Disclaimer

This document has been reviewed in accordance with U.S. Environmental

Protection Agency policy and approved for publication. Mention of trade names or

commercial products does not constitute endorsement or recommendation for use.

III-ii
Preface

In 1971, the U.S. Environmental Protection Agency (EPA) promulgated National

Ambient Air Quality Standards (NAAQS) to protect the public health and welfare from

adverse effects of photochemical oxidants. In 1979, the chemical designation of the standards

was changed from photochemical oxidants to ozone (O3). This document focuses primarily

on the scientific air quality criteria for O3 and, to a lesser extent, on those for other

photochemical oxidants such as hydrogen peroxide and the peroxyacyl nitrates.

The EPA promulgates the NAAQS on the basis of scientific information contained

in air quality criteria issued under Section 108 of the Clean Air Act. The previous O3 criteria

document, Air Quality Criteria for Ozone and Other Photochemical Oxidants, was released in

August 1986 and a supplement, Summary of Selected New Information on Effects of Ozone on

Health and Vegetation, was released in January 1992. These documents were the basis for a

March 1993 decision by EPA that revision of the existing 1-h NAAQS for O3 was not

appropriate at that time. That decision, however, did not take into account some of the newer

scientific data that became available after completion of the 1986 criteria document. The

purpose of this revised air quality criteria document for O3 and related photochemical

oxidants is to critically evaluate and assess the latest scientific data associated with exposure

to the concentrations of these pollutants found in ambient air. Emphasis is placed on the

presentation of health and environmental effects data; however, other scientific data are

presented and evaluated in order to provide a better understanding of the nature, sources,

distribution, measurement, and concentrations of O3 and related photochemical oxidants and

their precursors in the environment. Although the document is not intended to be an

exhaustive literature review, it is intended to cover all pertinent literature available through

1995.

This document was prepared and peer reviewed by experts from various state and

Federal governmental offices, academia, and private industry and reviewed in several public

meetings by the Clean Air Scientific Advisory Committee. The National Center for

Environmental Assessment (formerly the Environmental Criteria and Assessment Office) of

EPA’s Office of Research and Development acknowledges with appreciation the contributions

provided by these authors and reviewers as well as the diligence of its staff and contractors in

the preparation of this document at the request of the Office of Air Quality Planning and

Standards.

III-iii

Air Quality Criteria for Ozone

and Related Photochemical Oxidants

Table of Contents

Volume I

1. Executive Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-1

2. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-1

3. Tropospheric Ozone and Its Precursors . . . . . . . . . . . . . . . . . . . . . . . . 3-1

4. Environmental Concentrations, Patterns, and Exposure Estimates . . . . . . 4-1

Appendix A: Abbreviations and Acronyms . . . . . . . . . . . . . . . . . . . . . . . . A-1

Volume II

5. Environmental Effects of Ozone and Related Photochemical

Oxidants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-1

Appendix A: Abbreviations and Acronyms . . . . . . . . . . . . . . . . . . . . . . . . A-1

Appendix B: Colloquial and Latin Names . . . . . . . . . . . . . . . . . . . . . . . . . B-1

Volume III

6. Toxicological Effects of Ozone and Related Photochemical Oxidants . . . 6-1

7. Human Health Effects of Ozone and Related Photochemical Oxidants . . . 7-1

8. Extrapolation of Animal Toxicological Data to Humans . . . . . . . . . . . . 8-1

9. Integrative Summary of Ozone Health Effects . . . . . . . . . . . . . . . . . . . 9-1

Appendix A: Abbreviations and Acronyms . . . . . . . . . . . . . . . . . . . . . . . . A-1

III-v

Table of Contents

Page

List of Tables ............................................. III-xiv

List of Figures ............................................. III-xix

Authors, Contributors, and Reviewers ............................. III-xxiii

U.S. Environmental Protection Agency Science Advisory Board,

Clean Air Scientific Advisory Committee ......................... III-xxxi

U.S. Environmental Protection Agency Project Team for Development

of Air Quality Criteria for Ozone and Related Photochemical Oxidants .... III-xxxiii

6. TOXICOLOGICAL EFFECTS OF OZONE AND RELATED

PHOTOCHEMICAL OXIDANTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6-1

6.1 INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6-1

6.2 RESPIRATORY TRACT EFFECTS OF OZONE . . . . . . . . . . . . 6-3

6.2.1 Biochemical Effects . . . . . . . . . . . . . . . . . . . . . . . . . . 6-3

6.2.1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 6-3

6.2.1.2 Cellular Targets of Ozone Interaction . . . . . . . 6-4

6.2.1.3 Effects of Ozone Exposure on Lung

Lipid Metabolism . . . . . . . . . . . . . . . . . . . . . 6-7

6.2.1.4 Effects of Ozone on Lung Antioxidant

Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6-8

6.2.1.5 Effects of Ozone on Lung Protein

Metabolism ......................... 6-13

6.2.1.6 Effects of Ozone Exposure on Lung Xenobiotic

Metabolism ......................... 6-17

6.2.1.7 Summary ........................... 6-19

6.2.2 Lung Inflammation and Permeability Changes ........ 6-20

6.2.2.1 Introduction ......................... 6-20

6.2.2.2 Permeability Changes .................. 6-21

6.2.2.3 Concomitant Changes in Permeability and

Inflammatory Cell Populations in the Lung . . . 6-29

6.2.2.4 Sensitive Populations ................... 6-31

6.2.2.5 Repeated Exposures .................... 6-33

6.2.2.6 Mediators of Inflammation and Permeability . . 6-33

6.2.2.7 Summary ........................... 6-35

6.2.3 Effects on Host Defense Mechanisms .............. 6-36

6.2.3.1 Introduction ......................... 6-36

6.2.3.2 Mucociliary Clearance .................. 6-36

6.2.3.3 Alveolobronchiolar Transport Mechanism .... 6-37

6.2.3.4 Alveolar Macrophages .................. 6-39

III-vii
Table of Contents (cont’d)

Page

6.2.3.5 Immunology ......................... 6-43

6.2.3.6 Interaction with Infectious Agents .......... 6-48

6.2.3.7 Summary ........................... 6-52

6.2.4 Morphological Effects ........................ 6-54

6.2.4.1 Introduction ......................... 6-54

6.2.4.2 Sites Affected ........................ 6-57

6.2.4.3 Considerations of Exposure Regimens

and Methods ......................... 6-76

6.2.4.4 Considerations of Degree of Susceptibility to

Morphological Changes ................. 6-78

6.2.4.5 Summary .......................... 6-80

6.2.5 Effects on Pulmonary Function .................. 6-83

6.2.5.1 Introduction ......................... 6-83

6.2.5.2 Brief Ozone Exposures (Less Than

30 Minutes) ......................... 6-85

6.2.5.3 Acute Ozone Exposures (Less Than

One Day) ........................... 6-91

6.2.5.4 Repeated Acute Exposure Experiments (More

Than Three Days) ..................... 6-99

6.2.5.5 Longer Term Exposure Studies ............ 6-100

6.2.5.6 Summary ........................... 6-102

6.2.6 Genotoxicity and Carcinogenicity of Ozone ......... 6-103

6.2.6.1 Introduction ......................... 6-103

6.2.6.2 Ozone-Induced Deoxyribonucleic Acid

Damage ............................ 6-104

6.2.6.3 Induction of Mutation by Ozone ........... 6-106

6.2.6.4 Induction of Cytogenetic Damage by Ozone . . . 6-108

6.2.6.5 Induction of Morphological Cell Transformation

by Ozone ........................... 6-109

6.2.6.6 Possible Direct Carcinogenic, Co-carcinogenic,

and Tumor-Promoting Effects of Ozone as

Studied in Whole Animal Carcinogenesis

Bioassays ........................... 6-111

6.2.6.7 Possible Effects of Ozone on Injected Tumor

Cells That Lodge in the Lung and Form Lung

Colonies ............................ 6-117

6.2.6.8 Summary and Conclusions ............... 6-118

6.3 SYSTEMIC EFFECTS OF OZONE ..................... 6-121

6.3.1 Introduction ............................... 6-121

6.3.2 Central Nervous System and Behavioral Effects ...... 6-122

6.3.3 Cardiovascular Effects ........................ 6-124

6.3.4 Hematological and Serum Chemistry Effects ......... 6-126

III-viii
Table of Contents (cont’d)

Page

6.3.5 Other Systemic Effects ........................ 6-128

6.3.6 Summary ................................. 6-128

6.4 INTERACTIONS OF OZONE WITH OTHER

CO-OCCURRING POLLUTANTS ...................... 6-129

6.4.1 Introduction ............................... 6-129

6.4.2 Simple (Binary) Mixtures Containing Ozone ......... 6-130

6.4.2.1 Nitrogen Dioxide as Copollutant ........... 6-141

6.4.2.2 Acidic Compounds as Copollutants ......... 6-146

6.4.2.3 Other Copollutants .................... 6-148

6.4.3 Complex (Multicomponent) Mixtures Containing

Ozone ................................... 6-149

6.4.4 Summary ................................. 6-151

6.5 SUMMARY AND CONCLUSIONS ..................... 6-152

6.5.1 Introduction ............................... 6-152

6.5.2 Molecular Mechanisms of Effects ................ 6-153

6.5.3 Respiratory Tract Effects ...................... 6-154

6.5.3.1 Effects on Host Defenses ................ 6-154

6.5.3.2 Effects on Inflammation and Permeability .... 6-155

6.5.3.3 Effects on Structure, Function, and

Biochemistry ........................ 6-156

6.5.3.4 Genotoxicity and Carcinogenicity of Ozone . . . 6-161

6.5.3.5 Factors That Influence Ozone Exposure ...... 6-162

6.5.4 Systemic Effects ............................ 6-163

6.5.4.1 Central Nervous System and Behavioral

Effects ............................. 6-163

6.5.4.2 Cardiovascular Effects .................. 6-163

6.5.4.3 Reproductive and Developmental Effects ..... 6-164

6.5.4.4 Other Systemic Effects ................. 6-164

6.5.5 Effects of Mixtures .......................... 6-164

REFERENCES ......................................... 6-166

7. HUMAN HEALTH EFFECTS OF OZONE AND RELATED

PHOTOCHEMICAL OXIDANTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7-1

7.1 INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7-1

7.2 CONTROLLED HUMAN EXPOSURE STUDIES . . . . . . . . . . . 7-2

7.2.1 Pulmonary Function Effects of One- to Three-Hour

Ozone Exposures . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7-2

7.2.1.1 Healthy Subjects . . . . . . . . . . . . . . . . . . . . . . 7-2

7.2.1.2 Subjects with Preexisting Disease .......... 7-17

7.2.1.3 Influence of Gender, Age, Ethnic, and

Environmental Factors .................. 7-25

III-ix
Table of Contents (cont’d)

Page

7.2.1.4 Repeated Exposures to Ozone ............. 7-40

7.2.1.5 Effects on Exercise Performance ........... 7-49

7.2.2 Pulmonary Function Effects of Prolonged (Multihour)

Ozone Exposures ............................ 7-53

7.2.3 Increased Airway Responsiveness ................ 7-61

7.2.4 Inflammation and Host Defense .................. 7-67

7.2.4.1 Introduction ......................... 7-67

7.2.4.2 Inflammation Assessed by Bronchoalveolar

Lavage ............................. 7-73

7.2.4.3 Inflammation Induced by Ambient Levels

of Ozone ........................... 7-75

7.2.4.4 Time Course of Inflammatory Response ..... 7-76

7.2.4.5 Effect of Anti-Inflammatory Agents on

Ozone-Induced Inflammation ............. 7-76

7.2.4.6 Use of Nasal Lavage To Assess OzoneInduced Inflammation in the Upper

Respiratory Tract ..................... 7-76

7.2.4.7 Changes in Host Defense Capability Following

Ozone Exposure ...................... 7-77

7.2.5 Extrapulmonary Effects of Ozone ................ 7-78

7.2.6 Ozone Mixed with Other Pollutants .............. 7-79

7.2.6.1 Ozone and Sulfur-Containing Pollutants ...... 7-80

7.2.6.2 Ozone and Nitrogen-Containing Pollutants .... 7-85

7.2.6.3 Ozone, Peroxyacetyl Nitrate, and More

Complex Mixtures ..................... 7-87

7.2.6.4 Summary ........................... 7-88

7.3 SYMPTOMS AND PULMONARY FUNCTION IN

CONTROLLED STUDIES OF AMBIENT AIR EXPOSURES . . 7-88

7.3.1 Mobile Laboratory Studies ..................... 7-88

7.3.2 High-Altitude Studies ......................... 7-92

7.4 FIELD AND EPIDEMIOLOGY STUDIES ................ 7-92

7.4.1 Acute Effects of Ozone Exposure ................ 7-92

7.4.1.1 Introduction ......................... 7-92

7.4.1.2 Individual-Level Studies ................ 7-93

7.4.1.3 Aggregate Population Time Series Studies .... 7-121

7.4.1.4 Summary and Conclusions ............... 7-142

7.4.2 Chronic Effects of Ozone Exposure ............... 7-143

7.4.2.1 Introduction ......................... 7-143

7.4.2.2 Recent Epidemiological Studies of Effects of

Chronic Exposure ..................... 7-144

7.4.2.3 Conclusions ......................... 7-158

III-x
Table of Contents (cont’d)

Page

7.5 SUMMARY AND CONCLUSIONS ..................... 7-160

7.5.1 Controlled Human Studies of Ozone Exposure ....... 7-160

7.5.1.1 Effects on Pulmonary Function ............ 7-160

7.5.1.2 Symptom Responses to Ozone ............ 7-164

7.5.1.3 Effects on Exercise Performance ........... 7-165

7.5.1.4 Effects on Airway Responsiveness ......... 7-165

7.5.1.5 Inflammation and Host Defense Effects ..... 7-167

7.5.1.6 Factors Modifying Responsiveness to Ozone . . 7-167

7.5.1.7 Extrapulmonary Effects of Ozone .......... 7-169

7.5.1.8 Effects of Ozone Mixed with Other

Pollutants ........................... 7-169

7.5.2 Field and Epidemiology Studies of Ozone Exposure . . . 7-170

REFERENCES ......................................... 7-173

8. EXTRAPOLATION OF ANIMAL TOXICOLOGICAL DATA

TO HUMANS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8-1

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

8.2 OZONE DOSIMETRY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8-2

8.2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8-2

8.2.2 Summary of 1986 Review of Experimental and

Theoretical Dosimetry . . . . . . . . . . . . . . . . . . . . . . . . 8-2

8.2.3 Experimental Ozone Dosimetry Data . . . . . . . . . . . . . . 8-3

8.2.3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 8-3

8.2.3.2 In Vivo Ozone Dosimetry Studies . . . . . . . . . . 8-3

8.2.3.3 In Vitro Ozone Dosimetry Studies . . . . . . . . . . 8-7

8.2.3.4 Human Ozone Dosimetry Studies . . . . . . . . . . 8-9

8.2.3.5 Intercomparison of Ozone Dosimetry Studies . . 8-15

8.2.4 Dosimetry Modeling ......................... 8-22

8.2.4.1 Background ......................... 8-22

8.2.4.2 Dosimetry Model Predictions ............. 8-28

8.3 SPECIES SENSITIVITY: LUNG FUNCTION AND

INFLAMMATORY ENDPOINTS EXEMPLIFYING

AN APPROACH .................................. 8-33

8.3.1 Introduction ............................... 8-33

8.3.1.1 Dosimetry .......................... 8-34

8.3.2 Homology of Response ....................... 8-35

8.3.2.1 Lung Function Endpoints as Homologous

Indicators ........................... 8-35

8.3.2.2 Inflammatory and Antioxidant Endpoints

as Homologous Indicators ............... 8-35

8.3.3 Studies of Lung Function ...................... 8-36

III-xi
Table of Contents (cont’d)

Page

8.3.3.1 Confounding Influences in Lung Function

Studies ............................. 8-36

8.3.3.2 Acute Exposure Data ................... 8-39

8.3.3.3 Prolonged Exposure Studies .............. 8-52

8.4 QUANTITATIVE EXTRAPOLATION OF ACUTE OZONE

EFFECTS ....................................... 8-55

8.4.1 Introduction ............................... 8-55

8.4.2 Intraspecies Delivered Dose Response ............. 8-56

8.4.3 Interspecies Delivered Dose Response ............. 8-56

8.5 QUANTITATIVE EXTRAPOLATION OF CHRONIC OZONE

EFFECTS ....................................... 8-60

8.5.1 Introduction ............................... 8-60

8.5.2 Factors Considered in Estimating Dose ............ 8-62

8.5.2.1 Human ............................. 8-62

8.5.2.2 Monkeys ........................... 8-68

8.5.2.3 Rats ............................... 8-68

8.5.3 Results and Discussion ........................ 8-70

8.5.3.1 Simulation Results .................... 8-70

8.5.3.2 Interpretation of Chronic Site-Specific

Dose-Effect Estimates .................. 8-72

8.6 SUMMARY AND CONCLUSIONS ..................... 8-76

8.6.1 Ozone Dosimetry ............................ 8-76

8.6.2 Species Homology and Sensitivity ................ 8-78

8.6.3 Quantitative Extrapolation ...................... 8-79

REFERENCES ......................................... 8-81

9. INTEGRATIVE SUMMARY OF OZONE HEALTH EFFECTS . . . . . . . 9-1

9.1 INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9-1

9.2 EXPOSURE-DOSE RELATIONSHIPS . . . . . . . . . . . . . . . . . . . 9-2

9.3 EFFECTS OF SHORT-TERM OZONE EXPOSURES . . . . . . . . 9-4

9.3.1 Physiological Responses to Ozone Exposure . . . . . . . . . 9-4

9.3.1.1 Respiratory Symptom Responses . . . . . . . . . . . 9-4

9.3.1.2 Lung Function Responses . . . . . . . . . . . . . . . . 9-5

9.3.1.3 Changes in Airway Responsiveness . . . . . . . . . 9-7

9.3.2 Exacerbation of Respiratory Disease . . . . . . . . . . . . . . 9-7

9.3.3 Morphological and Biochemical Abnormalities . . . . . . . 9-9

9.3.3.1 Inflammation and Cell Damage . . . . . . . . . . . . 9-9

9.3.3.2 Host Defense ........................ 9-12

9.3.4 Quantitative Ozone Exposure-Response

Relationships ............................... 9-13

9.3.4.1 Prediction and Summary of Mean

Responses .......................... 9-15

III-xii
Table of Contents (cont’d)

Page

9.3.4.2 Prediction and Summary of Individual

Responses .......................... 9-19

9.4 EFFECTS OF LONG-TERM OZONE EXPOSURES ......... 9-26

9.4.1 Repeated Exposures .......................... 9-26

9.4.2 Prolonged Exposures ......................... 9-27

9.4.3 Genotoxicity and Carcinogenicity of Ozone ......... 9-31

9.5 EFFECTS OF COMBINED POLLUTANT EXPOSURES ...... 9-31

9.6 CONCLUSIONS .................................. 9-32

REFERENCES .................................... 9-37

APPENDIX A: ABBREVIATIONS AND ACRONYMS . . . . . . . . . . . . . . . A-1

III-xiii
List of Tables

Number Page

6-1 Effects of Ozone Exposure on Lung Lipids . . . . . . . . . . . . . . . . . 6-9

6-2 Effects of Ozone Exposure on Lung Antioxidants ............ 6-11

6-3 Effects of Ozone Exposure on Lung Proteins ................ 6-15

6-4 Effects of Ozone Exposure on Lung Xenobiotic Metabolism ..... 6-18

6-5 Lung Inflammation and Permeability Changes Associated

with Ozone Exposure ................................ 6-22

6-6 Effects of Ozone on Host Defense Mechanisms:

Physical Clearance .................................. 6-38

6-7 Effects of Ozone on Host Defense Mechanisms:

Macrophage Alterations ............................... 6-40

6-8 Effects of Ozone on Host Defense Mechanisms:

Immunology ...................................... 6-45

6-9 Effects of Ozone on Host Defense Mechanisms:

Interactions with Infectious Agents ....................... 6-50

6-10 Effects of Ozone on Conducting Airways .................. 6-58

6-11 Effects of Ozone on Lung Structure: Short-Term

Exposures (Less Than Two Weeks) ...................... 6-61

6-12 Effects of Ozone on Lung Structure: Long-Term

Exposures (More Than Two Weeks) ...................... 6-64

6-13 Effects of Ozone on Pulmonary Function .................. 6-86

6-14 Effects of Ozone on Airway Reactivity .................... 6-88

6-15 Effects of Ozone on Deoxyribonucleic Acid Damage .......... 6-105

6-16 Summary of Findings on the Mutagenicity of Ozone .......... 6-107

6-17 Effects of Ozone on Morphological Cell Transformation ........ 6-110

III-xiv
List of Tables (cont’d)

Number Page

6-18 Summary of Results on the Possible Carcinogenicity of Ozone . . . 6-112

6-19 Alveolar/Bronchiolar Tumor Incidence in B6C3F1 Mice in the

National Toxicology Program’s Chronic Ozone Study .......... 6-116

6-20 Effects of Inhaled Ozone on the Ability of Injected Tumor

Cells to Colonize the Lungs of Mice ..................... 6-118

6-21 Summary of Data on the Genotoxicity of Ozone ............. 6-119

6-22 Effects of Ozone on Behavior .......................... 6-123

6-23 Effects of Ozone on the Cardiovascular System .............. 6-125

6-24 Hematology and Serum Chemistry Effects .................. 6-127

6-25 Toxicological Interactions of Ozone and Nitrogen Dioxide ...... 6-131

6-26 Toxicological Interactions to Binary Mixtures of Ozone with

Acids and Other Pollutants ............................ 6-136

7-1 Controlled Exposure of Healthy Human Subjects to Ozone . . . . . . 7-4

7-2 Ozone Exposure in Subjects with Preexisting Disease .......... 7-18

7-3 Gender Differences in Pulmonary Function Responses to Ozone . . 7-26

7-4 Hormonal Influences on Pulmonary Function Responses to

Ozone ........................................... 7-33

7-5 Age Differences in Pulmonary Function Responses to Ozone .... 7-34

7-6 Changes in Forced Expiratory Lung Volume After Repeated

Daily Exposure to Ozone ............................. 7-41

7-7 Pulmonary Function Effects with Repeated Exposures

to Ozone ......................................... 7-43

7-8 Ozone Effects on Exercise Performance ................... 7-50

7-9 Pulmonary Function Effects After Prolonged Exposures to

Ozone ........................................... 7-54

III-xv
List of Tables (cont’d)

Number Page

7-10 Increased Airway Responsiveness Following Ozone Exposures . . . 7-63

7-11 Bronchoalveolar Lavage Studies of Inflammatory Effects from

Controlled Human Exposure to Ozone .................... 7-68

7-12 Additional Studies of Inflammatory and Host Defense Effects from

Controlled Human Exposure to Ozone .................... 7-70

7-13 Ozone Mixed with Other Pollutants ...................... 7-81

7-14 Acute Effects of Ozone in Ambient Air in Field Studies with a

Mobile Laboratory .................................. 7-90

7-15 Acute Effects of Photochemical Oxidant Pollution: Lung Function

in Camp Studies .................................... 7-97

7-16 Slopes from Regressions of Forced Expiratory Volume in One

Second on Ozone for Six Camp Studies ................... 7-103

7-17 Acute Effects of Photochemical Oxidant Pollution: Lung Function

in Exercising Subjects ................................ 7-106

7-18 Acute Effects of Photochemical Oxidant Pollution: Daily Life

Studies of Lung Function and Respiratory Symptoms .......... 7-110

7-19 Acute Effects of Photochemical Oxidant Pollution: Symptom

Prevalance ........................................ 7-114

7-20 Aggravation of Existing Respiratory Diseases by Photochemical

Oxidant Pollution ................................... 7-117

7-21 Hospital Admissions/Visits in Relation to Photochemical

Oxidant Pollution: Time Series Studies ................... 7-124

7-22 Comparison of Regressions of Daily Summertime Respiratory

Admissions on Ozone and Temperature in Toronto, Ontario,

and Buffalo, New York, for the Summer of 1988 ............. 7-133

7-23 Summary of Effect Estimates for Ozone in Recent Studies of

Respiratory Hospital Admissions ........................ 7-136

III-xvi
List of Tables (cont’d)

Number Page

7-24 Daily Mortality Associated with Exposure to Photochemical

Oxidant Pollution ................................... 7-138

7-25 Pathologic and Immunologic Changes Associated with Chronic

Ozone Exposure .................................... 7-147

7-26 Effects of Chronic Ozone Exposure on Pulmonary Function,

Respiratory Symptoms, and Chronic Respiratory Disease ....... 7-148

7-27 Effects of Chronic Ozone Exposure on the Incidence of

Cardiovascular and Malignant Diseases .................... 7-159

8-1 Experimental Studies on Ozone Dosimetry . . . . . . . . . . . . . . . . . 8-4

8-2 Total Respiratory Tract Uptake Data ...................... 8-16

8-3 Unidirectional Upper Respiratory Tract Uptake Efficiency Data . . . 8-17

8-4 Lower Respiratory Tract Uptake Efficiency Data ............. 8-18

8-5 Theoretical Ozone Dosimetry Investigations ................ 8-23

8-6 Assumption for Application of Dosimetry Model to Breathing

Frequency Responses to Ozone ......................... 8-32

8-7 Comparison of Total Respiratory Tract Uptake Data with

Model Predictions ................................... 8-32

8-8 Pulmonary Antioxidant Substances in Various Laboratory Animal

Species and Humans ................................. 8-37

8-9 Polymorphonuclear Leukocyte and Protein Permeability Response

to Ozone by Species ................................. 8-48

8-10 The Basis of Information for Model Parameters .............. 8-63

8-11 Estimating Monkey Ventilatory Parameters ................. 8-69

8-12 Summary of Simulation Results ......................... 8-71

8-13 Summaries of Study Data Used in Extrapolation of Chronic

Ozone Effects ..................................... 8-74

III-xvii
List of Tables (cont’d)

Number Page

9-1 Gradation of Individual Responses to Short-Term Ozone

Exposure in Healthy Persons ............................... 9-24

9-2 Gradation of Individual Responses to Short-Term Ozone

Exposure in Persons with Impaired Respiratory Systems ............ 9-25

III-xviii
List of Figures

Number Page

6-1 Major secondary products of ozone interaction with

lung cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6-5

6-2 Schematic representation of intrapulmonary conducting airways

and acini from animals with respiratory bronchioles (human

and nonhuman primates) and without respiratory bronchioles

(rats and most rodents) ............................... 6-55

6-3 Electron micrograph of alveolar septa in the centriacinar region

of the lungs from laboratory rats exposed to a simulated pattern

of ambient ozone for 78 weeks, showing thickened basement

membrane ........................................ 6-74

6-4 Schematic comparison of the duration-response profiles for

epithelial hyperplasia, bronchoalveolar exudation, and

interstitial fibrosis in the centriacinar region of lung

exposed to a constant low concentration of ozone ............ 6-81

7-1 Individual concentration-response curves for five separate

subjects exposed to 0.10, 0.15, 0.20, and 0.25 ppm ozone for

two hours with moderate intermittent exercise ............... 7-13

7-2 Mean percent change in post-minus prevalues of

forced expiratory volume in one second for each

gender-race group ................................... 7-29

7-3 The forced expiratory volume in one second is shown

in relation to exposure duration at different ozone

concentrations ..................................... 7-57

7-4 The distribution of response for 87 subjects exposed to

clean air and at least one of 0.08, 0.10, or 0.12 ppm ozone is

shown here ....................................... 7-58

7-5 The forced expiratory volume in one second is shown in

relation to exposure duration under three exposure conditions .... 7-60

7-6 Airway function can be measured before and immediately after

the inhalation of an aerosolized bronchoconstrictor drug

like methacholine ................................... 7-62

III-xix
List of Figures (cont’d)

Number Page

8-1 Total respiratory tract uptake as a function of inspiratory

flow in humans .................................... 8-19

8-2 Unidirectional uptake efficiency in the upper respiratory

tract by the nasal pathway ............................. 8-20

8-3 Unidirectional uptake efficiency in the upper respiratory

tract by the oral pathway .............................. 8-21

8-4 Uptake efficiency of the lower respiratory tract as a

function of inspiratory flow in humans .................... 8-22

8-5 Net dose and tissue dose versus sequential segments along

anatomical model airway paths for human, rat, guinea pig,

and rabbit ........................................ 8-29

8-6 Parallelogram paradigm for utilizing animal data for human

health predictions ................................... 8-34

8-7 Comparison of changes in frequency of breathing after ozone

exposure in humans and animals ........................ 8-40

8-8 Comparison of changes in resistance after ozone exposure in

humans and animals ................................. 8-43

8-9 Comparison of changes in forced vital capacity after ozone

exposure in humans and animals ........................ 8-47

8-10 Composite of data from Slade et al. (1989), Koren et al.

(1989b), and Crissman et al. (1993) comparing basal

bronchoalveolar lavage ascorbate levels to ozone-induced

changes in bronchoalveolar lavage protein .................. 8-50

8-11 Composite of data comparing polymorphonuclear leukocytes

obtained by bronchoalveolar lavage 16 to 18 hours after

ozone exposure of humans (with exercise) to those of rats

exposed to ozone at rest or hyperventilated with carbon

dioxide .......................................... 8-51

8-12 Comparison of changes in forced vital capacity in

humans and frequency of breathing in rats with up to

five consecutive days of ozone exposure ................... 8-53

III-xx
List of Figures (cont’d)

Number Page

8-13 Changes in forced expiratory volume in one second versus

pulmonary tissue dose ................................ 8-57

8-14 Relationship between change in alveolar wall thickness

and predicted ozone dose as a function of distance

from the bronchiole-alveolar duct junction .................. 8-58

8-15 The maximum ratio of ozone-altered breathing frequency to

control breathing frequency at various ozone concentrations versus

predicted average dose rate to the proximal alveolar region ..... 8-59

8-16 Protein in the bronchoalveolar lavage for several laboratory

animal species and humans, as related to the estimated

pulmonary dose .................................... 8-60

8-17 The variation in exposure concentration for the New York City

adult and child ..................................... 8-66

8-18 Change from control of total interstitial and acellular thickness

for rats exposed to ozone in the U.S. Environmental Protection

Agency (Chang et al., 1992) and National Toxicology Program/

Health Effects Institute (Chang et al., 1994) studies ........... 8-73

9-1 Mean predicted changes in forced expiratory volume in one second

following two-hour exposures to ozone with increasing levels of

intermittent exercise ................................. 9-16

9-2 Predicted mean decrements in forced expiratory volume in one

second for one- and two-hour exposures to ozone with

intermittent heavy exercise and 6.6-hour exposures with

moderate prolonged exercise ........................... 9-17

9-3 Derived means of bronchoalveolar lavage protein denoted by

symbols and the exponential model shown by lines as time of

exposure varies from two to eight hours ................... 9-17

9-4 Predicted mean forced vital capacity for rats exposed to

ozone while undergoing intermittent carbon dioxide-induced

hyperpnea ........................................ 9-18

III-xxi
List of Figures (cont’d)

Number Page

9-5 Average number of adjusted respiratory admissions among all

168 hospitals by decile of the daily one-hour maximum ozone

level, lagged one day ................................ 9-18

9-6 Predicted mean decrements in forced expiratory volume

in one second following two-hour exposures to ozone

while undergoing heavy intermittent exercise for three ages ...... 9-19

9-7 The distribution of response for 87 subjects exposed to

clean air and at least one of 0.08, 0.10, or 0.12 ppm

ozone ........................................... 9-20

9-8 Histograms of regression slopes for forced expiratory volume in

one second versus one-hour ozone concentration in children

attending a summer camp in northwestern New Jersey ......... 9-21

9-9 Proportion of heavily exercising individuals predicted to

experience a 10% decrement in forced expiratory volume in one

second following a one- or two-hour exposure to ozone ........ 9-22

9-10 Proportion of heavily exercising individuals predicted

to experience mild cough following a two-hour

ozone exposure .................................... 9-22

9-11 Proportion of moderately exercising individuals exposed to ozone

for 6.6 hours predicted to experience 5, 10, or 15% decrements

in forced expiratory volume in one second as a function of

concentration times time for age equal to 24 years ............ 9-23

9-12 A summary of the morphologic lesions found in the terminal

bronchioles and centriacinar region of the lung following

exposure of laboratory rats to filtered air or a simulated

ambient pattern of ozone for up to 78 weeks ................ 9-28

9-13 Schematic comparison of the duration-response profiles for

epithelial hyperplasia, bronchoalveolar exudation, and

interstitial fibrosis in the centriacinar region of lung exposed

to a constant low concentration of ozone ................... 9-29

III-xxii
Authors, Contributors, and Reviewers

Chapter 6. Toxicological Effects of Ozone

and Related Photochemical Oxidants

Principal Authors

Dr. David J.P. Bassett—Department of Occupational and Environmental Health, College of

Pharmacy and Allied Health Professions, Shapero Hall, Wayne State University, Detroit, MI

48202

Dr. Deepak K. Bhalla—Department of Community and Environmental Medicine, University of

California, Irvine, CA 92717

Dr. Judith A. Graham—National Exposure Research Laboratory (MD-75), U.S. Environmental

Protection Agency, Research Triangle Park, NC 27711

Dr. George J. Jakab—Department of Environmental Health Sciences, The Johns Hopkins

University, School of Hygiene and Public Health, 615 N. Wolfe Street, Baltimore, MD 21209

Dr. Joseph R. Landolph—Department of Microbiology, USC Comprehensive Cancer Center,

USC School of Medicine, Norris Cancer Hospital and Research Institute,

1441 Eastlake Avenue, Los Angeles, CA 90033

Dr. Richard B. Schlesinger—Institute of Environmental Medicine, New York University

Medical Center, Long Meadow Road, Tuxedo, NY 10987

Dr. Jeffrey S. Tepper—Genentech, Inc., 460 Point San Bruno Blvd., South San Francisco, CA

94080

Dr. Walter S. Tyler—Department of Anatomy, School of Veterinary Medicine, University of

California, Davis, CA 95616

Contributors and Reviewers

Dr. Gary A. Boorman—National Institute of Environmental Health Sciences, P.O. Box 12233,

Research Triangle Park, NC 27709

Dr. Daniel L. Costa—National Health and Environmental Effects Research Laboratory

(MD-82), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

III-xxiii
Authors, Contributors, and Reviewers (cont’d)

Dr. Max Costa—Department of Environmental Medicine, New York University Medical

Center, 550 First Avenue, New York, NY 10016

Dr. Donald L. Dungworth—Department of Veterinary Pathology, School of Veterinary

Medicine, University of California, Davis, CA 95616

Dr. Ian Gilmour—Center for Environmental Medicine and Lung Biology, U.S. Environmental

Protection Agency (MD-92), Research Triangle Park, NC 27711

Dr. Kenneth B. Gross—Biomedical Science Department, General Motors Research Laboratory,

Warren, MI 48090

Dr. Gary E. Hatch—National Health and Environmental Effects Research Laboratory (MD-82),

U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Rogene F. Henderson—Inhalation Toxicology Research Institute, Lovelace Biomedical and

Environmental Research Institute, P.O. Box 5890, Albuquerque, NM 87185

Dr. Dallas M. Hyde—Department of Anatomy, School of Veterinary Medicine, University of

California, Davis, CA 95616

Dr. Jerald A. Last—California Primate Research Center, University of California, Davis, CA

95616

Dr. Daniel B. Menzel—Department of Community and Environmental Medicine, College of

Medicine, University of California, Irvine, CA 92715

Dr. Robert R. Mercer—Department of Medicine, Division of Allergy and Respiratory Disease,

P.O. Box 3177, Duke University Medical Center, Durham, NC 27710

Dr. Frederick J. Miller—Chemical Industry Institute of Toxicology, P.O. Box 12137, Research

Triangle Park, NC 27709

Dr. Kathleen M. Nauss—Health Effects Institute, 141 Portland St., Suite 7300,

Cambridge, MA 02139

Dr. Steven C. Nesnow—National Health and Environmental Effects Research Laboratory

(MD-68), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Robert F. Phalen—Department of Community and Environmental Medicine, University of

California, Irvine, CA 92717

III-xxiv
Authors, Contributors, and Reviewers (cont’d)

Dr. Charles G. Plopper—Department of Anatomy, School of Veterinary Medicine, University

of California, Davis, CA 95616

Dr. Edward M. Postlethwait—Pulmonary Division H-76, Department of Internal Medicine,

University of Texas Medical School, Galveston, TX 77550

Mr. Mark E. Raizenne—Health and Welfare Canada, Environmental Health Center, Tunney’s

Pasture, Ottawa, Ontario K1A OL2, CANADA

Dr. Edward S. Schelegle—Department of Human Physiology, School of Medicine, Building 1-

A, Room 4140, University of California, Davis, CA 95616

Dr. MaryJane Selgrade—National Health and Environmental Effects Research Laboratory

(MD-92), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. David Warshawsky—Kettering Laboratories, University of Cincinnati, School of Medicine,

Department of Environmental Health, 3223 Eden Avenue, Cincinnati, OH 45267

Dr. M. Jean Wiester—National Health and Environmental Effects Research Laboratory

(MD-82), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Jeannette Wiltse—National Center for Environmental Assessment (8601), U.S.

Environmental Protection Agency, 401 M. Street, S.E., Washington, DC 20460

Dr. Hanspeter R. Witschi—Toxic Substances Research and Teaching Program, University of

California, Davis, CA 95616

Chapter 7. Human Health Effects of Ozone

and Related Photochemical Oxidants

Principal Authors

Dr. Robert M. Aris—Department of Medicine, The University of North Carolina,

724 Burnette-Womack Bldg., Chapel Hill, NC 27599

Dr. John R. Balmes—Center for Occupational and Environmental Health, San Francisco

General Hospital, 1001 Potrero Avenue, Bldg. 30, 5th Floor, San Francisco, CA 94110

Dr. Robert B. Devlin—National Health and Environmental Effects Research Laboratory

(MD-58), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

III-xxv
Authors, Contributors, and Reviewers (cont’d)

Dr. Deborah M. Drechsler-Parks—Environmental Stress Laboratory, Neuroscience Research

Institute, University of California, Santa Barbara, CA 93106

Dr. Lawrence J. Folinsbee—National Health and Environmental Effects Research Laboratory

(MD-58), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Henry Gong, Jr.—Rancho Los Amigos Medical Center, 7601 East Imperial Highway,

Downey, CA 90242

Dr. Patrick L. Kinney—School of Public Health, Columbia University, 60 Haven Avenue,

New York, NY 10032

Dr. Edward S. Schelegle—Department of Human Physiology, School of Medicine, Building 1-

A, Room 4140, University of California, Davis, CA 95616

Dr. Ira B. Tager—School of Public Health, 140 Earl Warren Hall, University of California,

Berkeley, CA 94720

Dr. George D. Thurston—Institute of Environmental Medicine, New York University Medical

Center, Long Meadow Road, Tuxedo, NY 10987

Contributors and Reviewers

Dr. William C. Adams—Department of Physical Education, University of California,

Davis, CA 95616

Dr. Rebecca Bascom—The University of Maryland School of Medicine, 10 S. Pine St.,

MSTF-800, Baltimore, MD 21201

Dr. David V. Bates—Department of Health Care and Epidemiology, University of British

Columbia, 5804 Fairview Ave., Vancouver, British Columbia V6T1Z3, CANADA

Dr. William S. Beckett—Yale School of Medicine, 333 Cedar St., New Haven, CT 06510

Dr. Philip A. Bromberg—Department of Medicine, The University of North Carolina,

724 Burnett-Womack Bldg., 229H, Chapel Hill, NC 27599

Dr. Douglas Dockery—Harvard School of Public Health, Environmental Epidemiology,

665 Huntington Avenue, Boston, MA 02115

Dr. William Eschenbacher—Methodist Hospital, 6565 Fannin, M.S., F980,

Houston, TX 77030

III-xxvi
Authors, Contributors, and Reviewers (cont’d)

Dr. Mark Frampton—Pulmonary Disease Unit, Box 692, University of Rochester Medical

Center, 601 Elmwood Avenue, Rochester, NY 14642

Dr. Judith A. Graham—National Center for Environmental Assessment (MD-52),

U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Milan J. Hazucha—Department of Medicine, Center for Environmental Medicine and Lung

Biology, The University of North Carolina, Trailer #4, Medical Bldg. C 224H, Chapel Hill,

NC 27599

Dr. Steven M. Horvath—Environmental Stress Laboratory, Neuroscience Research Institute,

University of California, Santa Barbara, CA 93106

Dr. Howard R. Kehrl—National Health and Environmental Effects Research Laboratory

(MD-58), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Jane Q. Koenig—Department of Environmental Health, School of Public Health and

Community Medicine, University of Washington, SC-34, Seattle, WA 98195

Dr. Hillel S. Koren—National Health and Environmental Effects Research Laboratory

(MD-58), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Debra L. Laskin—Department of Pharmacology and Toxicology, College of Pharmacy,

Rutgers University, Piscataway, NY 08855

Mr. William S. Linn—Rancho Los Amigos Medical Center, 51 Medical Science Building,

7601 East Imperial Highway, Downey, CA 90242

Dr. Fred Lipfert—23 Carll Ct., Northport, NY 11768

Dr. William F. McDonnell—National Health and Environmental Effects Research Laboratory

(MD-58), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Mr. Mark E. Raizenne—Health and Welfare Canada, Environmental Health Center, Tunney’s

Pasture, Ottawa, Ontario K1A OL2, CANADA

Dr. Jonathan M. Samet—Department of Epidemiology, School of Hygiene and Public Health,

Johns Hopkins University, 615 N. Wolfe St., Baltimore, MD 21205

Dr. Joel Schwartz—Environmental Epidemiology Program, Harvard School of Public Health,

665 Huntington Avenue, Boston, MA 02115

III-xxvii
Authors, Contributors, and Reviewers (cont’d)

Dr. Elston Seal—National Health and Environmental Effects Research Laboratory (MD-58),

U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Dalia M. Spektor—2242 20th Street (#1), Santa Monica, CA 90405

Chapter 8. Extrapolation of Animal Toxicological Data

to Humans

Principal Authors

Dr. Daniel L. Costa—National Health and Environmental Effects Research Laboratory

(MD-82), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Timothy R. Gerrity—Medical Research Services, Department of Veterans Affairs,

810 Vermont Ave., N.W., Washington, DC 20420

Dr. John H. Overton—National Health and Environmental Effects Research Laboratory

(MD-82), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Reviewers

Dr. Daniel B. Menzel—Department of Community and Environmental Medicine, College of

Medicine, University of California, Irvine, CA 92715

Dr. Robert R. Mercer—Department of Medicine, Division of Allergy and Respiratory Disease,

P.O. Box 3177, Duke University Medical Center, Durham, NC 27710

Dr. Frederick J. Miller—Chemical Industry Institute of Toxicology, P.O. Box 12137, Research

Triangle Park, NC 27709

Dr. Kathleen M. Nauss—Health Effects Institute, 141 Portland St., Suite 7300,

Cambridge, MA 02139

Dr. Edward M. Postlethwait—Pulmonary Division H-76, Department of Internal Medicine,

University of Texas Medical School, Galveston, TX 77550

Mr. Mark E. Raizenne—Health and Welfare Canada, Environmental Health Center, Tunney’s

Pasture, Ottawa, Ontario K1A OL2, CANADA

III-xxviii
Authors, Contributors, and Reviewers (cont’d)

Dr. James S. Ultman—Department of Chemical Engineering, Pennsylvania State University,

University Park, PA 16802

Dr. M. Jean Wiester—National Health and Environmental Effects Research Laboratory

(MD-82), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Chapter 9. Integrative Summary of Ozone Health Effects

Principal Authors

Dr. Daniel L. Costa—National Health and Environmental Effects Research Laboratory

(MD-82), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Robert B. Devlin—National Health and Environmental Effects Research Laboratory

(MD-58), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Lawrence J. Folinsbee—National Health and Environmental Effects Research Laboratory

(MD-58), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Timothy R. Gerrity—Medical Research Services, Department of Veterans Affairs,

810 Vermont Ave., N.W., Washington, DC 20420

Dr. Judith A. Graham—National Center for Environmental Assessment (MD-52),

U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. William F. McDonnell—National Health and Environmental Effects Research Laboratory

(MD-58), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Mr. James A. Raub—National Center for Environmental Assessment (MD-52),

U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Contributors and Reviewers

Dr. Frederick J. Miller—Chemical Industry Institute of Toxicology, P.O. Box 12137, Research

Triangle Park, NC 27709

Dr. Edward S. Schelegle—Department of Human Physiology, School of Medicine, Building 1-

A, Room 4140, University of California, Davis, CA 95616

III-xxix
Authors, Contributors, and Reviewers (cont’d)

Dr. Walter S. Tyler—Department of Anatomy, School of Veterinary Medicine, University of

California, Davis, CA 95616

Dr. Jeannette Wiltse—National Center for Environmental Assessment, U.S. Environmental

Protection Agency (8601), 401 M. Street, S.E., Washington, DC 20460

III-xxx
U.S. Environmental Protection Agency

Science Advisory Board

Clean Air Scientific Advisory Committee

Ozone Review

Chairman

Dr. George T. Wolff—General Motors Corporation, Environmental and Energy Staff,

General Motors Bldg., 12th Floor, 3044 West Grand Blvd., Detroit, MI 48202

Members

Dr. Stephen Ayres—Office of International Health Programs, Virginia Commonwealth

University, Medical College of Virginia, Box 980565, Richmond, VA 23298

Dr. Jay S. Jacobson—Boyce Thompson Institute, Tower Road, Cornell University, Ithaca, NY

14853

Dr. Joseph Mauderly—Inhalation Toxicology Research Institute, Lovelace Biomedical and

Environmental Research Institute, P.O. Box 5890, Albuquerque, NM 87185

Dr. Paulette Middleton—Science & Policy Associates, Inc., Western Office, Suite 140,

3445 Penrose Place, Boulder, CO 80301

Dr. James H. Price, Jr.—Research and Technology Section, Texas Natural Resources

Conservation Commission, P.O. Box 13087, Austin, TX 78711

Invited Scientific Advisory Board Members

Dr. Morton Lippmann—Institute of Environmental Medicine, New York University Medical

Center, Long Meadow Road, Tuxedo, NY 10987

Dr. Roger O. McClellan—Chemical Industry Institute of Toxicology, P.O. Box 12137,

Research Triangle Park, NC 27711

Consultants

Dr. Stephen D. Colome—Integrated Environmental Services, University Tower, Suite 280,

4199 Campus Drive, Irvine, CA 92715

III-xxxi
U.S. Environmental Protection Agency

Science Advisory Board

Clean Air Scientific Advisory Committee

(cont’d)

Dr. A. Myrick Freeman—Department of Economics, Bowdoin College, Brunswick, ME 04011

Dr. Allan Legge—Biosphere Solutions, 1601 11th Avenue, NW, Calgary, Alberta T2N 1H1,

CANADA

Dr. William Manning—Department of Plant Pathology, University of Massachusetts, Amherst,

MA 01003

Dr. D. Warner North—Decision Focus, Inc., 650 Castro Street, Suite 300, Mountain View,

CA 94041

Dr. Frank E. Speizer—Harvard Medical School, Channing Lab, 180 Longwood Avenue,

Boston, MA 02115

Dr. George E. Taylor—Department of Environmental and Resource Sciences, 130 Fleischmann

Agriculture Bldg. 199, University of Nevada, Reno, NV 89557

Dr. Mark J. Utell—Pulmonary Disease Unit, Box 692, University of Rochester Medical

Center, 601 Elmwood Avenue, Rochester, NY 14642

Designated Federal Official

Mr. Randall C. Bond—Science Advisory Board (1400), U.S. Environmental Protection

Agency, 401 M Street, SW, Washington, DC 20460

Staff Assistant

Ms. Lori Anne Gross—Science Advisory Board (1400), U.S. Environmental Protection

Agency, 401 M Street, SW, Washington, DC 20460

III-xxxii
U.S. Environmental Protection Agency

Project Team for Development of Air Quality Criteria

for Ozone and Related Photochemical Oxidants

Scientific Staff

Mr. James A. Raub—Health Scientist, National Center for Environmental Assessment

(MD-52), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. A. Paul Altshuller—Physical Scientist, National Center for Environmental Assessment

(MD-52), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Mr. William G. Ewald—Health Scientist, National Center for Environmental Assessment (MD52), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. J.H.B. Garner—Ecologist, National Center for Environmental Assessment (MD-52),

U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Judith A. Graham—Associate Director, National Center for Environmental Assessment

(MD-52), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Ms. Ellie R. Speh—Secretary, National Center for Environmental Assessment (MD-52),

U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Ms. Beverly E. Tilton—Physical Scientist, National Center for Environmental Assessment

(MD-52), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Technical Support Staff

Mr. Douglas B. Fennell—Technical Information Specialist, National Center for Environmental

Assessment (MD-52), U.S. Environmental Protection Agency, Research Triangle Park, NC

27711

Mr. Allen G. Hoyt—Technical Editor and Graphic Artist, National Center for Environmental

Assessment (MD-52), U.S. Environmental Protection Agency, Research Triangle Park, NC

27711

Ms. Diane H. Ray—Technical Information Manager (Public Comments), National Center for

Environmental Assessment (MD-52), U.S. Environmental Protection Agency, Research

Triangle Park, NC 27711

III-xxxiii
U.S. Environmental Protection Agency

Project Team for Development of Air Quality Criteria

for Ozone and Related Photochemical Oxidants

(cont’d)

Mr. Richard N. Wilson—Clerk, National Center for Environmental Assessment (MD-52), U.S.

Environmental Protection Agency, Research Triangle Park, NC 27711

Document Production Staff

Ms. Marianne Barrier—Graphic Artist, ManTech Environmental Technology, Inc.,

P.O. Box 12313, Research Triangle Park, NC 27709

Mr. John R. Barton—Document Production Coordinator, ManTech Environmental Technology,

Inc., P.O. Box 12313, Research Triangle Park, NC 27709

Ms. Lynette D. Cradle—Word Processor, ManTech Environmental Technology, Inc., P.O. Box

12313, Research Triangle Park, NC 27709

Ms. Shelia H. Elliott—Word Processor, ManTech Environmental Technology, Inc.,

P.O. Box 12313, Research Triangle Park, NC 27709

Ms. Sandra K. Eltz—Word Processor, ManTech Environmental Technology, Inc.,

P.O. Box 12313, Research Triangle Park, NC 27709

Ms. Jorja R. Followill—Word Processor, ManTech Environmental Technology, Inc.,

P.O. Box 12313, Research Triangle Park, NC 27709

Ms. Sheila R. Lassiter—Word Processor, ManTech Environmental Technology, Inc.,

P.O. Box 12313, Research Triangle Park, NC 27709

Ms. Wendy B. Lloyd—Word Processor, ManTech Environmental Technology, Inc.,

P.O. Box 12313, Research Triangle Park, NC 27709

Ms. Carolyn T. Perry—Word Processor, ManTech Environmental Technology, Inc.,

P.O. Box 12313, Research Triangle Park, NC 27709

Ms. Cheryl B. Thomas—Word Processor, ManTech Environmental Technology, Inc.,

P.O. Box 12313, Research Triangle Park, NC 27709

Mr. Peter J. Winz—Technical Editor, ManTech Environmental Technology, Inc.,

P.O. Box 12313, Research Triangle Park, NC 27709

III-xxxiv
U.S. Environmental Protection Agency

Project Team for Development of Air Quality Criteria

for Ozone and Related Photochemical Oxidants

(cont’d)

Technical Reference Staff

Mr. John A. Bennett—Bibliographic Editor, ManTech Environmental Technology, Inc.,

P.O. Box 12313, Research Triangle Park, NC 27709

Ms. S. Blythe Hatcher—Bibliographic Editor, Information Organizers, Inc., P.O. Box 14391,

Research Triangle Park, NC 27709

Ms. Susan L. McDonald—Bibliographic Editor, Information Organizers, Inc., P.O. Box 14391,

Research Triangle Park, NC 27709

Ms. Carol J. Rankin—Bibliographic Editor, Information Organizers, Inc., P.O. Box 14391,

Research Triangle Park, NC 27709

Ms. Deborah L. Staves—Bibliographic Editor, Information Organizers, Inc., P.O. Box 14391,

Research Triangle Park, NC 27709

Ms. Patricia R. Tierney—Bibliographic Editor, ManTech Environmental Technology, Inc.,

P.O. Box 12313, Research Triangle Park, NC 27709

III-xxxv