels
Altered glycoprotein
  secretions
Increased alveolar
  protein and
  permeability changes
Increased LDH
  activity
 Increased NADPH -
  cytochrome -C-
  reductase activity

 Increased succinate
  oxidase
 Increased GSH
    0.1, 0.2
    0.1, 0.2, 0.8
    0.2, 0.5, 0.8
    0.8
    0.7,
    0.7,
0.8
0.8
    0.5, 0.8
    0.5
    0.2, 0.8
    0.5
    0.45
    0.8
    0.8

    0.5, 0.6, 0.8
    0.5, 0.6, 0.8
    0.6, 0.8

    0.26, 0.51, 1.0
    0.5, 1.0
    0.6, 1.0
    1.0

    0.1
    0.5
    0.8

    0.2, 0.35,  0.8
    0.2, 0.5, 0.8
    0.2, 0.5, 0.8

    0.35, 0.5,  0.8
    0.2, 0.5, 0.8
    0.45
    0.8
    0.8
     0.1
     0.5,
     0.2,
     0.8
     0.32
     0.45
     0.5
                                 1.0
                                 0.5, 1.0
Mustafa (1975)
Mustafa and Lee (1976)
Mustafa et al. (1973)

Chow et al. (1974)
Dillard et al. (1972)
Castleman et al.  (1973)

Hussain et al. (1976a,b)
Last and Greenberg (1980)
                 Costa et al. (1983)
                 Last et al. (1979)
                 Bhatnagar et al. (1983)
                 Hesterberg and Last (1981)
                 Hussain et al. (1976a,b)

                 Last and Kaizu (1980)
                 Last and Cross (1978)
                 Last et al. (1977)

                 Hu et al.  (1982)
                 Alpert et  al. (1971a)
                 Williams et al. (1980)
                 Reasor et  al. (1979)

                 Chow et al. (1981)
                 Chow et al. (1977)
                 Chow and Tappel (1973)

                 Mustafa and Lee (1976)
                 Schwartz et al. (1976)
                 Delucia et al.  (1972, 1975)

                 Mustafa and Lee (1976)
                 Schwartz et al. (1976)
                 Mustafa et al.  (1982)
                 Chow et al. (1976)
                 Elsayed et al.  (1982a)

                 Chow et al.  (1981)
                 Fukase et  al.  (1978)
                 Fukase et  al.  (1975)
                 DeLucia  et al.  (1975)
                 Moore  et al.  (1980)
                 Mustafa  et al.  (1982)
                 Chow et  al.  (1975)
 0190GC/A
             1-112
                                       6/28/84

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           TABLE 1-15.  BIOCHEMICAL CHANGES IN EXPERIMENTAL ANIMALS
                         EXPOSED TO OZONE (continued)
Effect/response
Increased GSH
peroxidase








Increased GSH
reductase









Increased G-6-PD














Increased 6-P-GD



Increased NPSH



03 concentration, ppm
0.1
0.1, 0.2
0.2, 0.5, 0.8
0.2, 0.5, 0.8
0.5, 1.0
0.45
0.5
0.7, 0.75
0.8
0.9
0.9
0.8
0.1
0.1, 0.2
0.2, 0.5, 0.8
0.2, 0.5, 0.8
0.5, 1.0
0.2, 0.5, 0.8
0.45
0.5
0.7, 0.75
0.9
0.9
0.8
0.8
0.7, 0.75
0.1
0.1, 0.2
0.2, 0.35, 0.5, 0.8
0.5, 0.8
0.2, 0.5, 0.8
0.5, 1.0
0.2, 0.5, 0.8
0.32
0.45
0.5
0.45
0.75, 0.8
0.8

0.1, 0.2
0.2, 0.5, 0.8
0.45
0.8
References
Chow et al. (1981)
Plopper et al. (1979)
Mustafa and Lee (1976)
Chow et al . (1974)
Fukase et al. (1975)
Mustafa et al. (1982)
Chow et al. (1975)
Chow and Tappel (1972, 1973)
Chow et al. (1976)
Tyson et al. (1982)
Tyson et al . (1982)
Chow et al. (1976)
Chow et al. (1981)
Plopper et al. (1979)
Mustafa and Lee (1976)
Chow et al. (1974)
Fukase et al. (1975)
DeLucia et al. (1975)
Mustafa et al. (1982)
Chow et al. (1975)
Chow and Tappel (1972, 1973)
Lunan et al. (1977)
Tyson et al. (1982)
Elsayed et al. (1982a)
Chow et al. (1976)
Chow and Tappel (1972, 1973)
Chow et al. (1981)
Plopper et al . (1979)
Mustafa and Lee (1976)
Chow et al. (1974)
Schwartz et al . (1976)
Fukase et al. (1975)
DeLucia et al . (1972, 1975)
Moore et al. (1980)
Mustafa et al. (1982)
Chow et al. (1975)
Mustafa et al . (1982)
Chow and Tappel (1973)
Elsayed et al. (1982a,b;
1983)
Plopper et al. (1979)
DeLucia et al. (1975)
Mustafa et al. (1982)
Chow et al. (1976)
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in this animal model, resulting in death.  Such infections occur because of a
breakdown in a complex host defense  system involving tissue  morphology,  transport
mechanisms, phagocytic ability,  and  various immune  factors.
     The data obtained  in  various experimental  animal  studies indicate that
short-term ozone exposure can reduce the effectiveness  of several  vital  defense
systems including  (1) the  ability  of  the lung to  inactivate  bacteria  and
viruses (Coffin et al.,  1968; Coffin  and Gardner,  1972a,b;  Goldstein et al.,
1974, 1977; Hurst et  al., 1970; Hurst and Coffin, 1971; Ibrahim et al., 1976;
Nakajima et al., 1972;  Ehrlich  et al.,  1979);  (2)  the mucociliary transport
system (Phalen et al., 1980; Frager  et al., 1979;  Kenoyer et al.,  1981;  (3) the
immunological  system  (Campbell  and  Hilsenroth, 1976;  Thomas et al., 1981;
Aranyi et al., 1983;  and (4)  the  pulmonary macrophage (Dowell et al., 1970;
Goldstein et al., 1971; Hadley et  al., 1977;  McAllen et al., 1981; Witz et al.,
1983; Amoruso et al.,  1981).  Studies have also indicated that the activity
level of the  test  subject  and the presence  of  other airborne chemicals are
important variables that can influence the determination of  the lowest effective
concentration of the  pollutant  (Gardner et al., 1977; Aranyi  et  al.,  1983;
Ehrlich, 1980, 1983;  Grose  et al.,  1980, 1982; Phalen et al.,  1980; Goldstein
et al., 1974;  111 ing et al., 1980).
     A major  problem  remains  in assessing the relevance of  these  animal data
to humans.  If  this  animal  model  is  to  be used to  reflect  the toxicological
response occurring in humans, then the endpoint for comparison of  such studies
should not be mortality, since today few individuals die of  bacterial pneumonias.
A better comparison in humans would  be the increased prevalence of respiratory
illness in  the  community.   Such a comparison is proper  since  both mortality
from respiratory infections (animals) and morbidity from respiratory infections
(humans) result from a loss in pulmonary defenses.
     Ideally, studies  of pulmonary  host defenses should be performed in man,
using  epidemiological  or volunteer  methods  of study.   Unfortunately,  such
studies have  not been reported yet.  Attention must therefore be paid to the
results of host-defense experiments  conducted with animals.
     In the area of host defense,  present knowledge of the physiology, metabo-
lism, and function have come primarily from the study of various animal systems,
but  it  is  generally accepted that  the  basic mechanisms of  action of  these
defense cells and  systems  function   similarly in  both animals and man.   The
effects  seen  in animals represent  alterations  in  basic biological systems.
One  would  not expect to see an equivalent response  (e.g., mortality) in man,
0190GC/A                            1-114                               6/28/84

-------
but one can assume that similar alterations in basic defense mechanisms could
occur in humans since  they possess equivalent pulmonary defense systems.   It
is understood,  however,  that different exposure  levels  may be required to
produce similar  responses  in humans.   The  concentration of ozone at which
effects become  evident can be  influenced  by  a number of  factors,  such as
preexisting disease,  dietary factors,  concurrent exposure to other pollutants,
or the presence of other  environmental stresses, or a combination of these.
Thus, one  could hypothesize that  humans exposed  to ozone could experience
similar effects.  At the  present  time, however, one cannot predict the exact
concentration at which  effects may occur in man nor the severity of the effects.
     The effects of  ozone  on host defense mechanisms in experimental animals
are summarized  in Figure 1-13 and  Table 1-16  (see Section  1.10.1 for criteria
used in developing this summary).
1.10.3.5  Tolerance.   Examination  of responses to short-term, repeated exposures
to 0- clearly  indicates  that with some of  the  parameters measured,  animals
have an increased capacity to resist the effects of subsequent exposure.  This
tolerance persists for varying  times,  depending on the degree of development
of the tolerance.   Previous low levels of exposure to 0, will certainly protect
against subsequent lethal  doses and the development of edema (Stokinger et al.,
1956; Fairchild, 1967; Coffin and Gardner, 1972a).   The delay in mucociliary
activity (i.e.,  clearance  reported for 0,) can  also be eliminated by  pre-
exposure to a  lower  concentration. This effect is only for a short period of
time  and  is lost as soon as the  mucus  secretion rate returns to normal.
However, not  all  of the  toxic  effects of CL,  such as  reduced functioning
activity of the  pulmonary  defense system (Gardner et al., 1972); hyperplasia
of the type 2 cells  (Evans et al., 1971, 1976a,b); increased susceptibility to
respiratory disease  (Gardner  and  Graham,  1977);  loss of pulmonary enzymatic
activity (Chow, 1976,  Chow et al.  , 1976); and inflammatory response (Gardner
et al. , 1972)  can be  prevented by prior treatment with  low levels  of 0^.
Dungworth et al. (1975b)  and Castleman et al.  (1980) have attempted to explain
tolerance by careful examination of the morphological changes  that occur with
repeated 0-  exposures.   These investigators  suggest that during continuous
exposure to  03 the  injured  cells  attempt to initiate  early repair  of the
specific lesion.  This repair thus results  in a reduction of the  effect first
observed.   At  this time, there  are a  number of  hypotheses proposed to  explain
the mechanism  of this  phenomenon  (Mustafa  and Tierney,  1978;  Schwartz  et al.,
1976; Mustafa  et al. ,  1977;  Berliner  et al. , 1978; Gertner et al. , 1983b;
0190GC/A                            1-115                              6/28/84

-------
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Figure 1-13.  Summary of effects of ozone on host defense mechanisms in experi-
              mental animals.   See Table 1-16 for reference citations for studies
              summarized here.

-------
                 TABLE 1-16.   EFFECTS OF OZONE ON HOST DEFENSE
                      MECHANISMS IN EXPERIMENTAL ANIMALS
  Effect/response
03 concentration, ppm
                            References
Inhibited bactericidal
  activity
 0.5
 0.99
 0.62
 0.7
 0.7
 0.4
 0.4
Delayed mucociliary      0.4,  0.8,  1.0
  clearance; accelerated 1.0
  alveolar clearance     0.8
Altered macrophage
  membrane
Decreased macrophage
  function
Altered no.  of defense
  cells
Increased suscepti-
  bility to infection
 0.1, 1.0
 0.5
 0.5
 0.5, 1.0

 0.25, 0.5
 0.5
 0.5, 0.67
 0.5, 0.67
 0.8
 1.0
 1.0

 0.2
 0.2, 0.35, 0.5, 0.8
 0.2, 0.35
 0.2, 0.5, 0.8
 0.25
 0.5
 0.5, 0.88
 0.5
 0.54, 0.88
 0.8
 1.0
 1.0
 0.5, 0.88
 0.5, 0.8
 0.2
 0.2
 0.08
 0.08,
0.1
                         0.
                         0.
                         0.
                   Friberg et al.  (1972)
                   Goldstein et al.  (1971a)
                   Goldstein et al.  (1971b)
                   Bergers et al.  (1983)
                   Warshauer et al.  (1974)
                   Coffin and Gardner (1972b)
                   Goldstein, E.,  et al. (1972)

                   Kenoyer et al.  (1981)
                   Abraham et al.  (1980)
                   Phalen et al.  (1980)

                   Gardner et al.  (1971)
                   Dowel 1 et al.  (1970)
                   Hadley et al.  (1977)
                   Goldstein et al.  (1977)

                   Hurst et al. (1970, 1971)
                   Alpert et al.  (1971b)
                   Coffin et al.  (1968)
                   Coffin and Gardner (1972b)
                   Schwartz and Christman (1979)
                   Shingu et al.  (1980)
                   McAllen et al.  (1981)

                   Plopper et al.  (1979)
                   Dungworth et al.  (1975b)
                   Castleman et al.  (1977)
                   Boorman et al.  (1977, 1980)
                   Barry et al. (1983)
                   Zitnik et al.  (1978)
                   Stephens et al.  (1974a)
                   Last et al. (1979)
                   Freeman et al.  (1974)
                   Castleman et al.  (1980)
                   Freeman et al.  (1973)
                   Cavender et al.  (1977)
                   Brummer et al.  (1977)
                   Eustis et al.  (1981)
                   Dungworth (1976)
                   Stephens et al.  (1976)
                         0.4,
      0.3
      0.7
Coffin et al.
Miller et al.
Ehrlich et al
Aranyi et al.
Illing et al.
Bergers et al
(1968)
(1978)
 (1977)
(1983)
(1980)
 (1983)
0190GC/A
            1-117
                                        6/28/84

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                 TABLE  1-16.   EFFECTS OF OZONE ON  HOST  DEFENSE
                MECHANISMS  IN  EXPERIMENTAL  ANIMALS (continued)
  Effect/response
03 concentration, ppm
References
Increased suscepti-
bility (cont'd)

Altered immune
activity



0.3
0.7,
1.0
0.1
0.5,
0.5,
0.59


0.9


0.8
0.8


Abraham et al. (1982)
Coffin and Blommer (1970)
Thomas et al. (1981b)
Aranyi et al . (1983)
Osebold et al . (1979, 1980)
Gershwin et al . (1981)
Campbell and Hilsenroth
(1976)
Bhatnagar et al. ,  1983).   From this  literature,  it would appear that tolerance,
as seen in animals,  may not be the  result of any one single biological  process,
but instead may result  from a number of different  routes,  depending on the
specific response measured.   Tolerance  does not imply  complete  or  absolute
protection, because  continuing injury does  still occur,  which could  potentially
lead to nonreversible pulmonary changes.

1-10-4  Extrapulmonary Effects of Ozone
     It was  formerly believed that 03,  on  contact with respiratory system
tissue, immediately  reacted and thus was not absorbed or transported to extra-
pulmonary sites.  However,  several  studies  suggest  that either 03 or products
formed by  the interaction  of  0-  and respiratory system  tissue produce  effects
in  lymphocytes, erythrocytes,  and serum, as well as  in  the  parathyroid gland,
the myocardium, the  liver,  and the  CNS.  Ozone  exposure also produces  effects
on  animal  behavior  that may be caused by pulmonary consequences of 0^, or by
nonpulmonary (CNS) mechanisms.  The mechanism by which QS causes extrapulmonary
changes is unknown.   Mathematical models of 0~ dosimetry predict that  very little
0~  penetrates to the blood of the alveolar capillaries.   Whether these effects
 J
result from 0, or a reaction product of 03 which penetrates to the blood and is
transported is the subject of  speculation.
1.10.4.1   Central Nervous  System and Behavioral  Effects.   Ozone  significantly
affects  the behavior of  rats during exposure  to  concentrations as low as
235 ug/m   (0.12 ppm)  for  6 hr.   With  increasing concentrations of 03>  further
decreases  in  unspecified  motor activity and in  operant  learned behaviors have
 0190GC/A
             1-118
             6/28/84

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been observed  (Konigsberg  and  Bachman,  1970; Tepper  et  al. ,  1982;  Murphy
et al. ,  1964; and Weiss et al., 1981).  Tolerance to the  observed decrease in
motor activity may occur on repeated exposure.  At low O, exposure concentra-
               3
tions (490 pg/m ,  0.25 ppm) an increase in activity is observed after exposure
                                          3
ends.   Higher 0.,  concentrations (980 pg/m ,  0.5 ppm) produce  a  decrease in
                O
rodent activity that  persists for several hours  after  the  end of exposure
(Tepper et al.,  1982,  1983).
     The mechanism  by which  behavioral performance  is reduced is unknown.
Physically active  responses appear to enhance the effects of 0,,  although this
may be the  result  of  an enhanced minute  volume that  increases the effective
concentration delivered  to the lung.  Several  reports  indicate  that it  is
unlikely that animals have reduced physiological  capacity to respond, prompt-
ing Weiss et al. (1981) to suggest that 0,. impairs the inclination to respond.
Two studies  indicate  that mice will  respond to  remove  themselves  from an
                                           3
atmosphere containing greater than 980 |jg/m   (0.5 ppm)  (Peterson and Andrews,
1963, Tepper et al.,  1983).   These  studies suggest that the aversive effects
of 0,, may  be due  to lung irritation.  It is unknown whether lung irritation,
odor, or a  direct effect on the CNS causes change in  rodent behavior at lower
0., concentrations.
1.10.4.2  Cardiovascular Effects.   Studies on the effects of 0- on the  cardio-
vascular system are few, and  to date there are  no reports of attempts to con-
firm these  studies.   Structural changes   in the cell  membranes and nuclei  of
the myocardium  muscle  fibers  in mice were found after 3 weeks of exposure to
        3
392 pg/m  (0.2 ppm) (Brinkman et al., 1964), and these effects were reversible
in clean air.  The exposure of  rats to 0- alone or in combination with  cadmium
          3
(1176 pg/m  , 0.6 ppm 03) resulted in measurable increases in systolic pressure
and heart rate (Revis et al., 1981).   No  additive or antagonistic response was
observed with the combined exposure.   Pulmonary capillary blood  flow and PaO?
                                                          3
decreased  30 min  following exposure  of  dogs to  588  pg/m  (0.3  ppm) of 0~
(Friedman et al., 1983).   The decrease in pulmonary  capillary  blood  flow per-
sisted for as long as 24 hr following exposure.
1.10.4.3   Hematological  and Serum Chemistry  Effects.   The data base for the
effects of  CL  on  the hematological system is extensive and indicates that 03
or  one  of  its  reactive products can cross  the blood-gas barrier, causing
changes in  the  circulating erythrocytes   (RBC) as well as significant differ-
ences in various components of  the serum.
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     Effects of 03 on  the  circulating RBCs can be readily identified by exa-
mining either  morphological  and/or biochemical endpoints.  These  cells are
structually and metabolically well understood and are available through rela-
tively non-invasive methods, which makes them ideal candidates for both human
and animal  studies.  A wide range of structural effects have been reported  in
a variety of species  of  animals,  including an  increase  in  the fragility of
RBCs isolated from monkeys  exposed to 1470  ug/m  (0.75 ppm)  of 0_  4 hr/day for
                                                                 ^
4 days (Clark  et al.,  1978).   A  single 4-hr exposure to 392 ng/m  (0-2 ppm)
also caused increased  fragility as well as  sphering of RBCs  of rabbits (Brinkman
et al., 1964).   An increase in the number of RBCs with Heinz bodies was detected
                                       3
following a  4-hr  exposure  to 1666 ug/m  (0.85  ppm).   The  presence of  such
inclusion bodies in RBCs is  an indication of oxidant stress (Menzel et al.,
1975a).
     These morphological  changes  are frequently accompanied  by a wide range of
                                                           3
biochemical  effects.    RBCs of  monkeys exposed to 1470 ug/m   (0.75 ppm) of 0~
for 4  days  also had  a decreased  level of glutathione (GSH)  and  decreased
acetylcholinesterase  (AChE) activity,  an enzyme bound to the  RBC membranes.
The RBC  GSH  activity  remained significantly lower 4 days postexposure (Clark
et al., 1978).
     Animals deficient in  vitamin  E  are  uniquely sensitive to 0-.  The RBCs
from these  animals, after  being  exposed to 0~, had a significant increase in
the activity of GSH peroxidase, pyruvate kinase, and lactic  dehydrogenase, but
                                                      3
had a  decrease in  RBC GSH  after exposure  to 1568 |jg/m  (0.8 ppm)  for  7 days
(Chow  and Kaneko,  1979).   Animals with a vitamin E-supplemented diet did not
have  any changes  in  glucose-6-phosphate dehydrogenase  (G-6-PD),  superoxide
                                                                3
dismutase,  or  catalase activities.   At a  lower level  (980  ug/m ,  0.5 ppm),
there  were  no  changes in GSH level or in the activities of GSH peroxidase or
GSH reductase  (Chow  et al. ,  1975).   Menzel et al.  (1972)  also  reported a
significant  increase  in  lysis  of  RBCs from vitamin E-deficient animals after
                                3
23 days  of  exposure  to 980 ug/m  (0.5 ppm).  These effects were not observed
in  vitamin  E-supplemented  rats.   Mice on  a  vitamin E-supplemented diet and
those  on a  deficient  diet showed an  increase  in G-6-PD  activity  after an
                    3
exposure  of  627 ug/m   (0.32  ppm)  of 0~ for 6 hr.  Decreases observed  in AChE
activity occurred in both groups (Moore et al., 1980).
     Other  blood  changes are attributed to Ov   Rabbits  exposed  for  1 hr to
         3
392 ug/m  (0.2 ppm) of 0,  showed a significant drop in total blood serotonin
                                                                    3
(Veninga, 1967).  Six- and 10-month exposures of rabbits to 784 ug/m   (0.4 ppm)
0190GC/A                            1-120                              6/28/84

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of 0., produced  an  increase in serum protein  esterase  and in serum trypsin
    «3
inhibitor.   This latter  effect  may be a result  of  thickening of the small
pulmonary arteries.   The same exposure caused a significant decrease in albumin
levels and an  increase  in alpha and gamma globulins (P'an and Jegier, 1971,
1976; P'an et al., 1972;  and Jegier, 1973).   Chow et al.  (1974)  reported that
the  serum  lysozyme  level  of  rats increased  significantly after 3  days  of
continuous exposure to 0. but was not affected when the exposure was interim't-
                                                                            3
tent (8 hr/day,  7 days).   The CL concentration in both  studies was  1568 |jg/m
(0.8 ppm) of 03.
     Short-term  exposure  to low concentrations  of  03  induced an immediate
change in the serum creatine phosphokinase level in mice.  In this  study, the
0  doses were  expressed  as the product of concentration and time.  The C x T
value for this effect ranged from 0.4 to 4.0 (Veninga et al., 1981).
     A few of the hematological  effects observed in animals (i.e., decrease in
GSH and AChE activity and the formation of Heinz bodies) following exposure to
0., have also been seen following jjn vitro exposure of RBCs from humans (Freeman
and Mudd, 1981;  Menzel  et al. ,  1975b; Verweij and Van  Steveninck,  1981).  A
common effect observed  by a number of  investigators is  that 0-  inhibits the
membrane ATPase activity of RBCs (Koontz and Heath, 1979; Kesner et al.,  1979;
Kindya and  Chan, 1976;  Freeman  et al., 1979; Verweij  and Van  Steveninck,
1980).   It has been postulated that this inhibition of ATPase could be related
to the spherocytosis  and  increased fragility  of  RBCs seen  in animal and human
cells.
     Although these i_n vitro data are useful  in studying mechanisms of action,
it is difficult to extrapolate these data to any effects observed in man.   Not
only is the method of exposure not physiological, but the actual concentration
of 0., reaching the RBC cannot be determined with any accuracy.
1.10.4.4  Cytogenetic and Teratogenic Effects
     Uncertainty still  exists  regarding possible reproductive,  teratogenic,
and mutational  effects of exposure to  ozone.  Based on  various  vn vitro data,
a  number  of  chromosomal  effects of ozone  have  been described for  isolated
cultured cell  lines,  human  lymphocytes,  and microorganisms (Fetner, 1962;
Hamelin et al.,  1977a,  1977b,  1978; Hamelin and Chung, 1975, 1978; Scott and
Lesher, 1963; Erdman  and Hernandez,  1982; Guerrero et  al.,  1979; Dubean and
Chung, 1979, 1982).   The interpretation,  relevance, and predictive values of
such studies  to human health are  questionable  since  (1) the concentrations
used were many-fold greater than what is found in the ambient air (see
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Chapter 10); (2) attempts to extrapolate jm  vitro exposure concentrations to
human exposure dose  is  not  yet possible;  and (3)  direct exposure of isolated
cells to ozone is highly artifactual  since  it bypasses all  the defenses of the
host that would normally be functioning in protecting the  individual from the
inhaled gas.  Furthermore,  the  direct  exposure of isolated cells i_n vitro to
ozone may result  in  chemical  reactions between ozone and  culture media that
might not occur j_n vivo.
     Important questions still exist regarding jm vivo cytogenetic  effects of
ozone  in  rodents  and humans.   In 1971, Zelac  et al.  reported chromosomal
abnormalities in peripheral leukocytes  of  hamsters  exposed to CL (0.2 ppm).
Combined exposures to ozone and radiation (227-233 rads) produced an additive
effect on the  number of chromosome breaks in  peripheral  leukocytes.   These
specific findings were not  confirmed by Gooch et al.  (1976) or by Tice et al.
(1978), but  sufficient differences in the various experimental protocols make
a  direct  comparison  difficult.   The  latter group  did report significant
increases in the number  of chromatid deletions and achromatic lesions resulting
from exposure to 0.43 ppm ozone.
     Because  the  volume of air inspired  during pregnancy is  significantly
enhanced, the pregnant  animal  may be at greater  risk to low  levels of ozone
exposure.   Early  studies  on the possible teratogenic  effects  of ozone have
suggested that exposures as low as 0.2 ppm can reduce infant survival rate and
cause  unlimited  incisor growth  (Brinkman et  al.,  1964; Veninga et al. , 1967).
Kavlock et al. (1979, 1980) found that pregnant rats exposed to 1.0 and 1.49 ppm
ozone  showed  a  significant  increase  in  embryo  resorption rate, slower  growth,
slower  development  of righting reflexes,  and  delayed grooming  and rearing
behavior.
1.10.4.5  Other Extrapulmonary Effects.  A  series of  studies  was conducted  to
show  that 0  increases  drug-induced sleeping  time  in a  number of species of
            O
animals  (Gardner  et  al.,  1974; Graham, 1979;  Graham  et al.,  1981,  1982a,b,
                        3
1983a,b).   At  1960 ug/m   (1.0  ppm),  effects were observed after 1, 2,  and  3
days  of  exposure.  As the  concentration of  0,  was reduced, increasing  numbers
of daily 3-hr exposures were required to produce a significant effect.  At the
lowest  concentration studied  (196 ug/m ,  0.1 ppm),  the increase was observed
at days 15  and 16.of exposure.  It appears that this  effect is not  specific  to
the  strain  of mouse or to  the three species of  animals  tested, but it is
sex-specific,  with   females being more susceptible.   Recovery was  complete
within  24 hr after  exposure.   Although a  number  of mechanistic  studies  have
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been conducted, the  reason  for this effect on pentobarbital-induced sleeping
time is not  known.   It has  been hypothesized that some common aspect related
to  liver  drug  metabolism is quantitatively  reduced  (Graham  et al.,  1983a).
     Several  investigators  have attempted to  elucidate the involvement of the
endocrine system  in  0_  toxicity.   Most of these studies were designed  to
investigate the hypothesis  that the survival  rate of mice and  rats exposed to
lethal  concentrations  of 0, could  be increased by use  of  various  thyroid
blocking agents or by thyroidectomy.  To follow up these findings,  demons and
Garcia (1980a,b)  investigated  the  effects  of a 24-hr exposure  to 1960 ng/m
(1.0 ppm) of 03 on the hypothalamo-pituitary-thyroid system of rats.  These
three  organs  regulate the  function of  each  other through various hormonal
feedback mechanisms.   Ozone  caused decreases in serum concentration of thyroid
stimulating hormone  (TSH),  in  circulating thyroid hormones (T~  and T.) and in
protein-bound  iodine.   No  alterations were  observed  in many other  hormone
levels measured.   Thyroidectomy prevented the effect of 0,, on TSH.   The thyroid
                                                         O
gland  itself was  altered (e.g.,  edema) by 0,.  The authors interpreted these
findings  as  an 0~~induced  lowering of the hypothalamic  set point  for the
pituitary-thyroid axis  and  a  simultaneous  reduction of  the activity of pro-
lactin inhibiting factor  in the hypothalamus.  The anterior pituitaries had
fewer cells but more  TSH per cell.   These cells also released a greater amount
of TSH into the culture medium.
     The extrapulmonary effects of ozone in experimental animals are summarized
in  Figure 1-14 and Table 1-17.   Criteria used in developing the summary were
presented in Section  1.10.1

1.10.5  Effects of Other Photochemical Oxidants
     There have been  far too few controlled  toxicological  studies  with  the
other oxidants to permit any sound scientific evaluation of their contribution
to  the toxic action  of  photochemical  oxidant  mixtures.   The few toxicological
studies on PAN indicate  that it is  much  less  acutely toxic than 0_.  When the
effects seen after exposure to 03 and  PAN  are  examined and compared, it is
obvious that the  test animals  must be  exposed  to concentrations of  PAN much
greater than those needed with 0_ to  produce a similar  effect on lethality,
behavior  modification,  morphology,  or significant  alterations  in  host pul-
monary defense system (Campbell  et al., 1967; Dungworth et al. , 1969; Thomas
et al., 1979,  1981a).   The  concentrations  of PAN required  to  produce these
effects are many  times  greater than what has been measured in the atmosphere
(0.037 ppm).
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     TABLE 1-17.   EXTRAPULMONARY EFFECTS OF OZONE IN EXPERIMENTAL ANIMALS
  Effect/response
03 concentration, ppm
         References
CNS effects
Hematological  effects
Chromosomal,  reproduc-
  tive,  teratological
  effects
Liver effects
Endocrine system
  effects
 0.05, 0.5
 0.1 - 1.0
 0.12 - 1.0
 0.2, 0.3, 0.5, 0.7
 0.5
 0.5
 0.5
 0.6
 1.0
 1.0

 0.06, 0.12, 0.48
 0.2
 0.2, 1.0

 0.25, 0.32, 0.5
 0.4
 0.4
 0.5
 0.64
 0.75
 0.8
 0.8
 0.85
 0.86
                           0
                           0
 1.0

 0.1
 0.2
 0.44
 1.0
 0.24, 0.3
 0.43

 0.1, 0.25,  0.5, 1.0

 0.82
 1.0

 0.75
 0.75
 0.75
 1.0
Konigsberg and Bachman (1970)
Weiss et al. (1981)
Tepper et al.  (1982)
Murphy et al.  (1964)
Tepper et al.  (1983)
Reynolds and Chaffee (1970)
Xintaras et al.  (1966)
Peterson and Andrews (1963)
Fletcher and Tappel (1973)
Trams et al. (1972)

Calabrese et al.  (1983a)
Brinkman et al.  (1964)
Veninga (1967, 1970)
Veninga et al. (1981)
Moore et al. (1980; 1981a,b)
Jegier (1973)
P'an and Jegier (1972, 1976)
Menzel et al.  (1972)
Larkin et al.  (1983)
Clark et al. (1978)
Chow and Kaneko (1979)
Chow et al.  (1974)
Menzel et al.  (1975a)
Schlipkoter and Bruch (1973)
Dorsey et al.  (1983)
Mizoguchi et al.  (1973)
Christiansen and Giese (1954)

Brinkman et al.  (1964)
Veninga (1967)
Kavlock et al. (1979)
Kavlock et al. (1980)
Zelac et al. (1971a)
Tice et al.  (1978)

Graham (1979)
Graham et al.  (1981, 1982a,b)
Veninga et al. (1981)
Gardner et al. (1974)

Atwal and Wilson (1974)
Atwal et al. (1975)
Atwal and Pemsingh (1981)
demons and Garcia (1980a,b)
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     Similarly,  most of the investigations reporting H?0? toxicity have involved
concentrations much higher than  those  found in the ambient air (0.1 ppm),  or
the investigations were conducted  by  using various iji vitro  techniques  for
exposure.   Very limited information is  available on the health significance of
inhalation exposure to  gaseous  H-O^.   Because H-C"  is highly soluble, it  is
generally assumed that  it does not penetrate  into  the alveolar regions of  the
lung but is instead deposited on the surface of the upper airways (Last et al.,
1982).   Unfortunately,  there  have  not  been studies designed to look for pos-
sible effects in this region of the respiratory tract.
     A few jj} vitro studies have reported cytotoxic, genotoxic, and biochemical
effects of H?0?  when  using isolated cells  or organs  (Stewart et al., 1981;
Bradley et al. ,  1979;  Bradley and  Erickson, 1981; Speit et al., 1982; MacRae
and Stich, 1979).  Although these studies can provide useful data for studying
possible mechanisms of  action,  it  is not yet possible  to extrapolate these
responses to those that might occur in the mammalian system.
     Field and epidemiological  studies  have shown that  human  health  effects
from exposure to ambient  mixtures  of oxidants  and other airborne pollutants
can produce  adverse human  health effects  (Chapter  12).   Few such  studies have
been conducted with laboratory animals, because  testing  and measuring  of such
mixtures is not only complicated, but extremely costly.  In these studies, the
investigators attempted to  simulate the photochemical reaction products pro-
duced  under  natural  conditions  and to define the  cause-effect relationship.
     Exposure  to complex mixtures  of  oxidants plus the  various  components
found  in  UV-irradiated auto exhaust indicates  that  certain effects,  such  as
histopathological changes,  increase in  susceptibility  to infection, a variety
of  altered pulmonary  functional  activities  were  observed in this oxidant
atmosphere which was not reported in the  nonirradiated exhaust (Murphy et  al. ,
1963;  Murphy, 1964; Nakajima et al. ,  1972;  Hueter et al. , 1966).   Certain
other  biological responses were observed  in both treatment  groups,  including a
decrease  in  spontaneous activity,  a decrease in infant survival  rate, fertil-
ity,  and certain pulmonary  functional  abnormalities  (Hueter  et al.,  1966;
Boche  and  Quilligan, 1960; Lewis et al.,  1967).
     Dogs  exposed to  UV-irradiated  auto  exhaust containing oxidants  either
with or without  SO  showed significant pulmonary  functional abnormalities  that
                  X.
had relatively  good correlation with structural  changes (Hyde et al., 1978;
Gillespie,  1980; Lewis et al. , 1974).  There were no  significant differences

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in the magnitude  of  the response in these  two  treatment groups, indicating
that oxidant gases and  SO  did not interact  in any synergistic or additive
                          s\
manner.
1.11  EFFECTS OF OZONE AND OTHER PHOTOCHEMICAL OXIDANTS IN CONTROLLED EXPOSURES
1.11.1   Pulmonary Function Effects in Controlled Human Studies:  Mechanical
        Function of the Lung
     Controlled  human  exposure (clinical)  studies  typically evaluate much
smaller numbers  of subjects  for shorter periods of time compared with large-
scale population studies.   A major advantage of these studies is that exposures
to either  single pollutants or  combinations of pollutants are usually carried
out in environmentally controlled chambers in which relative humidity, tempera-
ture, and  pollutant concentrations are well defined and carefully controlled.
Exposure conditions  are designed to approximate  representative ambient  air
exposure conditions,  especially those thought to be associated with the induc-
tion of acute  effects.   Inherent in the design, however,  of controlled human
exposure studies are  limitations on the range of pollutant exposures, types of
subjects studied,  and types  of effects  studied.  Conditions  are strictly
monitored  by human rights  and medical  ethics committees  to  assure  that the
experimental exposures to the pollutants being tested will not lead to serious
morbidity or irreversible illness.   Consequently, the types of acute pulmonary
responses  assessed in controlled  exposure  studies could be considered  as
"transient" and "reversible."  Depending, however, upon the population at risk,
the method  of  exposure, and the  level of  subject activity, the  so-called mild
and reversible  health  effects measured in controlled  human  exposure  studies
may be  indicators  of  other more serious  health  effects  likely  to occur if
prolonged or repeated ambient exposures to the same concentrations of pollutants
were encountered by study  subjects.  In addition, relatively small changes in
lung function  of no  particular concern for healthy,  non-sensitive adults may
be medically important for sensitive individuals or for those having compromised
pulmonary functions.
1.11.1.1   General Population.   A number  of  controlled human  studies have
reported significant decrements  in  pulmonary  function associated with ozone
exposure,   including  the presence  of  respiratory symptoms.   The increased
severity of reported  symptoms generally parallels the observed impairment in
pulmonary  function.   Table 1-18 summarizes pertinent  studies on controlled
human exposure  to ozone.
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TABLE 1-18.   SUMMARY TABLE:   RESULTS OF CONTROLLED HUMAN EXPOSURES TO OZONE
Ozone3
concentration Measurement 'c Exposure
ug/m5
HEALTHY
627
1960
980
980
1470
ppm method duration
ADULT SUBJECTS AT REST
0.32 MAST, NBKI 2 hr
1.0
0.5 CHEM, NBKI 2 hr
0.50 CHEM, NBKI 2 hr
0.75
Activity
level (VE) Observed effect(s)

R Specific airway resistance increased with
acetylchol ine challenge; subjective symptoms
in 3/14 at 0.32 ppm and 8/14 at 1.0 ppm.
R (10) Decrement in forced expiratory volume and
flow.
R (8) Decrement in forced expiratory volume and
flow.
No. and sex
of subjects Reference

13 male Konig et al. , 1980
1 female
40 male Folinsbee et al.,
(divided into four 1978
exposure groups)
8 male Horvath et al . ,
7 female 1979
EXERCISING HEALTHY ADULTS
235
353
470
588
784
392
686
0.12 CHEM, UV 2.5 hr
0.18
0.24
0.30
0.40
0.20 UV, UV 1 hr
0.35 (mouth-
piece)
IE (65) Decrement in forced expiratory volume and
@ 15-min intervals flow suggested at 0.12 ppm with larger
decrements at > 0.18 ppm; respiratory
frequency and specific airway resistance
increased and tidal volume decreased at
> 0.24 ppm; coughing reported at all
concentrations, pain and shortness of
breath at s 0.24 ppm.
IE (77.5) @ vari- Decrement in forced expiratory volume and
able competitive flow with IE and CE; subjective symptoms
intervals increased with 03 concentration and may
CE (77.5) limit performance; respiratory frequency
increased and tidal volume decreased with
CE.
135 male McDonnell et al . ,
(divided into six 1983
exposure groups)
10 male Adams and Schelegle,
(distance runners) 1983

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TABLE 1-18 (cont'd)   SUMMARY TABLE:   RESULTS OF CONTROLLED HUMAN EXPOSURES TO OZONE
Ozone3
concentration Measurement ' Exposure
ug/m3
392
823
980
412
588
__, 980
I
ro
<^>
725
980
1470
784
784
ppm method duration
0.2 UV, UV 2 hr
0.42
0.50
0.21 UV, UV 1 hr
0.3 CHEM, NBKI 2 hr
0.5
0.37 MAST, NBKI 2 hr
0.50
0.75
0.4 UV, NBKI 2 hr
0.4 CHEM, NBKI & 3 hr
MAST, UV
Activity
level (VE)
IE (30 for male,
18 for female
subjects)
@ 15-min intervals
CE (81)
R (10), IE (31,
50, 67)
@ 15-min intervals
R (11) & IE (29)
@ 15-min intervals
IE (2xR)
@ 15-min intervals
IE (4-5xR)
for 15 min
Observed effect(s)
Repeated daily exposure to 0.2 ppm did not
affect response at higher exposure concen-
trations (0.42 or 0.50 ppm); large inter-
subject variability but individual
pulmonary function responses were highly
reproducible.
Decrement in forced expiratory volume and
flow; subjective symptoms may limit per-
formance.
Decrement in forced expiratory volume and
flow; the magnitude of the change was
related to Q3 concentration and V£.
Total lung capacity and inspiratory
capacity decreased with IE (50, 67); no
change in airway resistance or residual
volume even at highest IE (67). No
significant changes in pulmonary function
were observed at 0.1 ppm.
Good correlation between dose (concen-
tration x VE) and decrement in forced
expiratory volume and flow.
Specific airway resistance increased with
histamine challenge; no changes were
observed at concentrations of 0.2 ppm.
Decrement in forced expiratory volume was
greatest on the 2nd of 5 exposure days;
attenuated response by the 4th day of
exposure.
No. and sex
of subjects
8 male
13 female
6 male
1 female
(distance cyclists)
40 male
(divided into four
exposure groups)
20 male
8 female (divided into
six exposure groups)
12 male
7 female
(divided into three
exposure groups)
10 male
4 female
Reference
Gliner et al . , 1983
Fol insbee et al . ,
1984
Fol insbee et al . ,
1978
Silverman et al. ,
1976
Dimeo et al . , 1981
Farrell et al . , 1979

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                                           TABLE 1-18 (cont'd).   SUMMARY  TABLE:   RESULTS  OF  CONTROLLED  HUMAN  EXPOSURES  TO  OZONE
Ozone3 b c
concentration Measurement ' Exposure
ug/m3 ppm method duration
784 0.4 CHEM, UV 3 hr








Activity
level (VE)
IE (4-5xR)
for 15 min







Observed effect(s)
Decrement in forced expiratory volume was
greatest on the 2nd of 5 exposure days;
attenuation of response occurred by the
5th day and persisted for 4 to 7 days.
Enhanced bronchial reactivity with
methacholine on the first 3 days;
attenuation of response occurred by
the 4th and 5th day and persisted
for > 7 days.
No. and sex
of subjects Reference
13 male Kulle et al . , 1982
11 female
(divided into two
exposure groups)





—'   823    0.42      UV, UV
 I
                                      2 hr
                                                    IE (30)
                      Decrement in forced expiratory volume and
                      flow greatest on the 2nd of 5 exposure
                      days; attenuation of response occurred by
                      the 5th day and persisted for < 14 days with
                      considerable intersubject variability.
                                                                                                                          24  male
                                                                                                                                                   Horvath et al . ,  1981
     921    0.47      UV, NBKI
                                      2 hr
                                                    IE (3xR)
                      Decrement in forced expiratory volume and
                      flow greatest on the 2nd of 4 exposure
                      days; attenuation of response occurred by
                      the 4th day and persisted for 4 days.
                                                8 male
                                                3 female
                                                                                                                                                   Linn et al . ,  1982b
1176    0.6       UV,  NBKI
                                      2 hr
                                      (noseclip)
IE (2xR)
@ 15-min intervals
Specific airway resistance increased in 7
nonatopic subjects with histamine and
methacholine and in 9 atopic subjects
with histamine.
11 male
5 female (divided
by history of atopy)
Holtzman et al . ,
1979
    1470
            0.75
                      MAST, NBKI
                                      2 hr
IE (2xR)
@ 15-min intervals
Decrements in spirometric variables
(20%-55%); residual volume and closing
capacity increased.
                                                                                                                          12  male
                         Hazucha et al.,
                         1973

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                                      TABLE Irl8 (cont'd).   SUMMARY TABLE:   RESULTS OF CONTROLLED HUMAN EXPOSURES TO OZONE
Ozone3
concentration Measurement >c Exposure
ug/m3
ppm method duration
Activity
level (VE)
Observed effect(s)
No. and sex
of subjects
Reference
ASTHMATICS
392
490
SUBJECTS
235
353
490
392
588
784
0.2 CHEM, NBKI 2 hr
0.25 CHEM, NBKI 2 hr
WITH CHRONIC OBSTRUCTIVE LUNG DISEASE
0.12 UV, NBKI 1 hr
0.18 UV, NBKI 1 hr
0.25
0.2 CHEM, NBKI 2 hr
0.3
0.41 UV, UV 3 hr
IE (2xR)
@ 15-min intervals
R

IE (variable)
@ 15-min intervals
IE (variable)
@ 15-min intervals
IE (28) for
7.5 min each
half hour
IE (4-5xR)
for 15 min
No significant changes in pulmonary func-
tion. Small changes in blood biochemistry.
Increase in symptom frequency reported.
No significant changes in pulmonary func-
tion.

No significant changes in forced expiratory
performance or symptoms. Decreased arterial
oxygen saturation during exercise was
observed.
No significant changes in forced expiratory
performance or symptoms. Group mean arterial
oxygen saturation was not altered by 03
exposure.
No significant changes in pulmonary function
or symptoms. Decreased arterial oxygen
saturation during exposure to 0.2 ppm.
Small significant decreases in FVC and FEV3.0.
20 male
2 female
5 male
12 female

18 male
7 female
15 male
13 female
13 male
17 male
3 female
Linn et al. , 1978
Silverman, 1979

Linn et al . , 1982a
Linn et al . , 1983
Solic et al. , 1982
Kehrl et al. , 1983
Kulle et al. , 1984
Ranked by lowest observed effect level.
Measurement method:  MAST = Kl-Coulometric (Mast meter); CHEM = gas phase chemiluminescence; UV = ultraviolet photometry.
Calibration method:  NBKI = neutral buffered potassium iodide; UV = ultraviolet photometry.
Minute ventilation reported in L/min or as a multiple of resting ventilation.   R = rest; IE = intermittent exercise; CE = continuous exercise.

-------
     Studies employing at-rest  (no  exercise)  exposures to ozone  have  shown
that ozone concentrations > 0.5  ppm  produce significant decrements in pulmonary
function.   Subsequent studies have  employed various levels of exercise will
enhance to modify the change in function during ozone exposure.  The severity
of exercise is  expressed in terms  of minute ventilation (VV).   (See Volumes IV
and V  for  a  glossary of terms.)  Increased minute  ventilation accompanying
exercise will enhance pulmonary decrements during ozone exposure.   While the
most recent reports include actual measurements of minute ventilation obtained
during exposure, earlier publications often included only a description of the
exercise  regimen.   Table 1-19  presents estimates of the  minute ventilation
associated with given exercise  regimens.   This table compares  the level  of
exercise with the  work  performed  (watts or kg-m/min),  the minute ventilation
required, and representative activities of  individuals  for that  level  of work
(exercise).
     Based on reported  studies  of 1 to 3  hr duration,  significant pulmonary
function impairment (decrement)  occurs when exercise is combined with exposure
to ozone:

     1.   Light exercise (V£ < 25 L/min) - Effects at > 0.37 ppm 03;
     2.   Moderate  exercise  (V£ = 26-43 L/min) - Effects  at  > 0.30 ppm 03;
     3.   Heavy exercise  (V£ =  44-63 L/min) -  Effects  at  > 0.24 ppm 03;  and
     4.   Very  heavy  exercise  (VV > 64 L/min)  -  Effects at > 0.18 ppm  03,
          with  suggestions of decrements at 0.12 ppm 0.,.

For  the majority of these  studies,  15-min intermittent exercise  alternated
with  15-min  rest  was employed for the duration of the  exposure.   Whether the
exercise  is  intermittent or continuous does not appear  to affect the pulmonary
function  response at a given concentration  and ventilation.
      Experimental design factors  that influence the level of pulmonary function
changes  observed,  in terms of group means  associated with an  exposure study,
include  the  number  of subjects tested, timing  of the pulmonary function measure-
ments,  and  the  ozone  measurement  and  calibration  techniques.  A critical
minimum  number  of  subjects  is required to  determine the significance of pulmonary
function  changes associated with  a  given ozone  exposure.   For  example, individual
responses in males versus females  have been  difficult to analyze because of
the  limited number of females  in the  reported studies.  In virtually all of
the  reported studies, pulmonary  function  measurements  have  been made at the
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   TABLE 1-19.  ESTIMATED VALUES OF OXYGEN CONSUMPTION AND MINUTE VENTILATION ASSOCIATED WITH REPRESENTATIVE TYPES OF  EXERCISE3

Level of work
Light
Light

-
CO
co


Light
Moderate
Moderate
Moderate
Heavy
Heavy
Very heavy
Very heavy

Severe
Work perforned .
watts kg-m/min
25
50
75
100
125
150
175
200
225
250
300
150
300
450
600
750
900
1050
1200
1350
1500
1800
02 consumption,
L/mi n
0.
0.
1.
1.
1.
2.
2.
2.
3.
3.
4.
65
96
25
54
83
12
47
83
19
55
27
Minute
ventilation,
L/min
13
19
25
30
35
40
55
63
72
85
100+
Representative activities
Level walking at 2 mph; washing clothes
Level walking at 3 mph; bowling; scrubbing floors
Dancing; pushing wheelbarrow with 15- kg load;
simple construction; stacking firewood
Easy cycling; pushing wheelbarrow with 75- kg load;
using sledgehammer
Climbing stairs; playing tennis; digging with spade
Cycling at 13 mph; walking on snow; digging trenches
Cross-country skiing; rock climbing; stair climbing
with load; playing squash and handball; chopping
with axe
Level running at 10 raph; competitive cycling
Competitive long distance running; cross-country
skiing
aSee text for discussion.
 kg-m/min = work performed each minute to move a mass of 1 kg through a vertical distance of 1 m against the force of gravity.
cAdapted from Astrand and Rodahl (1977).

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beginning and end of exposure.   Intermittent exercise protocols during exposures
would permit pulmonary function to be measured shortly after the completion of
each exercise period (during the intervening rest period), but few investigators
have  included  them in  their  design protocol.  The precise  timing  of this
measurement, however,  does not appear to be as critical for ozone exposures as
it is for sulfur dioxide exposures.
     Other  variables  have not  been adequately addressed  in the available
clinical studies.   Information  derived  from the exposure of smokers and non-
smokers to  ozone  is sparse and somewhat inconsistent, perhaps partly because
of  undocumented  variability  in smoking histories.  Although some degree of
attenuation  appears to  occur in smokers,  a  definite  conclusion is not  yet
possible.   Further and more precise studies are required to answer the complex
problems associated with  personal  and ambient pollutant  exposures.   While a
few studies have investigated sex differences in responses to ozone, they have
not conclusively demonstrated that men and women respond differently to  ozone.
Furthermore, gender differences in pulmonary  capacities have not been adequately
considered  in  the  response evaluation.   Environmental  conditions  such as heat
and relative humidity may  enhance subjective  symptoms and physiological  impair-
ment  following ozone exposure,  but the results to  date  indicate that  the
effects  are no more than  additive.   Other  variables,  such as seasonal  effects
and age, need  to be considered. In particular, responses  in  the very young and
the  aged  need  to be examined.  In addition, there may be  interactions between
and among these variables  that  may modify  the response to CL, but such informa-
tion  is generally  lacking.
      In  the majority  of the studies  reported, assessment of the  significance
of  results  was typically  based on the mean  ±  variance  of changes in lung
function  resulting from exposure to  ozone as compared to exposure  to control
                                 i
clean air.   Decrements  in  pulmonary  function  can be  expressed  as  a  function  of
the  effective  dose of ozone, where  effective  dose is  defined as  the product  of
ozone concentration,  minute ventilation, and exposure duration.   The relative
contribution of these variables to  pulmonary decrements  is  greater for  ozone
concentration  than for minute  ventilation, which is greater  than  that  for
exposure  duration.  Figure 1-15  uses  the  pulmonary  function measurement FEV,
for relating group mean decrements  in lung function  to ozone concentration and
ventilation.   Other measures of  spirometric  pulmonary function (volumes and
 flows) are  consistent with  FEV,  and hence are not  depicted here.   Although
mean changes  are  useful  for  making statistical inferences  about homogeneous
 0190GC/A                            1-134                               6/28/84

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8
ui
5
3
EC
O

S
CC

Z
X
LJU

Q
UJ
O
cc
O
a.

O
UJ
Ifl
   120
   110
   100
    90
80
70
60
    50
    40
                                                                          LIGHT

                                                                          EXERCISE
                                                                     MODERATE
                                               VERY HEAVY

                                               EXERCISE
       EXERCISE

'HEAVY    \.

 EXERCISE
                                                                          X   _
               0.1        0.2        0.3        0.4        0.5


                                 OZONE CONCENTRATION, ppm
                                                             0.6
         0.7
0.8
     Figure 1-15. Group mean decrements in 1-sec forced expiratory volume during 2-hr

     ozone exposures with different levels of intermittent exercise: light (Vg <25 L/min);

     moderate (V^ = 26-43 L/min); heavy (Vg  = 44-63 L/min); and very heavy (Vg ^64

     L/min). (Concentration-response curves are taken from Figures 13-2 to 13-5 in

     Chapter 13, Volume V).
                                         1-135

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populations, they may not be adequate for describing differences in responsive-
ness to ozone among  individuals.  While the significant mean changes observed
demonstrate that  the differences in  response between ozone and  clean air
exposures are not  the  result of chance, the variance of responses was quite
large in many studies.   Characterization of reports of individual  responses to
ozone is pertinent since it permits  the assessment of a segment of the general
population or special subpopulations that are potentially at-risk to 03 exposure.
Since  there is  good intrasubject reproducibility,  the  response of a  given
individual  to a  single ozone exposure is probably a reliable estimate of the
intrinsic responsiveness  of that individual  to ozone.  Sensitive individuals
in  any  given  study group apparently weight  the  group mean response of that
study,  such that the mean  decrement is  the  result of a greater contribution
from  a  small  proportion of  the  group rather  than  more or  less  equal  contribu-
tions  across  the entire study group.  In any given study, it is desirable to
have  a  sufficiently  large overall subject group in order to be  able to perform
either  post hoc  categorization of subjects or determine a distribution of both
group and individual responses.
1.11.1.2   Subjects with Preexisting Disease.   In the past,  individuals  with
compromised lung function have been considered  to be potentially at-risk to
ozone exposure  compared to  healthy  nonsmokers (U.S.  Environmental Protection
Agency, 1978).   Significant decrements  in pulmonary  function are  not observed,
however,  in mild asthmatic  subjects exposed  to <0.25 ppm 03 for  2 hr  at  rest
or with intermittent  light exercise.   In patients with chronic  obstructive
 lung disease  (COLD) performing  light  intermittent exercise, no decrements  in
pulmonary function are observed for 1-  and  2-hr exposures to  <0.30 ppm 03-
Although these  results which are derived from spirometric  tests  suggest that
 asthmatics  and  patients with COLD may not be more sensitive to ozone than are
 healthy  subjects,  experimental-design  considerations  in reported  studies
 suggest that this  issue  is still  unresolved.  Ethical concern  with triggering
 adverse reactions in  these individuals  dictates that experimental protocols
 use  only low ozone  concentrations  and light-to-moderate exercise levels.  In
 one  study, however, subjects with mild chronic bronchitis were exposed to 0.4
 ppm ozone and were found to be less sensitive than healthy nonsmokers.
      In addition  to overt  changes  in pulmonary function, enhanced nonspecific
 bronchial reactivity has been observed following exposures to  ozone concentra-
 tions  > 0.3 ppm.  Exposure to 0.2 ppm of ozone with  intermittent light exercise
 does not affect nonspecific bronchial  reactivity.
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1.11.1.3  Intersubject Variability.   Group mean decrements in pulmonary function
can be predicted with some degree of accuracy when expressed as a function of
effective dose of ozone, defined, again, as the product of ozone concentration,
minute ventilation, and exposure duration.  The relative contribution of these
variables to pulmonary  decrements,  as  noted in section 1.11.1.1,  is greatest
for ozone concentration, followed by minute ventilation and exposure duration,
in order.  A greater degree of predictive accuracy is obtained if the contribu-
tion of each of these variables is appropriately weighted.  Several  additional
factors, however, make the interpretation of prediction equations  more difficult.
Intrasubject variability  is  relatively  small,  and the  responses of a given
individual to a  given  ozone  concentration are quite reproducible.  There is
considerable intersubject variability,  however,  in the  magnitude of pulmonary
function changes with ozone  exposure.   The data clearly  indicate  that some
individuals in  the general  population  are more responsive  than  others to
ozone.  No information is available to account for these differences.   Consider-
ing the  great variability among individuals in  their pulmonary responses to
ozone exposure, prediction equations that  use some form of effective  dose may
not be  adequate for predicting differences in  responsiveness  to  0,  among
                                                                    O
individuals.
1.11.1.4  Attenuation with Repeated Exposures.   During repeated daily exposures
to ozone, decrements in pulmonary function (spirometric variables)  are greatest
on the second exposure  day;  thereafter, pulmonary responsiveness  to ozone is
attenuated, with smaller decrements occurring on each successive day until the
fourth or fifth exposure day, when very small or even no changes are observed.
Following a sequence of repeated daily exposures, there  is  a gradual time-
related  return  of  susceptibility  of  pulmonary  function  to  ozone  exposure
similar to that observed prior to repeated exposures.   This attenuated pulmonary
responsiveness usually persists for 3 to 7 days,  but apparently can last up  to
3 weeks in sensitive individuals.
     The  following  general  observations  appear  appropriate:   (1)   the  time
required to abolish  pulmonary  response  to ozone is  directly related  to the
magnitude of  the  initial  response; (2) the  longer  the period required for
attenuation of pulmonary response to ozone, the longer the attenuation persists;
and (3) the severity of symptomatic responses is associated with the magnitude
of functional  changes during repeated exposures.
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     Attenuation of bronchial  reactivity has  also been observed in response to
ozone.   The time for attenuation of the initial  enhancement in bronchial  reac-
tivity is reported to be equivalent to that for  decrement in pulmonary function;
however, this attenuation appears to last longer.
     In studies exposing healthy nonsmokers and  subjects with chronic bronchi-
tis to  0.4  ppm ozone,  those with chronic  bronchitis  were  less sensitive to
ozone,   showed  attenuation of the initial pulmonary function response earlier,
and lost the attenuated response sooner than  the healthy nonsmokers.
     Repeated daily exposure to a given  low (0.20 ppm) concentration of  ozone
does not affect  the  magnitude  of decrement in  pulmonary  function resulting
from exposure at higher (0.40 to 0.50 ppm) ozone concentrations.   This finding
is consistent with the proposition that functional adaptation may not occur in
the airways  of individuals  living  in communities where the  ambient ozone
levels do not exceed 0.2 ppm.   The difficulty,  however, of drawing such infer-
ences on the basis of narrowly defined laboratory studies is that under ambient
conditions a  number of  uncontrollable  factors will modify  the  response.  Most
notably, other pollutants may  interact with ozone to  modify  changes in the
host at  lower concentrations during generally more protracted  exposures.   The
evidence suggesting that  Los  Angeles  residents  exhibit functional adaptation
is sparse and requires confirmation.
     Some evidence suggests that exercise performance may be limited by exposure
to ozone.   Decrements  in  forced  expiratory flow occurring  with ozone exposure
                                  •
during  prolonged  heavy  exercise  (VV = 65  to 81 L/min) along with increased
respiratory  frequency  and decreased tidal  volume  might be  expected to  produce
ventilatory  limitations  at  near  maximal exercise.  Results  from exposure  to
ozone  during  high exercise  levels  (68  to 75 percent of max V0?)  indicate that
discomfort  associated  with  maximal  ventilation  may be an  important factor  in
limiting performance.  There are not enough data available, however, to  address
this issue adequately.
     An  issue that merits attention and  needs resolution is whether attenuated
pulmonary responsiveness  is beneficial or  detrimental.  It may possibly  reflect
the presence  or development of underlying  changes in neural responses  that  are
protective  and do not exact a physical  penalty or it  may  reflect progressive
injury  to lung tissues.

1.11.2   Other Effects of  Ozone in Controlled Human Exposures
     No consistent cytogenetic or functional changes  have  been demonstrated in
circulating  lymphocytes from human  subjects exposed to ozone  concentrations as
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high as  0.4  to 0.6 ppm.  Chromosome or chromatid aberrations would therefore
be unlikely at lower ozone levels.   Limited data have indicated that ozone can
interfere with biochemical mechanisms  in blood  erythrocytes  and sera, but the
physiological significance of these studies is questionable.

1.11.3  Effects of Peroxyacetyl Nitrate and Mixtures in Controlled Human
        Exposures                          '            ~~~~~~
     No  significant enhancement  of respiratory effects has been consistently
demonstrated  for  combined exposures of ozone with  sulfur  dioxide,  nitrogen
dioxide, and sulfuric acid or particulate aerosols, or with multiple combinations
of these pollutants.   Most of the available studies with other photochemical
oxidants have been limited to a series of studies on the effects of peroxyacetyl
nitrate  (PAN)  on healthy  young  and middle-aged  males  during intermittent
exercise on a treadmill.  No significant effects were observed at PAN concentra-
tions of 0.25  to  0.27 ppm, which  are  an  order of magnitude higher than the
daily maximum concentrations of PAN reported for relatively high oxidant areas
of the  country  (0.047 ppm).   Two  additional studies at 0.24  and 0.30 ppm of
PAN have suggested a possible limitation on forced expiratory volume and flow,
but there are  not enough data yet  for  evaluating the  significance of  this
effect.   Further  studies  are  also  required on  the  more  complex mixtures of
pollutants found in the natural environment.
1.12  FIELD AND  EPIDEMIOLOGICAL  STUDIES OF THE EFFECTS OF OZONE AND OXIDANTS
1.12.1  Introduction
     Field and epidemiological studies, when properly executed, offer a unique
view of health effects research because they involve the real world, i.e., the
study of  human populations  in their natural setting.  However, these studies
also have attendant limitations that must be considered in a critical evaluation
of their results.  One major problem in singling out the effects of one pollu-
tant in field studies of either morbidity or mortality in populations has been
the interference of other critical variables in the  environment.   Limitations
also exist for epidemiological  research on the health  effects of oxidants,
including interference or interaction  between  oxidants and other pollutants;
meteorological factors such  as temperature; proper exposure assessments includ-
ing individual activity patterns and location of pollutant monitors; difficulty


0190GC/A                            1-139                              6/28/84

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in identifying oxidant species  responsible  for observed effects;  and charac-
teristics of the populations  such  as  hygiene practices, smoking habits, and
socioeconomic status.
     Investigative  approaches comparing communities with  high 0_ concentra-
                                                                O
tions to  those  with low 0- concentrations  have  usually been unsuccessful,
often because actual  pollutant levels have  not  differed  enough during the
study and other important variables have not been adequately controlled.  The
terms "oxidant"  and "ozone"  and their association with health  effects are
often insufficiently clarified.   Moreover,  our knowledge about the measurement
and calibration methods  used  is still lacking.  Also,  as  our knowledge and
skills in epidemiology improve,  the  incorporation of new  key variables into
the analyses is  required.  Thus, the  incorporation of  individual exposure data
(e.g., from the  home and  workplace) becomes more of a  necessity.
     Both acute  and chronic  exposure situations  have been reported in the
literature on photochemical  oxidants.   Relevant studies  providing quantitative
information on effects associated with acute exposure  include those on irrita-
tive  symptoms,  pulmonary function, and aggravation of  existing respiratory
disease  (Table 1-20).  A few  studies, of limited quality, have  been reported
on morbidity, mortality, and  chromosomal  effects from chronic exposures.

1.12.2  Field and Epidemiological Studies of Effects of  Acute Exposure
     Studies on  the irritative effects of  CL  have  been complicated by the
                                             3
presence of  other  photochemical  oxidants and their precursors in the ambient
environment.  That  0_ causes  the eye  irritation  normally  associated  with  smog
is doubtful.  Nevertheless, studies indicate that eye irritation  is  likely  to
occur at oxidant levels  of about 0.10 ppm.   A shown in Table 1-20, associations
between  oxidant  levels and symptoms such as eye,  nose,  and throat  irritation,
chest discomfort,  cough, and  headache have  been  reported  at >0.10  ppm  in  both
children and young adults (Hammer et al. ,   1974;  Makino and Mizoguchi,  1975;
Okawada  et  al.,  1979).   Zagraniski et al.  (1979)  also reported  an  association
                                             3
of these symptoms with approximately  157 ug/m  (0.08 ppm)  ozone in adults with
asthma and allergies.  Discomfort caused by  irritative  symptoms may  be  respon-
sible  for  the  impairment  of athletic performance  reported in  high school
students during  cross-country track meets  in Los  Angeles  (Wayne et al., 1967;
Herman,  1972).   Although several  additional  studies  have shown respiratory
irritation  apparently  related to ambient exposure  in community populations,
none  of  these studies provide satisfactory  quantitative data  on acute  respira-
tory  illnesses.
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                      TABLE 1-20.   SUMMARY  TABLE:   ACUTE  EFFECTS OF  OZONE  AND  OTHER  PHOTOCHEMICAL OXIDANTS  IN  POPULATION  STUDIES
Lowest
estimated
effect level ,
ppm
Average maximum
hourly concentration
range during study,
ppm
Observed effect(s)
Subjects
Reference
OXIDANTS
b
0.10
0.10C
0,03-0.15
0.02-0.21
<0.23
Daily asthma attack rates increased on days
with high oxidant and particulate levels and
on cool days during a 34-week period in Los
Angeles.
Eye irritation incidence rates increased with
oxidant concentration.
Symptoms of eye irritation, sore throat,
headache, and cough related to oxidant
concentration and temperature but not
S02, N02, or NO.
Juvenile and adult
asthmatics
Adolescents
Children and
adolescents
Whittemore and Korn, 1980
Okawada et al . , 1979
Makino and Mizoguchi, 1975
0.10-0.15
                      <0.04-0.50
                                          Symptoms  of  eye  irritation,  cough,  chest
                                          discomfort,  and  headache  related  to oxidant
                                          concentration  but  not  carbon monoxide,
                                          nitrogen  dioxide,  or daily minimum
                                          temperature.
Young adults
Hammer et al. ,  1974
0.12L
                      0.06-0.37
                                          Impaired  athletic  performance  related  to
                                          oxidant concentration  but  not  nitrogen
                                          oxide, carbon  monoxide,  or particulate
                                          levels 1  hr  before cross-country  track
                                          meets  in  Los Angeles.
Adolescents
Wayne et al.,  1967
Herman, 1972

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                TABLE 1-20.   SUMMARY TABLE:   ACUTE EFFECTS OF OZONE AND OTHER PHOTOCHEMICAL OXIDANTS  IN  POPULATION STUDIES  (continued)
Lowest Average maximum
estimated hourly concentration
effect level, range during study,
ppm ppm
Observed effect(s)
Subjects
Reference
OZONE
0.08 0.004-0.235
0.08 0.01-0.12
^ 0.08 0.01-0.12
ro
0.15 0.01-0.30
0.16e 0.16-0.17
Increased daily prevalence rates for cough,
eye, and nose irritation in smokers and
patients with predisposing illnesses; pH of
particulate was associated with eye, nose, and
throat irritation while suspended sul fates were
not associated with any symptoms.
Daily peak flows decreased 12.2 to 14.8% with
ozone and total suspended particulate matter.
Decreased daily peak flows and increased pre-
valence rate for acute symptoms associated
with ozone, low temperature, and high total
suspended particulate matter.
Increased airway resistance associated with
ozone, sulfur dioxide, and temperature.
Small decrement in forced expiratory function
and increased symptoms with exercise in both
normals and asthmatics.
Asthma and allergy
patients; normal
adults
Children and
young adults
Adult asthmatics
Adolescents
Normal and
asthmatic adults
Zagraniski et al . , 1979
Lebowitz et al., 1982a, 1983
Lebowitz, 1984
Lebowitz et al . , 1982a, 1983
Lebowitz, 1984
Kagawa and Toyoma, 1975
Kagawa et al. , 1976;
Kagawa, 1983
Linn et al . , 1980, 1983
 Ranked by lowest estimated effect level for oxidant or ozone.
 Not determined.
CU.S.  Environmental Protection Agency, 1978.
dHasselblad et al. , 1976.
eDaily mean concentration of ozone was monitored by ultraviolet photometry inside a mobile  laboratory;  Linn  et  al.,  1980,  report  concentrations
 multiplied by 1.25 that correspond to the neutral  buffered potassium iodide (KI) method.

-------
     Acute epidemiological  studies in children and young adults have suggested
that decreased peak flow and increased airway resistance occur over the range
                                          3
of 0,  concentrations  from  157  to 294 pg/m   (0.08  to  0.15 ppm) (Kagawa and
    O
Toyoma, 1975;  Kagawa et al.,  1976; Kagawa, 1983; Lebowitz et al.,  1982a,  1983;
Lebowitz, 1984).   Qualitative  studies  support this finding (McMillan et al.,
1969;   Lebowitz et al. , 1974; Fabbri  et al.,  1979).  No  controlled human expo-
sure studies  in  children are  presently  available for comparison, although
                                                            3
studies  in  adults  appear to show no effect  below  235  |jg/m .  (0.12  ppm)  03
(Chapter 11).
     In studies of exacerbation of asthma and chronic lung diseases, the major
problems  in  most of the studies  have  been  the lack of  information  on the
possible effects of medications,  the absence  of records  for all days on which
symptoms  could  have occurred,  and  the  possible concurrence of symptomatic
attacks.  Investigators who have  been able to control some  of  these variables
have found consistent  effects  of 0~ on  asthma  (Table 1-20).   Their findings
have been in  accordance  with  those  of some  of  the  earlier, more qualitative
studies.  Whittemore and Korn  (1980) found small  increases  in  the probability
of asthma attacks associated with increases of 0.10 ppm in oxidant levels.
Zagraniski et al. (1979) reported an increased prevalence rate for respiratory
                                     3
symptoms with approximately 157  (jg/m  (0.08 ppm)  03 in patients with asthma.
Linn et al.  (1980,  1983) found  decreased pulmonary function  and increased
symptoms in lightly exercising asthmatics exposed to 314 to 333 pg/m  (0.16 to
0.17 ppm) 0.,  or  greater,  regardless of  other  pollutants.   With  increased
                                                     3
exercise levels,  small effects  were  found at 235 ng/m  (0.12 ppm)  0~.   Lebowitz
et al.   (1982a, 1983) and Lebowitz (1984) showed effects  in  asthmatics, related
also to temperature,  at  03 levels of 102  to 235  ng/m   (0.052 to 0.12 ppm).
There  have been  no  consistent  findings  of symptom  aggravation or changes  in
lung function  in patients  with other chronic  lung  diseases besides asthma.

1.12.3  Epidemiological Studies of Effects of Chronic Exposure
     Apparent adaptations have been  observed under  controlled  conditions with
humans, but this effect would be difficult to demonstrate in community popula-
tions.    Recent  work with  animals suggests  that  the  processes involved in
adaptation may lead to other,  perhaps adverse effects, but  no  implications for
human  health can yet be drawn.
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     Although animal studies indicate that 0., impairs defenses against infec-
tion (Chapter 10), this impairment has not been examined in clinical studies.
No positive studies of  0~  effects  on acute respiratory  illnesses  have been
reported in human populations.   In addition, most studies have yet to address
the hypothesis that years  or decades of  air pollution exposures  beginning in
childhood,  especially  among the sensitive,  may increase the  risk  of developing
chronic illness  (U.S.  Environmental  Protection Agency, 1978).
     The lack of quantitative measures of oxidant levels limits the usefulness
of many studies  of  pollution exposure and mortality.  In addition, properly
designed studies have  not been  conducted  to address  the effects of  oxidants on
the growth  and development of the  lung or on the progression of chronic diseases,
although the available evidence is  consistent with toxicological  data indicating
that 0  is  not a strong mutagen or  a demonstrable carcinogen at ambient concen-
trations.   Most  long-term studies have employed average annual levels or have
involved broad ranges  of pollution;  others  have used a simple high-oxidant/low-
oxidant dichotomy and  compared  mortality  results.  Failure  to relate mortality
to specific  levels  (and types) of oxidant  pollutants makes formulation of
exposure-response relationships impossible.   Epidemiological identification of
chronic effects  of air pollution generally requires well-conducted replicated
studies of  large, well-defined  populations  over long periods of time, which
are not available at this time  for  0- or  other photochemical oxidants.
     Studies using quantitative measures  find that  "ozone  alerts"  occur fre-
quently in  association with high temperature.  The  latter may mask 0- effects
                                                                    *5
or by  itself  produce  excess mortality in susceptible elderly cardiopulmonary
patients.   When  attempts  have  been  made  to distinguish the effects of CL, no
                                                                        O
positive relationship  has been  found with mortality; rather, the  effect corre-
lates most closely with elevated temperature.
1.13  SUMMARY OF THE EVALUATION OF INTEGRATED HEALTH EFFECTS DATA
1.13.1  Health Effects in the General  Human Population
     Controlled human studies  of  at-rest exposures to 0-  lasting  2 to 4 hr
have demonstrated decrements in forced expiratory volume and flow occurring at
and above 0.5 ppm of 03-   Airway resistance was not changed at these 0., concen-
trations.  Breathing 0~ at rest at concentrations < 0.5 ppm did not significantly
impair pulmonary function although the occurrence of some 03~related pulmonary
symptoms has been suggested in a number of studies.
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     One of the principal  modifiers  of the magnitude  of  response to 0., is
minute ventilation  (VF),  which increases proportionately with  increases in
exercise work load.   Adjustment by the respiratory system to an increased work
load is characterized by increased frequency and depth of breathing.   Consequent
             *
increases in VL not only increase the overall  volume of inhaled pollutant,  but
such ventilatory patterns  also promote a deeper penetration of ozone into the
peripheral   lung, which is the region most sensitive to ozone and where a
greater absorption  of  ozone will  occur.  These processes are further enhanced
                     *
at high work loads  (V_ >  35  L/min),   since  the mode  of breathing will most
likely change at that VV from nasal to oronasal.
     Even in well-controlled  experiments  on a homogeneous group of subjects,
physiological responses to the same work and pollutant  loads will vary widely
among individuals.   Despite such large interindividual variability,  the magni-
tude of group  mean  lung function changes  is positively associated  with the
level of exercise and  ozone concentration.  Based on  reported studies of 1 to
3 hr duration,  significant pulmonary  function  impairment (decrement) occurs
when exercise is combined with exposure to ozone:

     1.    Light exercise (V£ < 25 L/min) - Effects at > 0.37 ppm 03;
     2.    Moderate  exercise (V£ = 26  to 43  L/min) -  Effects at >  0.30 ppm 03;
     3.    Heavy exercise (V£ = 44 to 63 L/min) - Effects at > 0.24 ppm 0~;  and
     4.    Very  heavy exercise (VV > 64 L/min)  - Effects at > 0.18 ppm 0^, with
          suggestions of decrements at 0.12 ppm 0».
                                                 O

For  the  majority  of  the  controlled  studies,  15-min intermittent exercise
alternated with 15-min rest  was  employed for  the duration  of the exposure.
Continuous exercise equivalent in duration to the sum of intermittent exercise
periods at comparable ozone concentrations (0.2 to 0.4 ppm) and minute ventila-
tion (60 to  80 L/min) seems to elicit  about  the  same  changes in pulmonary
function.   The maximum response  to 0, exposure can  be observed within  5 to
10 min following the  end  of  each exercise  period.   Functional  recovery, at
least from a single exposure with exercise, appears  to progress in two phases:
during the initial  rapid phase, lasting between 1 and 3 hr, pulmonary function
improves more than 50 percent; this is followed by a much slower  recovery that
is  usually  completed within  24 hr.   In  some  individuals, despite apparent
functional   recovery,  other regulatory  systems may  still  exhibit abnormal
responses when  stimulated; e.g.,  airway  hyperreactivity might persist  for
days.
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     A close association has  been observed between changes  in pulmonary function
and the occurrence of  respiratory  symptoms in response to acute exposure to
0~.  This association holds for both the time-course and magnitude of effects.
The symptoms found in association with clinical exposure to 0., alone and with
exposure to photochemical  air  pollution  are similar but not  identical.  Eye
irritation, one of the  most  common complaints associated with photochemical
pollution, is not characteristic of clinical exposures to 0^, even at  concen-
trations several times   higher than any likely to be encountered in ambient
air.  There is  also  evidence to suggest that  other  symptoms, indicative of
either  upper or  lower  respiratory tract irritation, are more likely to occur
in populations exposed to ambient air pollution than in subjects exposed to 0^
alone in chamber studies.  For example, cough has been reported at 0.08 ppm 0^
and at 0.10 ppm oxidants in epidemiological studies and during clinical exposure
to  0.12 ppm 0.3;  nose and throat irritation  have  been  reported in community
studies in  association  with  0.10 ppm  oxidants  but not at or  below 0.15 ppm  0^
in  laboratory  studies.   Between  0.15  and  0.30  ppm,  a variety of both  respira-
tory  and  nonrespiratory symptoms have been reported in controlled exposures.
They  include throat dryness, difficulty or pain during deep inspiration, chest
tightness,  substernal  soreness or  pain,  wheezing, lassitude, malaise,  and
nausea.   Symptoms  are  therefore  considered to  be  useful  adjuncts  in  assessing
the  effects  of 0, and  photochemical pollution, particularly  if combined with
                 O
objective measures of lung function.
      Only  a  few studies have  been  designed  to examine the  effects of 03 on
exercise  performance.   In one  study,  very heavy exercise (V^ > 64 L/min) at a
high  0., concentration  (0.75  ppm) reduced postexposure maximal  exercise capacity
by limiting maximal  oxygen consumption;  submaximal oxygen  consumption changes
were  inconsistent.   The extent of  ventilatory  and respiratory metabolic changes
observed  during or following the exposure appears to have  been related to the
magnitude  of pulmonary  function  impairment.  Whether such  changes are  consequent
to respiratory discomfort (i.e.,  symptomatic  effects)  or  are the result  of
changes in lung mechanics  or both  is  still  unclear and  needs to be  elucidated.
      Environmental  conditions  such as heat  and relative humidity may enhance
 subjective symptoms  and  physiological  impairment following  03  exposure.
Modification  of the effects of  0_ by these factors may be attributed to in-
 creased ventilation which,  like exercise,  increases the  overall volume of
 inhaled pollutant and  promotes  greater  penetration into peripheral areas  of
 the lung.
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     Additional factors suspected of altering sensitivity to ozone are numerous.
For example,  age  differences,  especially between the very young and the very
old;  gender differences,  especially  for children;  personal habits such  as
cigarette  smoking;  and  possibly  social,  cultural, or economic  factors  such as
differences  in  nutritional  status or differences in  immunological status may
predispose  individuals  to  susceptibility to ozone.    Those  actually  known to
alter sensitivity, however, are few, largely because  they have not been examined
adequately  to  determine definitively  their  effects  on sensitivity  to CL.  The
following  briefly  summarizes what is actually  known  from  the  data regarding
the importance of these factors:

     1.    Age.  Although changes  in growth and development  of the lung with
age have been postulated as one of many  factors capable of modifying responsive-
ness to  0^,  studies have  not been designed to test adequately for effects of
0- in different age groups.
     2.    Sex.  Sex  differences   in  responsiveness  to  ozone have  not been
adequately studied.  Lung function of women, as assessed by changes in FEV,  „,
appears  to  be  affected  more than  that of men  under  similar  exercise and expo-
sure conditions, but  the  differences have  not  been analyzed systematically.
Further research is needed to determine whether differences in lung volumes or
differences  in exercise capacity during exposure may lead to sex differences
in responses to CL.
                 O
     3.    Smoking Status.   Differences  between smokers  and nonsmokers have
been studied often, but the data are not documented well and are often confusing.
Published results indicate a discrepancy in findings.  There is some evidence,
however, to suggest that smokers  may be  less sensitive to CL.
                                                           O
     4.    Nutritional  Status.   Antioxidant properties of vitamin E in preventing
ozone-initiated peroxidation i_n vitro are well demonstrated and their protective
effects   i_n  vivo are clearly demonstrated in rats and mice.   No evidence indi-
cates, however, that man would benefit from increased vitamin E intake relative
to ambient ozone exposures.
     5.    Red Blood Cell Enzyme Deficiencies.   There  have been too few studies
performed to document reliably that individuals with a hereditary deficiency
of glucose-6-phosphate dehydrogenase may be at-risk to significant hematological
effects  from CL exposure.
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     Successive daily brief exposures  of healthy human subjects to 0_ (<0.7 ppm
                                                                    O
for approximately 2 hr)  induce a typical temporal  pattern of response.   Maximum
functional  changes that occur  after  the first or second exposure day become
progressively attenuated on each of the subsequent days.   By the fourth day of
exposure,  the  effects are,  on the average,  not different from those observed
following  control  (air) exposure.   Individuals need between 3 and 7 days to
develop full attenuation,  with  more  sensitive subjects requiring more time.
The magnitude  of  a peak response to 0~ appears to be directly related to its
concentration.    In  addition,  concentrations of 0_  that  have no detectable
effect appear  not  to  invoke changes in response  to  subsequent exposures at
higher CL  concentrations.   Full attenuation, even in ozone-sensitive subjects,
does not persist  for more  than  3 to 7  days  in  most individuals, while partial
attenuation might persist for up to 2 weeks.  Although symptomatic response is
generally  related to the magnitude of the functional  response, partial  sympto-
matic attenuation appears to persist longer, for up to 4 weeks.
     Whether populations  exposed to photochemical air pollution  develop at
least partial  attenuation  is  unknown.   No epidemiological  studies have  been
designed to test this hypothesis.  While there is limited information obtained
from controlled  laboratory studies  to support this hypothesis,  additional
information is required.
     Responses to  0~, whether  functional, biochemical, or morphological,  have
the potential  for altering responses in both man and laboratory animals during
repeated or  continuous  exposure.   At present, the underlying  mechanisms for
this response  are poorly  understood and the effectiveness of such mitigating
forces  in  protecting the  long-term health  of  the individual against 0^ is
still uncertain.   Therefore,  hyperresponsiveness  to CL, including changes in
bronchial   reactivity, and  the  subsequent  attenuation of  responsiveness  may be
viewed as  sequential states in  a continuing process.

1.13.2  Health Effects  in  Potentially  Susceptible Individuals
     Currently available  evidence  indicates that  individuals with preexisting
disease respond  to 0~ exposure  to a similar degree as normal subjects.   Patients
with chronic  obstructive  lung disease  and/or  asthma have not  shown  increased
sensitivity  to 0, in controlled  human exposure studies, but  there  is  some
                 O
indication from  epidemiological  studies that asthmatics may  be  symptomatically
and  possibly functionally more sensitive than healthy individuals to ambient

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air exposures.  Appropriate inclusion and exclusion criteria for selection of
these subjects,  however,  especially better clinical  diagnoses  validated by
pulmonary function, must  be  considered  before their sensitivity to CL can be
                                                                     O
adequately determined.  None  of  these  factors has been  sufficiently  studied
in relation to  0   exposures  to give definitive answers.  Thus, estimates of
at-risk populations are difficult to assess with any precision.
1.13.3  Extrapolation of Effects Observed in Animals to Human Populations
     Several  animal experiments have demonstrated  increased susceptibility to
respiratory infections  following CL exposure.  Thus,  it  could be hypothesized
that humans exposed  to  CL could experience decrements in their host defenses
against infection.  At  the present time, however,  these  effects have  not been
described in  humans  exposed  to CL,  so that concentrations  at  which effects
might occur in  man or the severity of such effects are unknown and difficult
to predict.
     Animal  studies have also reported a number of extrapulmonary responses to
CL, including cardiovascular,  reproductive,  and teratological  effects, along
with changes  in endocrine function.   The implications of these findings for
human health are difficult to judge at the present time.   In addition, central
nervous system effects,  alterations in red blood cell  morphology and enzymatic
activity,  as well  as chromosomal  effects on circulating lymphocytes, have been
observed in man and  laboratory animals  following exposure to high concentra-
tions of  0^.   It  is  unlikely,  however,  that these changes would  have any
functional  significance in humans  when  exposure schedules are used that are
representative of  exposures that the population at large might actually expe-
rience.
     Despite wide  variations  in study techniques  and experimental  designs,
acute and subchronic exposures of animals to levels of ozone <  0.5 ppm produce
similar types  of responses in all  species examined.  A characteristic inflamma-
tory lesion occurs at the junction of the  conducting airways  and the gas-
exchange regions of the lung  after acute CL exposure.   Dosimetry model Simula-
                                          O
tions predict that the  maximal tissue dose of CL occurs  in this region of the
                                               O
lung.   Continuation of  the inflammatory process during longer CL exposures is
                                                               *3
especially important  since it appears  to be correlated  with  increased lung
collagen content  and remodeling of the  centriacinar  airways.   There is no
evidence of emphysema,  however,  in  the  lungs of animals exposed  to 0, for
prolonged periods  of time.

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     Since substantial  animal  data exists  for 0_-induced changes  in  lung
                                                 «5
structure and function,  biochemistry,  and host defenses, it  is  conceivable
that man may experience  more  types of effects than have been established  in
human clinical  studies.  It  is  important to note, however, that this  is  a
qualitative probability; it does not permit assessment of the  ozone concentra-
tions at which  man might experience similar effects.

1.13.4   Health Effects of Other Photochemical Oxidants and Pollutant Mixtures
     Controlled human and animal exposures have not consistently demonstrated
any enhancement of respiratory effects for combined exposures of 0, with S0_,
N0?, CO, or  HLSO.  and other particulate  aerosols.   Ozone alone is considered
to be responsible for the observed effects of those combinations or of multi-
ple mixtures of these  pollutants.   In addition, there have been far too few
controlled toxicological  studies  with other oxidants, such as  peroxyacetyl
nitrate  or hydrogen  peroxide,  to  permit  any sound scientific  evaluation of
their contribution  to the toxic action  of photochemical oxidant mixtures.
Nevertheless, there  is  still some  concern that combinations of oxidant pollu-
tants with  other  pollutants may contribute  to  the symptom aggravation  and
decreased lung function  described  in epidemiological  studies on  individuals
with asthma and in children and young adults.  For this reason, the effects of
interaction between  inhaled  oxidant gases and other environmental pollutants
on the lung need to be systematically studied using exposure regimens that are
more  closely  representative of ambient  air  ratios of peak concentrations,
frequency, duration, and time intervals between events.

1.13.5    Identification of  Potentially At-Risk  Populations or  Subpopulations
     Despite uncertainties  that may  exist in the data,  it  is  possible to
identify three major subpopulations  that may be at particular  risk from  expo-
sure  to  ozone, based on  known  health effects, activity patterns,  personal
habits,  and actual or potential exposures to ozone.
     The  first major subpopulation that  appears to be at particular risk from
exposure  to  ozone is that  subgroup of the general  population  characterized as
having preexisting  disease.   Available data  on  actual differences in sensiti-
vity  between these  and healthy,   normal   members  of  the  general population
indicate  that  under the exposure  regimes  used  to date individuals with  pre-
existing disease  may not be more  sensitive  to ozone  than normal  individuals.

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Nevertheless, two considerations place these individuals among subpopulations
at potential risk from exposure to ozone.   First, it must be noted that concern
with triggering untoward reactions has necessitated the use of low concentra-
tions and low  exercise  levels in most studies  on  subjects with preexisting
disease.   Therefore,  few or no data on responses at higher concentrations and
higher exercise levels  are  available  for comparison with responses in normal
subjects.   Thus, definitive data on responses in individuals with preexisting
disease are not available and may not ever become available.   Second, however,
it must be  emphasized that  in individuals with already compromised pulmonary
function,  the  decrements in  function produced  by  exposure to ozone, while
similar to or even the same  as those experienced by normal  subjects,  represent
a  further  decline  in volumes and flows  that  are already diminished.  Such
declines may  be expected to  impair further the ability to  perform  normal
activities.   In individuals  with preexisting diseases such as asthma or aller-
gies, increases in  symptoms upon exposure to ozone, above  and beyond  symptoms
seen in the general  population, may also impair or further curtail the ability
to function normally.
     A second  major subpopulation  at  apparent  special risk from  exposure to
ozone consists  of  individuals ("responders")  in the  general population, not
yet characterized medically except for their responses to ozone, who experience
greater decrements  in lung function from exposure to ozone than those observed
in the remainder of the general population.   As yet no means of determining in
advance those  members of the  general population who are "responders"  has been
devised.
     Data presented in  this  chapter underscore the importance of exercise in
the  potentiation  of  effects  from  exposure  to  ozone.  Thus,  a  third major
subpopulation  potentially at  risk from exposure to  ozone is composed  of those
individuals  (healthy and otherwise) whose activities  out  of  doors,  whether
vocational or avocational, result in increases  in minute ventilation.  Although
many individuals with preexisting disease would not be expected to exercise at
the  same  levels one  would  expect in healthy  individuals,  any  increase in
activity level would  bring about a commensurate increase in minute ventilation.
To  the  extent  that the aged, the young, males, or females  participate in
activities  out  of  doors that raise their minute ventilations,  all of these
subgroups may  be  considered  to be potentially  at  risk, depending upon  other
determinants  of total ozone  dose, 0_ concentration,  and  exposure duration.

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     Other biological  and nonbiological  factors  are  suspected of influencing
responses to ozone.   Data remain  inconclusive  at  the  present,  however,  regard-
ing the  importance of age,  gender,  and other  factors in influencing response
to ozone.  Thus, at the  present  time,  no other subpopulations are thought to
be biologically predisposed to increased sensitivity to ozone.   It  must  be
emphasized, however,  that the  final  identification of those effects that  are
considered "adverse"  and  the final  identification of  "at-risk" populations are
both the domain of the Administrator.
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